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From our teachers and their teachers,
to our students and their students
LECTURE NOTES ON
Respiratory
Medicine
S.J. BOURKE
MD, FRCPI, FRCP, FCCP, DCH
Consultant Physician
Royal Victoria Infirmary
Newcastle upon Tyne
Senior Lecturer in Medicine
University of Newcastle upon Tyne
Sixth Edition
1975, 1980, 1985, 1991, 1998, 2003 by Blackwell Publishing Ltd
Blackwell Publishing, Inc., 350 Main Street, Malden, Massachusetts 02148-5018, USA
Blackwell Publishing Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UK
Blackwell Publishing Asia Pty Ltd, 550 Swanston Street, Carlton South,Victoria 3053,Australia
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All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or
transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or
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the prior permission of the publisher.
Bourke, S. J.
Lecture notes on respiratory medicine / S. J. Bourke. 6th ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 1-40510-675-1 (alk. paper)
1. Respiratory organsDiseasesOutlines, syllabi, etc.
[DNLM: 1. Respiratory Tract Diseases. WF 140 B8475L 2003]
I. Title.
RC731 .B69 2003
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2002015535
ISBN 1-4051-0675-1
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Preface, vi
Index, 197
v
Preface
It is now more than a quarter of a century since the first edition of Lecture Notes on
Respiratory Medicine was written by my predecessor and colleague, Dr Alistair
Brewis. It rapidly became a classic textbook which opened the eyes of a generation
of students to the special fascinations of the subject such that many were attracted
into the specialty.Thus, students became teachers, and continued to learn by teach-
ing. Subsequent editions show how respiratory medicine has developed over the
years to become such a major specialty in hospitals and in the community, treating a
wide range of diseases from cystic fibrosis to lung cancer, asthma to tuberculosis,
sleep disorders to occupational lung diseases.
In the sixth edition the text has been revised and expanded to provide a concise
up-to-date summary of respiratory medicine for undergraduate students and junior
doctors preparing for postgraduate examinations. A particular feature of respira-
tory medicine in recent years has been the focusing of skills from a variety of disci-
plines in providing the best care for patients with respiratory diseases, and this book
should be useful to colleagues such as physiotherapists, lung function technicians
and respiratory nurse specialists. Some of Dr Alistair Brewis original drawings, such
as the classic blue bloater and pink puffer, have been retained.The emphasis of Lec-
ture Notes on Respiratory Medicine has always been on information which is useful and
relevant to everyday clinical medicine, and the sixth edition remains a patient-based
book to be read before and after visits to the wards and clinics where clinical medi-
cine is learnt and practised. As Lecture Notes on Respiratory Medicine develops over
time, we remain grateful to our teachers, and their teachers, and we pass on our
evolving knowledge of respiratory medicine to our students, and their students.
S.J.Bourke
vi
CHAPTER 1
Anatomy and Physiology
of the Lungs
1
2 Chapter 1: Anatomy of the Lungs
B RO N CHO P U L M O N A R Y SE G M E N T S
Apical
Apical
Posterior
UL Posterior
Anterior UL
Anterior
Superior
LING
Inferior
Lateral
ML Apical
Medial Apical Lateral basal
lower
lower LL
Lateral basal Posterior basal
Fig. 1.1 Diagram of
LL Medial basal
Posterior basal Anterior basal bronchopulmonary segments.
Anterior basal LING, lingula; LL, lower lobe; ML,
middle lobe; UL, upper lobe.
S UR F A CE AN A T OM Y OF T H E L U N G S
Clavicle
4th Thoracic
spine RUL
RUL Level of
LUL angle of
Louis RML
RML
RLL 6th Costal
RLL LLL cartilage
8th Rib
Lower edge
of lung
10th Rib
Lower limit
Lower edge Lower limit of pleura of pleura
of lung
Mid-axillary line
(a) (b)
Fig. 1.2 Surface anatomy. (a) Anterior view of the bronchioles. In the bronchi, smooth muscle is
lungs. (b) Lateral view of the right side of chest at arranged in a spiral fashion internal to the carti-
resting end-expiratory position. LLL, left lower
laginous plates.The muscle coat becomes more
lobe; LUL, left upper lobe; RLL, right lower lobe;
complete distally as the cartilaginous plates be-
RML, right middle lobe; RUL, right upper lobe.
come more fragmentary. The epithelial lining is
ciliated and includes goblet cells. The cilia beat
with a whip-like action, and waves of contrac-
tion pass in an organised fashion from cell to cell
Alveolar ventilation 3
so that material trapped in the sticky mucus respiratory muscles gradually relax their force
layer above the cilia is moved upwards and out of contraction. About 8L of air are drawn into
of the lung. This mucociliary escalator is an the lungs each minute at rest but not all this air
important part of the lungs defences. Larger reaches the alveoli. About a quarter of the air
bronchi also have acinar mucus-secreting glands breathed in remains in the airways from the tra-
in the submucosa which are hypertrophied in chea to the terminal bronchioles and is not
chronic bronchitis. Alveoli are about 0.1 available for gas exchange.This is referred to as
0.2 mm in diameter and are lined by a thin layer the anatomical deadspace. The distribution
of cells of which there are two types: type I of air within the lungs is uneven because the re-
pneumocytes have flattened processes which sistance of the airways to airflow is not uniform
extend to cover most of the internal surface of and because the compliance of different parts of
the alveoli; type II pneumocytes are less numer- the lungs varies. The greater part of total air-
ous and contain lamellated structures which are way resistance to airflow during inspiration in
concerned with the production of surfactant the normal individual occurs in the larger air-
(Fig. 1.3).There is a potential space between the ways trachea, main bronchi, larynx. Increased
alveolar cells and the capillary basement mem- resistance occurring in disease generally origi-
brane which is only apparent in disease states nates in the more peripheral airways. During
when it may contain fluid, fibrous tissue or a cel- inspiration, pulmonary elastic recoil acts as a
lular infiltrate. force opening the airways. During expiration,
the outward traction on the walls of the airways
diminishes so that there is an increasing tend-
Alveolar ventilation ency towards closure of the airways. Compli-
ance is a physiological term expressing the
During inspiration the diaphragm descends, distensibility of the lungs. The inherent elastic
the lower ribs move upwards and outwards, and properties of the lungs cause them to retract
the upper ribs and sternum move upwards and from the chest wall producing a negative in-
forwards. The resultant expansion of the chest trapleural pressure. Lung compliance is ex-
results in a negative intrathoracic pressure pressed as the change in lung volume brought
sucking air into the lungs. Expiration, by com- about by unit change in transpulmonary (intraple-
parison, is a relatively passive procedure as the ural) pressure. The retractive forces of the lung
4 Chapter 1: Anatomy of the Lungs
are balanced by the semi-rigid structure of the the distribution of blood with perfusion being
thoracic cage and the action of the respiratory preferentially distributed to the lung bases.
muscles. The effect of gravity results in the Hypoxia is a potent stimulus to pulmonary
weight of the lungs keeping the upper parts vasoconstriction and seems to exert a direct ef-
under a greater stretch than the more depen- fect on arterial smooth muscle. This reflex acts
dent zones. The upper parts are less compliant as a form of autoregulation, diverting blood
and less receptive to air entry during inspira- away from underventilated areas of the lung.
tion.Thus, the lower zones receive more venti- The pulmonary capillaries may also be com-
lation than the upper zones. Local differences in pressed as they pass through the alveolar walls if
compliance and airway resistance are present to alveolar pressure rises above capillary pressure.
a small degree even in normal lungs but occur to
a much greater extent in diseased lungs.
Gas exchange and
ventilation/perfusion (V/Q)
Lung perfusion relationships
The lungs receive a blood supply from both the During steady-state conditions the relationship
pulmonary and systemic circulations. The pul- between the amount of carbon dioxide pro-
monary artery arises from the right ventricle duced by the body and the amount of oxygen
and divides into left and right pulmonary arter- absorbed depends upon the metabolic activity
ies, which further divide into branches accom- of the body and is referred to as the respira-
panying the bronchial tree. The pulmonary tory quotient (RQ). The actual value varies
capillary network in the alveolar walls is very from 0.7 during pure fat metabolism to 1.0 dur-
dense and provides a very large surface area for ing pure carbohydrate metabolism. The RQ is
gas exchange.The pulmonary venules drain lat- usually about 0.8 but it is often assumed to be
erally to the periphery of lung lobules and then 1.0 to make calculations easier.
pass centrally in the interlobular and interseg- If carbon dioxide is being produced by the
mental septa, ultimately joining to form the four body at a constant rate the PCO2 of alveolar air
main pulmonary veins which empty into the left depends upon the amount of outside air that the
atrium. Several small bronchial arteries usu- carbon dioxide is mixed with in the alveoli, i.e.
ally arise from the descending aorta and travel in PCO2 depends only upon alveolar ventilation and
the outer layers of the bronchi and bronchioles arterial PCO2 is a measure of alveolar ven-
supplying the tissues of the airways down to the tilation. If alveolar ventilation falls, PCO2 rises.
level of the respiratory bronchiole. Most of the The level of alveolar PO2 also varies with alveolar
blood drains into radicles of the pulmonary vein ventilation but measurement of arterial PO2 is
contributing a small amount of desaturated less reliable than measurement of PCO2 as an
blood which accounts for part of the physiol- index of alveolar ventilation because it is pro-
ogical shunt observed in normal individuals. foundly affected by regional changes in ventila-
The bronchial arteries may undergo hypertro- tion/perfusion ratios.
phy when there is chronic pulmonary inflamma- The possible combinations of PCO2 and PO2
tion, and major haemoptysis in diseases such as are shown in Fig. 1.4. Moist atmospheric air at
bronchiectasis or aspergilloma usually arises 37C has a PO2 of about 20 kPa (150 mmHg). In
from the bronchial rather than the pulmonary this model, oxygen could be exchanged with car-
arteries and may be treated by therapeutic bon dioxide in the alveoli to produce any combi-
bronchial artery embolisation. The pulmonary nation of PO2 and PCO2 described by the oblique
circulation normally offers a much lower resis- line which joins PO2 20 kPa (150 mmHg) and PCO2
tance and operates at a lower perfusion pres- 20 kPa (150 mmHg).The position of the cross on
sure than the systemic circulation.At rest in the this line represents the composition of a hypo-
erect position, gravity exerts a major effect on thetical sample of alveolar air. A fall in alveolar
Control of breathing 5
OX Y G E N C A R BON DI OX I DE DI AGRAM
mmHg kPa
150 20
16
100
RQ = 1
12
PCO2
Fig. 1.4 Oxygencarbon RQ = 0.8
dioxide diagram.The
continuous and interrupted 8 (b)
(c) Underventilation
lines describe the possible 50
combinations of PCO and PO2 in
2 40 5.3 Overventilation
alveolar air when the RQ is 1 (a)
4
and 0.8, respectively. (a) A PO2 of air
hypothetical sample of arterial
blood. (b) Progressive 4 8 12 16 20 kPa
underventilation. (c) PO2 lower 0 50 100 150 mmHg
than can be accounted for by PO2
underventilation alone.
ventilation would result in an upward movement ation curves for oxygen and carbon dioxide are
of this point along the line and conversely an in- very different and are shown together on the
crease in alveolar ventilation would result in a same scale in Fig. 1.5. Over the range normally
downward movement of the point. Point (a) rep- encountered the amount of carbon dioxide car-
resents the PCO2 and PO2 of arterial blood (it lies ried by the blood is roughly proportional to the
a little to the left of the RQ 0.8 line because of the PCO2. However, the quantity of oxygen carried is
small normal alveolararterial oxygen tension roughly proportional to the PO2 only over a very
difference). Point (b) represents the arterial gas limited range of about 37 kPa (2252 mmHg).
tension after a period of underventilation. If the Above 13.3 kPa (100 mmHg) the haemoglobin is
arterial PCO2 and PO2 were those represented by fully saturated and hardly any additional oxygen
point (c) this would imply that the fall in PO2 was is carried. The different shapes of the dissocia-
more than could be accounted for on the tion curves of oxygen and carbon dioxide ex-
grounds of reduced alveolar ventilation. plain why ventilation/perfusion mismatch has a
There is normally a small difference (<2.5 kPa greater effect on PO2 than on PCO2 levels.
or 20 mmHg) between alveolar and arterial
oxygen tensions. This gradient may be roughly
calculated using the simplified formula: Control of breathing
Alveolar - arterial ( A - a) gradient
The respiratory centre in the brain stem con-
= P1o2 - (Po2 + Pco2 ) sists of an ill-defined group of interconnected
(PIO 2 is the partial pressure of fractional inspired neurones, responsible for generating phasic
oxygen which for atmospheric air at 37C is motor discharges which ultimately pass via
20 kPa). phrenic and intercostal nerves to the respira-
The quantity of gas carried by blood when ex- tory muscles. Some of the more important fac-
posed to different partial pressures of the gas is tors influencing the output of the respiratory
described by the dissociation curve.The dissoci- centre are shown in Fig. 1.6.The PCO2 of arterial
OXYG EN AN D C A R B O N D I O XI DE
DIS S O CIA TIO N C UR V E S
d
ce
du d
Re a te
70
gen IDE
y OX
Ox DI
Volume of gas contained in blood (ml/100 ml)
ON
RB
60 CA
Venous blood
50
Arterial blood
40
30
Arterial blood
20
OXYGEN
Venous blood
10
4 8 12 16 20 kPa
Fig. 1.5 The blood oxygen and
0 20 40 60 80 100 120 140 160 mmHg
Partial pressure carbon dioxide dissociation
curves drawn to the same scale.
CON TR O L O F V E N T I L A T I O N
Higher centres
PCO2
Inflation
J
Respiratory
CSF centre Vagus
PCO2
[H+] Irritant
?
a Chest
wall
Respiratory
Limb
muscles
joints
blood is the most important factor in the regula- flex is doubtful in humans. Stimulation of J re-
tion of ventilation. An increase in PCO2 stimu- ceptors, situated deep in the lung parenchyma,
lates sensitive areas on the surface of the brain increases ventilation. Excitation of stretch re-
stem directly provoking an increase in ventila- ceptors in muscles, joints and chest wall may
tion.An increase in [H+] (fall in pH) also stim- also enhance ventilation.
ulates ventilation. Hypoxaemia sensitises the
respiratory centre to carbon dioxide probably
via an effect on the carotid and aortic bodies. Further reading
However, the effect of hypoxaemia is small
above a PO2 of about 8.8 kPa (60 mmHg). Input Brewis RAL, White FE. Anatomy of the thorax. In:
from higher centres is important, with alarm Brewis RAL, Corrin B, Geddes DM, Gibson GJ, eds.
and excitement stimulating ventilation, and Respiratory Medicine. London: WB Saunders Co.,
1995: 2253.
sleep and coma reducing the response to nor-
Cotes JE. Lung Function: Assessment and Application in
mal ventilatory stimuli. The vagus nerve car- Medicine. Oxford: Blackwell Science, 1993.
ries afferent stimuli from the respiratory tract Gibson GJ. Clinical Tests of Respiratory Function.
which may influence breathing. In animals, Oxford: Chapman and Hall, 1996.
stretching of the lungs causes reflex inhibition of West JB. Pulmonary Pathophysiology The Essentials.
subsequent inspiration (HeringBreuer infla- Baltimore:Williams and Wilkins, 1987.
tion reflex) although the importance of this re-
CHAPTER 2
Symptoms and Signs of
Respiratory Disease
8
Symptoms 9
Pulmonary vasculitis
History
Goodpastures syndrome
Wegeners granulomatosis
Past medical history
Table 2.2 Major causes of haemoptysis. Did the patient suffer any major illness in child-
hood? Did the patient have frequent absences
from school? Was the patient able to play games
at school? Did any abnormalities declare them-
oedema and pulmonary vasculitis (Table 2.2). In selves at a pre-employment medical examina-
some cases no cause is found and the origin of tion or on chest X-ray? Has the patient ever
the blood may have been in the upper airway, been admitted to hospital with chest disease? A
e.g. nose (epistaxis), pharynx or gums. long history of childhood bronchitis may in fact
indicate asthma. Severe whooping cough or
Chest pain measles in childhood may cause bronchiectasis.
Pain which is aggravated by inspiration or Tuberculosis acquired early in life may re-
coughing is described as pleuritic pain, and the activate many years later.
patient can often be seen to wince when
breathing in, as the pain catches. Irritation of General medical history
the pleura may result from inflammation Has the patient any systemic illness which may
(pleurisy), infection (pneumonia), infarction of involve the lungs, e.g. rheumatoid arthritis? Is
underlying lung (pulmonary embolism) or the patient taking any medications which might
tumour (malignant pleural effusion). Chest wall affect the lungs, e.g. amiodarone, which can
pain resulting from injury to the intercostal cause interstitial lung disease, or b-blockers
muscles or fractured ribs, for example, is also (e.g. atenolol), which may provoke bron-
aggravated by inspiration or coughing and is chospasm? What effect will the patients lung
associated with tenderness at the point of injury. disease have on other illnesses, e.g. fitness for
surgery?
In addition to these major respiratory symp-
toms it is important to consider other associ- Family history
ated symptoms. For example, anorexia and Is there any history of lung disease in the family?
weight loss are features of malignancy or An increased prevalence of lung disease in a fam-
chronic lung infections (e.g. lung abscess). ily may result from shared genes, i.e. inherited
Pyrexia and sweating are features of acute traits such as cystic fibrosis, a1-anti-trypsin
Examination 11
A I R W A Y S OB STRUC TI ON
deficiency, asthmatic tendency; or from shared ferent stages in the assessment of the respira-
environment, e.g. tuberculosis. tory system is useful in focusing attention on
the features of particular importance to be
Social history sought. Powers of observation are developed
Does the patient smoke, or has he or she ever by training, and knowing what to look for and
smoked? Is the patient exposed to passive how to look for it are learned by experience.
smoking at home? It is important to obtain a
clear account of total smoking exposure over General examination
the years so as to assess the patients risk for dis- Be alert to clues to respiratory disease which
eases such as lung cancer or COPD. Does the may be evident from the moment the patient is
patient keep any pets or participate in any first seen (Fig. 2.1) or which become apparent
sports (e.g. diving) or hobbies (e.g. pigeon rac- during history taking.These include the rate and
ing) which may be important in assessing the character of breathing, signs of respiratory
lung disease? distress such as use of accessory muscles of
respiration (e.g. sternocleidomastoids), the
Occupational history shape of the chest, spine and shoulders, and
What occupations has the patient had over the the character of any cough. Hoarseness of the
years, what tasks were performed and what ma- voice may be a clue to recurrent laryngeal nerve
terials used? Did symptoms show a direct rela- damage by a carcinoma. Stridor or wheeze
tionship to the work environment as in the case may be audible. Count the respiratory rate
of occupational asthma improving away from over a period of 30 seconds. The respiratory
work and deteriorating on return to work? Has rate is best counted surreptitiously, perhaps
the patient been exposed to substances which while feeling the pulse, as patients tend to breath
may give rise to disease many years later as in faster if they are aware that you are focusing on
the case of mesothelioma arising from exposure their breathing.Avoid proceeding directly to ex-
to asbestos 20 40 years previously? amination of the chest but first pause to look for
signs in the hands such as clubbing, tar stain-
ing or features of rheumatoid arthritis.
Examination Signs of carbon dioxide retention include pe-
ripheral vasodilatation and asterixis, a flap-
Examination of the respiratory system is, of ping tremor detected by asking the patient to
course, integrated into the general examination spread his or her fingers and cock the wrists
of the patient as a whole, but outlining the dif- back. It may be accentuated by applying gentle
12 Chapter 2: Symptoms and Signs of Respiratory Disease
pressure against the patients hands in this posi- notably bronchial carcinoma and fibrotic lung
tion. Count the pulse rate over 30 seconds and disease, such as cryptogenic fibrosing alveolitis
note any abnormalities in rhythm (e.g. atrial fib- and asbestosis.Advanced clubbing is sometimes
rillation) or character (e.g. a bounding pulse of associated with hypertrophic pulmonary os-
carbon dioxide retention). Next examine the teoarthropathy in which there is new bone for-
head and neck, particularly seeking signs of mation in the subperiosteal region of the long
cyanosis, anaemia (pallor of conjunctiva), ele- bones of the arms and legs which is detectable
vation of jugular venous pressure or lymph on X-ray and is associated with pain and
node enlargement. Be alert for uncommon tenderness.
signs such as Horners syndrome (ptosis,
meiosis, enophthalmos, anhydrosis) indicating Cyanosis
damage to the sympathetic nerves by a tumour This is a bluish discoloration of the skin and
situated at the lung apex (see Chapter 13). mucous membranes as a result of an exces-
sive amount of reduced haemoglobin (usually
Clubbing >5g/dL). Central cyanosis is best seen on the
This is increased curvature of the nail with loss tip of the tongue and is the cardinal sign of
of the angle between the nail and nail bed (Fig. hypoxaemia, although it is not a sensitive sign
2.2). It is a very important sign which is associ- because it is not usually detectable until the
ated with a number of diseases (Table 2.3), most oxygen saturation has fallen to well below 85%,
Gastrointestinal
Hepatic cirrhosis
(c)
Crohns disease
Coeliac disease
Fig. 2.2 Clubbing. (a) Normal, showing the angle.
(b) Early clubbing; the angle is absent. (c) Congenital
Advanced clubbing.The nail shows increased Idiopathic familial clubbing
curvature in all directions, the angle is absent, the
base of the nail is raised up by spongy tissue and Table 2.3 Causes of clubbing.
the end of the digit is expanded.
Answer to question in Fig. 2.1: (b) has airways obstructionnote the high position of the shoulders.
Examination 13
corresponding to a PO 2 of <8 kPa (60 mmHg). is reduced if the lungs are hyperinflated (e.g. em-
Cyanosis is more difficult to detect if the patient physema) or have reduced compliance (e.g.
is anaemic or has dark-coloured skin. Because fibrosis). The costal margins normally move
of the poor sensitivity of cyanosis it is essential upwards and outwards in inspiration as the
to measure oxygenation by oximetry or arterial chest expands. In a chest which is already
blood gas sampling in patients at risk for hypox- severely overinflated (e.g. COPD) there is
aemia. Peripheral cyanosis may be caused by sometimes paradoxical movement of the costal
local circulatory slowing in the peripheries re- margins such that they are drawn inwards
sulting in more complete extraction of oxygen during inspiration: costal margin paradox
from the blood, e.g. blue hands and ears in cold (Fig. 2.3). The abdominal wall normally moves
weather. outwards on inspiration as the diaphragm
descends. Abdominal paradox, in which the
Jugular veins abdominal wall moves inwards during inspira-
Jugular veins are examined with the patient in a tion when the patient is supine, is a sign of
semi-reclining position with the trunk at an diaphragm weakness.
angle of about 45 from the horizontal.The head
is turned slightly to the opposite side and fully Palpation
supported so that the sternocleidomastoid Chest movements during respiration may be
muscles are relaxed.The jugular venous pulse is more easily appreciated by placing the hands
seen as a diffuse superficial pulsation of multiple exactly symmetrically on either side of the
wave form which is distinct from the carotid ar- upper sternum with the thumbs in the midline.
terial pulse.The height of the pulse wave is mea- The relative movement of the two hands and
sured from the top of the oscillating column of the separation of the thumbs reflect the overall
blood vertically to the sternal angle.The jugular movement of the chest and any asymmetry be-
venous pressure normally falls during inspira- tween the two sides. The position of the medi-
tion. It is elevated in right heart failure which astinum is assessed by locating the tracheal
may occur as a result of pulmonary embolism or position and the cardiac apex beat. Inserting
cor pulmonale in COPD, for example. Other a finger between the trachea and the sternoclei-
signs of right heart failure such as hepatomegaly domastoid muscle on each side is a useful way of
and peripheral oedema may also be present. detecting any tracheal deviation. Running a fin-
ger gently up and down the trachea from the
Chest examination cricoid cartilage to the sternal notch may indi-
Ask the patient to undress to the waist, and pro- cate the direction of the trachea as it enters the
ceed to examine the chest in a methodical way chest. Reduction in the crico-sternal dis-
using the techniques of inspection, palpation, tance is a sign of a hyperinflated chest.The apex
percussion and auscultation. beat is the most inferior and lateral point at
which the cardiac impulse can be felt.The inter-
Inspection costal space in which the apex beat is felt should
Look at the chest from the front, back and sides be counted down from the second intercostal
noting the overall shape and any asymmetry, space which is just below the sternal angle, and
scars or skeletal abnormality. The normal its location should also be related to landmarks
chest is flattened anteroposteriorly whereas such as the mid-clavicular or anterior axillary
the hyperinflated chest of COPD is barrel- lines. It is normally located in the fifth left inter-
shaped with an increased anteroposterior costal space in the mid-clavicular line.The medi-
diameter. Watch the movement of the chest astinum may be deviated towards or away from
carefully as the patient breathes in and out. Di- the side of disease. For example, fibrosis of the
minished movement of one side of the chest is a apex of the lung caused by previous tuberculosis
clue to disease on that side. Overall movement may pull the trachea to that side, whereas a large
14 Chapter 2: Symptoms and Signs of Respiratory Disease
Inspiration
Expiration
Fig. 2.3 Movement of the costal margin.The over the area of a pneumothorax, although it is
arrows indicate the direction of movement in rarely a reliable sign. Percussion technique is im-
normal individuals and in those with airways
portant and requires practice.The resting finger
obstruction (see text).
should be placed flat against the chest wall in an
intercostal space. The percussing finger should
pleural effusion or tension pneumothorax may strike the dorsal surface of the middle phalanx
push the trachea and apex beat away from the and should be lifted clear after each percussion
side of the lesion. Tactile fremitus refers to stroke. All areas should be percussed, paying
the ability to palpate vibrations set up by the particular attention to comparison between the
voice in the large airways and transmitted to the two sides. When percussing the back of the
chest wall.Ask the patient to say ninety-nine or chest it is helpful to ask the patient to rotate his
one, one, one and palpate the vibrations, or her arms such that one elbow is placed on
which are reduced in conditions such as pleural top of the other in order to bring the scapulae
effusion or pleural thickening which muffle the forward and out of the way.
transmission of the vibrations from the lung to
the chest wall (Fig. 2.4). Consolidation of the Auscultation
lung may sometimes enhance transmission of Listen with the diaphragm or bell of the stetho-
the vibration. scope to the intensity and character of the
breath sounds, comparing both sides sym-
Percussion metrically, and note any added sounds (e.g.
Percussion over normal air-filled lung produces wheeze, crackles, pleural rub). The sources of
a resonant note whereas percussion over audible sound in the lungs are turbulent airflow
solid organs such as the liver or heart produces in the larynx and central airways and the voice.
a dull note. Abnormal dullness is found over Reduction in the intensity of breath sounds
areas of lung consolidation (e.g. lobar pneumo- (sometimes loosely referred to as reduced air
nia) or fluid (e.g. pleural effusion). Hyper- entry) over an area of lung is an important sign
resonance may be present in emphysema or which may, for example, indicate obstruction of
Examination 15
S O U N D T R A N SM I SSI ON I N TH E LUNG
L Normal
Consolidation
Effusion
Fig. 2.4 Summary of sound transmission in the some of the lower pitched sound.This results in
lung. Sound is generated either by turbulence in loud high-pitched breath sounds (bronchial
the larynx and large airways, or by the voice. Both breathing), high-pitched bleating vocal resonance
sources are a mixture of high- (H) and low- (L) (aegophony) and easy transmission of high-
pitched components. Normal aerated lung filters off pitched consonants of speech (whispering
the high-pitched component but transmits the pectoriloquy). Pleural effusion causes reduction in
low-pitched component quite well.This results in the transmission of all sound probably because
soft low-pitched breath sounds, well-conducted of reflection of sound waves at the airfluid
vocal resonance and easily palpable very-low- interface. Breath sounds are absent, vocal
pitched sound (vocal fremitus). Consolidated lung resonance much reduced and vocal fremitus is
transmits high-pitched sound well and filters off absent.
a large bronchus preventing air from entering a thought that crackles are produced by the
lobe of the lung, or the presence of a pleural opening of previously closed bronchioles. The
effusion reducing transmission of sound to the crackling noise may be imitated by rolling a few
stethoscope. In normal individuals the inspira- hairs together close to the ear. Early crackles
tory phase of respiration is usually longer than are sometimes heard at the beginning of inspira-
the expiratory phase. Prolongation of the ex- tion in patients with COPD but these usually
piratory phase is a feature of airways obstruc- disappear when the patient is asked to cough.
tion and this is often accompanied by wheeze Persistent pan-inspiratory or late-inspiratory
(rhonchi) a high-pitched whistling or sighing crackles are a feature of pulmonary oedema,
sound. Diffuse wheeze is a feature of asthma or lung fibrosis (e.g. cryptogenic fibrosing alveoli-
COPD. Wheeze localised to one side, or one tis) or bronchiectasis. During inspiration, areas
area of the lung, suggests obstruction of a of lung open up in sequence according to their
bronchus by a carcinoma or foreign body (e.g. compliance (distensibility). In airways obstruc-
inhaled peanut). Crackles (crepitations) may tion there may be terminal airway closure
be loud and coarse or fine and high pitched, and during expiration, particularly in relatively
may occur early or late in inspiration. It is compliant (floppy) parts of the lung damaged by
16 Chapter 2: Symptoms and Signs of Respiratory Disease
S IGN S O F L O CA L I Z E D L UN G D I SE A SE
Pleural effusion
Tension pneumothorax
emphysema. During inspiration air initially whispering over consolidated lung, whisper-
enters these areas more readily and crackles ing pectoriloquy. The term bronchial
are probably produced by the opening of these breathing refers to the harsher breath sounds
airways early in inspiration. Coarse late inspira- normally heard over the trachea and main
tory crackles are particularly associated with bronchi. It is also heard over areas of consoli-
diseases where there is reduced lung compli- dated lung which conduct the higher frequency
ance (increased stiffness), which is to some ex- hiss component from the larger airways.
tent patchily distributed. During inspiration, air
first enters the more compliant parts of the lung
and then enters the stiffer parts later in inspira- Signs
tion as elastic recoil forces build up in the
stretching lung. Pleural rubs are creaking See Fig. 2.5 for signs of localised lung disease. It
sounds which are often quite localised and indi- is important to realise that major disease of the
cate roughening of the normally slippery pleural lungs may be present without any detectable
surfaces. physical signs and it is therefore essential to
Vocal resonance is assessed by listening obtain a chest X-ray where there is good reason
over the chest with the stethoscope as the to suspect localised lung disease.
patient says ninety-nine or one, one, one in
much the same way as vocal fremitus is palpated.
Normal aerated lung transmits the booming Further reading
low-pitched components of speech and attenu-
ates the high frequencies. Consolidated lung, Naish JM, Read AE, Burns-Cox CJ. The Clinical Appren-
however, filters off the low frequencies and tice. Bristol: John Wright and Sons, 1978.
transmits the higher frequencies so that speech Ogilvie C. Chamberlains Symptoms and Signs in Clinical
takes on a bleating quality, aegophony. The Medicine. Bristol: John Wright and Sons, 1980.
Spiteri M, Cook D, Clarke S. Reliability of eliciting
facilitated transmission of high frequencies can
physical signs in examination of the chest. Lancet
be demonstrated by the clear transmission of 1988; i: 8735.
CHAPTER 3
Pulmonary Function Tests
L UN G V O L U M ES
Full inspiration
Tidal Vital
volume capacity Total
lung
capacity
Functional
residual Full expiration
capacity
Residual
volume
Fig. 3.1 Total lung capacity and
its subdivisions.
VIT A L O G R A P H D R Y SP I R OM E TE R
)
(TOP
Fig. 3.2 Schematic view of Vitalograph dry and a motor causes the record chart to move
spirometer.The main components are a bellows steadily from left to right.The combination of
and a moving record chart. An arm attached to the lateral movement of the chart and forward
bellows carries a writing point which moves movement of the writing point causes an oblique
across the chart as air enters the bellows. As soon line to be inscribed upon the chart (see Fig. 3.4).
as the bellows moves, a microswitch is triggered
exhaling with maximum effort, in which case it is reduced lung compliance (e.g. lung fibrosis,
referred to as the forced vital capacity loss of lung volume);
(FVC). It may also be measured by a slow exha- chest deformity (e.g. kyphoscoliosis, ankylos-
lation and this is sometimes referred to as the ing spondylitis);
slow VC. In normal individuals, slow VC and muscle weakness (e.g. myopathy, myasthenia
FVC are very similar but in patients with airways gravis);
obstruction air trapping occurs during forced airways obstruction (e.g. chronic obstructive
expiration so that the FVC may be significantly pulmonary disease (COPD) air trapping
smaller than the slow VC.The following circum- causes increased residual volume and reduced
stances may reduce VC: VC).
20 Chapter 3: Pulmonary Function Tests
than peak inspiratory flow.There is a steady fall stomach and oesophagus.The chest X-ray can
in expiratory flow as expiration progresses.The be used to give a rough estimate of total lung
flowvolume loop is particularly used in assess- capacity. In airways disease, residual volume is
ing localised narrowing of the central airways as often increased as a manifestation of air trapping
illustrated in Figs 3.6 and 3.7. Interpretation of and total lung capacity increased as a manifesta-
the flowvolume loop may be difficult and the tion of hyperinflation. Total lung capacity is re-
inspiratory portion is less reproducible than the duced in restrictive lung disease.
expiratory portion, but flowvolume loops are
useful in suggesting less common causes of cen-
tral airways obstruction such as bilateral Transfer factor for
vocal cord palsy, tracheal tumours or tracheal carbon monoxide
compression by mediastinal disease. In practice,
there is often difficulty in diagnosing these con- The rate at which gas passes from the
ditions, usually because the possibility is not alveoli to the bloodstream can be measured
considered and the patient is misdiagnosed as using a low concentration of carbon monoxide.
having asthma. Flowvolume loops or subtle The transfer of carbon monoxide across the
changes on spirometry may point to the diagno- alveolar capillary membrane is similar to that of
sis and indicate the need for a definitive inves- oxygen. Oxygen diffusion is difficult to measure
tigation such as bronchoscopy or computed because transport stops when haemoglobin
tomography, for example. becomes saturated. At one time it was thought
that the main factor limiting gas exchange in dis-
ease was the ability of gases to diffuse across the
Total lung capacity alveolar capillary membrane. This led to the
concept of diffusing capacity for carbon
Whereas VC and its subdivisions can be mea- monoxide (DLco). It was later realised that many
sured directly by spirometry, measurement of other factors (e.g. ventilation/perfusion match-
residual volume and total lung capacity require ing) influenced gas transfer and the expression
the use of helium dilution or plethysmog- was renamed transfer factor (TLco). The
raphy methods. In the dilution technique a gas transfer coefficient (Kco) is an expression
of known helium concentration is breathed of gas transfer standardised for the alveolar
through a closed circuit and the volume of gas in volume (VA).
the lungs is calculated from a measure of the di-
lution of the helium, which, being an inert gas, is Single-breath method (Fig. 3.8)
neither absorbed nor metabolised.This dilution The patient inspires a gas mixture of helium and
method measures only gas in communication carbon monoxide, holds the breath for 10 sec-
with the airways and tends to underestimate onds and then breathes out. An initial volume
total lung capacity in patients with severe air- equivalent to the deadspace is discarded and
ways obstruction because of the presence of then a sample of the expired gas is collected and
poorly ventilating bullae. The body plethysmo- analysed for alveolar concentrations of helium
graph is a large airtight box that allows the si- and carbon monoxide. The change in concen-
multaneous determination of pressurevolume tration of helium between the inspired and alve-
relationships in the thorax of a patient placed olar sample is the result of gas dilution and gives
inside the box. When the plethysmograph is a measurement of the alveolar gas volume (VA).
sealed, changes in lung volume are reflected by The expired concentration of carbon monox-
an increase in pressure within the plethysmo- ide is also lower than the inspired level but the
graph. Plethysmography tends to overestimate fall is proportionately greater than in the case of
total lung capacity because it measures all in- helium because some of the carbon monoxide
trathoracic gas, including gas in bullae, cysts, has been absorbed into the bloodstream. The
22 Chapter 3: Pulmonary Function Tests
5 5
4 4
3 3
Litres
Litres
2 2
1 1
0 1 2 3 4 5 6 0 1 2 3 4 5 6
(a) Seconds (b) Seconds
5 5
4 4
3 3
Litres
Litres
2 2
1 1
0 1 2 3 4 5 6 0 1 2 3 4 5 6
(c) Seconds (d) Seconds
5 5
4 4
3 3
Litres
Litres
2 2
1 1
0 1 2 3 4 5 6 0 1 2 3 4 5 6
(e) Seconds Seconds
(f)
5 5
4 4
3 3
Litres
Litres
2 2
1 1
0 1 2 3 4 5 6 0 1 2 3 4 5 6
(g) Seconds (h) Seconds
Transfer factor for carbon monoxide 23
rate of uptake of carbon monoxide can then be ed by estimating a deadspace ventilation for car-
calculated as the uptake of carbon monoxide bon dioxide and assuming that this same volume
per minute per unit of partial pressure of carbon was filled with unchanged inspired carbon
monoxide (mmol/min/kPa), or as the carbon monoxide mixture.The shortfall in expired car-
monoxide transfer coefficient (Kco) which is bon monoxide must then be entirely brought
the TLco standardised for VA. about by a lower concentration in the alveolar
fraction which can be calculated, and the trans-
Steady-state method fer of carbon monoxide can be derived.
The patient breathes air containing a known low Although TLco and Kco are influenced by
concentration of carbon monoxide from a many factors (e.g. ventilation/perfusion (V/Q)
Douglas bag and expired air is collected in an- imbalance, area of alveolar membrane, haemo-
other Douglas bag over a timed period of some globin level) they are very useful measurements
minutes.The rate of carbon monoxide transfer in clinical practice. A reduced TLco is a strong
can be calculated from the difference between indicator of a parenchymal lung disorder in-
inspired and expired concentrations. A mean volving the alveoli or their blood supply. It is re-
alveolar carbon monoxide level can be calculat- duced, for example, in emphysema, fibrotic lung
Fig. 3.4 Forced expiratory spirogram tracing become lower with each expiration. Patient with
obtained with a Vitalograph spirometer. asthma.These features suggest poor control of
(a) Normal. Four expirations have been made. asthma and liability to severe attacks.
Three of these were true maximal forced (f ) A non-maximal expiration. Compare with (a). In a
expirations as indicated by their reproducibility. true forced expiration the steepest part of the
The forced expiratory volume in 1 second (FEV1) is curve always occurs at the beginning of
3.2L and the forced vital capacity (FVC) is 3.8L.The expiration which is not the case in (f). A falsely
forced expiratory ratio (FEV1/FVC) is 84%. low FEV1 and forced expiratory ratio are obtained.
(b) Restrictive ventilatory defect. Patient with Usually the patient has not understood what is
pulmonary fibrosis.The FVC in this case was 2L required or is unable to coordinate his or her
less than the predicted value for the subject.The actions. Some patients wish to appear worse than
FEV1 is also reduced below the predicted value but they really are.This pattern is unlikely to be
it represents a large part of the FVC.The forced mistaken for a true forced expiration because of
expiratory ratio is greater than 90%. its shape and because it cannot be reproduced
(c) Obstructive ventilatory defect. The FEV1 is much repeatedly.
reduced.The rate of airflow is severely reduced as (g) Escape of air from the nose or lips during
indicated by the reduced slope of the curve. Note expiration.
that the forced expiratory time is increased the (h) Inability to perform the manoeuvre. Five attempts
patient is still blowing out at 5 seconds.The vital have been made. In some the patient has
capacity has not been adequately recorded in this breathed in and out. Other attempts are either not
case because the patient did not continue the maximal forced expirations or are unfinished .
expiration after the chart stopped moving; he or Bizarre patterns such as this are often seen in
she could have expired further. (This is a common patients with psychogenic breathlessness and in
technical error.) the elderly and demented. Even with poor
(d) Severe airways obstruction. The FEV1 is about cooperation it is often possible to obtain useful
0.5L. FVC is also reduced but not so strikingly as information. In the example shown (h),
FEV1. Forced expiratory ratio is 23%.Very low significant airways obstruction can be excluded
expiratory flow rate.This pattern of a very brief because of the steep slope of at least two of the
initial rapid phase followed by a straight line expirations which follow an identical course and
indicating little change in maximal flow rate with show appropriate curvature (dotted line) and the
change in lung volume is sometimes associated FVC can be estimated as not less than 3.2L.The
with severe emphysema. pattern seen in large airways obstruction is
(e) Airways obstruction and bronchial hyper-reactivity. shown in Fig. 3.6.
Five expirations have been made. FEV1 and FVC
24 Chapter 3: Pulmonary Function Tests
T H E F L O W VO L U M E L O O P
PEF
Expiratory
flow rate
Volume expired
Z Z Fig. 3.5 The flowvolume loop.
Airflow is represented on the
TLC RV
vertical axis and lung volume
Inspiratory on the horizontal axis.The line
flow rate ZZ represents zero flow.
Expiratory flow appears above
the line; inspiratory flow below.
PEF, peak expiratory flow; RV,
Vital capacity
residual volume; TLC, total lung
capacity.
disease (e.g. cryptogenic fibrosing alveolitis) ing may show paradoxical upward movement
and pulmonary embolism. It may be increased of a weakened diaphragm during inspiration.
in asthma (probably because of improved distri- When there is severe respiratory muscle weak-
bution of ventilation and perfusion), poly- ness ventilatory failure develops with hyper-
cythaemia and alveolar haemorrhage (because capnia. Global respiratory muscle function
extravasated blood binds carbon monoxide). may be assessed by measuring mouth pres-
Adjusting the TLco for alveolar volume, giving sures. Maximum inspiratory mouth pressure,
the transfer coefficient (Kco), is useful in assess- PI max, is measured during maximum inspira-
ing if the reduced transfer factor is a result of a tory effort from residual volume against an
loss of surface area for diffusion. For example, a obstructed airway using a mouthpiece and
patient who has had one lung removed will have transducer device, and maximum expiratory
a reduced TLco but a normal Kco if the remain- mouth pressure, PE max, is measured during a
ing lung is normal. maximal expiratory effort from total lung ca-
pacity. The maximum transdiaphragmatic
pressure generated during contraction can
Respiratory muscle be measured in specialist laboratories using
function tests balloon catheters in the oesophagus and
stomach.
Weakness of the respiratory muscles causes a
restrictive ventilatory defect with reduced
total lung capacity and VC. Comparison of the Arterial blood gases
VC in the erect and supine position is useful be-
cause the pressure of the abdominal contents A sample of arterial blood may be obtained
on a weak diaphragm typically causes a fall of from any artery but the radial artery at the
>30% in the supine VC. Chest X-ray often wrist or the brachial artery in the antecubital
shows small lung fields with basal atelectasis and fossa are the sites most commonly used.
high hemidiaphragms. Fluorosocopy screen- Arterial puncture may be a painful procedure if
Oximetry 25
2 Respiratory failure
1
Respiratory failure is a clinical term used to de-
scribe failure to maintain oxygenation (usually
0 1 2 3 4 5 6 taken as an arbitrary cut-off point of Po2 8.0kPa
Seconds
(60mmHg).
Type I respiratory failure is hypoxaemia in the
Fig. 3.6 Large (central) airways obstruction.
Typical tracing obtained with a Vitalograph
absence of hypercapnia and usually indicates a
spirometer.The subject has made three maximal severe disturbance of V/Q relationships in the
forced expirations. Each shows a striking straight lungs.This pattern is seen in many conditions in-
section which then changes relatively abruptly, at cluding pulmonary oedema, asthma, pulmonary
about the same volume, to follow the expected embolism and lung fibrosis (Table 3.1).
curve of the forced expiratory spirogram.The
Type II respiratory failure is hypoxaemia with
straight section is not as reproducible as a normal
hypercapnia and indicates alveolar hypoventila-
spirogram. A family of similar tracings is thus
obtained, each with straight and curved sections. tion.This may occur from lack of neuromuscular
Explanation: over the straight section, flow is control of ventilation (e.g. sedative overdose,
limited by the fixed intrathoracic localised cerebrovascular disease, myopathy) or from
obstruction.This is little influenced by lung recoil lung disease (e.g. COPD).
so the critical flow is similar during expiration
and the spirogram appears straight. A lung
volume is eventually reached where maximum
flow is even lower than that permitted by the
Oximetry
central obstruction.The ordinary forced
expiratory spirogram is described after this point. Oxygen saturation can be measured non-
In the example shown there must be an element invasively and continuously using a pulse oxime-
of diffuse airways obstruction, as forced ter. Oxygenated blood appears red whereas re-
expiratory time is somewhat prolonged (see Fig. duced blood appears blue (clinical sign of
3.4c).
cyanosis). An oximeter measures the ratio of
oxygenated to total haemoglobin in arterial
blood using a probe placed on a finger or ear
there is difficult in entering the artery quickly lobe, which comprises two light-emitting
and directly so that local anaesthetic (e.g. 1% diodes one red and one infrared and a de-
lidocaine (lignocaine)) may be helpful.The blood tector. The light absorbed varies with each
enters the heparinised needle and syringe pulse, and measurement of light absorption at
under its own pressure with a pulsatile action. two points of the pulse wave allows the oxygen
The syringe containing the arterial blood is saturation of arterial blood to be determined.
capped, placed in ice and analysed in the labora- The accuracy of measurement is reduced if
tory within 30 minutes of sampling. there is reduced arterial pulsation (e.g. low-out-
26 Chapter 3: Pulmonary Function Tests
FLOWVOLUME LOOPS
Ef
Tidal Tidal
(a) (b)
(c) (d)
Fig. 3.7 Further flowvolume loops.The dotted representing quiet tidal breathing. It is clear that
outline represents a typical normal loop.The every expiration is limited by maximum flow.
small graphs show the appearances of a forced Expiratory wheezing or purse lip breathing would
expiration on a Vitalograph spirometer (as in be expected.There is some inspiratory reserve of
Fig. 3.4). flow but hardly any expiratory reserve.Ventilation
(a) Demonstration of maximum flow. A normal could be increased slightly by adopting an even
individual makes an unhurried expiration from higher lung volume and by speeding up
full inspiration and then about halfway through inspiration.
the vital capacity, a maximal expiratory effort (Ef) (c) Fixed intrathoracic large airways obstruction: for
is made.The flowvolume tracing rejoins the example, tracheal compression by a mediastinal
maximum flowvolume curve which describes tumour. Here the peak inspiratory and expiratory
the highest flow which can be achieved at that flows have been truncated in a characteristic
lung volume. Also shown in (a) is the flowvolume pattern.
loop of typical tidal breathing. At the resting lung (d) Variable extrathoracic obstruction. Severe
volume there is an abundant reserve of both extrathoracic obstruction results in inspiratory
inspiratory and expiratory flow available. collapse of the airway below the obstruction (but
(b) Very severe airways obstruction in an individual still outside the thorax). In this example
with emphysema. Maximum expiratory flow is expiration is normal, and this suggests a variable
very severely reduced.There is a brief peak check-valve mechanism such as might be caused
(probably caused by airway collapse) after which by bilateral vocal cord paralysis.
flow falls very slowly. Also shown in (b) is a loop
Oximetry 27
He
Fig. 3.8 Measurement of
transfer factor by the
Theoretical
single-breath method.
alveolar
Schematic 0.1 5
mixture at CO
representation of the
start of
helium and carbon
breath-holding
monoxide
concentrations in the
inspired mixture and in 0 5 10
alveolar air during Breath-holding (seconds)
breath-holding.
Aa gradient: the alveolar to arterial gradient = Pio2 - (Po2 + Pco2) (see Chapter 1).
Table 3.1Examples of arterial gas measurements is also inaccurate in the presence of car-
in various conditions. boxyhaemoglobin (e.g. in carbon monoxide
poisoning) which the oximeter detects as oxy-
put cardiac states) or increased venous pulsa- haemoglobin.The relationship of Po2 to oxygen
tion (e.g. tricuspid regurgitation, venous con- saturation is described by the oxyhaemoglo-
gestion). Skin pigmentation or use of nail varnish bin dissociation curve (see Fig. 1.5, p. 6).This
may interfere with light transmission. Oximetry curve is sigma-shaped so that oxygen saturation
28 Chapter 3: Pulmonary Function Tests
is closely related to Po 2 only over a short range almost unchanged. This pattern is seen where
of about 37kPa. Above this level the dissocia- there is acute hypoventilation, e.g. obstruction
tion curve begins to plateau and there is only a of the airway, overdose of sedative drugs or
small increase in oxygen saturation as the Po 2 acute neurological damage.
rises. Oximetry can reduce the need for arteri- Respiratory alkalosis: pH raised, PCO2
al puncture, but arterial blood gas analysis is reduced, bicarbonate normal. Alveolar
necessary to determine accurately the Po 2 on hyperventilation causes a fall in Pco2 and a
the plateau part of the oxyhaemoglobin dissoci- corresponding rise in pH. Bicarbonate con-
ation curve, to measure carbon dioxide level centration is virtually unchanged unless there
and to assess acidbase status. is a longstanding respiratory alkalosis which is
unusual. This pattern is seen in any form of
acute hyperventilation, e.g. anxiety-related
Acidbase balance hyperventilation, salicylate poisoning, acute
asthma.
The three variables principally involved in Metabolic acidosis: pH reduced, PCO2 re-
acidbase balance in the body are hydrogen duced, bicarbonate reduced. The primary
ion concentration ([H+]), PCO2 and bicar- disturbance is generally an increase in acid.This
bonate [HCO-3]. [H+] is generally expressed has an effect on the equilibrium H++HCO-3
as pH which is the negative logarithm of [H+]. H2O+CO2 pushing it to the right. The car-
These variables are directly related to each bon dioxide produced is removed by increased
other in terms of the HendersonHasselbalch ventilation and the net result is a lowering of
equation [H+]Pco2/[HCO-3]. There is a di- plasma bicarbonate. In practice the fall in pH
rect linear relationship between Pco2 and [H+]. causes respiratory stimulation so that carbon
Bicarbonate concentration can be calculated if dioxide is promptly blown off. This respiratory
Pco2 and pH are known or it can be measured compensation is an inevitable accompaniment
directly: the actual bicarbonate concentra- of metabolic acidosis acute and chronic un-
tion. Standard bicarbonate is a calculated less there is some other factor limiting ventila-
value indicating what the bicarbonate would be tory function or responsiveness.This pattern is
at a standard Pco2 of 5.3kPa (40mmHg). The seen in diabetic ketoacidosis, renal tubular aci-
base excess is a further parameter of the dosis, and acute circulatory failure and other
buffering capacity of the blood which recognises forms of lactic acidosis.
the fact that there are other buffers apart from Metabolic alkalosis: pH raised,PCO2 normal
bicarbonate in the blood. Changes in pH which or slightly raised, bicarbonate raised. An
are caused primarily by an alteration in Pco2 are increase in bicarbonate concentration causes a
termed respiratory, and are determined by rise in pH. The compensatory fall in alveolar
alveolar ventilation. Changes in pH which ventilation is usually slight, therefore Pco2 usual-
are brought about by changes in bicarbonate ly increases a little. This pattern is seen where
concentration are termed metabolic. The there has been administration of excessive alka-
renal tubules modulate bicarbonate concentra- li, loss of acid through vomiting, or reabsorption
tion in response to the prevailing Pco2 but this is of bicarbonate (e.g. in hypokalaemia).
a slow process. Chronic respiratory acidosis: pH normal or
Acute respiratory acidosis: pH reduced, PCO2 slightly reduced, PCO2 raised,bicarbonate
raised, bicarbonate normal. A reduction in raised. If alveolar hypoventilation is sustained
alveolar ventilation causes an increase in arteri- for some days, renal tubular reabsorption of bi-
al Pco2.The pH falls in relation to the Pco2. In the carbonate will achieve significant elevation of
short term there is insufficient time for renal plasma bicarbonate level tending to correct the
compensation by reabsorption of bicarbonate acidosis (chronic compensated respiratory aci-
so that the bicarbonate concentration remains dosis). This pattern is seen in any cause of sus-
Further reading 29
A C I D B A SE DI S TURBANC E S
100 Chronic
90 respiratory acidosis 12
80 Acute
respiratory 10
70 (d)
acidosis
60 oic 8
(b) tab s
Me alosi
50 a lk
6
PCO2 (mmHg)
(a)
40
PCO2 (kPa)
Re
4
sp
30
is
ir a
os
to
id
ry
ac
Fig. 3.9 Acidbase
al
ic
ka
disturbances.The oval indicates 20 ol
lo
ab
sis
the normal position.The
et
(c)
M
tained hypoventilation, e.g. COPD, chronic neu- where severe lactic acidosis exists and ventila-
romuscular disease. tion has been insufficient. Point (c) could repre-
Mixed disturbances: mixed respiratory and sent the situation in severe aspirin poisoning
metabolic disturbances are common and where aspirin-induced hyperventilation has
there are usually a number of possible explana- been complicated by aspirin-induced metabolic
tions, therefore it is essential to consider all the acidosis. Point (d) could represent the situation
clinical details before interpreting the acidbase in an individual with chronic hypercapnia as a re-
data. Figure 3.9 shows the situations that may sult of COPD who is stimulated to increase ven-
arise in complex acidbase disturbances. For tilation by a pulmonary embolism.
example, point (a) in Fig. 3.9 (low pH, normal
Pco2, low bicarbonate) indicates a mixed meta-
bolic and respiratory acidosis.This could arise in Further reading
a patient with acute pulmonary oedema who is
hypoxaemic with low cardiac output.The meta- Cotes JE. Lung Function: Assessment and Application in
bolic acidosis results from lactic acidosis and the Medicine. Oxford: Blackwell Scientific Publications,
patients ability to hyperventilate is compro- 1993.
Flenley DC. Interpretation of blood-gas and
mised.The same situation could arise in a totally
acidbase data. Br J Hosp Med 1978; 20: 38494.
different set of clinical circumstances (e.g. a pa- Gibson GJ. Clinical Tests of Respiratory Function.
tient in renal failure given a narcotic sedative Oxford: Chapman and Hall, 1996.
suppressing ventilatory response to acidosis) so Gibson GJ. Measurement of respiratory muscle
that acidbase data have limited diagnostic po- strength. Respir Med 1995; 89: 52935.
tential considered alone. Point (b) could repre- Hanning CD, Alexander-Williams JM. Pulse oximetry:
a practical review. BMJ 1995; 311: 36770.
sent the situation soon after a cardiac arrest
CHAPTER 4
Radiology of the Chest
30
Abnormal features 31
DI A G R A M OF C H E S T X - RAY
(P OST E R O -A N TE RI OR)
Fig. 4.1 Diagram of chest X-ray
(PA view).The right (c)
hemidiaphragm is 13cm
higher than the left (a) and on
full inspiration it is intersected
by the shadow of the anterior
part of the sixth rib (b).The
trachea (c) is vertical and
central or very slightly to the
right.The horizontal fissure (d)
is found in the position shown,
or slightly lower and should be (d)
truly horizontal. It is a very (e)
valuable marker of change in
(f)
volume of any part of the right
(g)
lung.The left border of the
cardiac shadow comprises: (i)
(e) aorta; (f) pulmonary artery; (h)
(g) concavity overlying the
left atrial appendage; (h) left
ventricle.The right border of the (a)
cardiac shadow normally
(b)
overlies the right atrium (i) and
above that the superior vena
cava.
produces its own particular appearance on obstructing carcinoma which may be confirmed
chest X-ray (Figs 4.3 and 4.4) with shift of land- by bronchoscopy.
marks such as the mediastinum resulting from
loss of volume. Obstruction of a main bronchus Consolidation
usually causes obvious asymmetry (Fig. 4.5). Air in the lungs appears black on X-ray. Con-
Compensatory expansion of other lobes solidation appears as areas of opacification
may result in increased transradiency of adja- sometimes conforming to the outline of a lobe
cent areas of the lung. In right middle lobe col- or segment of lung in which the air has been re-
lapse there may be little to see on a PA X-ray placed by an inflammatory exudate (e.g. pneu-
apart from lack of definition of the right heart monia), fluid (e.g. pulmonary oedema), blood
border. This is a useful sign which helps to dis- (e.g. pulmonary haemorrhage) or tumour (e.g.
tinguish it from lower lobe collapse where the alveolar cell carcinoma). Bronchi containing air
right border of the heart remains clearly de- passing through the consolidated lung are
fined. Left lower lobe collapse is manifest as a sometimes clearly visible as black tubes of air
triangular area of increased density behind the against the white background of the consoli-
heart shadow, often with a shift of the heart dated lung: air bronchograms (see Fig. 18.2,
shadow to the left and increased transradiency p. 177). Structures such as the heart, medi-
of the left hemithorax because of compensa- astinum and diaphragm are usually clearly out-
tory expansion of the left upper lobe (Fig 4.4). lined as a silhouette on an X-ray because of the
Collapse is a sinister sign often indicating an contrast between the blackness of aerated lung
32 Chapter 4: Radiology of the Chest
DIAG R A M O F C H E ST X-R A Y
(LA TERAL VIEW )
(a)
(b)
Ao x
(c)
and the whiteness of these structures. When (e.g. lymph node enlargement) and whether the
there is abnormal shadowing in the lung adja- lesion is solitary or whether multiple lesions
cent to these structures there is loss of the are present, may provide clues to diagnosis.
sharp outline, and this is often referred to as the However, these features are often not reliable
silhouette sign (Fig. 4.6). indicators of aetiology, and the X-ray appear-
ances must be interpreted in the context of all
Pulmonary masses (Table 4.1) the clinical information. Further investigations
Various descriptive terms such as rounded such as computed tomography (CT) and biopsy
opacity, nodule or coin lesion are used to (bronchoscopic, percutaneous, surgical) are
refer to pulmonary masses. Carcinoma of the often necessary.
lung is the most important cause of a mass on
chest X-ray but several other diseases may Cavitation
cause a similar appearance. Features such as Cavitation is the presence of an area of radio-
cavitation, calcification, rate of growth, lucency within a mass lesion. It is a feature of
the presence of associated abnormalities bronchial carcinoma (particularly squamous
Abnormal features 33
R A DI OG R A P H I C PATTE RNS
O F L O B A R C O L LAPS E
RUL LUL
carcinoma) (Fig. 4.7), tuberculosis, lung fication containing multiple circular translucen-
abscess, pulmonary infarcts, Wegeners cies a few millimetres in diameter.
granulomatosis (see p. 164) and some
pneumonias (e.g. Staphylococcus aureus, Mediastinal masses
Klebsiella pneumoniae). Metastatic tumour or lymphomatous involve-
ment of the mediastinal lymph nodes are the
Fibrosis most common causes of mediastinal masses
Localised fibrosis produces streaky shadows but there are a number of other diseases which
with evidence of traction upon neighbouring may cause mediastinal masses (Fig. 4.8).Thymic
structures. Upper lobe fibrosis causes traction tumours, thyroid masses and dermoid cysts
upon the trachea and elevation of the hilar vas- are most commonly situated in the anterior
cular shadows. Generalised interstitial fibrosis mediastinum whereas neural lesions (e.g. neu-
produces a hazy shadowing with a fine reticu- rofibroma) and oesophageal cysts are often sit-
lar (net-like) or nodular pattern (see uated posteriorly. Aneurysmal enlargement of
Chapter 14). Advanced interstitial fibrosis re- the aorta or ventricle may produce masses in
sults in a honeycomb pattern with diffuse opaci- the middle compartment of the mediastinum.
34 Chapter 4: Radiology of the Chest
T H E SI L H O U E T TE S I GN
Oesophageal
cyst
Thyroid
Thymus
Hilar mass
Carcinoma
Lymphoma
Dermoid
Sarcoidosis
Tuberculosis
Pericardial
cyst
Neurofibroma
Fat pad
Morgagni Fig. 4.8 Mediastinal masses.
Hiatus hernia
diaphragmatic Diagram of lateral view of the
hernia chest, indicating the sites
favoured by some of the more
common mediastinal masses.
Computed tomography 37
M E D I A ST I N A L S TRUC TURE S
3 4
the bronchial tree) in detecting and determining parenchyma and can provide a detailed image of
the extent of bronchiectasis (see Chapter 9). emphysema (see Chapter 12) and interstitial
High-resolution CT scans are much more sensi- lung disease. A ground glass appearance on a
tive than plain X-ray in assessing the lung high-resolution CT scan of a patient with cryp-
38 Chapter 4: Radiology of the Chest
P R IN C I P A L M E D I A ST I N A L
S TR U C T UR E S ON C T
svc ao
1 2 3 4 5
Fig. 4.10 Principal mediastinal structures on shape representing the aortic arch is seen (ao);
computed tomography (CT).The sections (a) to (d) oes, oesophagus which is visible in all of the
are at levels (a) to (d) in Fig. 4.9.The sections sections; svc, superior vena cava. (c) Section below
should be regarded as being viewed from below the aortic arch. Both ascending (aao) and
(i.e. the left of the thorax is on the right of the descending (dao) aortas are visible, the trachea is
figure). (a) Section above the aortic arch. Many large bifurcating and the pulmonary arteries are seen;
vessels and an anterior sausage shape are seen; pa, left pulmonary artery. (d) Section at the level of
the trachea has not bifurcated (black circle). pulmonary veins (pv). Lower lobe intrapulmonary
Numerals refer to Fig. 4.9 and its legend. (b) Section arteries and bronchi are not shown in the
at the level of aortic arch. A large oblique sausage diagram.
Pharyngitis
Common cold
Pharyngitis may occur as part of the common
The common cold (coryza) is an acute illness cold or as a separate illness. Most cases are
characterised by rhinorrhoea, sneezing, nasal caused by viruses (Table 5.1) but pharyngitis
obstruction and sore throat (pharyngitis) with may also be caused by group A b-haemolytic
minimal fever or systemic symptoms. It may be streptococci, Mycoplasma pneumoniae or
caused by about 200 different strains of viruses Chlamydia pneumoniae, for example.The pa-
including rhinoviruses, coronaviruses, res- tient complains of a sore throat and there is ery-
40
Sinusitis 41
ACU TE RES P IR A T OR Y I N F E C T I ON S
Acute bronchitis
LOWER
RESPIRATORY
TRACT Infective
INFECTIONS exacerbation of
chronic bronchitis
(Chapter 12)
Pneumonia
(Chapter 6)
Fig. 5.1 Acute respiratory infections. caused by bacterial infection antibiotics are not
usually necessary as the illness tends to be self-
limiting. Local extension of infection may result
in otitis media, tonsillitis or quinsy (peritonsillar
thema of the pharynx often with enlargement of abscess). Streptococcal infection may be com-
the tonsils. Infectious mononucleosis (glan- plicated by glomerulonephritis or rheumatic
dular fever) often involves pharyngitis but is fever but these are rare nowadays. Antibiotic
also associated with lymphadenopathy and treatment of pharyngitis is usually only given to
splenomegaly, and is caused by the EpsteinBarr severe or complicated cases. Streptococci are
virus. A blood film may show atypical mononu- sensitive to penicillin V or amoxicillin. Myco-
clear cells and the Monospot or heterophile plasma pneumoniae or Chlamydia pneumoniae
antibody tests are positive. Characteristically, require a tetracycline or macrolide antibiotic
patients with infectious mononucleosis develop (e.g. erythromycin, clarithromycin).
a rash if given amoxicillin as treatment of
pharyngitis. It is not possible to distinguish be-
tween viral and bacterial pharyngitis on clinical Sinusitis
grounds. b-haemolytic streptococci may be
found on microbiology of a throat swab but this Infection of the maxillary sinuses causes facial
does not differentiate between active infection pain, nasal obstruction and discharge, often
and a carriage state. Even when pharyngitis is accompanied by fever and malaise. A variety of
42 Chapter 5: Upper Respiratory Tract Infections
RESPIRATORY VIRUSES
Virus Disease Notes
Rhinovirus Common cold, pharyngitis, chronic bronchitic More than 100 serotypes;
exacerbations identification and study
difficult
Herpes simplex Stomatitis, rarely pharyngitis, pneumonia in One serotype, severe infection
immunosuppressed treatable with aciclovir or
vidarabine
organisms may cause sinusitis including res- tory tract infection in patients with bronchiec-
piratory viruses, Haemophilus influenzae, tasis caused by cystic fibrosis, hypogammaglob-
Streptococcus pneumoniae, Staphylococ- ulinaemia or ciliary dyskinesia. Post-nasal drip
cus aureus, and anaerobic bacteria. In from sinusitis is irritating to the larynx and is
chronic sinusitis X-rays may show mucosal quite a common cause of a persistent cough.
thickening, opacification or the presence of a Sinusitis is usually treated with antibiotics (e.g.
fluid level in the sinus. Recurrent sinusitis may amoxicillin, trimethoprim), nasal decongestants
be accompanied by more widespread respira- (e.g. ephedrine) and analgesia (e.g. paraceta-
Influenza 43
mol). Surgical drainage may be necessary for hospital and attempts at examining the upper
relief of chronic sinusitis. airway should only be performed when facilities
are available for tracheal intubation and ventila-
tion. Because of possible amoxicillin resistance
Acute laryngitis chloramphenicol or cefuroxime are appropri-
ate antibiotics.
This term is used when temporary hoarseness
or loss of voice occurs with pharyngitis or the
common cold, and is caused by oedema of the Influenza
vocal cords. No treatment is necessary.
Influenza is an acute illness characterised by
pyrexia, malaise, myalgia, headache and prostra-
Croup tion as well as upper respiratory symptoms.
Lethargy and depression may persist for several
Croup (acute laryngotracheobronchitis) is usu- days afterwards. Although the term flu is used
ally caused by viruses such as parainfluenza very loosely by the public, it is the systemic fea-
virus, respiratory syncytial virus, influenza A and tures which characterise true infection with
B, rhinoviruses, adenovirus and measles. Char- the influenza viruses. Influenza virus type A
acteristically, the child develops a harsh barking undergoes frequent spontaneous changes in its
cough with an upper respiratory infection and haemagglutinin and neuraminidase surface anti-
this may progress to stridor. Often no treat- gens. Minor changes, referred to as antigenic
ment is required but some children develop drift, result in outbreaks of influenza in the
more severe lower respiratory infections and winter months each year. Major changes,
progressive respiratory distress requiring intu- referred to as antigenic shift, result in epi-
bation and ventilation. Oral prednisolone is demics and pandemics of infection reflecting the
sometimes beneficial in severe croup and nebu- lack of immunity in the population to the new
lised high-dose budesonide may be associated strain. Type B is more antigenically stable and
with more rapid recovery in less severely produces less severe disease. Type C causes
affected patients. only mild sporadic cases of upper respiratory
infection.
Influenza is highly infectious so that all mem-
Acute epiglottitis bers of a household often become ill together.
Outbreaks of influenza cause considerable
Epiglottitis is a very serious disease which is usu- morbidity even in healthy adults. It is usually a
ally caused by virulent strains of Haemophilus self-limiting illness but can be complicated by
influenzae type B, and there is often an ac- bronchitis, otitis media and secondary bacterial
companying septicaemia. Death may result from pneumonia (e.g. Staphylococcus aureus, Strepto-
occlusion of the airway by the inflamed oedema- coccus pneumoniae or Haemophilus influenzae).
tous epiglottis. It is most common in children of The greatest morbidity and mortality occur in
about 23 years of age, but cases have also oc- patients who are elderly with underlying cardiac
curred in adults. The patient is ill with pyrexia, or respiratory disease. Primary influenzal pneu-
sore throat, laryngitis and painful dysphagia. monia is rare but severe.
Symptoms of upper airway obstruction may The diagnosis of influenza can be confirmed
develop rapidly with stridor and respiratory by immunofluorescent microscopy of nasal se-
distress. A lateral neck X-ray may show the cretions or by serology. Zanamivir is a drug de-
epiglottic swelling. Blood cultures often isolate livered by dry powder inhalation which acts by
Haemophilus influenzae type B. Patients with inhibiting the neuraminidase activity of both in-
suspected epiglottitis should be admitted to fluenza A and B viruses. It reduces the duration
44 Chapter 5: Upper Respiratory Tract Infections
of symptoms by a median of one day and re- disease, asthma, bronchiectasis, etc.), chronic
duces complications (eg bronchitis, pneumonia) heart disease, renal failure, diabetes mellitus,
in high-risk patients. It is not recommended for immunosuppression and for elderly patients liv-
otherwise healthy adults but should be used to ing in nursing homes.
treat at-risk adults (e.g. elderly patients with Adverse reactions to influenza vaccine are
chronic cardiorespiratory diseases) if they can usually mild, consisting of fever and malaise in
start treatment within 48 hours of onset of some patients and local reactions at the site of
symptoms of influenza. Use of aspirin or para- injection. The vaccine is contraindicated in pa-
cetamolrelievessymptoms.Antibiotics are used tients with egg allergy. Patients should be ad-
when there are features of secondary bacterial vised that the vaccine will not protect them
infection (e.g. otitis media, sinusitis). Pneumonia from all respiratory viruses.
associated with influenza may be severe and re-
quires treatment with broad-spectrum anti-
biotics including flucloxacillin because of the Further reading
risk of Staphylococcus aureus infection.
Husby S, Agertoft L, Mortensen S, Pedersen S. Treat-
Influenza vaccination ment of croup with nebulised steroid (budesonide):
The influenza vaccine is prepared each year a double-blind placebo controlled study. Arch Dis
Child 1993; 68: 3526.
using the virus strains most likely to be preva-
Little PS, Williamson I, Shvartzman P. Are antibiotics
lent that year. The vaccine contains inactivated appropriate for sore throats? BMJ 1994; 309:
virus and is about 7080% effective in protecting 101012.
against infection. Where infection occurs de- Mansel JK, Rosenow EC, Smith TF, Martin JW.
spite vaccination it is usually less severe and as- Mycoplasma pneumoniae. Chest 1989; 95: 63946.
sociated with less morbidity and mortality than Nguyen-Van-Tam JS. Zanamivir for influenza: a public
the disease seen in unvaccinated patients. Selec- health prospective. BMJ 1999; 319: 6556.
Vernon DD, Sarnaik AP.Acute epiglottitis in children: a
tive immunisation is recommended to protect
conservative approach to diagnosis and manage-
those most at risk of serious illness or death ment. Crit Care Med 1986; 14: 235.
from influenza. Annual vaccination is recom- Wilson R. Influenza vaccination. Thorax 1994; 49:
mended for those with chronic respiratory 107980.
disease (e.g. chronic obstructive pulmonary
CHAPTER 6
Pneumonia
45
46 Chapter 6: Pneumonia
LIKE L Y CAU S ES OF P N E UM ON I A
Fig. 6.1 Likely causes of pneumonia in different clinical circumstances. Age and previous health are
important factors.
Classification in relation to clinical context 47
a normal person so that identification of an or- neumonia. Infection of the lung parenchyma
ganism in respiratory tract secretions may not with extensive consolidation of a lobe of a lung
be sufficient to implicate it as the cause of the ill- lobar pneumonia is usually caused by or-
ness. Conversely the same pathogen can cause ganisms of greater virulence (e.g. Streptococcus
various illnesses at different levels in the respira- pneumoniae). Infection may spread to the pleura
tory tract such as sinusitis, bronchitis or pneu- resulting in empyema, or to the bloodstream
monia, and different bacteria may cause an causing septicaemia.
identical clinical syndrome such as pneumonia.
A clinical approach to pneumonia focuses on Age of the patient
the clinical context of the illness, the patients In children under the age of 2 years pneumonia
previous health status and on the circumstances is commonly caused by viruses such as respira-
of the illness. Pneumonia is the result of a com- tory syncytial virus (RSV), adenovirus, influenza
plex interaction between the patient, the en- and parainfluenza viruses. Chlamydia trachomatis
vironment and the infecting organism, and infection may be transmitted to the infant from
the pattern of the disease depends on the viru- the mothers genital tract during birth resulting
lence of the pathogen and the vulnerability of in pneumonia. In older children and adults of all
the patient. The circumstances of the illness in- ages Streptococcus pneumoniae is the most com-
clude: mon cause of primary pneumonia. Mycoplasma
site of infection in the respiratory tract; pneumoniae infection is rare in the elderly and
age of the patient; particularly affects young adults. The incidence
community- or hospital-acquired infection; of pneumonia increases greatly in the elderly
concurrent disease; and the high frequency of underlying chronic
environmental and geographical factors; diseases (e.g. chronic obstructive pulmonary
severity of the illness; and disease (COPD), heart failure) in this group is
microbiology of the pneumonia. associated with a high mortality.
Fig. 6.2 This 60-year-old man was admitted to admission without improvement. Chest X-ray
hospital with a 2-week history of myalgia, shows extensive bilateral multilobar
headache, dyspnoea and cough without sputum. consolidation. He kept birds as a hobby and one of
He was severely ill, cyanosed and delirious with a his budgerigars had died recently.The clinical
fever of 39C, tachycardia of 110/min, respiratory diagnosis of psittacosis was subsequently
rate 40/min and blood pressure of 110/60 mmHg. confirmed by serology tests. He was treated with
PO2 was 5.7 kPa (43 mmHg), PCO2 4.9 kPa (37 mmHg), intravenous fluids, oxygen and tetracycline and
white cell count 4.6 109/L and urea 31mmol/L. recovered fully.
He had received amoxicillin for 6 days before
Sputum Gram stain may give a valuable tal (see Table 6.1) and elective transfer to an
and rapid clue to the responsible organism in an ITU should be considered for patients with se-
ill patient. vere disease.
Sputum culture is the main test used to de- Sufficient oxygen should be given to maintain
tect bacterial causes of pneumonia but con- arterial PO2 >8kPa (60mmHg) and oxygen satu-
tamination of the sample by oropharyngeal ration >90%.Adequate non-sedative analgesia
organisms, prior use of antibiotics and inability (e.g. paracetamol or non-steroidal anti-
to produce sputum limit the sensitivity and inflammatory drugs) should be given to control
specificity of the test. pleuritic pain. Fluid balance should be
Blood cultures should be performed on all optimised, using intravenous rehydration as re-
patients admitted to hospital but are positive in quired for dehydrated patients. Chest physio-
only about 15% of cases. therapy may be beneficial to patients with
Pleural fluid should be aspirated in all COPD and copious secretions but is not helpful
patients with pleural effusions and may yield a in patients without underlying lung disease. Nu-
causative organism or reveal empyema (see tritional support (e.g. oral dietary supplements,
Chapter 17). nasogastric feeding) should be given in pro-
Antigen detection tests are available for longed illnesses.The patients general condition,
some pathogens. Pneumococcal antigen may pulse, blood pressure, temperature, respiratory
be identified in sputum, urine, pleural fluid rate and oxygen saturation should be monitored
or blood and may be positive in cases where frequently and any deterioration should prompt
prior antibiotics limit the sensitivity of cultures. reassessment of the need for transfer to ITU.
Direct fluorescent antibody staining may detect
Legionella pneumophila in bronchoalveolar Antibiotic treatment
lavage fluid, and tests for Legionella antigen in The initial choice of antibiotics is based upon an
urine are available in some laboratories. assessment of the circumstances and severity of
Serological tests allow a retrospective di- the pneumonia. Treatment is then adjusted in
agnosis of the infecting organism if a rising titre accordance with the patients response and
is found between acute and convalescent the results of microbiology investigations. For
samples. This is most useful for some viruses community-acquired pneumonia, Strepto-
and pneumonia caused by atypical organisms coccus pneumoniae is the most likely pathogen
such as Mycoplasma pneumoniae or Chlamydia and amoxicillin 500mg1g t.d.s. orally is an ap-
pneumoniae. propriate antibiotic.Where there is a suspicion
Invasive investigations such as bronchoscopy of an atypical pathogen (e.g. Mycoplasma
with bronchoalveolar lavage may be indicated in pneumoniae, Chlamydia psittaci) addition of a
severe pneumonia and in immunocompromised macrolide antibiotic, such as erythromycin 1g
patients. q.d.s. or clarithromycin 500mg b.d. is required.
In severe pneumonia the initial antibiotic
regimen must cover all likely pathogens and
Treatment allow for potential antibiotic resistance, and
intravenous cefuroxime 1.5g t.d.s. and
General clarithromycin 500mg b.d. are appropriate.
Mild pneumonia in a fit patient can be treated at In hospital-acquired pneumonia, Gram-
home. Admission to hospital is necessary for negative bacteria are common pathogens,
patients who demonstrate features of severe and a combination of an aminoglycoside
pneumonia, who have concomitant disease or (e.g. gentamicin) and a third-generation
who do not have adequate family help at home. cephalosporin (e.g. ceftazidime) or an anti-
The severity of the pneumonia should be for- pseudomonal penicillin (e.g. azlocillin) is
mally assessed at the time of admission to hospi- commonly used.
52 Chapter 6: Pneumonia
Failure to respond or failure of the C-reactive tients with chronic lung disease, diabetes, renal
protein level to fall by 50% within 4 days suggests and cardiac disease and for patients who are as-
the occurrence of a complication (e.g. em- plenic or immunodeficient (e.g. hypogamma-
pyema), infection with an unusual pathogen globulinaemia, HIV).
(e.g. Legionella pneumophila), the presence of
antibiotic resistance or incorrect diagnosis (e.g. Haemophilus influenzae
pulmonary embolism). pneumonia
Haemophilus influenzae is a Gram-negative
bacillus. Virulent strains are encapsulated
Specific pathogens and divided into six serological types.
Haemophilus influenzae type B is a virulent
Pneumococcal pneumonia encapsulated form which causes epiglottitis,
Streptococcus pneumoniae is the causative organ- bacteraemia, meningitis and pneumonia.
ism in about 60% of community-acquired Haemophilus influenzae type B (Hib) vaccine is
pneumonias and in about 15% of hospital- given to children to reduce the risk of meningitis
acquired pneumonias. Research studies using and this vaccine also provides protection against
tests for pneumococcal antigen suggest that it epiglottitis. However, it is the less virulent form
may account for many cases where no organism of the organism non-typeable unencapsu-
is identified. It is a Gram-positive coccus, which lated Haemophilus influenzae which is a
can cause infections at all levels in the respira- common cause of respiratory tract infection,
tory tract including sinusitis, otitis media, bron- predominantly where there has been damage to
chitis and pneumonia. Up to 60% of people the bronchial mucosa by smoking or viral infec-
carry Streptococcus pneumoniae as a commen- tion. Haemophilus influenzae often forms part of
sal in the nasopharynx and infection is trans- the normal pharyngeal flora. Deficient mucocil-
mitted in airborne droplets. Nasopharyngeal iary clearance in patients with smoking-induced
carriage may progress to infection where there chronic bronchitis facilitates spread of the or-
is a breach in the respiratory tract defences, and ganism to the lower respiratory tract, where it
smoking and viral infections are important fac- gives rise to exacerbations of COPD. Spread
tors disrupting surface defence mechanisms. of infection into the lung parenchyma causes
There are many different serotypes which bronchopneumonia. It is usually treated
vary in their virulence, but virulent strains with amoxicillin but about 10% of strains are
can render a previously fit and healthy person resistant and alternative antibiotics include
critically ill within a few hours. Pneumococcal co-amoxiclav (amoxicillin with clavulanic acid),
infection in asplenic patients (e.g. post-splenec- trimethoprim and cefixime.
tomy) is severe with a high mortality, such that
these patients are usually given pneumococcal Staphylococcal pneumonia
vaccination and long-term prophylactic phe- Staphylococcus aureus is a Gram-positive coc-
noxymethylpenicillin 500mg b.d. Streptococcus cus which forms clusters resembling a bunch of
pneumoniae is usually sensitive to penicillin grapes. Although it is a relatively uncommon
antibiotics (e.g. amoxicillin or benzyl peni- cause of either community- or hospital-
cillin) but antibiotic resistance is an emerg- acquired pneumonia it may produce a very se-
ing problem particularly in certain countries vere illness with a high mortality. It partic-
such as Spain, where about 30% of isolates are ularly occurs as a sequel to influenza so that
resistant, so that it is necessary to give broad anti-staphylococcal antibiotics should be given
antibiotic cover to a patient who has acquired to patients who develop pneumonia after in-
pneumonia in a country with a high prevalence fluenza. Infection may also reach the lungs via
of antibiotic-resistant pneumococcus. Pneu- the bloodstream when staphylococcal bacter-
mococcal vaccine is recommended for pa- aemia arises from intravenous cannulae in hos-
Specific pathogens 53
pitalised patients or from intravenous drug mis- isms are difficult to culture in the laboratory
use, for example.The production of toxins may and the diagnosis is often made retrospectively
cause tissue necrosis with cavitation, pneuma- by demonstrating a rising antibody titre on
tocele formation and pneumothoraces. It is serological tests.
usually sensitive to cefuroxime but the standard
treatment is with b-lactamase-resistant peni- Mycoplasma pneumonia
cillins such as flucloxacillin. Mycoplasma pneumoniae is a small free-living or-
ganism, which does not have a rigid cell wall and
Klebsiella pneumonia which is therefore not susceptible to antibiotics
Klebsiella pneumoniae is a Gram-negative or- such as penicillin which act on bacterial cell
ganism which generally causes pneumonia walls. Infection is transmitted from person to
only in patients who have impaired resis- person by infected respiratory droplets. It par-
tance to infection (e.g. alcohol misuse, mal- ticularly affects children and young adults
nutrition, diabetes) or underlying lung although any age group may be affected. Infec-
disease (e.g. bronchiectasis). It often produces tion typically occurs in outbreaks every 4
severe infection with destruction of lung tissue, years and spreads throughout families, schools
cavitation and abscess formation. Treat- and colleges. Mycoplasma pneumoniae typically
ment requires attention to the underlying dis- causes an initial upper respiratory tract infec-
ease state and prolonged antibiotic therapy, tion with pharyngitis, sinusitis and otitis, fol-
guided by the results of microbiology culture lowed by pneumonia in about 30% of cases. A
and sensitivity. Often a combination of a third- variety of extrapulmonary syndromes may
generation cephalosporin (e.g. ceftazidime) occur and may be related to immune responses
and an aminoglycoside (e.g. gentamicin) is ap- to infection. These include lymphocytic menin-
propriate. goencephalitis, cerebellar ataxia, peripheral
neuropathy, rashes, arthralgia, splenomegaly
Pseudomonas aeruginosa and hepatitis. Cold agglutinins to type O red
pneumonia cells are often present and haemolytic anaemia
Pseudomonas aeruginosa is a Gram-negative may occur. Mycoplasma pneumoniae causes
bacillus which is a common cause of pneumo- significant protracted morbidity but is rarely
nia in hospitalised patients, particularly life-threatening.
those with neutropenia and those receiving
endotracheal ventilation in ITU. It is usually Chlamydial respiratory infections
treated with a combination of an aminoglyco- There are three chlamydial species which cause
side (e.g. gentamicin) and a third-generation respiratory disease.
cephalosporin (e.g. ceftazidime) or anti- Chlamydia psittaci is primarily an infection
pseudomonal penicillin (e.g. azlocillin). of birds which is transmitted to humans as a
zoonosis (a disease contracted from animals)
Pneumonia caused by atypical by inhalation of contaminated droplets. Psitta-
pathogens cosis or ornithosis is the name given to the
Atypical pathogens is an imprecise term which resultant illness which is often severe and
is sometimes used in clinical practice to refer to characterised by high fever, headache, delirium,
certain pathogens which cause pneumonia such a macular rash and severe pneumonia.
as Mycoplasma pneumoniae, chlamydial organ- Chlamydia pneumoniae was identified as a
isms and Legionella pneumophila. Characteristi- respiratory pathogen in 1986. Infection is con-
cally, these organisms are not sensitive to fined to humans and there is no avian or animal
penicillins and require treatment with tetra- reservoir of infection. Infection with this organ-
cycline or macrolide (e.g. erythromycin ism is extremely common in all age groups and
or clarithromycin) antibiotics. These organ- spreads directly from person to person, with
54 Chapter 6: Pneumonia
outbreaks occurring in families, schools cally causes a severe pneumonia with pros-
and colleges. It typically produces upper respi- tration, confusion, diarrhoea, abdominal pain
ratory disease including pharyngitis, otitis and and respiratory failure, with an associated high
sinusitis but may also cause pneumonia which is mortality. Direct fluorescent antibody staining
usually mild. may detect the organism in bronchoalveolar
Chlamydia trachomatis is a common cause lavage fluid, and tests to detect Legionella antigen
of sexually transmitted genital tract infection in urine are available, and allow rapid diagnosis.
and infants may acquire respiratory tract infec- A combination of erythromycin and rifampicin
tion with this organism from their mothers gen- is often used to treat severe Legionella
ital tract during birth. pneumonia.
Legionella pneumonia
Legionella pneumophila is a Gram-negative Further reading
bacillus which is widely distributed in nature in
water.The organism was first identified in 1976 American Thoracic Society. Hospital-acquired pneu-
when an outbreak of severe pneumonia affected monia in adults: diagnosis, assessment of severity,
delegates at a convention of the American initial antimicrobial therapy, and preventative
strategies. Am J Respir Crit Care Med 1995; 153:
Legion, who contracted infection from a con-
171125.
taminated humidifier system (Legionnaires Baudouin SV. Critical care management of community
disease). In sporadic cases there is often no ap- acquired pneumonia. Thorax 2002; 57: 26771.
parent source for the infection. Sometimes in- Bourke SJ. Chlamydial respiratory infections. BMJ
fection can be traced back to a contaminated 1993; 306: 121920.
water system such as a shower in a hotel British Thoracic Society. Guidelines for the manage-
room. Epidemics of infection may occur from a ment of community-acquired pneumonia in adults.
Thorax 2001; 56 (suppl. IV).
common source such as a contaminated hu-
Obaro SK, Monteil MA, Henderson DC. The pneu-
midification plant, water storage tanks or heat- mococcal problem. BMJ 1996; 312: 15215.
ing circuits. Infection does not spread from Roig J, Domingo C, Morera J. Legionnaires disease.
patient to patient. Legionella pneumophila typi- Chest 1994; 105: 181724.
CHAPTER 7
Tuberculosis
Tuberculosis is an infection caused by Mycobac- virus (HIV). At present in the UK about 40% of
terium tuberculosis which may affect any part of tuberculosis occurs in the white population,
the body but most commonly affects the lungs. 40% in people of Indian subcontinent origin and
16% in people of black African origin. Infection
may have been contracted in childhood and lain
Epidemiology dormant for years before reactivating. Factors
which reduce resistance and precipitate reacti-
The World Health Organisation estimates that vation include ageing, alcohol misuse, poor
1.72 billion people (one-third of the nutrition, debility from other diseases, use of
worlds population) have latent infection immunosuppressive drug therapy, and co-
with Mycobacterium tuberculosis, 1520 infection with HIV. In the UK, overlap between
million people have active disease and 3 the population with HIV infection (mainly young
million deaths occur each year from tuber- white men) and the population with tuberculo-
culosis (95% in the developing world). One hun- sis (mainly older white people and younger im-
dred years ago in the UK more than 30 000 migrants from the Indian subcontinent) is
people died from tuberculosis each year (about limited so that only 5% of patients with acquired
the same as for lung cancer at present). Mortal- immune deficiency syndrome (AIDS) have
ity and notification rates declined steadily from tuberculosis and about 3% of patients with
1900 onwards because of improvement in nu- tuberculosis are identified as having HIV infec-
tritional and social factors, with a sharper de- tion. However, 4.5 million people world-
cline occurring from the late 1940s onwards wide are estimated to be co-infected with
after the introduction of effective treatment. HIV and tuberculosis (98% in developing
Overall, the decline in notification rates has lev- countries).
elled off over the last decade, with some areas
noting increases (Fig. 7.1). Notification rates in
England and Wales reached a low point of about Clinical course (Fig. 7.2)
5000 a year in 1987 but have increased again to
about 6500 a year recently. This increased inci- The clinical course of tuberculosis often evolves
dence of tuberculosis is mainly seen in inner city over many years and represents a complex in-
areas, particularly London, and the risk is high- teraction between the infecting organism
est in ethnic minority groups, the homeless, (Mycobacterium tuberculosis) and the persons
those misusing drugs and alcohol and people co- specific immune response and non-specific re-
infected with the human immunodeficiency sistance to infection.Traditional descriptions of
55
56 Chapter 7: Tuberculosis
T UBERCU L O S IS N OT I F I C A T I ON S A N D DE ATH S
60
50 Notifications
Deaths
Notifications/deaths (thousands)
40
30
20
10
0
19501995
Fig. 7.1 Notifications of tuberculosis and deaths complex appears on chest X-ray as a peripher-
in England and Wales, 19501995. Notifications of al area of consolidation (Gohn focus) and hilar
tuberculosis have declined from about 50 000 in
adenopathy. Occasionally, erythema nodosum
1950 to 5000 in 1987, since when notifications
develops at this stage.An immune response de-
have plateaued. (Reproduced with permission
from The Prevention and Control of Tuberculosis in the velops, the tuberculin test becomes positive and
United Kingdom, Department of Health, 1996.) healing often takes place.This stage of the dis-
ease is often asymptomatic but may leave calci-
fied nodules on chest X-rays representing the
tuberculosis divide the disease into two main healed primary focus. Active progression of
patterns, primary and post-primary tuber- first infection may occur. Bronchial spread of in-
culosis, although these are mainly based upon fection may cause progressive consolidation
the characteristic evolution of the disease in the and cavitation of the lung parenchyma, and
days before effective chemotherapy. pleural effusions may develop. Lymphatic spread
of infection may cause progressive lymph node
Primary tuberculosis enlargement, which in children may compress
Primary tuberculosis is the pattern of disease bronchi with obstruction, distal consolidation
seen with first infection in a person (often a and the development of collapseand bronchiec-
child) without specific immunity to tuber- tasis. Bronchiectasis of the middle lobe is a very
culosis. Infection is acquired by inhalation of typical outcome of hilar node involvement
organisms from an infected individual, and the by tuberculosis in childhood. Haematogenous
initial lesion typically develops in the peripheral spread of infection results in early generalisa-
subpleural region of the lung followed by a reac- tion of disease which may cause miliary tubercu-
tion in the hilar lymph nodes. The primary losis, and the lethal complication of tuberculous
Clinical course 57
N A TU RAL HI ST O R Y OF T U B E R C U L O S I S
Primary complex
Most asymptomatic Calcified primary
healing in 48 weeks focus
Healed quiescent
tuberculosis
Reactivation
Lymph
node ?
Reinfection
Collapse
bronchiectasis
Miliary TB
Effusion Pneumonic spread (Often
'occult')
Blood- (+ extrapulmonary
borne forms)
spread Miliary
TB TB meningitis
(Late)
Fig. 7.2 Summary of the natural history of direct progression of the initial infection or
tuberculosis. result from endogenous reactivation of infec-
tion or from exogenous re-infection (inhala-
tion of Mycobacterium tuberculosis from another
meningitis (particularly in young children). In- infected individual) in a patient who has had pre-
fection spread during this initial illness may lie vious contact with the organism and has devel-
dormant in any organ of the body (e.g. bone, oped a degree of specific immunity. Reactivation
kidneys) for many years only to reactivate particularly occurs in old age and in circum-
many years later. stances where immunocompetence is impaired
(e.g. illness, alcohol misuse, immunosuppres-
Post-primary tuberculosis sive drug treatment). The lungs are the most
Post-primary tuberculosis is the pattern of usual site of post-primary disease and the apices
disease seen after the development of of the lungs are the most common pulmonary
specific immunity. It may occur following site.
58 Chapter 7: Tuberculosis
Fig. 7.4 This 68-year-old man was persuaded to tuberculosis sensitive to standard drugs. He was
consult a doctor because of a 6-month history of treated with directly observed anti-tuberculosis
cough, haemoptysis, night sweats and weight therapy. Six of 38 residents of the hostel were
loss. He suffered from alcoholism and lived in a found to have active tuberculosis. DNA
hostel for homeless men. His chest X-ray shows fingerprinting techniques showed that this
cavitating consolidation throughout the right cluster of six cases was caused by three different
upper lobe with further areas of consolidation in strains of Mycobacterium tuberculosis arising as a
the left upper and right lower lobes. Sputum acid- result of both reactivation of latent tuberculosis in
and alcohol-fast bacilli (AAFB) stains were debilitated elderly men and spread of infection
positive and cultures yielded Mycobacterium within the hostel.
nodes).The term miliary tuberculosis refers AAFB which appear as red rods on a blue
to a situation where there has been widespread background. Sputum cultures require special
haematogenous dissemination of tuberculosis, media (e.g. LwensteinJensen medium) and
usually with multiple (millet-seed size) nodules the tubercle bacillus grows slowly taking 4 7
evident on chest X-ray. Chest symptoms are weeks to give a positive culture and a further 3
often minimal and typically the patient is ill and weeks for the in vitro testing of antibiotic sensi-
pyrexial with anaemia and weight loss. tivity. Biopsy of an affected site (e.g. pleura,
lymph node, liver, bone marrow) may show the
Laboratory diagnosis characteristic features of caseating granulo-
Identification of Mycobacterium tuberculosis by ma (central cheesy necrosis of a lesion formed
laboratory tests may take some time and by macrophages, lymphocytes and epithelial
anti-tuberculosis treatment may have to be cells). Biopsy specimens should also be submit-
commenced based on clinical and radiological ted for mycobacterial cultures. Newer tech-
features while awaiting the results of laboratory niques are being developed to improve the
tests. Once the diagnosis is suspected, repeated speed, sensitivity and specificity of the labora-
sputum samples should be examined by the tory diagnosis of tuberculosis. The Bactec ra-
ZiehlNeelsen (ZN) method looking for diometric system, for example, uses a liquid
60 Chapter 7: Tuberculosis
TUBERCULOSIS TREATMENT
Dose
6 months of rifampicin and isoniazid, with pyrazinamide and ethambutol for first 2 months
Monitor treatment meticulously (e.g. monthly review)
Check compliance
Use directly observed therapy if problems with compliance
Notify the diagnosis to Public Health Authorities
Contact tracing of close family contacts
Table 7.1 Treatment of tuberculosis. berculous cavities developed in the lungs at-
tempts were made to collapse the cavities by in-
medium containing a radioactively labelled 14C- ducing an artificial pneumothorax, crushing the
labelled substance which releases 14CO2 when phrenic nerve, instilling various materials out-
metabolised, and detection of this reflects the side the pleura to compress the lung (plombage)
growth of Mycobacterium tuberculosis. DNA or performing thoracoplasty, whereby the ribs
techniques using the polymerase chain reac- were excised and the lung compressed against
tion are being developed and may, for example, the mediastinum. In the late 1940s strepto-
prove useful in detecting evidence of infection in mycin and para-amino salicylic acid (PAS)
cerebrospinal fluid in tuberculous meningitis. were introduced into clinical practice and the
DNA fingerprint techniques make it pos- outlook for patients with tuberculosis was rev-
sible to distinguish different strains of My- olutionised. It soon became apparent that treat-
cobacterium tuberculosis.This can give useful ment had to be prolonged and combinations
insights into the likely sources and spread of in- of antibiotics had to be used because of the ca-
fection and help assess the relative contribution pacity of the tubercle bacillus to lie dormant in
of newly acquired and reactivated infection in lesions for long periods and to develop resis-
different populations. tance to antibiotics.
The current standard treatment of tubercu-
losis consists of 6 months of rifampicin and
Treatment (Table 7.1) isoniazid, supplemented by pyrazinamide
and ethambutol for the first 2 months. All
Before effective antibiotics became available in drugs are usually given in a single daily dose.
the late 1940s, about 50% of patients with spu- Rifampicin and isoniazid are bactericidal drugs
tum-positive tuberculosis died of the disease. which kill extracellular bacilli which are actively
Patients were admitted to sanatoria for bed metabolising. Both rifampicin and pyrazinamide
rest, sunshine and fresh air therapy and nutri- are effective against intracellular bacilli, within
tional support in an attempt to enhance their macrophages. Prolonged treatment is needed
own resistance to the disease. When large tu- to eradicate bacilli lying dormant.The use of the
Tuberculin testing 61
combination of drugs also prevents the emer- culosis very difficult to treat, and such a patient
gence of resistance from the small number of poses a risk to public health because he or she
bacilli which are naturally resistant to any one of may infect others with drug-resistant tubercu-
the antibiotics. Ethambutol is bacteriostatic and losis. Some outbreaks of multidrug-resistant
is included in the treatment regimen to prevent tuberculosis have occurred in prisons and
the emergence of resistance to other drugs. It hospitals with high mortality rates.
may be omitted in patients with a low risk of The most dangerous of the adverse reac-
resistance to isoniazid (i.e. white patients tions to anti-tuberculosis treatment is hepa-
who have not had previous antituberculosis totoxicity, and patients should be advised to
treatment and who do not have HIV infection). stop treatment and report for medical advice if
Patients from ethnic minority groups have a sig- they develop fever, vomiting, malaise or jaun-
nificantly higher risk of resistance to isoniazid dice. Isoniazid, rifampicin and pyrazinamide may
and other drugs, and should be commenced on all cause hepatitis and allergic reactions such as
the four-drug combination. Meticulous super- rashes. Isoniazid may cause a peripheral neu-
vision of treatment is essential and patients ropathy and this is preventable by pyridoxine
should be seen at least monthly for prescription 10mg/day, which is given routinely to those at
of medication, checking of compliance with risk of neuropathy (e.g. patients with diabetes
treatment and monitoring for side-effects (e.g. or alcohol misuse). Intermittent rifampicin may
liver function tests). Errors in the prescription cause flu-like symptoms, and the induction of
of medication or failure of the patient to comply microsomal hepatic enzymes reduces the
with treatment may have disastrous conse- serum half-life of drugs such as warfarin,
quences with the emergence of resistant organ- steroids, phenytoin and oestrogen contracep-
isms. Directly observed therapy should be tives so that patients may need adjustment in
instituted for patients who have difficulty com- dosage of medications and may need to use al-
plying with treatment, whereby the patient is ternative contraceptive measures. Rifampicin
observed to ensure that he or she swallows the produces a reddish discoloration of urine
medication. Sometimes this can be achieved by (which may be used to monitor compliance) and
giving high doses of the anti-tuberculosis med- may cause staining of soft contact lenses. Pyraz-
ication three times per week with the patient inamide sometimes causes initial facial flushing,
attending a hospital or general practice clinic to and may cause an elevation of uric acid levels
be given the medication under the supervision with arthralgia. Ethambutol causes a dose-
of a doctor or nurse. Flexible strategies are re- related optic neuropathy, which is rare at
quired to ensure compliance of patients with doses below 15 mg/kg/day. Patients should have
social (e.g. homelessness) or psychological (e.g. their visual acuity checked before starting treat-
alcohol misuse, mental illness) problems and ment and should be warned to stop the drug if
there is an important role for community visual symptoms occur, and the drug should be
health workers or trained lay persons in these avoided if possible in patients with impaired
circumstances. renal function or pre-existing visual problems.
At present, drug-resistant tuberculosis is
rare in the initial treatment of white patients in
the UK. About 6% of patients from the Indian Tuberculin testing (Fig. 7.5)
subcontinent have tuberculosis which is resis-
tant to isoniazid, and it is for this reason that Hypersensitivity to the tubercle bacillus can be
ethambutol is added to the treatment regimen. detected by the intradermal injection of a puri-
Multidrug-resistant tuberculosis results fied protein derivative (PPD) of the organism.
from inadequate previous treatment.The devel- The response is of the type IV cell-mediated
opment of resistant organisms in a patient failing variety and results in a raised area of induration
to comply with treatment may make the tuber- and reddening of the skin. In the Mantoux test
62 Chapter 7: Tuberculosis
T UB ERCU L IN T E ST I N G
MANTOUX HEAF
Test dose
1 : 10 000 1
1 : 1000 10
1 : 100 100
Grade I
1 mm 4 papules
Grade II
10 mm confluent ring
Grade III (< 10 mm)
Papule + raised centre
Grade IV (>10 mm)
+ vesiculation
Positive reactions
Papule 1 mm high Grade III and IV
10 mm diameter reactions
with 100 TU or less
Fig. 7.5 Tuberculin testing.
0.1ml of tuberculin solution is injected intrader- placed on the volar surface of the forearm and
mally (not subcutaneously) and the test is read the gun is used to puncture through the PPD
at 4872 hours. A positive result is indicated by solution. The reaction is graded from I to IV
redness and induration at least 10 mm in diame- according to the formation of papules and the
ter. If active tuberculosis is suspected the lowest extent of induration. A positive tuberculin test
dilution may be used initially to prevent a severe indicates the presence of hypersensitivity to tu-
reaction, and higher concentrations used if berculin resulting from either previous infection
there is no reaction. The Heaf test is with tubercle bacillus or from bacillus Cal-
performed with a spring-loaded needled gun. metteGurin (BCG) vaccination.A weak reac-
A drop of undiluted PPD (100 000 TU/ml) is tion may be non-specific and indicate contact
Control 63
with other non-tuberculous environmental my- large number of contacts with tuberculosis,
cobacteria. A strongly positive test in a child consideration should be given to widening the
who has not received BCG vaccination is likely circle of contacts who are offered screening.
to indicate primary infection. If there is evidence About 11% of close contacts of smear-positive
of active disease, full anti-tuberculosis treat- cases are found to have active disease.
ment is required; if there is no evidence of active Screening of contacts consists of a combina-
disease chemoprophylaxis is advisable.A source tion of checking for symptoms of tuberculosis,
amongst adult contacts of the child must be chest X-ray, tuberculin testing (Heaf or
carefully sought. A negative tuberculin test Mantoux testing) and assessment of BCG sta-
makes active tuberculosis unlikely and indicates tus. Most cases of active tuberculosis are found
a lack of immunity so that BCG vaccination is at the first clinic visit in unvaccinated close con-
recommended. tacts of smear-positive disease. If the contact
has not had BCG vaccination a tuberculin
test is performed and if this is negative vaccina-
Control tion is recommended. For children a tuberculin
test is the usual initial screening test. Children
Treating active disease with a strongly positive tuberculin test should
Prompt identification and treatment of pa- have a chest X-ray.A strongly positive tuberculin
tients with active tuberculosis limits the spread test (e.g. Heaf grade III or IV) with a normal
of infection. Sputum-positive patients (AAFB chest X-ray suggests that the child has been in-
positive) should be considered as potentially fected with tubercle bacillus, has not developed
infectious until they have completed 2 weeks of active disease but remains at risk of doing so in
treatment.The patients family will already have the future. The risk of future activation of such
been exposed to the risk of infection so that latent infection is reduced by chemoprophy-
segregation of the patient from contact with his laxis which consists of treatment for 6 months
or her family at the time of diagnosis is not with isoniazid alone, or for 3 months with isoni-
useful, and most patients can be treated as azid and rifampicin.Those with a negative tuber-
outpatients. Where patients with suspected or culin test should have it repeated 6 weeks later
confirmed tuberculosis are admitted to hospital (to ensure they are not in the process of devel-
they should be kept in a single room. Particular oping immunity to recently acquired infection),
care is required if the patient has multidrug- and if they remain tuberculin-negative BCG vac-
resistant tuberculosis and these patients should cination is advisable.
be treated in a negative pressure ventilation
room to prevent transmission of infection to Screening of immigrants
other patients or health-care workers. Immigrants from areas with a high prevalence of
tuberculosis (e.g. Indian subcontinent) should
Contact tracing be screened for tuberculosis on arrival in a
When a diagnosis of tuberculosis is made there country of low-prevalence such as the UK.
is a statutory requirement in the UK for the Adults should have a chest X-ray and children
doctor to notify the patient to the public health should have a tuberculin test. Thereafter
authorities who are then responsible for under- the procedure is as for close contacts, with
taking screening of contacts. The index treatment of active disease, chemoprophylaxis
patient may have acquired infection from, or of latent infection or BCG vaccination as
transmitted infection to, someone in his or her appropriate.
close environment. It is usual to limit contact
tracing to household contacts and to close BCG vaccination
friends sharing a similar level of contact with the BCG is a live attenuated strain of tuberculosis
index patient. If initial investigations reveal a which provides about 75% protection
64 Chapter 7: Tuberculosis
against tuberculosis for about 15 years. It on the basis of their characteristics on labora-
is given by intradermal injection (not subcuta- tory culture tests. Treatment is often difficult
neous injection) and produces a local skin reac- requiring prolonged (e.g. 2 years) treatment
tion. It is currently given to children aged 13 with rifampicin and ethambutol because these
years in the UK and to certain groups at higher organisms often show resistance to some
risk of exposure to tuberculosis. standard anti-tuberculosis antibiotics. Some
more recently developed antibiotics, e.g. clar-
ithromycin or ciprofloxacin, may be useful in
Opportunist mycobacteria treatment. These organisms are low-grade
(atypical mycobacteria) pathogens and do not pose a threat to contacts
of infected patients so that there is no need for
There are a number of other mycobacteria that contact tracing procedures.
can cause pulmonary disease and that do not
belong to the Mycobacterium tuberculosis com-
plex. These are called atypical or opportunist Further reading
mycobacteria and the most common of these
are Mycobacterium kansasii, Mycobacteri- Campbell IC. Management of opportunist mycobac-
um avium-intracellulare complex, Mycobac- terial infection. Thorax 2000; 55: 21018.
terium malmoense and Mycobacterium Morse DI. Directly observed therapy for tuberculosis.
BMJ 1996; 312: 71920.
xenopi. They are widespread in nature and can
Ormerod LP. Chemotherapy and management of tu-
be found in water and soil so that sometimes berculosis in the United Kingdom. British Thoracic
contamination of clinical specimens occurs Society guidelines. Thorax 1998; 53: 53648.
from environmental sources. They act as low- Ormerod LP. Control and prevention of tuberculosis
grade pathogens which do not usually pose a in the United Kingdom. Thorax 2000; 55: 887
risk to normal individuals. Infections occur 901.
mainly in patients with impaired immunity, e.g. Rose AMC.Tuberculosis at the end of the 20th centu-
ry in England and Wales. Thorax 2001; 56: 1739.
AIDS (see Chapter 8) or in those with damaged
Sudre P, Dam G, Kochi A. Tuberculosis: a global
lungs (e.g. advanced emphysema or lung cavities overview of the situation today. BullWHO 1992; 70:
from previous Mycobacterium tuberculosis infec- 14959.
tion). They are often associated with chronic Van Soolingen D, Hermans PWM. Epidemiology of
symptoms such as cough, sputum production, tuberculosis by DNA fingerprinting. Eur Respir J
haemoptysis and weight loss. Diagnosis is made 1995; 8 (suppl. 20): 64956.
CHAPTER 8
Respiratory Disease in AIDS
and Immunocompromised
Patients
donated blood in the developed countries has localised in lymphoid tissue and the disease en-
stopped transmission of infection in blood ters a chronic symptomless phase. Persistent
products and transfusions. generalised lymphadenopathy may devel-
op with enlarged nodes in more than one site
persisting for more than 3 months. Some
Human immunodeficiency patients develop symptoms such as malaise,
virus infection weight loss and fevers which are caused by HIV
infection but not the consequence of oppor-
HIV is a retrovirus which has a high affinity for tunistic infections. AIDS is diagnosed when
the CD4 molecule of T lymphocytes. After an HIV-seropositive patient develops certain
binding to the CD4 receptor the virus pen- major opportunistic infections (e.g. Pneumocys-
etrates the cell wall and initiates a cycle of viral tis carinii pneumonia, Mycobacterium avium
replication within the cell. The replication of intracellulare) or defined malignancies (e.g.
retroviruses is driven by the enzyme reverse Kaposis sarcoma, non-Hodgkins lymphoma).
transcriptase which translates the single-
stranded viral RNA back to double-stranded
DNA hence the term retro or reverse. The Highly active anti-retroviral
viral DNA is integrated into the genome of therapy (Table 8.1)
the cell by the viral enzyme, integrase, and this
provirus is then propagated in subsequent gen- Highly active anti-retroviral therapy (HAART)
erations after each round of cell division. The became available from 1996 onwards and has
provirus may remain silent during the lifetime of resulted in a dramatic decline in the rate of pro-
the cell or be transcribed, producing new viral gression of patients from HIV infection to AIDS,
particles which form buds on the cell mem- and in AIDS-related mortality in the developed
brane. The transcription of the provirus is con- countries. These drugs are expensive and are
trolled by various proteins derived from the largely not available to the millions of patients
virus itself and from the host cell. On death of with HIV infection in the developing world.
the T cell the virus is released and taken up by Three classes of anti-retroviral drugs are cur-
new cells, propagating infection further. HIV rently available (Table 8.1). Reverse transcrip-
infection results in a progressive fall in the num- tase catalyses the conversion of single-stranded
ber and function of CD4 T lymphocytes. The HIV RNA to double-stranded DNA, which is
pace at which immunodeficiency develops and incorporated into the nucleus of the CD4
the susceptibility to opportunistic infections is cell. Nucleoside reverse transcriptase in-
reflected in the CD4 lymphocyte count. It is hibitors block the action of this enzyme and
possible to measure the HIV replication rate by are also incorporated into the DNA sequence
measuring plasma concentrations of HIV RNA, causing DNA chain termination. The non-
and this is often referred to as the viral load. nucleoside reverse transcriptase in-
The average time from initial infection with hibitors bind to reverse transcriptase inhibit-
HIV to the development of AIDS is about 1012 ing enzyme activity. Protease inhibitors
years. After primary infection with HIV there is block the HIV protease enzyme which is re-
an asymptomatic period of about 4 weeks.Then sponsible for processing proteins required in
many patients will suffer a 23-week serocon- the formation of new infective particles.
version illness which resembles glandular The optimum time for initiation of therapy
fever with malaise, arthralgia, lymphadenopa- depends on the plasma viral load and CD4
thy, headache, rashes and fever. This phase is cell count, which are monitored through-
associated with high levels of viraemia, and out treatment. The development of drug
towards the end of this phase antibodies to HIV resistance is reduced by using complex
are detectable. The virus then becomes mainly combinations of drugs. Drug toxicity and
Pulmonary complications of human immunodeficiency virus infection 67
Non-infectious diseases
Pulmonary complications of Neoplastic
human immunodeficiency virus Kaposis sarcoma
infection (Table 8.2) B-cell lymphoma
Inflammatory
Lymphocytic alveolitis ( TLCO)
Although CD4 T lymphocytes are the main Non-specific interstitial pneumonitis
target of HIV infection, the virus also infects Lymphocytic interstitial pneumonitis
other cells in the body including pulmonary Airways disease and emphysema
macrophages. A lymphocytic alveolitis and Primary pulmonary hypertension
impaired gas diffusion (reduced transfer
factor for carbon monoxide) are found even Table 8.2 Pulmonary complications of HIV
in asymptomatic patients who do not have infection.
68 Chapter 8: Respiratory Disease in AIDS
contraindicated in HIV infection because of the disseminated infection but usually meningoen-
risk of active infection developing with the cephalitis dominates the clinical picture. Treat-
live attenuated vaccine bacillus in severely ment is with fluconazole or amphotericin.
immunocompromised patients. Because of Pulmonary histoplasmosis and coccid-
their impaired cellular immunity, patients ioidomycosis may occur in areas where these
with HIV are very susceptible to contracting fungi are endemic (e.g. USA).
and transmitting tuberculosis so that strict
isolation precautions are warranted, par- Human immunodeficiency virus-
ticularly for patients with multidrug-resistant related neoplasms
tuberculosis. Kaposis sarcoma
This is the most common malignancy in HIV-
Mycobacterium aviumintracellulare complex infected patients. Characteristically, it occurs in
This is an opportunistic mycobacterium which HIV-infected homosexual men and it is thought
does not usually cause disease in normal sub- that this may relate to co-infection with
jects but which commonly infects patients with human herpes virus 8. Pulmonary Kaposis
advanced AIDS, particularly when the CD4 sarcoma is nearly always accompanied by le-
count is <100/mL. Extrapulmonary disease is sions in the skin or buccal mucosa. Chest X-ray
more common than pulmonary disease and appearances are variable as the tumour may af-
the diagnosis of disseminated Mycobacterium fect the bronchi, lung parenchyma, pleura or
aviumintracellulare complex (MAIC) is usually mediastinal lymph nodes. At bronchoscopy
made when the organism is cultured from Kaposis sarcoma appears as red or purple le-
blood, bone marrow, lymph node or liver biop- sions. The diagnosis is usually made on the
sy. The organism is not usually responsive to basis of the visual appearances in the context of
standard anti-tuberculous drugs and it is treated mucocutaneous Kaposis sarcoma as biopsy of
with a combination of rifabutin, ethambutol, the bronchial lesions is often non-diagnostic
clarithromycin or azithromycin. and may cause haemorrhage. Anti-retroviral
therapy (HAART) may lead to regression of
Viral infections Kaposis sarcoma but anti-neoplastic chemo-
Cytomegalovirus (CMV) infection is com- therapy (e.g. vincristine, bleomycin) may be
mon in AIDS, usually causing systemic infection needed.
with hepatitis, retinitis, encephalitis and colitis,
rather than overt pulmonary infection. CMV is Lymphoma
often isolated from the lungs of AIDS patients Late in the course of AIDS, high-grade B-cell
but it is not always pathogenic, sometimes being lymphomas arise.The lungs are often involved as
present as a commensal. It is treated with ganci- part of multiorgan involvement. The response
clovir. EpsteinBarr virus, adenovirus, in- to chemotherapy is often poor.
fluenza and herpes simplex virus may cause
pneumonia in AIDS patients. Herpes simplex Interstitial pneumonitis
virus is frequently present in the mouth of HIV- Patients with HIV infection may develop non-
infected patients so that its isolation from the specific interstitial pneumonitis (NIP).
respiratory tract often indicates colonisation This presents as episodes of dyspnoea with pul-
rather than infection. monary infiltrates, reduced gas diffusion and
hypoxaemia. Bronchoalveolar lavage is negative
Fungal pulmonary infections for infection and transbronchial biopsy shows
Invasive pulmonary infections with Aspergillus evidence of lymphocytic inflammation. It may be
fumigatus or Candida albicans are unusual a manifestation of direct HIV infection of the
but may occur late in the course of AIDS. Cryp- lung. It is often self-limiting but prednisolone
tococcal pneumonia may occur as part of a may be beneficial.
Pulmonary complications of human immunodeficiency virus infection 71
PULMONARY INFILTRATES IN
IMMUNOCOMPROMISED PATIENTS
Chest X-ray infiltrates
Is it the underlying disease?
Is it a reaction to drugs?
Is it infection?
Is it some other disease process?
Pulmonary infiltrates
Clinical assessment
Microbiology of sputum, urine, blood (e.g.TB, bacteria)
Induced sputum (e.g. PCP)
Bronchoscopy + bronchoalveolar lavage (CMV, PCP,TB)
Transbronchial lung biopsy
Surgical lung biopsy (histology)
Diagnosis Specific treatments
Table 8.3 Differential diagnosis of pulmonary the lung with the HIV virus, on the pulmonary
infiltrates in immunocompromised patients. circulation.
pneumonia (e.g. PCP, tuberculosis), despite an- The problem is often that of a patient with one
tibiotic therapy, may occur as the patient of these conditions presenting with pulmonary
mounts an inflammatory response.This may be infiltrates on chest X-ray accompanied by dysp-
severe enough to cause acute respiratory fail- noea and sometimes fever. The infiltrates in
ure and requires corticosteroid therapy. In pa- these circumstances may be caused by pul-
tients presenting with HIV infection and low monary involvement by the underlying dis-
CD4 counts, opportunistic infections should be ease process, a reaction to drug treatment,
sought and treated before starting HAART. infection resulting from immunosuppression
or to other coincidental disease processes.
Treatment is crucially dependent upon accurate
Other immunocompromised diagnosis.
patients Assessment involves a careful clinical history
and examination focusing on the clinical context
There is an increasing number of patients who and clues to aetiology (Table 8.3). Microbiology
are severely immunocompromised by a variety of sputum, urine and blood may identify specific
of diseases and by use of immunosuppressive pathogens. Induced sputum is particularly useful
drugs. Patients with neutropenia are particu- in diagnosing PCP. If these initial tests are not di-
larly vulnerable to bacterial infections (e.g. agnostic it is often advisable to proceed directly
Streptococcus pneumoniae, Gram-negative to bronchoscopy with bronchoalveolar lavage
bacteria) and invasive fungal infections (e.g. for detailed microbiology. Transbronchial lung
Aspergillus fumigatus, Candida albicans), and pa- biopsy is useful in obtaining tissue for histologi-
tients with depressed T-lymphocyte function cal diagnosis but carries the risk of pneumotho-
are vulnerable to PCP, tuberculosis and rax or haemorrhage. Occasionally, surgical lung
CMV infection, for example. biopsy is warranted.
There are three particular situations where
profound immunosuppression commonly
arises. Further reading
1 Patients with cancer receiving anti-
neoplastic chemotherapy. Beck JM, Rosen MJ, Peavy HH. Pulmonary complica-
2 Patients with inflammatory diseases (e.g. tions of HIV infection. Am J Respir Crit Care Med
connective tissue diseases, Wegeners granulo- 2001; 64: 21206.
Brown M, Miller RF.AIDS and the lung. Medicine 2001;
matosis, etc.) receiving immunosuppressive
29 (4): 1821.
drugs (e.g. corticosteroids, cyclophosphamide, Grant AD, De Cock KM. HIV infection and AIDS in the
methotrexate). developing world. BMJ 2001; 322: 14759.
3 Patients post-organ transplantation Maynaud C, Cadranel J. AIDS and the lung in a chang-
(bone marrow, renal, lung, etc.) receiving ing world. Thorax 2001; 56: 4236.
immunosuppressive drugs (e.g. ciclosporin, Miller R. HIV-associated respiratory diseases. Lancet
azathioprine). 1996; 348: 30712.
Williams IG, Weller IVD. Antiretroviral drugs. BMJ
2001; 322: 141012.
CHAPTER 9
Bronchiectasis and
Lung Abscess
B RO NCHIECTA SI S
Mucus
hypersecretion
Impaired
Inflammatory ciliary action
response
Loss of
3
ciliated cells
3
3
Bacterial
proliferation
1
4 Proteases Bacterial
proliferation
Tissue
damage 2
5
Accumulation of
secretions Fig. 9.1 Bronchiectasis evolves
through a vicious circle of steps.
ASP ERG IL L U S L U N G DI SE A SE
Incidental finding
Incidental isolation from sputum
Isolation in atopic asthma (a)
(a)
(b)
Allergic aspergillosis
Asthma (a)
(a)
Fleeting lung shadows (b)
Eosinophilia
(c) Later:
Upper lobe fibrosis (c)
(d)
'Proximal' bronchiectasis (d)
Mucoid impaction
Recurrent, segmental or lobar
collapse associated with
aspergillus plugs and bronchial
(e) damage (e)
(f)
Mycetoma (f)
Fungus ball in cavity from old TB,
cystic disease or ? spontaneous
Haemoptysis or symptomless
Fig. 9.2 Summary of the clinical spectrum of croscopy. Ciliary function can also be studied by
Aspergillus lung disease. microscope photometry which assesses the
beat frequency of cilia obtained by brush biopsy
of nasal mucosa. A bedside estimate of ciliary
fossa). Ciliary dyskinesia with situs inversus is function can be obtained by timing the nasal
known as Kartageners syndrome. clearance of saccharin. In this test a 1-mm cube
Mucociliary clearance can be assessed by of saccharin is placed on the inferior turbinate
measuring the rate of removal from the lung of of the nose. The time from placing the particle
an inhaled radiolabelled aerosol.The ultrastruc- to the patient tasting the saccharin is usually less
ture of cilia can be studied by electron mi- than 30 minutes, and is a measure of nasal ciliary
Bronchiectasis 77
Fig. 9.3 This 70-year-old woman had suffered hyphae were seen on sputum microscopy and
from tuberculosis in the 1950s which had resulted Aspergillus precipitins were present in her blood.
in bilateral apical lung fibrosis and severely Tests for carcinoma and tuberculosis were
impaired lung function (forced expiratory volume negative. Bronchial arteriography showed marked
in 1 second, 0.5L; forced vital capacity, 1.1L). She hypertrophy of the bronchial artery to the left
presented with recurrent major haemoptysis, and upper lobe and therapeutic embolisation was
chest X-ray showed features characteristic of an performed resulting in resolution of the
aspergilloma with an opacity in the left apex haemoptysis.
surrounded by a halo of radiolucency. Aspergillus
clearance. In men, sperm motility may be as- vere, requiring therapeutic embolisation of hy-
sessed by microscopy of seminal fluid. pertrophied bronchial arteries to control the
bleeding source. Infective exacerbations may be
Associated diseases associated with fever and pleuritic pain.
Patients with certain diseases seem to have an Chronic severe bronchiectasis may cause
increased incidence of bronchiectasis. These malaise, weight loss and halitosis (foul
diseases include rheumatoid arthritis, ulcera- breath). Coarse crackles may be audible over
tive colitis, Crohns disease and coeliac disease affected areas and clubbing is common. Sys-
but the mechanism by which bronchiectasis temic spread of infection (e.g. cerebral abscess)
arises in these diseases is unclear. and secondary amyloidosis are now very rare
because of control of infection by antibiotics.
Clinical features
The cardinal feature of bronchiectasis is chron- Investigations (Fig. 9.4)
ic cough productive of copious purulent spu- A chest X-ray may show features of
tum. There is considerable variation in the bronchiectasis such as peribronchial thickening,
severity of the disease and mild cases are often which is evident as parallel tramline shadowing,
misdiagnosed as chronic bronchitis. Haemop- or cystic dilated bronchi. However, the chest X-
tysis is common and may occasionally be se- ray is often normal in less severe cases and high-
78 Chapter 9: Bronchiectasis and Lung Abscess
Fig. 9.4 This 50-year-old man had suffered bronchi, cyst formation and patchy peribronchial
pertussis pneumonia at the age of 18 months. He consolidation. He was treated with postural
had chronic cough productive of copious purulent drainage physiotherapy, salbutamol, long-term
sputum isolating Pseudomonas aeruginosa on nebulised antibiotics (colistin) and intermittent
culture. Computed tomography showed extensive courses of oral ciprofloxacin or intravenous
bilateral bronchiectasis with dilatation of ceftazidime and gentamicin.
LU NG AB S CESS
Bronchial obstruction
Foreign body (e.g. peanut)
Tumour
Aspiration Cavitating pneumonia
Unconsciousness (e.g. alcohol) Staphylococcus aureus
Oropharyngeal sepsis Klebsiella pneumoniae
Oesophageal disease Streptococcus pneumoniae
Neuromuscular disease Tuberculosis
obstruction caused by a tumour or foreign with multiple abscesses forming, often with a
body (e.g. inhaled peanut).The centre of an area pleural empyema and evidence of infec-
of destructive pneumonia may break down to tion elsewhere, e.g. septic arthritis,
form a lung abscess particularly when the pneu- osteomyelitis. Prolonged anaerobic blood
monia results from Staphylococcus aureus or culture is required to identify the organism,
Klebsiella pneumoniae.Tuberculosis may present which is sensitive to metronidazole.
as a lung abscess. Blood-borne infection may
occur by intravenous injection of infected mate-
rial by drug addicts. Pulmonary emboli may Bronchopulmonary
cause pulmonary infarction, with secondary in- sequestration
fection giving rise to an abscess. Penetrating
chest trauma is an unusual cause of lung ab- Bronchopulmonary sequestration is a congeni-
scess. Transdiaphragmatic spread of infec- tal anomaly in which an area of lung is not
tion may occur from a subphrenic abscess (e.g. connected to the bronchial tree (i.e. se-
post-cholecystectomy) or a hepatic abscess questered) and has an anomalous blood
(e.g. amoebic abscess). supply usually from the aorta. If infection devel-
Drainage of pus from the abscess cavity is a ops in the sequestration it often progresses to
key aspect of treatment. This can often be an abscess because of lack of drainage to the
achieved by bronchial drainage using postural bronchial tree. Surgical resection is required
drainage physiotherapy. Sometimes percuta- but preoperative bronchial arteriography is
neous drainage is achieved by positioning a necessary to identify the anomalous blood
catheter drainage tube under radiological guid- supply.
ance. Prolonged antibiotic therapy is given in
accordance with the likely organism and the re-
sults of microbiology tests (e.g. metronidazole Further reading
for anaerobic infections). Surgical excision of
the abscess cavity is sometimes required where Chapel HM. Consensus on diagnosis and manage-
medical treatment fails. ment of primary antibody deficiencies. BMJ 1994;
308: 5815.
Chippindale AJ, Patel B, Mamtora H. A case of
necrobacillosis. Thorax 1990; 45: 745.
Necrobacillosis Ellis DA,Thornley PE,Wightman AJ et al. Present out-
look in bronchiectasis: clinical and social study and
Necrobacillosis (Lemires disease) is an unusu- review of factors influencing prognosis. Thorax
al cause of lung abscess which is associated with 1981; 36: 65964.
a very characteristic clinical picture first de- Munro NC, Cooke JC, Currie DC et al. Comparison
scribed by Lemire. Typically, a young adult de- of thin section computed tomography with bron-
chography for identifying bronchiectatic segments
velops a severe sore throat with cervical
in patients with chronic sputum production. Thorax
adenopathy because of infection with the 1990; 45: 1359.
anaerobe, Fusobacterium necrophorum.This is as- Neild JE, Eykyn SJ, Phillips I. Lung abscess and empye-
sociated with a local venulitis followed by a sep- ma. Q J Med 1985; 57: 87582.
ticaemic illness with haematogenous spread Stockley RA. Role of bacteria in the pathogenesis and
of infection. The lungs are frequently involved progression of acute and chronic lung infection.
Thorax 1998; 53: 5862.
CHAPTER 10
Cystic Fibrosis
Lungs
Introduction
In the bronchial mucosa failure of chloride
transport results in secretions of abnormal
Cystic fibrosis is the most common potentially
viscosity which interfere with mucociliary
lethal inherited disease of white people. It af-
clearance mechanisms and the high salt con-
fects about 1 in 2500 live births in the UK
tent of airway surface fluid inactivates
and is inherited in an autosomal recessive man-
defensins which are naturally occurring
ner.About 1 in 25 of the population is a car-
antimicrobial peptides on the epithelial surface.
rier of the disease.
There is some evidence that the CFTR also has
a role in the normal uptake and processing of
Pseudomonas aeruginosa from the respiratory
The basic defect tract. Patients with cystic fibrosis also have
abnormal mucus glycoproteins which act as
Cystic fibrosis is a result of a defect in a gene on binding sites such that bacteria adhere to the
the long arm of chromosome 7 which codes for mucosa and proliferate. Thus, the gene defect
a 1480-amino-acid protein, named cystic fi- results in dysfunction of CFTR and predisposes
brosis transmembrane conductance reg- to severe chronic lung infection by a variety of
ulator (CFTR). More than 800 mutations of mechanism at the cellular level.The inflammato-
this gene have been identified but the most ry response is unable to clear the infection and
common is designated DF508, in which muta- a vicious cycle of infection and inflamma-
tion of a single codon of the gene results in the tion develops, progressing to lung damage,
loss of phenylalanine (delta F) at position 508 bronchiectasis, respiratory failure and
of the protein. CFTR functions as a chloride death.
channel in the membrane of epithelial cells and
the primary physiological defect in cystic fibro- Gastrointestinal tract
sis is reduced chloride conductance at epithelial In the pancreas the abnormal ion transport re-
membranes, most notably in the respiratory, sults in the plugging and obstruction of ductules
gastrointestinal, pancreatic, hepatobiliary and with progressive destruction of the gland. The
reproductive tracts. In sweat ducts, failure of re- pancreatic enzymes (e.g. lipase) fail to reach the
absorption of chloride ions results in elevated small intestine and this results in malabsorp-
concentrations of chloride and sodium in the tion of fats with steatorrhoea and failure to gain
sweat, a characteristic feature of the disease and weight. Progressive destruction of the en-
the basis for the sweat test used in diagnosis. docrine pancreas may cause diabetes. Abnor-
81
82 Chapter 10: Cystic Fibrosis
malities of bile secretion and absorption cause zae and Streptococcus pneumoniae. By teenage
an increased incidence of gallstones and bil- years many have become infected with mucoid
iary cirrhosis. Sludging and desiccation of in- strains of Pseudomonas aeruginosa. Burk-
testinal contents probably accounts for the holderia cepacia is a Gram-negative plant
occurrence of meconium ileus (neonatal in- pathogen which causes onion rot. It was initially
testinal obstruction) in about 10% of babies thought that this organism was not pathogenic
with cystic fibrosis, and for the development of to humans but in the 1980s it became apparent
distal intestinal obstruction syndrome that patients with cystic fibrosis were vulnera-
(meconium ileus equivalent) in older children ble to this bacterium and that infection could
and adults. spread from patient to patient in an epidemic
way, particularly amongst children with cystic fi-
brosis in close social contact in holiday camps,
Clinical features (Fig. 10.1) for example.The clinical course of patients with
Burkholderia cepacia infection is very variable
Infants and young children but some show an accelerated rate of decline in
About 10% of children with cystic fibrosis pre- lung function and some develop a fulminant
sent at birth with meconium ileus, a form of necrotising pneumonia, the so-called cepacia
intestinal obstruction caused by inspissated vis- syndrome (Fig. 10.3). It is now recognised
cid faecal material resulting from lack of pancre- that there are many different strains of this bac-
atic enzymes and from reduced intestinal water terium but Burkholderia cepacia genomovar III is
secretion. More than half of children affected by associated with the worst prognosis. Because of
cystic fibrosis have obvious malabsorption by the potential for transmission of infection be-
the age of 6 months with failure to thrive as- tween patients with cystic fibrosis it is now stan-
sociated with abdominal distension and copious dard practice to segregate patients with
offensive stools from steatorrhoea as a result different infections such that they attend
of malabsorbed fat. Rectal prolapse occasion- different clinics and wards, and social contact
ally occurs. Recurrent respiratory infections between patients with cystic fibrosis is
rapidly become a prominent feature with cough, discouraged.
sputum production and wheeze. As the cycle of infection and inflammation
progresses, lung damage worsens with deterio-
Older children and adults rating airways obstruction, destruction of lung
Respiratory disease (Fig. 10.2) parenchyma, impairment of gas exchange and
Persistent cough and purulent sputum charac- the development of hypoxaemia, hypercap-
terise the development of bronchiectasis. nia and cor pulmonale. The persistent pul-
Progressive lung damage is associated with the monary inflammation provokes hypertrophy of
development of digital clubbing and progressive the bronchial arteries, and haemoptysis be-
airways obstruction, sometimes associated comes common. Occasionally, when severe
with wheeze. Serial measurements of forced bleeding occurs, therapeutic embolisation of
expiratory volume in 1 second (FEV1) give an in- the bronchial arteries may be required. Pneu-
dication of the severity and progression of the mothorax occurs in about 510% of patients
disease. Some patients show a significant asth- with advanced disease and may require prompt
matic component with reversible airways ob- tube drainage. Pleurodesis may be required for
struction and some develop colonisation of the recurrent pneumothoraces but this should be
bronchi by Aspergillus fumigatus and may show performed with care so as not to compromise
features of allergic bronchopulmonary as- future potential lung transplantation.
pergillosis (see Chapter 9). Initially, the typical
organisms isolated in sputum cultures are Gastrointestinal disease
Staphylococcus aureus, Haemophilus influen- About 85% of patients with cystic fibrosis have
Clinical features 83
CY S TIC F IB R O SI S
Psychosocial problems
Reduced life expectancy
Coping with complex disease Upper airway
Sinusitis
Nasal polyps
Lungs
Infection
Salty sweat
(e.g. Staph. aureus,
Sweat test +ve
Ps aeruginosa)
Salt loss in heat
Airways obstruction
Bronchiectasis
Liver Respiratory failure
Biliary cirrhosis Pneumothorax
Hepatosplenomegaly Haemoptysis
Portal hypertension Allergic aspergillosis
Gallstones
Pancreatic insufficiency
Intestines
Malabsortption
Meconium ileus
Malnutrition
Distal intestinal obstruction
Diabetes
Rectal prolapse
Clubbing
Male infertility
Arthropathy
Fig. 10.1 Clinical features of cystic fibrosis. Cystic channel on epithelial membranes. Failure of
fibrosis is a multisystem disease resulting from chloride conductance results in abnormal
mutations of the gene which codes for a protein, secretions and organ damage in the respiratory,
cystic fibrosis transmembrane conductance pancreatic, hepatobiliary, gastrointestinal and
regulator (CFTR), which functions as a chloride reproductive tracts.
Fig. 10.2 Chest X-ray of this 37-year-old man with ceftazidime and gentamicin at home each year.
cystic fibrosis shows hyperinflation, peribronchial His forced expiratory volume in 1 second is 1.5L
thickening, cystic bronchiectasis and perihilar (42% of predicted) and his general condition and
fibrosis. A Portacath central venous system is in lung function have remained stable over the
place with the access port situated last 5 years on treatment including long-term
subcutaneously in the left lower chest. He has nebulised colistin, nebulised deoxyribonuclease,
chronic Pseudomonas aeruginosa infection and physiotherapy and nutritional supplements.
receives about three courses of intravenous
focal biliary fibrosis, and about 5% of patients diocontrast Gastrografin (sodium diatrizoate).
develop multinodular cirrhosis with he- This agent has detergent properties which
patosplenomegaly, portal hypertension, oe- allow it to penetrate the inspissated fatty ma-
sophageal varices and liver failure. Distal terial and its hypertonicity then draws fluid
intestinal obstruction syndrome (meconi- into the faecal bolus. In the absence of complete
um ileus equivalent) (Fig. 10.4) results from obstruction the bowel can be flushed using
inspissated fatty semi-solid faecal material balanced intestinal lavage solution. Other mea-
obstructing the terminal ileum. A number of sures include rehydration, stool softeners (e.g.
factors contribute to the development of this lactulose) and N-acetylcysteine which probably
complication including malabsorption of fat, acts by cleaving disulphide bonds in the muco-
disordered intestinal motility and dehydrated protein faecal bolus. Prevention of recurrence
intestinal contents resulting from defective in- requires adequate pancreatic enzyme supple-
testinal chloride transport.The clinical features ments, avoidance of dehydration and some-
vary depending on the severity of the obstruc- times use of laxatives.
tion. Typically, the patient suffers recurrent
episodes of colicky abdominal pain and consti- Other complications
pation, and there is often a palpable mass in the Nearly all male patients are infertile be-
right iliac fossa. In severe cases complete intesti- cause of congenital bilateral absence of the vas
nal obstruction may develop with abdominal deferens. The exact mechanism by which this
distension, vomiting and multiple fluid levels in complication occurs is not known but it has
distended small bowel on an erect X-ray of ab- been suggested that it may result from resorp-
domen. It is treated by administration of the ra- tion of the vas deferens after it has become
86 Chapter 10: Cystic Fibrosis
plugged with viscid secretions in fetal life. Fe- um concentrations are a characteristic feature
males have near normal fertility although some of the disease. Sweating is induced by pilo-
abnormalities of cervical mucus are present. carpine iontophoresis, the sweat is collected
Pregnancy places additional burdens on the on filter paper and then analysed for sodium and
mothers health and is sometimes associated chloride. Pilocarpine is placed on the skin of the
with a deterioration in the disease because of forearm and a small electrical current is passed
increased nutritional stress and impaired across it to enhance its penetration of the skin
bronchial clearance. However, the main risk is and stimulation of the sweat ducts. Meticulous
of the mother failing to maintain all aspects of technique is required to avoid evaporation of
her own treatment as she focuses on the care of secretions or contamination. A sweat flow rate
the baby. of at least 100mL/min is required for accurate
Upper airway involvement causes trouble- analysis and sweat chloride levels above
some sinusitis and nasal polyps. Cystic fibro- 60mmol/L on repeated tests are abnormal.
sis arthropathy probably results from the
deposition in joints of antigenantibody com- DNA analysis
plexes produced by the immune response to The discovery of the cystic fibrosis gene in 1989
bacterial lung infections. Vasculitic rashes may led to the development of genotyping as an
also occur. In hot weather, patients with cystic aid to diagnosis. Genotyping can also be used
fibrosis are at risk of developing heat prostra- to detect carrier status, and can be applied to
tion as a result of excess loss of salt in sweat.As chorionic villus biopsy material for antenatal
these patients are living longer, a number of diagnosis. However, there are more than 800
other complications are being described such as mutations of the cystic fibrosis gene currently
osteoporosis and amyloidosis. Patients with identified and it is only possible to test for the
cystic fibrosis face major social and emo- more common mutations so that it can be diffi-
tional stresses relating to their reduced life cult to exclude cystic fibrosis resulting from
expectancy, outlook for employment, ability to rare mutations. DNA analysis has established
form relationships and undertake marriage, and the diagnosis in some individuals with only mild
their general capacity to cope with a complex clinical features, and this has extended our
disease and its treatment. knowledge of the clinical spectrum of the dis-
ease to include some very rare older, less se-
verely affected patients. Affected individuals
Diagnosis have two gene mutations (e.g. DF508|DF508),
one inherited from each of their parents.
The diagnosis of cystic fibrosis is based upon the Carriers of the disease have only one abnormal
demonstration of elevated sweat chloride gene, and do not show any evidence of the
concentrations on a sweat test, in association disease.
with characteristic clinical features such as
recurrent respiratory infections and evidence Screening
of pancreatic insufficiency. Nowadays the diag- Early diagnosis of cystic fibrosis allows specific
nosis is usually confirmed by the demonstration treatment to be commenced rapidly, and this is
of two known cystic fibrosis mutations associated with an improved prognosis. Infants
(e.g. DF508|DF508) on DNA analysis. with cystic fibrosis have elevated serum im-
munoreactive trypsin activity. This can be
Sweat testing measured on a single dried blood spot obtained
In cystic fibrosis the ion-transport defect results on a Guthrie card as part of the neonatal screen-
in a failure to reabsorb chloride ions from the ing programme for diseases such as phenylke-
sweat, so that elevated sweat chloride and sodi- tonuria and hypothyroidism.
Treatment 87
PA THO P HYS I OL OG Y A N D T R E A T M E NT OF C F
Antibiotics INFECTION
Anti-inflammatory drugs
Corticosteroids INFLAMMATION Anti-elastastases
Ibuprofen Leucocyte proteinase
inhibitor
Bronchodilators PROGRESSIVE LUNG DAMAGE Anti-oxidants
Physiotherapy
Lung transplantation
Oxygen RESPIRATORY FAILURE developments
Lung transplantation
Fig. 10.5 Summary of pathophysiology and bronchiectasis and progressive lung damage,
treatment of cystic fibrosis lung disease.The leading to respiratory failure and death, over a
genetic defect results in a lack of cystic fibrosis median period of 30 years. Key elements of
transmembrane conductance regulator (CFTR) treatment at all stages of the disease are
and abnormal chloride transport in airway nutrition, antibiotics, chest physiotherapy and
epithelium.The resultant viscid secretions psychosocial support. A variety of currently
predispose to the acquisition and persistence of available and prospective treatments target the
bacterial infection.The inflammatory response is different pathophysiological stages of the disease
unable to clear infection and a vicious cycle of to improve the outlook for patients with cystic
infection and inflammation causes fibrosis.
sure devices to aid dislodgement and expecto- bramycin with additional courses of intravenous
ration of sputum from the peripheral airways. anti-pseudomonal antibiotics during infective
As patients mature it is important that they exacerbations or when there is a decline in lung
learn to perform bronchial clearance them- function. Usually an aminoglycoside (e.g. gen-
selves. The active cycle of breathing technique tamicin, tobramycin) is given in combination
is often effective and popular with adult pa- with a third-generation cephalosporin (e.g.
tients.This involves a cycle of breathing con- ceftazidime) or a modified penicillin (e.g.
trol, thoracic expansion exercises and the piperacillin). Treatment is usually given for 14
forced expiratory technique (huffing) days and high doses are required to achieve ade-
which releases secretions from peripheral quate penetration of antibiotics into scarred
bronchi. Exercise is an excellent adjunct to bronchial mucosa because patients with cystic
physiotherapy but should not replace it. fibrosis have increased renal clearance of
antibiotics.
Antibiotics Intravenous antibiotic treatment is often
Children with cystic fibrosis should be immu- given at home by the patient after training.
nised against pertussis and measles as part of Where venous access is difficult a totally im-
the childhood vaccination programme, and planted central venous device can be inserted
should receive annual influenza vaccination (e.g. Portacath). This comprises a central ve-
thereafter.They should avoid contact with peo- nous cannula connected to a subcutaneous port
ple with respiratory infections and avoid inhala- which is accessed by inserting a special non-
tion of cigarette smoke. A variety of antibiotic cutting needle through the skin and the di-
strategies are used. Staphylococcus aureus is a aphragm of the subcutaneous chamber.
major pathogen in the disease from early child- Burkholderia cepacia is usually resistant to
hood and long-term continuous flucloxacillin many of the commonly used anti-pseudomonal
is often used to suppress this infection. Further antibiotics such as colistin, ciprofloxacin and
oral antibiotics are given during exacerbations aminoglycosides, but is often sensitive to cef-
in accordance with sputum cultures and sensi- tazidime or meropenem.
tivity testing. Common pathogens include
Haemophilus influenzae and Streptococcus Bronchodilator medication
pneumoniae which are usually sensitive to Some patients with cystic fibrosis have a re-
amoxicillin. versible component to their airways obstruc-
Infection with Pseudomonas aeruginosa be- tion, and benefit from bronchodilator drugs
comes an increasing problem as children get (e.g. salbutamol, terbutaline) and inhaled
older, and an important strategy in antibiotic steroids (e.g. beclometasone, budesonide,
therapy is to postpone for as long as possible the fluticasone).
colonisation of the airways by this organism.
Frequent sputum cultures are performed and Deoxyribonuclease
intensive anti-pseudomonal antibiotic therapy is The sputum of patients with cystic fibrosis con-
given when the organism is first isolated. This tains high levels of DNA which is derived from
often comprises an initial prolonged course the nuclei of decaying neutrophils. This makes
of oral ciprofloxacin and nebulised col- the sputum very viscid and difficult to expecto-
istin. If this does not eradicate infection then rate. Recombinant human deoxyribonuclease
intravenous anti-pseudomonal antibi- (Dnase/dornase alfa) is a genetically engineered
otics are recommended. Eventually, chronic in- enzyme which cleaves DNA. This recently de-
fection with Pseudomonas aeruginosa becomes veloped treatment can be administered by neb-
established.Attempts at suppressing the effects ulisation and improves the lung function and
of this infection involve long-term use of nebu- reduces the number of exacerbations in some
lised antibiotics such as colistin or to- patients.
Prospective treatments 89
40
35
30
25
Years
20
15
10 Fig. 10.6 Projected median
5 survival of patients with cystic
fibrosis by year of birth from
0
1955 60 65 70 75 80 85 1990 1959 to 1990. (Reproduced with
Year of birth permission from Elborn et al.,
1991.)
new treatments are being directed at each stage sponse involve the assessment of the role of
of the disease process. Perhaps the most excit- some currently available (e.g. ibuprofen) and
ing approach to treatment is the direct replace- some novel anti-inflammatory agents (e.g.
ment of the defective gene by gene therapy. pentoxifylline, anti-elastases, serum leucocyte
The DNA of CFTR has been cloned and has proteinase inhibitors (SLPIs)). Improvements in
been given to patients in experimental trials the field of lung transplantation offer the
using a vector such as a modified adenovirus or best hope for patients in the advanced stages of
liposome to introduce the gene into epithelial the disease.Advances in many different areas of
cells. Expression of the gene can be detected by scientific research are being brought into clini-
measuring transepithelial potential differences. cal practice in order to improve the outlook for
However, many practical difficulties have to patients with cystic fibrosis.
be overcome before gene therapy can be con-
sidered as a clinically effective treatment for
patients. Further reading
New pharmacological approaches are being
attempted to correct the ion transport defect Alton EW, Geddes DM. Gene therapy for cystic fibro-
by stimulating alternative chloride channels or sis. Eur Respir J 1997; 10: 2579.
inhibiting sodium channels. Nebulised amiloride Davis PB. Evolution of therapy for cystic fibrosis. N
Engl J Med 1994; 331: 6723.
has been shown to have a small effect in that
Elborn JS, Shale DJ, Britton JR. Cystic fibrosis: current
regard, and newer agents such as adenosine survival and population estimates to the year 2000.
triphosphate (ATP) and uridine triphosphate Thorax 1991; 46: 8815.
(UTP) are being assessed. Nebulised DNase Hoiby N, Koch C. Pseudomonas aeruginosa infection in
represents a novel approach to reducing the vis- cystic fibrosis and its management. Thorax 1990; 45:
cosity of the sputum.This drug is currently avail- 8814.
able and improves the lung function and reduces Jones AM, Dood ME, Webb AK. Burkholderia cepacia:
current clinical issues, environmental controver-
the number of exacerbations in some patients.
sies and ethical dilemmas. Eur Respir J 2001; 17:
Attempts at modifying the inflammatory re- 295301.
CHAPTER 11
Asthma
Definition Prevalence
Asthma is a disease characterised by chronic Asthma has been recognised since ancient times
airway inflammation with increased air- and it is now estimated that 130 million people
way responsiveness resulting in symptoms worldwide have asthma. The term is derived
such as wheeze, cough and dyspnoea, and from the Greek word asqma, meaning short-
airways obstruction which is variable drawn breath or panting and was in use in the
over short periods of time or reversible with time of Hippocrates (460 370 BC), although it
treatment. was probably used to refer to many different
It is not a static uniform disease state but causes of breathlessness.This problem of termi-
rather a dynamic heterogeneous clinical nology continues in that the reported preva-
syndrome which has a number of different lence of asthma greatly depends on the criteria
patterns and which may progress through dif- used to define asthma and is confused by
ferent stages so that not all features of the dis- changes in diagnostic habit (labelling shift)
ease may be present in an individual patient at a whereby patients may now be diagnosed as
particular point in time. For example, many pa- having asthma whereas previously they were la-
tients with well-controlled asthma are asymp- belled as having wheezy bronchitis in the case
tomatic with normal lung function between of children, or COPD in the case of adults, for
attacks although if further investigations were example. However, despite such labelling shifts
performed there would usually be evidence there is a general consensus that the preva-
of airway inflammation and increased airway lence of asthma is gradually increasing.
responsiveness. By contrast, in some patients Studies using objective measures of reversible
with chronic asthma the disease progresses to a airways obstruction and airway hyper-
state of irreversible airways obstruction. Some responsiveness in combination with symptoms
patients with smoking-related chronic obstruc- suggest that about 7% of the adult popula-
tive pulmonary disease (COPD), bronchiectasis tion in the UK have asthma.There is consid-
or cystic fibrosis may demonstrate airways ob- erable interest in the reasons for the increasing
struction with a degree of reversibility but it is prevalence of asthma and it is likely that such
important to appreciate that these diseases are changes relate to environmental rather than ge-
different from asthma with distinct aetiologies, netic factors.
pathologies, natural history and responses to
treatment.
91
92 Chapter 11: Asthma
AET IO L O G Y O F A ST H M A
Outdoor environment
Pollens
NO2
AIRWAY HYPER-RESPONSIVENESS SO2
TRIGGER FACTORS to histamine, methacholine, Ozone
Cold air exercise Particulates
Exercise
Infections
Occupational environment
Air pollution
Isocyanates
Drugs (b-blockers)
Epoxyresins etc.
Menstrual cycle
(see Chapter 15)
AIRWAY OBSTRUCTION
PEFR FEV1
Co-factors
SYMPTOMS Infections
Wheeze, cough, dyspnoea Smoking
Diet
Fig. 11.1 Asthma is multifactorial in origin, ing asthma may vary from patient to patient. In
arising from a complex interaction of genetic and many cases the most important environmental
environmental factors, which result in airway
factors are the intensity, timing and mode of ex-
inflammation and hyper-responsiveness, such
posure to aeroallergens which stimulate the
that bronchoconstriction develops in response to
a variety of trigger factors. production of IgE.Additional environmental de-
terminants are the concurrent exposure to co-
factors such as cigarette smoke, atmospheric
Aetiology (Fig. 11.1) pollutants and respiratory tract infections.
of nitrogen dioxide have increased over the last dry weather may cause a rapid rise in pollen
30 years. Use of catalytic converters in cars concentrations and also in levels of O3, nitrogen
reduces exhaust emissions. dioxide and sulphur dioxide because of atmos-
Sulphur dioxide (SO2) is created by the burn- pheric stability. Gusts of wind at the start of a
ing of fossil fuels containing sulphur. Power thunderstorm lift allergens into the air. Rain dis-
stations are the main source of sulphur dioxide rupts pollen grains into a number of smaller al-
emissions although domestic coal burning is lergenic particles. Under these circumstances
an important source in some areas. Diesel vehi- atopic individuals with pre-existing asthma or
cles also emit sulphur dioxide. Levels of sulphur hay fever are particularly vulnerable to the re-
dioxide emissions are gradually declining. sultant allergen challenge.The effects of atmos-
Ozone (O3) is formed by a photochemical re- pheric pollutants and allergens on asthmatics is
action involving sunlight, oxygen and nitrogen influenced by factors such as use of asthma
dioxide. Its production is dependent on weath- medication, time spent outdoors and exercise
er conditions. Although nitrogen dioxide and (which increases ventilation).
sulphur dioxide levels tend to be higher in cities,
ozone levels tend to be higher in rural areas. Occupational environment
Airborne particulates: this is a term used to de- Many agents encountered in the workplace
scribe elements of black smoke consisting may induce occupational asthma, e.g. iso-
of small particles produced by incomplete cyanates, epoxyresins, persulphates, hard wood
combustion. dusts (see Chapter 15).
Antigens: levels of grass and flower pollens
vary considerably depending on the climatic Co-factors in asthma
conditions and time of year, as do levels of aller- A number of other factors influence the devel-
gens from rape seed, soy bean and other plants opment of asthma.
and crops. Infections: many respiratory infections (e.g.
Interactions between atmospheric pollu- influenza A, Mycoplasma pneumoniae, Chlamydia
tants, aeroallergens and climatic conditions pneumoniae) provoke a transient increase in air-
have complex effects on asthma. Some studies way responsiveness in normal individuals and in
suggest that exposure to air pollution may en- asthmatics. Conversely, there is some evidence
hance airway responses to common allergens, that viral infections (e.g. measles) in the first
thereby potentially having a role in both the ini- year of life may protect against asthma.
tiation of asthma and in the triggering of acute Smoking: cigarette smoking is associated
attacks. Climatic conditions such as high with increased levels of IgE and with increased
pressure and humidity with calm still air can re- sensitisation to certain occupational allergens
sult in an accumulation of airborne pollutants in particular (e.g. anhydrides). Maternal
(e.g. particulates, ozone) and of allergens (e.g. smoking during pregnancy is thought to in-
pollens, fungal spores). Investigation of several crease the risk of developing atopic disease in
epidemics of asthma in Barcelona in the 1980s infancy and passive exposure to smoking has
established that the number of patients referred an adverse effect on asthma and other respira-
to hospital with acute attacks of asthma coin- tory diseases.
cided with days when soy bean was being un- Diet: some studies suggest that breast-
loaded from ships in the port in conditions of feeding may offer protection against the subse-
high barometric pressure and little wind. Sever- quent development of asthma, possibly because
al epidemics of acute asthma have been associ- of reduced exposure to food allergens in the
ated with thunderstorms, and these have neonatal period. Airway responsiveness may be
particularly affected patients with pre-existing influenced by dietary salt intake, although
atopic asthma and IgE reactions to specific anti- studies show conflicting results. In some pa-
gens such as pollens and fungal spores. Warm tients asthmatic attacks may occasionally be
Pathogenesis and pathology 95
P A T H O L O G Y OF AS TH M A
Thickened
basement Mucus plugging
membrane Mucosal
shedding
Goblet cells
Fig. 11.2 Summary of the
pathological features of
asthma. Half of a cross-section
of a bronchiole is shown.
Although these features are
characteristic of appearances
Hypertrophied Cellular
after death from asthma,
muscle infiltration
identical appearances are
present patchily in patients Oedema Eosinophils
who are apparently untroubled Dilated blood vessels Inflammatory exudate
by their asthma at the time.
precipitated by certain foods such as milk, egg, atopic asthmatics have high levels of specific IgE
wheat and food additives and preservatives which binds to receptors on inflammatory cells,
(e.g. tartrazine). Diets high in oily fish appear to most notably mast cells. Interaction of the IgE
be protective. antibody and inhaled antigen results in the acti-
Drugs: b-blocking drugs can induce bron- vation of these inflammatory cells and release
choconstriction in asthmatics, sometimes even of preformed mediators such as histamine,
when given in eye drops (e.g. timolol for glauco- prostaglandins and leukotrienes which cause
ma). A small percentage of asthmatics develop contraction of smooth muscle of the airways
bronchoconstriction when given salicylates producing bronchoconstriction. The inflamma-
(e.g. aspirin) or non-steroidal anti- tory response in asthma is highly complex in-
inflammatory drugs (e.g. ibuprofen). These volving the full spectrum of inflammatory
drugs block arachidonic acid metabolism down cells including mast cells, eosinophils, B and T
the prostaglandin pathway diverting it to the lymphocytes and neutrophils, which release an
leukotriene pathway. A reaction to aspirin is array of mediators and cytokines. These
more common in asthmatics with nasal polyps. mediators regulate the response of other in-
flammatory cells, and have a number of effects
resulting in contraction of airway smooth
Pathogenesis and pathology muscle, increased vascular permeability
(Fig. 11.2) and stimulation of airway mucus secretion.T-
helper lymphocytes have an important role in
A series of factors combine to produce increas- the regulation of the inflammatory response.
ing airway inflammation and airway responsive- These cells may be divided into two main sub-
ness, and when these features reach a sufficient sets on the basis of the profile of cytokines
level bronchoconstriction and asthma symp- which they produce. Th2 cells produce inter-
toms are triggered.Typically, the inhalation of an leukin 4 (IL-4), IL-5, IL-6 and IL-10 and up-
allergen in a sensitised atopic asthmatic results regulate the specific form of airway inflam-
in a two-phase response consisting of an early mation of asthma by enhancing IgE synthesis and
asthmatic reaction reaching its maximum at eosinophil and mast-cell function. In contrast,
about 20 minutes, and a late asthmatic reac- Th1 cells produce IL-2, interferon g (IFN-g)
tion developing about 612 hours later. These and lymphotoxin and down-regulate the
96 Chapter 11: Asthma
atopic response. In those who are genetically sistent. In episodic asthma the patient is often
susceptible to developing asthma, antigen pre- asymptomatic between episodes but suffers at-
sentation to T-helper cells leads to a Th2 re- tacks of asthma during viral respiratory tract in-
sponse. Infection with respiratory syncytial fections or after exposure to certain allergens.
virus augments a Th2 response, whereas some This pattern of asthma is commonly seen in chil-
other microbial antigens lead to a Th1 response. dren and young adults who are atopic and sen-
It has been suggested that exposure to allergens sitised to common antigens (e.g. grass pollens,
and infections in early childhood is important in pet dander). Because episodes of asthma can
determining the pattern of immune response often be related to inhaled environmental anti-
thereby modulating the genetic susceptibility to gens the clinical term extrinsic asthma is oc-
developing asthma. In affluent countries declin- casionally used. Sometimes the clinical pattern
ing family size, improved household amenities is of persistent asthma with chronic wheeze
and higher standards of cleanliness seem to be and dyspnoea. This pattern is more common in
associated with an increased incidence of asth- older patients with adult-onset asthma who
ma. The hygiene hypothesis suggests that are non-atopic and whose symptoms are not re-
allergic diseases may be prevented by certain in- lated to any apparent antigen exposure so that
fections in early childhood. Thus, for example, the term intrinsic asthma is sometimes
children with older siblings are more likely to be used.The variable nature of symptoms is a char-
exposed to childhood infections and have a acteristic feature of asthma. Typically, there is
lower incidence of asthma. a diurnal pattern (Fig. 11.3) with symptoms
The wall of the airway in asthma is thickened and peak expiratory flow measurements being
by oedema, cellular infiltration, increased worse early in the morning so-called morn-
smooth-muscle mass and glands (Fig. 11.2). ing dipping. Symptoms such as cough and
With increasing severity and chronicity of the wheeze often disturb sleep and the term noc-
disease remodelling of the airway occurs turnal asthma emphasises this. Cough is
leading to fibrosis of the airway wall, fixed nar- often the dominant symptom and the lack of
rowing of the airway and a reduced response to wheeze or dyspnoea may lead to a delay in mak-
bronchodilator medication. Mucus plugging of ing the diagnosis: so-called, cough variant
the lumen of the airway is a prominent feature of asthma. Symptoms may be provoked by exer-
acute severe asthma. Although in clinical prac- cise: exercise asthma. These descriptive
tice patients with asthma are sometimes classi- clinical terms are useful in emphasising some
fied as having extrinsic asthma (occurring in characteristic features of asthma, and highlight
relation to inhalation of environmental anti- the fact that asthma is not a uniform static dis-
gens) or intrinsic asthma (occurring without any ease but a broad dynamic clinical syndrome.
definable relationship to an environmental anti- When assessing a patient with confirmed or
gen), the pathological features of the airway in- suspected asthma it is important to focus on key
flammation are identical. It is likely that the aspects of the history which not only aid diagno-
inflammatory cascade of asthma can be initiated sis but which are also important in assessing the
by a variety of different factors in different pattern of the asthma and in treatment.
patients. Family history: there is a significantly increased
prevalence of asthma in relatives of patients
with asthma or other atopic diseases (eczema,
Clinical features hay fever).
Home environment: smoking, or exposure to
The typical symptoms of asthma are wheeze, passive smoking in the home environment, is an
dyspnoea, cough and a sensation of chest adverse factor. Indoor allergens, e.g. house dust
tightness.These symptoms may occur for the mite, dog or cat dander may be important in
first time at any age and may be episodic or per- triggering attacks.
Investigations 97
SY M P T OM S I N AS TH M A
6 am 12 6 pm 12 6 am
Severity of asthma
Midday Midnight
VA R I A B I L I T Y A N D R E V ERS I BI LI TY
IN A ST H M A
500
PEF
Variability
0
(a) Over a few weeks
500
PEF
Reversibility
0
(b) Over a few weeks
500
Variability or
PEF
reversibility
0
(c) Over the course of a lifetime
Fig. 11.5 Variability and reversibility in asthma asthma is moderately severe and may be absent
three diagrammatic views. (a) In the course of an when asthma is either very mild or very severe. (c)
exacerbation and subsequent recovery, variability Over decades of chronic asthma, there is a general
(diurnal variation) is most marked when asthma tendency for a decline in overall ventilatory
is moderately severe and may be absent when performance, which is related to the duration and
asthma is either very mild or very severe. (b) In the severity of the earlier experience. Accompanying
course of an exacerbation and subsequent this there is a reduction in both variability and
recovery, reversibility after an inhaled reversibility. PEF, peak expiratory flow.
bronchodilator (arrows) is most marked when
S KIN P R ICK TE ST
diagnosis of asthma in routine practice but are ment. There is often associated severe airway
particularly useful in assessing changes in air- inflammation and mucus plugging resulting in
way responsiveness in relation to exposure bronchiectasis (see Chapter 9). In addition to a
to environmental or occupational allergens (see positive skin prick test to Aspergillus these pa-
Chapter 15), and in research studies. tients often have significant eosinophilia and
precipitating antibodies to Aspergillus in
Tests for hypersensitivity their serum. Very rarely, asthma occurs as
Skin prick tests (Fig. 11.6) may be performed part of an eosinophilic vasculitis such as
to identify atopy and to detect particular sen- ChurgStrauss syndrome (see Chapter 16), in
sitivity to a specific antigen with a view to exclu- which case very high levels of blood eosinophil-
sion of exposure where possible (e.g. cat ia occur.
allergens). Drops of antigen extracts are placed
on the flexor surface of the forearm and the tip General investigations
of a small stylet is pressed into the superficial Further general investigations may be necessary
epidermis through the drop of allergen. A posi- to exclude other cardiorespiratory diseases.
tive reaction is manifest as a weal with a Chest X-ray is essential in older patients who
surrounding erythematous flare at about 15 have smoked, to exclude bronchial carcinoma,
minutes. The reaction to allergens should be for example, and may be needed in children if
compared with the reaction to a drop of hista- there are any clinical features to suggest other
mine and to a drop of control solution contain- diseases such as cystic fibrosis or bronchiecta-
ing no antigens.Total IgE level is often elevated sis. Bronchoscopy is occasionally necessary
in patients with atopic asthma and they some- to assess for vocal cord dysfunction, inhaled
times have a mild peripheral blood eosinoph- foreign bodies, bronchial carcinoma or rarer
ilia. Radioallergosorbent testing (RAST) causes of bronchial obstruction such as
is a means of measuring the level of circulating carcinoid tumours.
IgE specifically directed towards a particular
antigen.
Some asthmatics develop an allergic reaction Diagnosis (Table 11.1)
to Aspergillus fumigatus, a ubiquitous fungus
which may colonise the airways. In these cir- Although diagnosing asthma is straightforward
cumstances the asthma is typically severe and when the patient presents with classic symp-
persistent requiring systemic steroid treat- toms and evidence of variable or reversible air-
Management 101
DIAGNOSING ASTHMA
Underdiagnosis: Could this patients symptoms be caused by asthma?
Overdiagnosis: Does this patient really have asthma?
Recognise symptoms suggestive of asthma, e.g. wheeze, cough, recurrent chest infections
Establish evidence of airways obstruction, e.g. peak flow, FEV1, FEV1/VC ratio
Assess variability, reversibility, provocability of airway obstruction: serial peak flow chart, e.g.
morning dipping; response to bronchodilator and steroid trial; exercise-induced fall in peak flow
Monitor progress and review diagnosis, e.g. has wheezy bronchitis of childhood evolved into
established asthma or was it a result of viral bronchiolitis?
Consider additional diagnoses, e.g. occupational asthma, allergic bronchopulmonary aspergillosis
Exclude alternative diagnoses
COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; VC,
vital capacity.
Table 11.1 Diagnosing asthma. All that wheezes of variable or reversible airways obstruction
is not asthma and not all asthma wheezes. that allows a firm diagnosis of asthma to be
established. Doubt may arise where it is difficult
to obtain accurate peak flow or spirometry
ways obstruction, there are many pitfalls, and measurements as in the case of young children.
errors in diagnosis are common. Failure to di- Even when the diagnosis of asthma is estab-
agnose asthma results in the patient being de- lished the diagnostic process should be taken
prived of appropriate asthma treatment, e.g. a further: could this be occupational asth-
child with cough receiving recurrent courses of ma? Is there evidence of additional lung disease
antibiotics for chest infections when in fact he such as bronchiectasis or allergic bronchopul-
or she is suffering from cough variant asthma. monary aspergillosis? The doctor needs to ex-
Conversely, incorrect diagnosis of asthma ercise good clinical skills in applying two critical
might expose the patient to the risks of inappro- questions: could this patients symptoms
priate treatment (e.g. recurrent courses of be caused by asthma? Does this patient
prednisolone) and delay appropriate manage- really have asthma?
ment of other lung disease, e.g. inhaled foreign
body in a child or tracheal tumour in an adult
producing wheeze simulating asthma. On Management (Fig. 11.7)
the one hand it is necessary to be alert to less
well-recognised presentations of asthma, e.g. Patient education
cough without wheeze, and on the other hand Successful management of asthma requires that
to be prepared to review the evidence for asth- patients, or the parents of a child with asthma
ma if the response to treatment is poor or if understand the nature of the condition and its
unusual features emerge (e.g. could this child treatment. Patient education should begin at
possibly have cystic fibrosis?). Evidence estab- the time of diagnosis and form part of every sub-
lishing the diagnosis of asthma and excluding sequent consultation between the patient and
other diseases often emerges over time and it is doctor. All members of the team should par-
sometimes wise to use interim terms such as ticipate in the process and there is a particular
suspected asthma while gathering evidence role for respiratory nurse specialists.
MA N AGEM E N T OF C H R ON I C A S TH M A
102
Step 5:
Step 1: Regular inhaled anti- b agonist bronchodilator agonists as required with mg daily or fluticasone
stepwise reduction in
inflammatory agents inhaled beclomethasone 4001000 mg daily via a
treatment may be
Occasional use of relief Inhaled short-acting b or budesonide 8002000 mg large volume spacer and
possible. In patients
bronchodilators Inhaled short-acting b agonists as required daily or fluticasone one or more of the long-
whose treatment was
agonists as required plus either 4001000 mg daily via a acting bronchodilators
recently started at step 4
Inhaled short-acting b plus beclomethasone or large volume spacer plus
or 5 or included steroid
agonists 'as required' for beclomethasone or budesonide increased to plus regular prednisolone
tablets for gaining control
symptom relief are budesonide 100400 mg 8002000 mg daily or a sequential therapeutic tablets in a single daily
of asthma this reduction
acceptable. If they are twice daily or fluticasone fluticasone 4001000 mg daily trial of one or more of dose
may take place after a
needed more than once 50200 mg twice daily. via a large volume spacer inhaled long-acting b
short interval. In other
daily move to step 2. Alternatively, use cromo- or agonists
patients with chronic
Before altering a glycate or nedocromil beclomethasone or sustained release
asthma a three to six
treatment step ensure sodium, but if control is budesonide 100400 mg theophylline
month period of stability
that the patient is not achieved start inhaled twice daily or fluticasone inhaled ipratropium or
should be shown before
having the treatment and steroids 50200 mg twice daily plus oxitropium
slow stepwise reduction
has a good inhaler salmeterol 50 mg twice daily. long-acting b agonist
is undertaken
technique In a very small number of tablets
Address any fears patients who experience side high-dose inhaled
effects with high dose bronchodilators
inhaled steroids, either the cromaglycate or
long-acting inhaled b agonist nedocromil
option is used or a sustained
release theophylline may be
added to step 2 medication.
Cromoglycate or nedocromil
may also be tried
Fig. 11.7 Management of chronic asthma. (Reproduced with permission from British Thoracic Society guidelines on asthma management.
Thorax 1997; 52 (suppl. 1).)
Management 103
Education involves the patient understanding asthma which does not impair their perfor-
the nature of asthma, learning the practical mance. Many such sports people lend their sup-
skills necessary to manage asthma and adopt- port to organisations such as the National
ing the appropriate actions in managing their Asthma Campaign in the UK which provide
asthma and adhering to treatment. Educa- literature and support to help patients with
tion of the patient often starts with a discussion asthma.
of the multifactorial aetiology of asthma and
identification of precipitating factors. It is Avoidance of precipitating factors
useful for patients to understand that inflamma- Most patients with atopic asthma react to many
tion of the airways is a key factor underlying different antigens so that environmental control
the development of wheeze as they can then measures are generally not particularly helpful.
appreciate the difference between reliever House dust mites are most prevalent in warm
(bronchodilator) and preventer (anti- moist areas containing desquamated human
inflammatory) medication. Sufficient time skin scales and they are almost universally dis-
should be invested in instructing the patient in tributed in mattresses, pillows, carpets, furnish-
the use of inhaler devices, as this is a crucial ings and soft toys. The level of house dust mite
aspect determining the effectiveness of pre- may be reduced by encasing mattresses in
scribed medication. occlusive covers and by frequent washing of
Use of a peak flow meter provides patients blankets and duvets. Humidity levels can be de-
with an objective measure of airway obstruc- creased by better ventilation. Avoidance of ex-
tion allowing them to see the variability of posure to pet allergens from dogs or cats, for
readings from day to day, the influence of precip- example, is more feasible but the result of these
itating factors and the effect of treatment. Most interventions is often disappointing. Similarly, it
patients with asthma should be able to moni- is difficult to avoid exposure to outdoor aller-
tor and manage their asthma themselves to a gens but some patients benefit from precau-
considerable degree and to recognise when tions such as increasing asthma treatment or
medical advice is needed, in much the same way remaining indoors with closed windows when
as patients with diabetes monitor their blood pollen counts are high.
sugar levels and adjust insulin therapy. Desensitisation (immunotherapy) is a
The amount of information given to each pa- highly specialised technique in which repeated
tient needs to be varied in accordance with their injections of an allergen are given to a sensitised
needs and aptitude but all patients should subject in an attempt to produce blocking anti-
know about features which indicate when their body of IgG type which prevents the allergen
asthma is deteriorating and what action to take binding to specific IgE on mast cells. It is most
in these circumstances. Doctors should be commonly used in the treatment of well-
aware that it is often those patients least inter- documented life-threatening anaphylactic reac-
ested in learning about their disease who are at tions to insect stings but there is little evidence
greatest risk and that features such as depres- of its benefit in asthma and there are major con-
sion, anxiety, denial of disease and non-compli- cerns about the risk of anaphylaxis.
ance with treatment are strongly associated Avoidance of irritants such as cigarette
with asthma deaths. Particular effort is required smoke or generally dusty environments is
to identify and target resources at such patients. advisable. Avoidance of b-blocker drugs
Information conveyed in discussion with the pa- is important for all patients with asthma, and
tient should be supplemented by personalised patients who are sensitive to aspirin should
written information. Many patients are avoid all aspirin-containing products and non-
frightened and anxious about the diagnosis of steroidal anti-inflammatory drugs. Viral infec-
asthma and it is often helpful to point out that tions often precipitate attacks of asthma so that
many top-class sports men and women have it is advisable for patients to monitor peak flow
104 Chapter 11: Asthma
measurements carefully during such infections viding symptom relief but not control of the
and to intensify asthma treatment as required. underlying inflammatory process (in much the
Because influenza infection may precipitate same way as a pain-killer relieves pain but does
severe exacerbations of asthma, annual in- not treat the cause). Increasing need for bron-
fluenza vaccination is recommended. chodilator medication is an indication of poorly
Exercise is a particular factor precipitating controlled asthma and a need to increase anti-
asthma. Bronchoconstriction may develop inflammatory medication.
within minutes of onset of vigorous activity.This Long-acting b2-agonists: (e.g. salmeterol, for-
response usually resolves within 30 minutes and moterol) have a duration of action of more than
there then follows a refractory period of about 12 hours and are particularly helpful in control-
2 hours when further exercise does not pro- ling nocturnal symptoms. Their use is only
voke bronchoconstriction. Therefore a warm- recommended as an adjunct to inhaled corti-
up period before the main exercise usually costeroids so that control of the airway inflam-
controls this problem. Use of b-agonist medica- mation is not neglected.
tion or sodium cromoglycate before exercise Anti-cholinergic bronchodilators: (e.g. ipratro-
usually prevents exercise-induced asthma, al- pium, oxitropium) produce bronchodilatation
lowing athletes with asthma to compete at the by blocking the bronchoconstrictor effect
highest level of their sport. For example, 67 ath- of vagal nerve stimulation on bronchial
letes at the 1984 Olympic Games had asthma, smooth muscle.They take about 1 hour to reach
and many won medals! their maximum effect and have a duration of ac-
tion of about 46 hours. Side-effects are un-
Drug treatment common but nebulised anti-cholinergic drugs
Bronchodilator drugs (relievers) are used may be deposited in the eyes, aggravating glau-
to relieve symptoms of bronchoconstriction. coma. In most patients with asthma they are less
Anti-inflammatory drugs (preventers) effective than b2-agonists but they may be useful
treat the underlying chronic inflammatory in young children and older patients.
process in asthma. Short courses of oral pred- Theophyllines increase cyclic adenosine
nisolone (rescue medication) are used to monophosphate (cAMP) stimulation of
treat exacerbations. Most patients with chronic b-adrenoceptors by inhibiting the metabo-
asthma can be managed very satisfactorily with lism of cAMP by the enzyme phosphodi-
regular inhaled steroids to control airway esterase. They may also have other effects
inflammation, an inhaled bronchodilator to be including some anti-inflammatory actions.They
taken as required to reverse wheezing, and are not available in inhaler form and absorption
training to initiate emergency prednisolone from the gastrointestinal tract and clearance of
treatment when needed. the drug by the liver are variable so that the dose
needs to be titrated carefully in accordance with
Bronchodilators blood levels. Side-effects such as nausea, vomit-
b2-agonists: (e.g. salbutamol, terbutaline) ing, headache, tachycardia and malaise are
stimulate b-adrenoceptors in the smooth mus- common. Hepatic clearance of theophyllines
cle of the airway, producing smooth-muscle re- is reduced by drugs such as cimetidine,
laxation and bronchodilatation.They have an ciprofloxacin and erythromycin, and toxicity
onset of action within 15 minutes and a duration can occur if these medications are prescribed
of action of 46 hours. Side-effects include without adjustment in the dose of theophylline.
tremor, palpitations and muscle cramps but Aminophylline is an intravenous form of theo-
these are uncommon unless high doses are phylline (combined with ethylenediamine for
used. The main concern about bronchodilator solubility) which may be used in severe attacks
medication is that over-reliance on these drugs of asthma not responding to b-agonist medica-
may disguise the severity of the asthma by pro- tion. It must be given slowly (over at least 20
Management 105
minutes) with careful adjustment of dose in ac- adrenal function, and increased bone turnover
cordance with blood levels in order to avoid se- are detectable in some patients.The clinical sig-
rious toxicity such as convulsions and cardiac nificance of such systemic effects needs to be
arrhythmias. It does not usually result in any ad- considered in the context of the dangers of
ditional bronchodilatation compared to stan- uncontrolled asthma and alternative therapies
dard treatment with nebulised bronchodilators such as oral prednisolone.The dosage of inhaled
and systemic steroids, and side-effects are com- steroids should be reviewed regularly to ensure
mon so that its use is usually reserved for very that the patient is taking as much as is required
severe asthma not responding to standard to control their asthma (step up) but, equally,
treatment. as little as necessary (step down) so as to min-
Magnesium: magnesium sulphate (1.22g as an imise the risk of side-effects with long-term
intravenous infusion over 20 minutes) acts as a usage.
smooth muscle relaxant and is safe and effective Sodium cromoglycate is a preventative inhaled
in treating patients with acute severe asthma treatment which has a number of anti-
who have not had a satisfactory initial response inflammatory action including stabilisation of
to nebulised salbutamol. mast cells. It is mainly used in children with mild
asthma and it has no significant side-effects.
Anti-inflammatory drugs However, it is less effective than inhaled steroids
Inhaled corticosteroids (e.g. beclometasone, in more troublesome asthma. Nedocromil is a
budesonide, fluticasone) are the mainstay of newer inhaled compound with similar proper-
asthma treatment because they counteract ties to cromoglycate.
airway inflammation which is the key under- Oral steroid treatment: rescue courses of
lying process in asthma. It is essential that the oral steroids may be needed to control exacer-
patient understands that this is a preventative bations of asthma. Typically, this consists of
treatment which needs to be taken regularly 30 40 mg/day prednisolone for about 714
and which does not provide immediate relief of days in an adult. Treatment is continued until
symptoms. Compliance is improved by using a asthma control has been achieved. Most pa-
twice-daily regimen whereby the patients pre- tients should be taught to start their own short
ventative steroid inhaler is left at their bedside course of oral prednisolone in accordance with
and taken regularly every night and morning a predetermined self-management plan: e.g.
whereas their reliever bronchodilator is car- when peak flow falls below 60% of the patients
ried around with them for use as required. The best value. Patients should understand the po-
dose is adjusted to give optimal control and tential side-effects of long-term use of pred-
varies greatly from patient to patient. Many nisolone and the difference between this and
adult patients with relatively mild asthma infrequent short-course usage which is safe. A
achieve good control with a dosage of about very small number of patients require long-
400 mg/day beclometasone, but some patients term systemic prednisolone to control se-
with chronic severe asthma may require vere asthma.These patients should be attending
2000 mg/day. In adult patients low-dose a hospital specialist and it should have been
(below the equivalent of about 1000 mg/day be- clearly established that their asthma cannot be
clometasone) inhaled steroids are not usually controlled by other measures. The dosage of
associated with any significant side-effects apart steroids needs to be kept as low as possible. In
from oropharyngeal candidiasis or hoarseness these circumstances the patient should be given
of the voice which can be reduced by using a a steroid treatment card documenting the
spacer device and gargling the throat with water dosage of steroids used, advising about side-
after inhalation. With high dose inhaled effects and warning patients that steroids
steroids (above about 1000 mg/day beclometa- should not be stopped suddenly because of the
sone) biochemical evidence of suppression of risk of adrenal insufficiency. Booster doses may
106 Chapter 11: Asthma
be required during illnesses and patients may be matory process in the airways. Treatment
particularly susceptible to infections such as should be stepped up as much as neces-
chickenpox: other adverse effects include sary to control the asthma; when control has
peptic ulceration, myopathy, osteoporosis, been achieved treatment may be stepped
growth suppression, depression, psychosis, down so that the patient is on no more
cataracts and cushingoid features. Patients re- treatment than is necessary.
ceiving long-term oral prednisolone should be Asthma is a dynamic condition changing over
considered for preventative treatment of os- time and ongoing management requires an as-
teoporosis such as smoking cessation, exercise, sessment of the level of control of the asthma
hormone replacement therapy, adequate di- that has been achieved and adjustment of med-
etary calcium intake and disodium etidronate/ ication to find the optimal balance between
calcium treatment where appropriate. control of the asthma, use of medication and
Leukotriene receptor antagonists (e.g. mon- potential side-effects of treatment. Assessing
telukast, zafirlukast) block the effects of cys- asthma control involves:
teinyl leukotrienes which are metabolites of measurement of peak flow or spirometry and
arachidonic acid with bronchoconstrictor and comparing the values with the patients best
pro-inflammatory actions. Leukotriene antago- value and predicted normal value;
nists are a new modality of anti-inflammatory monitoring of serial peak flow records over
therapy in asthma, which are given orally in several days to assess diurnal and day-to-day
tablet form.They improve lung function and re- variability;
duce bronchial hyper-responsiveness in patients assessment of the patients requirements for
with asthma. These effects are similar to those use of bronchodilator reliever medication and
seen with 400 mg/day beclometasone. Most rescue courses of oral steroids;
studies of leukotriene antagonists have shown noting absences from work or school be-
benefit in patients with mild asthma but they cause of asthma; and
may also be used as add-on therapy in patients assessment of level of symptoms, e.g. noctur-
whose asthma is not controlled on inhaled nal sleep disturbance or exercise-induced
corticosteroids. bronchospasm.
PR ES S U RIZ ED M E T E R E D D O SE I N H ALE R
gastrointestinal tract where it is absorbed into (cr) of pressurised aerosol is inserted into
the blood, but mostly metabolised by first-pass one end of the spacer device and the patient
metabolism in the liver. breathes through the other end via a one-way
Spacer devices (Fig. 11.9): poor inhaler tech- valve (v) which closes on expiration; (e) expira-
nique is a significant problem in the use of tory port.This reduces the need for coordi-
metered-dose inhalers. Large-volume spacer nation of inspiration and actuation of the
devices overcome some of these problems and inhaler. Distancing the inhaler from the mouth
improve deposition of the drugs in the lower (spacing) results in a fine aerosol of smaller
airway to about 20% on average. The canister particles improving delivery of the drug to
108 Chapter 11: Asthma
DRY - P O W D ER I N H A L E R S
(a) (b)
Fig. 11.10 Dry-powder inhalers: (a) Turbohaler mouthpiece is to the left.The individual doses are
(Astra); (b) Diskhaler (Allen and Hanbury). (a) contained in sealed blebs on a disk which is
Turbohaler: the inhaler is shown with the cover placed on a carousel assembly inside the inhaler.
removed, the mouth piece is to the left. Up to 200 With an inout movement of the front end of the
doses of the powdered drug are stored in a inhaler (double arrow) the disk rotates and a new
reservoir through which the air channel passes. A bleb moves into place.The bleb is perforated
dose of the dry powder is rotated into the air before inhalation by opening the top flap (arrow).
channel by turning the distal section (arrow).The When the patient inspires, air is directed through
number of doses remaining is indicated in a small the pierced bleb and the powder is dispersed into
window (w). (b) Diskhaler: the inhaler is shown the airstream.
with the mouthpiece cover removed; the
the lower airways. Spacer devices should be the reservoir solution. The aerosol is adminis-
cleaned monthly by washing in detergent and al- tered by mask, or via a mouthpiece. Nebulisers
lowing them dry in air.They should be replaced are a convenient means of giving high doses
at least every 12 months. of bronchodilator drugs in acute attacks
Dry-powder devices (Fig. 11.10): in these de- of asthma where coordination of inhaler ad-
vices the b-agonist or steroid drug is formulated ministration may be difficult in a distressed
as a dry powder without a propellant. Inspirato- patient. They may also be used for delivering
ry airflow releases the powder from the device inhaled steroids (e.g. budesonide) in very young
so that they are breath actuated, and this re- children although it is important to realise that
duces the problem of coordination of inspira- properly used dry-powder devices, e.g. turbo-
tion and inhaler actuation. haler, or metered-dose inhalers and spacer
Nebulisers (Fig. 11.11): in this form of inhaled devices deliver a greater percentage of the
therapy, oxygen or compressed air is directed administered dose to the lower airway and are
through a narrow hole creating a local negative therefore the devices of choice for routine long-
pressure (Venturi effect) which draws the drug term treatment. The danger of patients having
solution into the air stream from a reservoir machines at home for administration of bron-
chamber. The droplets are then impacted chodilators lies in the fact that they may over-
against a small sphere, and small particles are rely on the temporary alleviation of symptoms
carried as an aerosol, whereas larger particles by nebulised bronchodilators to the detriment
hit the side wall of the chamber and fall back into of regular anti-inflammatory therapy, and they
Acute severe asthma 109
N E B UL I Z E R T R E ATM E NT
To mask or
T piece
Drug
Fig. 11.11 Nebuliser treatment. solution
(a) Diagram of typical
nebulisation mechanism. (b)
Nebuliser mask for Oxygen or
administration of high-dose compressed air
(a) (b)
bronchodilator (see text).
may delay seeking urgent medical advice during Heart rate 110 beats/min.
acute severe asthma attacks. Peak expiratory flow 50% of predicted
normal or best.
4050 mg orally, or hydrocortisone 100 mg 6- (ITU) may be advisable so that their condition
hourly intravenously, or both, immediately. can be monitored more closely. Intermittent
If life-threatening features are present add positive pressure ventilation is only rarely nec-
the following. essary but is used when the patient shows signs
Nebulised ipratropium: add ipratropium 0.5 mg of exhaustion (e.g. rising PCO2), failure to main-
to the nebulised b-agonist. tain oxygenation or deterioration in vital signs.
Intravenous magnesium sulphate: 1.22g infu-
sion over 20 minutes should be considered for Management during recovery in
patients with acute severe asthma who have not hospital and following discharge
had a good initial response to nebulised bron- The opportunity should be taken to improve
chodilator therapy. the patients understanding of asthma and its
Intravenous bronchodilators: some patients management, and to provide written guidance
with very severe asthma may gain additional on future management. Ways of improving the
benefit from intravenous aminophylline patients response to worsening asthma should
(5 mg/kg loading dose over 20 minutes unless be identified. Most crises resulting in hospital
on maintenance oral therapy, then infusion admission are probably preventable.The impor-
of 0.5 mg/kg/hr). Intravenous b2-agonists are tance of peak flow measurement in determining
sometimes used (salbutamol or terbutaline treatment changes should be explained. Possi-
250 mg over 10 minutes, then infusion of ble precipitating factors should be identified.
5 mg/min) but they should be reserved for those Inhaler technique should be checked and
patients in whom nebulised therapy cannot be performance recorded. If necessary, alternative
used reliably. inhaler devices should be used.
Investigations
Arterial blood gases; urea and electrolyte Further reading
concentrations; electrocardiogram in older
patients; chest X-ray. Bascom R, Bromberg PA, Costa DL et al. Health
effects of outdoor air pollution. Am J Respir Crit
Monitoring treatment Care Med 1996; 153: 47798.
British Thoracic Society. Guidelines on the manage-
Continued vigilance is required. The patients
ment of asthma. Thorax 1993; 48 (suppl. 2); Review
condition may deteriorate some hours after an and position statement. Thorax 1997; 52 (suppl. 1).
initial improvement (e.g. during the night after- Hendrick DJ. Asthma: epidemics and epidemiology.
wards). Measure and record peak expiratory Thorax 1989; 44: 60913.
flow 1530 minutes after starting treatment and Rees J, Price J. ABC of Asthma. London: BMJ Publishing
thereafter according to the response (at least 4 Group, 1996.
times daily measurements). Monitor respira- Sampson A, Holgate S. Leukotriene modifiers in the
treatment of asthma. BMJ 1998; 316: 12578.
tory rate, pulse, patients general condition and
Strachan DP. Family size, infection and atopy: the
oxygen saturation frequently. Nursing staff hygiene hypothesis. Thorax 2000; 55 (suppl 1):
should be asked to call the doctor if there is a 210.
deterioration in these signs, and elective trans- Tattersfield AE, Sears MR, Holgate ST et al. Asthma.
fer of the patient to an intensive therapy unit Lancet 1997; 350 (suppl. 2): 127.
CHAPTER 12
Chronic Obstructive
Pulmonary Disease
COPD
Term Definition Diagnosis
Chronic bronchitis Cough and sputum for 3 months of 2 successive years Symptoms
Airways obstruction Diffuse airway narrowing with increased resistance FEV1/VC
to airflow PEF
Asthma Reversible airways obstruction with airway Bronchodilator and
inflammation and hyper-responsiveness steroid response
Emphysema Dilatation of the terminal airspaces with destruction Pathology
of alveoli CT scan
KCO, TLCO
Respiratory failure Failure to maintain oxygenation PO2
O2 sat
Cor pulmonale Right heart hypertrophy and failure caused by chronic Oedema
lung disease JVP
ECG
ECHO
CT, computed tomography; ECG, electrocardiogram; ECHO, echocardiography; FEV1, forced expiratory
volume in 1 second; JVP, jugular vein pulse; PEF, peak expiratory flow; VC, vital capacity.
EMP HYS EM A
(a)
L O SS OF E L A ST I C R E C O I L
Elastic
recoil
Fig. 12.2 Emphysema consists of dilatation of to maintain their patency (a). Alveolar destruction
the terminal air spaces of the lungs, distal to the in emphysema results in a loss of elastic recoil
terminal bronchiole with destruction of their and a loss of outward traction on the small
walls. Small peripheral airways lack cartilage and airways such that they collapse on expiration
depend on the support of the surrounding alveoli contributing to the airways obstruction (b).
as manifest by a reduced peak expiratory cal features which consist of dilatation of the
flow, forced expiratory volume in 1 sec- terminal air spaces of the lung distal to
ond (FEV1) and FEV1/vital capacity (VC) the terminal bronchiole with destruction
ratio.The diagnosis is based upon lung function of their walls. Physiologically, emphysema is
tests.A number of factors contribute to airways characterised by a reduction in the transfer fac-
obstruction in COPD. Loss of elastic recoil tor for carbon monoxide and transfer coeffi-
from destruction of alveoli by emphysema is an cient. High-resolution computed tomography
important factor in producing airway collapse. (CT) scans can demonstrate the parenchymal
Airway inflammation is also present and lung destruction of emphysema. Two main
provokes bronchoconstriction which is patterns of emphysema are recognised
partly reversible by bronchodilator medication. (Fig. 12.1): centriacinar (centrilobular) em-
Accumulation of mucous secretions and super- physema involves damage around the respi-
imposed infections may aggravate airways ratory bronchioles with preservation of the
obstruction. more distal alveolar ducts and alveoli. Charac-
The degree of reversibility of the airways teristically, it affects the upper lobes and upper
obstruction is assessed by measuring the re- parts of the lower lobes of the lung. Panacinar
sponse to bronchodilator and corticosteroid (panlobular) emphysema results in disten-
drugs, and this varies considerably with some sion and destruction of the whole of the
patients having a significant reversible com- acinus, and particularly affects the lower half of
ponent to their disease whereas others have the lungs. Although both types of emphysema
predominantly fixed airways obstruction. The are related to smoking and may be present
severity of the airways obstruction may be arbi- together, it is possible that they may arise by
trarily graded according to the FEV1 value: mild different mechanisms and give rise to different
6079% of predicted; moderate 4059% of patterns of impairment of lung function.
predicted; severe <40% of predicted. Panacinar emphysema is the characteristic fea-
ture of patients with a1-anti-trypsin enzyme
Emphysema deficiency.
Emphysema is defined in terms of its pathologi-
114 Chapter 12: Chronic Obstructive Pulmonary Disease
EF F E C T OF SM O K I N G
A N D ST O P P I N G SM O K I N G
75
Affected smoker
Stopped at 45
50
Stopped at 65
Disability
25
Death
0
25 50 75
Age (years)
Fig. 12.3 Change in forced expiratory volume in smoking and show the same decline as non-
1 second (FEV1) with age: effect of smoking and smokers. Some smokers are affected and show a
stopping smoking. Non-smokers show a small steeper decline.Those affected by smoking can
progressive decline in function with age. By the be detected by measurement of FEV1 many years
time disability is noted, ventilatory function is before they become disabled. Stopping smoking
seriously reduced to about one-third of predicted slows the rate of decline. (From Fletcher & Peto,
normal values. Many smokers are unaffected by 1977.)
B LUE B L O ATER A N D P I N K P U F F E R
features of right heart failure consist of peri- airways obstruction. Dyspnoea is usually in-
pheral oedema, elevation of the jugular venous tense but blood gases are often maintained in
pressure and hepatomegaly sometimes associ- the normal range at rest until the terminal
ated with a palpable right ventricular heave and stages of the disease. Blue bloaters have poor
tricuspid regurgitation. ventilatory drive and easily drift into respiratory
Two main clinical patterns of disturbance may failure with hypercapnia, hypoxaemia and right
be discerned in patients with advanced COPD, heart failure, particularly during exacerbations.
which differ mainly in the extent to which venti-
latory drive is preserved in the face of increasing
airways obstruction: pink puffers and blue Investigations
bloaters (Fig. 12.4). These represent two ex-
tremes of a spectrum and most patients do not Lung function tests
fit either pattern completely, but have some fea- Spirometry is more accurate than peak expi-
tures of both.Pink puffers have well-preserved ratory flow measurement in assessing and
ventilatory drive even in the presence of severe monitoring the degree of airways obstruction in
Investigations 117
Fig. 12.5 This 42-year-old man had smoked coefficient were reduced to 30% of the predicted
20 cigarettes a day since the age of 14. He values. High-resolution computed tomography
presented with a 5-year history of progressive shows extensive emphysematous bullae with
breathlessness and could walk only 100 metres. dilated distal airspaces, cysts and destruction of
He had severe airways obstruction with a forced alveolar architetcture. a1-Anti-trypsin levels were
expiratory volume in 1 second (FEV1) of 0.5L, and unrecordable.
transfer factor for carbon monoxide and transfer
T H E CO P D ES CA L A T OR
Healthy population
Antibiotics for acute infections
Worsening lung function
80
Occasional bronchodilator as required
Smoker's cough
More frequent/combination bronchodilators
Little or no dyspnoea FEV1 as % predicted
Steroid reversibility trial: inhaled steroids if +ve
No abnormal signs
60 Influenza vaccination
Dyspnoea on exertion Pulmonary rehabilitation
Cough and sputum Assessment for LTOT
Some abnormal signs Ambulatory oxygen
40
Dyspnoea on mild exertion
Hyperinflation and cyanosis
Wheeze and cough
20
Death
0
Increasing investigation and treatment
Fig. 12.6 The chronic obstructive pulmonary the number of treatments used rises. LTOT, long-
disease (COPD) escalator. Summary of the term oxygen therapy. (Reproduced with
principal components of a management plan for permission from Thorax. British Thoracic Society
COPD. Note that, as disease severity increases, guidelines on the management of COPD. Thorax
symptoms and signs become more obvious whilst 1997; 52 (suppl. 5).)
Treatment
Bronchodilators, e.g. nebulised salbutamol 2.55mg and ipratropium 250500mg; repeat as needed
and continue 46 hourly
Steroids: prednisolone 30mg/day orally for 510 days
Antibiotics, e.g. amoxicillin 500mg t.i.d. orally or intravenously. Check previous sputum
microbiology and consider ciprofloxacin, clarithromycin, co-amoxiclav if needed
Oxygen: aim for O2 sat. >90% without provoking hypercapnia and acidaemia using controlled
oxygen therapy (e.g. 24% Venturi mask) as necessary
Ventilatory support: intravenous doxapram, non-invasive ventilation or endotracheal ventilation
Additional treatments: consider need for diuretics, e.g. furosemide 40mg intravenously if in
cardiac failure; or venesection if severe polycythaemia (e.g. packed cell volume >58%)
Assisted early discharge services
Table 12.2 Treatment of severe exacerbations of nurses and from home aids such as stairlifts and
chronic obstructive pulmonary disease (COPD). bath aids. Depression and social isolation are
common and can be helped by psychological
support focusing on restoring coping skills. Pa-
Education of the patient and family about the tient self-help groups may be useful.Assessment
nature and cause of the disease with the aim of by a social worker allows the patient to obtain
improving the patients ability to cope with dis- appropriate allowances, such as disability or
ability and to comply with medication, oxygen mobility allowances, from government
therapy and smoking cessation. agencies.
Exercise training: breathless patients often Nutrition: obesity is common and weight re-
reduce their level of exercise and lose general duction can greatly improve exercise capacity.
fitness and muscle mass which cause a vicious However, some patients suffer from cachexia
cycle of deteriorating exercise capacity. Exer- and loss of muscle mass as energy expenditure is
cise training (e.g. walking, cycling) can counter- often increased by the work of breathing. Nutri-
act muscle atrophy and improve fitness. tional supplements may then be required.
Improvement in lower limb function may help In measuring the outcome of pulmonary re-
walking, and arm training improves perfor- habilitation it is important to include, not only
mance of day-to-day tasks such as lifting, dress- measurements of lung function and oxygena-
ing, washing and brushing hair, for example. tion, but also exercise capacity, quality of life and
Breathing control techniques involve pursed lip dyspnoea scores and assessment of activities of
breathing, slower deeper respirations and bet- daily living.
ter coordination of breathing patterns. Physio-
therapy techniques such as postural drainage, Surgery
chest percussion and forced expiratory tech- A small number of patients with COPD may
niques may be useful in patients who have benefit from surgery. Lung transplantation
difficulty expectorating secretions. is an option, particularly for patients with em-
Psychosocial support: patients with advanced physema caused by a1-anti-trypsin deficiency,
disability may have difficulty in performing daily although lack of donor organs severely limits
tasks such as climbing stairs, shopping and wash- the application of this procedure. Bullectomy
ing, and may benefit from help from community may be appropriate where a large bulla is com-
Management 121
pressing surrounding viable lung. In recent years Concentrations of about 4060% can be
volume reduction surgery is being attempt- achieved with simple masks in which oxy-
ed in selected patients with severe disability. In gen is supplied directly to the mask space
emphysema, destruction of the alveoli results in (Fig. 12.7).The effective concentration achieved
a loss of elastic recoil with collapse of small air- depends upon the oxygen flow and on the pat-
ways on expiration and hyperinflation of the tern of breathing because some air from the
lungs with flattening of the diaphragm. Volume room is drawn into the mask diluting the oxygen
reduction surgery aims to resect functionally concentration. Nasal cannulae (prongs) are
useless areas of lung thereby reducing the over- the most convenient way of administering oxy-
all volume of the lungs in order to restore elastic gen because, in contrast to masks, they are rela-
recoil so that there is an increased outward tively unobtrusive and do not interfere with
traction on the small airways, relief of compres- speech or eating.They are usually well tolerated
sion of normal lung and restoration of more and kept in place continuously so that oxygen
normal diaphragmatic and thoracic contours therapy is not interrupted during sleeping or
allowing better respiratory motion during eating.The oxygen concentration administered
breathing. Patients whose emphysema prefer- via nasal cannulae varies not only with the oxy-
entially affects the upper lobes may be the most gen flow rate but also with the patients ventila-
suitable patients for this procedure. However, it tory rate, tidal volume and degree of mouth
is a high-risk procedure, and patients who have breathing, so that it cannot be accurately pre-
an FEV1 <20% predicted, homogeneous diffuse dicted and provides a relatively uncontrolled
emphysema and a TLCO <20% predicted are at form of oxygen therapy. If an accurate and con-
high risk of death and unlikely to benefit from stantly controlled concentration of oxygen is
this form of surgery. required then a fixed performance Venturi
mask is necessary. Oxygen flow from a specifi-
Oxygen therapy cally designed pinhole orifice creates a local
Oxygen delivery to the tissues of the body de- negative pressure which entrains a constant
pends upon the inspired oxygen concentration, proportion of room air through side ports at
ventilation, gas exchange and distribution in the the base of the mask (small arrows, Fig. 12.7b).A
circulation. Oxygen therapy should be pre- selection of masks giving 24, 28 and 35% oxygen
scribed with due attention to the dose and is available and the concentration delivered is
method of administration and with careful dependent upon the size of the pinhole and the
monitoring of its effects. It is also important designs of the apertures and is relatively inde-
to optimise oxygen transport to the tissues by pendent of the patients pattern of breathing.
ensuring adequate haemoglobin level, cardiac Humidification of inspired oxygen is only need-
output and tissue perfusion. Oximetry and ar- ed when it is delivered directly to the trachea or
terial blood gas analysis are essential in initiating, at high flow rates, otherwise the oropharynx
monitoring and adjusting oxygen therapy. provides adequate humidification.
OXYG EN AD MI N I ST R A T I O N
Fig. 12.7 Oxygen administration. (a) Simple piratory acidosis.Very often this can be achieved
uncontrolled high concentration face mask with by measuring oximetry with the patient breath-
oxygen supplied directly to the mask space. (b)
ing air and then giving controlled oxygen thera-
Fixed performance Venturi mask delivering a
py, e.g. using a 24 or 28% fixed performance
controlled dose of low-concentration oxygen.
(c) Nasal cannulae delivering an uncontrolled Venturi mask to achieve an oxygen saturation
level of oxygen in a convenient continuous above 90%. Arterial blood gases are then
manner. analysed when the patient has been breathing
the required amount of oxygen for about 30
minutes. If the PCO2 is below 6 kPa (45 mmHg)
then it is safe to transfer to nasal cannulae using
high concentrations of oxygen they breathe less oximetry to determine the flow rate required
and underbreathing results in increasing hyper- (e.g. 12 L/min) to maintain oxygen saturation
capnia, acidosis, narcosis and ultimately respira- just above 90%. Judicious use of oximetry and
tory depression. Uncontrolled oxygen therapy measurement of arterial blood gases under pre-
poses a risk to a subset of patients with COPD cisely judged circumstances (e.g. when the pa-
(notably blue bloaters with hypercapnic (type tient has reached steady state on the required
2) respiratory failure), although this risk has concentration of oxygen as judged by oximetry)
often been exaggerated and must be balanced can limit the need for repeated arterial blood
against the threat of hypoxaemia. sampling. It is essential to document carefully
Because of the shape of the oxyhaemoglobin the amount of oxygen being breathed when
dissociation curve, there is little benefit in in- measuring arterial gases.Avoid measuring gases
creasing the patients oxygen saturation above immediately after the patient has received neb-
about 90% or the PO2 above about 8 kPa ulised drugs using high-flow oxygen. Sometimes
(60 mmHg). In treating patients with acute exac- there is concern about using high-flow oxygen
erbations of COPD, therefore, the aim of oxy- (e.g. 68 L/min) to nebulise bronchodilator
gen therapy is to correct hypoxaemia to a PO2 drugs in patients with hypercapnia and occa-
>8 kPa (60 mmHg) or oxygen saturation >90% sionally air is used to nebulise these drugs.
without provoking critical hypercapnia and res- However, nebulising drugs using air during acute
Management 123
exacerbations of COPD may leave the patient useful in detecting these patients. Hypoxaemia
dangerously hypoxic and it is probably better to is a powerful stimulus to pulmonary artery
continue using oxygen 68 L/min to nebulise the vasoconstriction which if persistent provokes
drug but to limit the nebulisation time strictly to pulmonary hypertension, right ventricular
1015 minutes so that the patient is not ex- hypertrophy and right heart failure (cor pul-
posed to the risk of either hypoxia or prolonged monale). In the early 1980s two major studies,
high-concentration oxygen. the American Nocturnal Oxygen Therapy Trial
(NOTT) and the British Medical Research
Ventilatory support Council (MRC) Study, showed that the ad-
Many patients admitted to hospital with an ex- ministration of oxygen for at least 15 hours/
acerbation of COPD and acute hypercapnic res- day (preferably longer) improved survival
piratory failure will improve rapidly with initial in patients with severe airflow obstruction
medical treatments and controlled oxygen (FEV1 < 1.5 L) and hypoxaemia (PO2 < 7.3 kPa
therapy. In those with deteriorating hypercapnia (55 mmHg)) who had peripheral oedema.
and acidosis (pH <7.35) on repeat arterial blood
gas analysis a respiratory stimulant such as intra- Prescribing criteria
venous doxapram may be useful in stimulating Long-term home oxygen therapy is indicated
ventilation. However, non-invasive ventila- for non-smoking patients with severe
tion (NIV) is increasingly being used in this situ- COPD (FEV1 <1.5 L) and persistent
ation, whereby ventilatory support is delivered hypoxaemia (PO 2 <7.3 kPa (55 mmHg)).
via a tight-fitting mask strapped in place over the Many patients who are hypoxaemic during an
nose and connected to a specifically designed exacerbation will recover over a few weeks and
ventilating machine. The spontaneous respira- will not require long-term oxygen. Arterial
tory efforts of the patient may be used to trigger blood gases should therefore be measured on
the ventilator to deliver additional tidal volume two occasions, at least 3 weeks apart, during
under positive pressure. Alternatively, manda- a stable phase before diagnosing persistent
tory controlled ventilation may be delivered to hypoxaemia. Patients with more borderline
the patient with a set tidal volume, inflation oxygen levels (7.38.0 kPa (5560 mmHg)) who
pressure and ventilatory rate and no patient ef- have elevated haematocrit or features of cor
fort is required . If the patient fails to improve on pulmonale such as oedema are also likely to
NIV, or is not suitable for NIV, then invasive benefit from long-term oxygen. The oxygen is
ventilation (i.e. endotracheal intubation and usually given via nasal cannulae at a flow rate of
ventilation on ITU) should be considered. about 2 L/min but the dose required and mode
In some cases the patients underlying disease of administration should be decided by a hospi-
has progressed to a stage where mechanical tal specialist in the context of the patients
ventilation in ITU is unlikely to be successful and arterial blood gas measurement.
a palliative approach towards relief of symp-
toms is more appropriate than futile treatment Oxygen concentrator
which may merely prolong the process of dying Long-term home oxygen therapy is provided
to the distress of the patient and his or her from an oxygen concentrator.This is an electri-
relatives. cally powered machine that separates oxygen
from the ambient air using a molecular sieve.
Long-term oxygen therapy The machine is installed in the patients house
Patients with COPD and chronic hypoxaemia and plastic tubing relays oxygen to points such
have a poor prognosis with a mortality rate of as the bedroom and living room. Providing oxy-
about 50% within 3 years.The clinical features of gen cylinders to the patients home for long-
hypoxaemia are non-specific, and periodic mea- term oxygen therapy is impractical and much
surement of oxygen saturation by oximetry is more expensive than installation of an oxygen
124 Chapter 12: Chronic Obstructive Pulmonary Disease
concentrator. The patient and family should be ment and stabilisation in hospital on-going care
warned not to smoke in the presence of oxygen is provided to the patient in their own home.
because of the risk of causing a fire. It is essential Such hospital at home services are safe,
that the patient understands that the main aim effective and very popular with patients.
of long-term oxygen therapy is to improve prog-
nosis (reduce mortality rate) rather than to alle-
viate symptoms and that it is necessary to Further reading
comply with oxygen therapy for at least 15
hours/day. The patient achieves this by using British Thoracic Society. Guidelines on the manage-
oxygen during sleep at night and while ordinary ment of chronic obstructive pulmonary disease.
domestic activities are performed during the Thorax 1997; 52 (suppl. 5).
British Thoracic Society. Guidelines on non-invasive
day.
ventilation in acute respiratory failure. Thorax 2002;
57: 192211.
Hospital at home for COPD Burge PS, Calverley PMA, Jones PW et al. Ran-
Novel ways of managing patients with acute domised, double blind, placebo controlled study of
exacerbations of COPD are being developed. fluticasone proprionate in patients with moderate
In some cases admission to hospital can be to severe COPD: the ISOLDE trial. BMJ 2000; 320:
avoided by undertaking an initial assessment, in- 1297303.
Fletcher C, Peto R. The natural history of chronic
cluding a chest X-ray, arterial blood gas analysis
airflow obstruction. BMJ 1977; 1: 1645.
and spirometry, in an acute respiratory as- Leach RM, Bateman NT. Acute oxygen therapy. Br J
sessment service and selecting patients who Hosp Med 1993; 49: 637 44.
can be safely managed at home with provision of Morgan MDL, Calverley PMA, Clark CJ et al. Pul-
oxygen, nebulised bronchodilators, antibiotics monary rehabiliation. Thorax 2001; 56: 82734.
and steroids, with daily domiciliary visits by Snow V, Lascher DVM, Mottur-Pilson et al. The evi-
dence base for management of acute exacerbations
trained nurse specialists who monitor progress
of COPD. Chest 2001; 119: 11859.
and provide education and reassurance. For Toma TP, Goldstraw P, Geddes DM. Lung volume
other patients assisted early discharge is reduction surgery. Thorax 2002; 57: 5.
more appropriate whereby after initial treat-
CHAPTER 13
Carcinoma of the Lung
MO R TAL ITY FR O M L U N G C A N C E R
10 000
8084
7579 Male
8000 + 7074
6569
Deaths per million
6064 + +
6000 5559 + +
+
5054
4549 +
4000
+
2000
0
192630 193640 194650 195660 196670 197680 198690
(a) Year of death
2000 8084
1800 7579 Female +
+ 7074
1600 6569 +
Deaths per million
1400 6064
5559
1200 +
5054
1000 4549
+
800 Fig. 13.1 (a) Male and (b) female
+
mortality from lung cancer by
600 +
+ age and year of death, England
+
400 + and Wales, 192190.
+
200 + (Reproduced with permission
+ +
+ from the Lung and Asthma
0
192630 193640 194650 195660 196670 197680 198690 Information Agency. From
(b) Year of death Trends in Lung Cancer and
Smoking. Factsheet 93/1.)
Diagnosis 127
LU NG CA NCE R G R OW T H R A T E S
Death
Usual diagnosis
First diagnosis
Small-cell carcinoma Squamous cell carcinoma Adenocarcinoma
Tumour volume doublings
40
30
20
10
0 2 4 6 8 10 12 14 16
Years
Fig. 13.2 Lung cancer growth rates. As a rough to about 30 doubling volumes. Symptoms usually
approximation, small-cell carcinomas double arise later than this. By 40 doublings death will
monthly, squamous cell carcinomas 3 monthly usually have occurred. Diagnosis occurs late in
and some adenocarcinomas 6 monthly. A tumour the course of the disease and most of the
typically becomes evident on a chest X-ray when tumours life history is subclinical.
it reaches about 1 cm in diameter, corresponding
increased risk of lung cancer with an approxi- cidence of adenocarcinomas seems to be rising
mately linear relationship between the dose of and is currently about 20%. These tumours
asbestos and the occurrence of lung cancer.The often arise in the periphery of the lung, some-
interaction between asbestos and smoking is times as scar carcinomas and show the least
multiplicative. relationship to smoking. About 10% of lung
cancers do not show squamous or glandular
differentiation and are classified as large cell
Pathology (Fig. 13.2) undifferentiated carcinomas.
PRES ENTATIO N S OF L UN G C A N C E R
Chest symptoms General symptoms Chest X-ray
Haemoptysis Weight loss Lobar collapse
Cough Anorexia Peripheral nodule
Wheeze Lethargy Cavitating mass
Stridor Anaemia Enlarged hilar nodes
Pain Pleural effusion
Hoarse voice
Fig. 13.3 Presentations of lung cancer. ADH, must be considered in patients presenting with a
inappropriate anti-diuretic hormone. variety of medical problems.
Tumours in certain specific locations may
tokines by the tumour.The syndrome of inap- cause problems by direct invasion of adjacent
propriate anti-diuretic hormone (ADH) structures. Direct invasion of the mediastinum
secretion is most common with small-cell may cause paralysis of the phrenic nerve,
cancer and results in a low serum sodium, manifest by elevation of the hemidiaphragm, or
potassium and urea, a serum osmolarity below of the recurrent laryngeal nerve, particu-
280mosmol/L and a urine osmolarity greater larly on the left side where it passes around the
than 500mosmol/L. Treatment consists of re- aortic arch to the superior mediastinum, caus-
striction of fluid intake, and demeclocycline ing vocal cord palsy with hoarseness and dimi-
6001200 mg/day because this drug competes nished cough reflex. Injection of Teflon into the
for ADH renal tubular binding sites. Hypercal- paralysed vocal cord under general anaesthesia
caemia in patients with lung cancer may be in- can improve voice quality by building up the
dicative of bone metastases but squamous cell volume of the vocal cord enabling better apposi-
carcinomas sometimes secrete a parathyroid tion. Obstruction of the superior vena
hormone-related protein which causes non- cava causes venous engorgement of the upper
metastatic hypercalcaemia. Clearly, some body with facial oedema, headache, distended
patients will present primarily with chest pulseless jugular veins and enlarged collateral
symptoms, often against a background of veins over the chest and arms.These symptoms
pre-existing smoking-related lung disease require urgent treatment by chemotherapy in
(e.g. chronic obstructive pulmonary disease the case of small-cell cancer or radiotherapy in
(COPD)). Equally, a diagnosis of lung cancer the case of other tumours. Occasionally, inser-
Diagnosis 129
Fig. 13.4 Pancoast tumour.This 68-year-old man mass at the apex of the left lung eroding the first
presented with a 3-month history of left shoulder and second ribs posteriorly. Percutaneous biopsy
pain. On examination he had features of showed squamous cell carcinoma. He was treated
a left Horners syndrome (ptosis, meiosis, with palliative radiotherapy.
enophthalmos, anhydrosis). Chest X-ray shows a
tion of an expandable metallic wire stent into mours may cause bronchial obstruction typical-
the strictured vein under radiological guidance ly giving rise to atelectatic collapse of a lung or
is useful in relieving symptoms.A Pancoast tu- lobe of a lung (Fig. 13.5), or to pneumonic con-
mour (Fig. 13.4) is a carcinoma situated in the solidation distal to the obstruction.Thus,loss of
superior sulcus of the lung where the subclavian volume of a lobe (atelectatic collapse) on a
artery forms a groove over the lung apex. chest X-ray in a patient with apparent pneumo-
Because of its particular anatomical location a nia is a sinister feature suggesting bronchial ob-
tumour here gives rise to a characteristic struction by a carcinoma. The chest X-ray may
syndrome: ipsilateral Horners syndrome show evidence of spread of the tumour to bone
(ptosis, meiosis, enophthalmos, anhydrosis) (e.g. rib or vertebral destruction), pleura (e.g.
because of stellate ganglion involvement; pain effusion), hilar or mediastinal structures.
caused by erosion of the posterior first and Histologicalcytological diagnosis should be
second ribs, and wasting of the small muscles of obtained wherever possible. Sputum cytol-
the hand as a result of brachial plexus invasion. ogy is positive in about 40% of cases of lung can-
The tumour may invade a vertebral foramen giv- cer. Bronchoscopy (Fig. 13.6) allows direct
ing spinal cord compression.These tumours are visualisation and biopsy of central tumours.
notoriously difficult to detect on a chest X-ray Peripheral tumours seen on chest X-ray may
and the cause of the patients pain is often mis- not be accessible to bronchoscopy and percu-
diagnosed initially. taneous needle biopsy of these lesions under
The chest X-ray plays a pivotal part in the in- radiological guidance is a useful technique. Small
vestigation of lung cancer, and a range of abnor- peripheral cancers need to be distinguished
malities may be apparent. A peripheral tumour from rare benign tumours (e.g. hamartomas)
may be seen as a small nodule or mass in the lung and from granulomas resulting from previous
field. A cavitating mass is characteristic of squa- tuberculosis, but it may be advisable to proceed
mous cell carcinoma (Fig. 4.7, p. 36). Central tu- to surgical resection without histological
130 Chapter 13: Carcinoma of the Lung
confirmation of the diagnosis if the risk of can- information about lung cancer and its treatment
cer is high. Diagnosis may also be achieved by useful.
obtaining material from a site of metastasis (e.g. Inevitably, patients will experience emotions
lymph node, skin, pleural effusion). such as shock, anger and denial and the doctor
must work through these emotions with the pa-
tient. It is useful to be able to bring the interview
Communicating the diagnosis to a conclusion on a more positive note by dis-
cussing a management plan. Many patients will
Telling a patient of the diagnosis of lung cancer is initially be too shocked to understand the infor-
a difficult clinical skill which needs to be devel- mation given and it is often useful to arrange a
oped by training and experience. Patients want further interview either with the hospital doc-
to talk honestly about what is happening to tor, nurse or general practitioner to answer the
them and to know more about the way ahead. patients questions. Rapid communication
The patients awareness of the diagnosis often between all members of the medical team is
emerges over a number of consultations and crucial in these circumstances.
the time that elapses between initial suspicion of
tumour and histological confirmation of the
diagnosis is often useful in allowing the patient Treatment (Fig. 13.7)
an opportunity to come to terms with the
situation. When discussing the diagnosis it is Treatment depends mainly on the histological
essential to allow adequate time for questions, cell type and the stage of the disease.
to ensure privacy during the interview, to
encourage a relative or friend to accompany Small-cell carcinoma (25%)
the patient for support and to have further Small-cell carcinoma is a highly malignant cancer
counselling available for the patient from which has usually disseminated widely by the
skilled nurses. Some patients may find written time of diagnosis such that systemic treatment
Treatment 131
B R O N CHO S CO P Y
Fig. 13.6 Bronchoscopy. Flexible fibreoptic tumour, and secretions and saline washings can
bronchoscopy is usually performed as an be aspirated for cytology or microbiology tests.
outpatient procedure under sedation Bronchoscopy is a very safe procedure but is
(e.g. midazolam) and topical anaesthesia contraindicated in patients with uncontrolled
(e.g. lidocaine to vocal cords and airways).The angina or recent myocardial infarction. Sedation
bronchoscope is usually passed transnasally into should be avoided or used with particular caution
the oropharynx, through the vocal cords into the in patients with respiratory depression. Pulse
trachea and bronchi to the subsegmental level. oximetry is used to monitor oxygen saturation
The bronchial tree is illuminated by light and supplemental oxygen is given.The scope is
transmitted from a light source to the tip of the carefully cleaned with detergent and immersed in
bronchoscope and the image is transmitted to the glutaraldehyde to prevent transmission of
eyepiece or displayed on a screen. About two- infection to patients. It is recommended that the
thirds of lung cancers are visible through the bronchoscopist and nurse should wear masks,
bronchoscope, and therefore bronchoscopy is a goggles and gowns to prevent contracting
key investigation for lung cancer or haemoptysis. infections (e.g. tuberculosis) from the patient by
A biopsy forceps or cytology brush may be passed aerosols generated by coughing.
through a channel to obtain samples from a
MA N A G EM EN T O F L U N G C A N C E R
SMOKING
PREVENTION
SYMPTOMS
DIAGNOSIS
CHEST X-RAY
HISTOLOGICAL DIAGNOSIS
(Bronchoscopy, sputum cytology) COMMUNICATING
DIAGNOSIS
PALLIATIVE CARE
Fig. 13.7 The 5-year mortality rate of lung cancer require careful staging and assessment for
is about 90%, emphasising the fact that the potential operability. About 1020% of non-small-
disease is usually disseminated at the time of cell carcinomas are suitable for surgery but only
presentation. Prevention of lung cancer by 30% of patients undergoing resection will be alive
avoidance of smoking is the most important in 5 years. A judicious plan of assessment allows
strategy in the fight against this disease. Choice of careful selection of the best choice of specific
treatment depends on cell type and stage of anti-cancer treatment with either curative or
disease. About 25% of lung cancers are small-cell palliative intent. Symptom relief and palliative
carcinomas and are best treated by chemotherapy care are crucial aspects in the overall
followed by radiotherapy.There is usually a good management, and the communication of
response to chemotherapy but relapse is likely. information between doctor and patient at all
About 75% are non-small-cell carcinomas and stages of the disease is of paramount importance.
Treatment 133
TNM STAGES
Stage TNM Operability 5-year survival (%)
I T12N0M0 5060
II
IIIa
IIIb
T12N1M0
T3N1M0
T12N21M0
T13N2M0
} Operable
30
20
0
IV
T4N0M0
Any T, any N, M1
} Inoperable
0
Tumour (T)
T1: <3 cm and not involving main bronchus or pleura
T2: >3 cm, or involving main bronchus and visceral pleura
T3: any size, invading chest wall, or within 2 cm of carina
T4: invading mediastinum, great vessels, trachea
Node (N)
N0: no regional node metastases
N1: ipsilateral hilar node metastases
N2: ipsilateral mediastinal or subcarinal node metastases
N3: contralateral mediastinal or hilar nodes
Metastases (M)
Table 13.2 Outline of some M0: no distant metastasis
examples of TNM stages of M1: distant metastasis
non-small-cell carcinoma.
about 11 months. For clinical purposes small- choose to wear a wig. Careful attention to anti-
cell cancer is staged as limited disease (involv- emetic medications (e.g. ondansetron, dom-
ing one hemithorax including ipsilateral or peridone, metoclopramide) can usually prevent
contralateral hilar, mediastinal or supraclavicu- nausea and vomiting.
lar nodes) or extensive disease (spread
beyond one hemithorax). Patients who have Non-small-cell cancer (75%)
limited stage disease with good general health Surgical resection of the tumour offers the
and who show a good response to chemo- best chance of cure in non-small-cell carcinoma
therapy have the best prognosis and 510% of but is only possible if the patient is fit for surgery
these patients achieve prolonged survival (more and if the tumour has not already metastasised.
than 2 years). Consolidation radiotherapy Staging (Table 13.2) is the assessment of the
is usually given to the site of the tumour and me- extent and spread of the disease and is impor-
diastinal nodes. Cerebral metastases are com- tant in determining the potential resectability of
mon so that prophylactic cranial radiotherapy is the tumour and the prognosis of the patient.
also given to patients who have responded to The TNM system is the most widely used and is
chemotherapy. Patients receiving chemothera- based upon the size, location and degree of inva-
py require careful monitoring of their full blood sion of the tumour (T), the presence of regional
count to avoid problems arising from bone mar- lymph node involvement (N) and distant metas-
row suppression such as anaemia, haemorrhage tases (M). The accuracy of staging depends
or infection. Hair loss occurs and patients may on the degree of assessment, e.g. staging at
134 Chapter 13: Carcinoma of the Lung
thoracotomy may show more advanced disease struction, haemoptysis or chest wall pain
than was apparent on computed tomography usually respond well to radiotherapy. Radical
(CT) scanning. radiotherapy, using larger doses, is occasionally
When staging a tumour the patients symp- used with curative intent for small localised
toms should be carefully reviewed for any indi- tumours that are not treatable by surgery be-
cation of metastatic disease (e.g. bone pain). cause of poor patient fitness.
Clinical examination may show evidence of Chemotherapy is being used increasingly
tumour spread to lymph nodes or reveal fea- for inoperable non-small-cell lung cancer, main-
tures of distant metastases. Bronchoscopy al- ly for palliation of symptoms. A combination of
lows direct visualisation of many tumours and mitomycin C, vinblastine and cisplatin is usually
may show features of inoperability (e.g. vocal given in pulses every 3 weeks. About 50% of
cord palsy, splaying of the carina by subcarinal patients with inoperable small-cell carcinoma
lymphadenopathy, or extension of the tumour show a response to chemotherapy with a re-
to within 2 cm of the main carina). Elevated liver duction in tumour size and a median survival of
function tests or bone biochemistry are indi- about 10 months.The role of chemotherapy be-
cations for imaging of the liver by ultrasound or fore (neo-adjuvant) or after (adjuvant) surgery
CT scans, and bone by isotope scans. Tumours is being studied in clinical trials.
which appear operable should then be assessed
by CT scanning of the chest, particularly to Palliative care
assess hilar and mediastinal nodes. Enlarged Palliative care focuses on improving the patients
(>1 cm) lymph nodes are suggestive of malig- functioning and psychosocial wellbeing with re-
nant involvement, but if the tumour otherwise lief of symptoms. Even when the disease cannot
appears operable then mediastinoscopy is a be cured, rapid assessment and diagnosis is im-
useful procedure whereby under general anaes- portant in addressing the patients symptoms
thesia, the mediastinum is explored and lymph and anxieties. Regular review of patients with
nodes are biopsied. Positron emission lung cancer is essential in providing support for
tomography (see Chapter 4) can detect the patient and his or her family and in identify-
metastatic disease in mediastinal nodes, even if ing the nature and origin of symptoms as they
they are not enlarged, and is a more accurate arise.
imaging technique in the staging of lung cancer. When dealing with a symptom such as pain,
The decision about the patients fitness to specific anti-cancer treatment (e.g. radiothera-
undergo resection of the tumour is based par- py) is often the most effective method of symp-
ticularly upon the lung function tests and the pa- tom relief. Where there is persistent pain,
tients general fitness. Unfortunately, these analgesics need to be given regularly and pro-
patients often have substantial cardiovascular phylactically in advance of the return of pain.
disease and smoking-related COPD. No single Mild pain may be treated by a non-opioid anal-
test predicts feasibility of surgical resection and gesic (e.g. a non-steroidal anti-inflammatory
greater risks may be justified for a tumour which drug (NSAID) or paracetamol). More severe
is otherwise curable by resection but a forced pain may be treated by a combination of a weak
expiratory volume in 1 second (FEV1) <50% of opioid (e.g. codeine) and a non-opioid (e.g.
predicted or the presence of hypoxaemia (PO2 naproxen) drug. Strong opioids should be
<8 kPa (60 mmHg)) would suggest that the pa- used immediately for any severe pain. Often pain
tient is not fit for thoracotomy. Unfortunately, control is achieved by use of slow-release mor-
only about 1020% of all non-small-cell carcino- phine tablets (e.g. MST continuous 12 hourly)
mas prove suitable for surgery. combined with a NSAID, with additional use of
Radiotherapy is chiefly undertaken for morphine solution for any breakthrough pain.
the relief of symptoms. Superior vena caval Certain types of pain may benefit from use of
obstruction, lobar collapse from bronchial ob- co-analgesics such as steroids (e.g. dexam-
Further reading 135
ethasone for nerve compression), benzodi- confined to one lobe surgical resection is the
azepines (anxiolytic), tricyclic anti-depressants treatment of choice.
or anti-epileptics (e.g. carbamazepine or
gabapentin for neuropathic pain). Whenever Carcinoid tumour
opiates are prescribed it is necessary to This rare tumour is less malignant than
prescribe a laxative (e.g. co-danthramer) to bronchial carcinomas in that it rarely metasta-
prevent constipation, and an anti-emetic (e.g. sises and is often slow growing, although it may
metoclopramide) may be required initially. invade locally. It is not related to smoking and
Anorexia, weight loss, fatigue and general often affects younger patients. Most arise in the
debility are common in the advanced stages of main bronchi and present with haemoptysis and
lung cancer. It is important to check for con- wheeze.At bronchoscopy the tumour often has
ditions requiring specific treatment such as a smooth rounded appearance resembling a
anaemia (blood transfusion) or hypercalcaemia cherry and it may bleed profusely on biopsy be-
(pamidronate). Prednisolone may be useful in cause of its vascularity. Most can be cured by
boosting appetite, and nutritional supplements surgical resection. Very rarely, a carcinoid
may be helpful. Attention needs to be given to tumour of lung metastasises to the liver where
the patients level of social support and help secretion of substances such as 5-hydroxy in-
often needs to be given with tasks of daily living. doleacetic acid (5-HIAA) produces the
If control of symptoms is not being achieved, carcinoid syndrome of flushing, diarrhoea and
help should be sought from a specialist in pallia- wheeze.
tive care.
Further reading
Other thoracic neoplasms
British Thoracic Society. Guidelines on the selection
Alveolar cell carcinoma of patients with lung cancer for surgery. Thorax
This is a rare malignant tumour which arises in 2001; 36: 89108.
Doll R, Hill AB.The mortality of doctors in relation to
the alveoli of the lung and spreads along the alve-
their smoking habits. BMJ 1954; i: 14515.
olar and bronchiolar epithelium. Histologically, Hackshaw AK, Law MR, Wald NJ. The accumulated
it resembles adenocarcinoma. Occasionally, evidence on lung cancer and environmental to-
this tumour produces large amounts of mucin bacco smoke. BMJ 1997; 315: 9808.
causing copious sputum production (bronchor- Lung and Asthma Information Agency. Trends in Lung
rhoea). On chest X-ray it may appear as more Cancer and Smoking. Factsheet 93/1.
diffuse shadowing, resembling pneumonic con- Osterlind K. Chemotherapy in small-cell lung cancer.
Eur Respir Monogr 2001; 17: 23458.
solidation, rather than as a discrete mass, and
PotterV,Woll PJ. Chemotherapy in non-small cell lung
it is sometimes multifocal in origin. A trans- cancer. Eur Respir Monogr 2001; 17: 21833.
bronchial biopsy of alveolar tissue is often Sell L, Devlin B, Bourke SJ et al. Communicating the
necessary for diagnosis. When the tumour is diagnosis of lung cancer. Respir Med 1993; 87: 613.
CHAPTER 14
Interstitial Lung Disease
Introduction, 136 Connective tissue diseases, 139 Extrinsic allergic alveolitis, 140
Cryptogenic fibrosing alveolitis, Cryptogenic organising Sarcoidosis, 141
137 pneumonitis, 140 Further reading, 145
136
Cryptogenic fibrosing alveolitis 137
T R A N SB R ON C H I AL LUNG BI OPS Y
sarcoidosis, for example. Many of these diseases has been found in some epidemiological studies,
are characterised in their early stages by an in- and about 30% of patients have autoantibodies
flammatory alveolitis, which is responsive to (e.g. rheumatoid factor, anti-nuclear factor) in
corticosteroids, whereas in the later stages their serum.The diagnosis is often made on the
there may be irreversible lung fibrosis. basis of the clinical features but lung biopsy helps
Careful clinical investigation of patients pre- to confirm the diagnosis, to exclude other caus-
senting with features of interstitial lung disease es and to give information about the stage of the
aims to move from this imprecise clinical label disease. The typical histological features are
to a diagnosis of a specific disease process cellular thickening of the alveolar walls with
(Fig. 14.2). fibrosis and an inflammatory cell infiltrate in the
alveoli. These features have been classified in
various ways but from a clinical point of view the
Cryptogenic fibrosing alveolitis degrees of cellularity and fibrosis are the most
important. Patients with a cellular pattern
Cryptogenic fibrosing alveolitis (idiopathic pul- (i.e. predominantly inflammatory cellular infil-
monary fibrosis) is a serious disease which kills trate with little fibrosis) are probably in an earli-
about 1000 people each year in the UK. It is er stage of the disease and show a better
more common in men (male/female ratio response to steroids than patients with a fibrot-
2 : 1) and in the elderly (mean age 67 years). ic pattern. A ground glass appearance on
It presents with the typical features of an inter- high-resolution CT scan corresponds to
stitial lung disease as progressive dyspnoea, the cellular pattern on histology whereas a
dry cough, crackles, restrictive defect in lung reticular pattern indicates fibrosis. Crypto-
function and reticulonodular infiltrates on genic fibrosing alveolitis is probably not a single
chest X-ray (Fig. 14.3). About 50% have club- disease process and careful analysis of histologi-
bing.The aetiology is unknown but the disease cal patterns has led to subclassification of the
probably represents the inflammatory and im- disease into a number of entities such as usual
mune response of the lung to tissue damage. A interstitial pneumonia (UIP), desquamative in-
possible association with previous exposure to terstitial pneumonia (DIP) and non-specific in-
environmental dusts (e.g. metal or wood dust) terstitial pneumonia (NSIP). Patients with NSIP
138 Chapter 14: Interstitial Lung Disease
INTER S TITIAL L U N G DI SE A SE
Inhaled toxins
Paraquat
Lung function
Restrictive defect Clubbing
Reduced gas diffusion
Hypoxaemia Drugs
Amiodarone
Blood tests Bleomycin
Rheumatoid factor Nitrofurantoin
Antinuclear factor
Eosinophils Systemic diseases
Avian precipitins Rheumatoid disease
Systemic sclerosis
Chest X-ray Systemic lupus erythematosus
Dermatomyositis
High-resolution CT scan DIFFUSE PARENCHYMAL Amyloidosis
SHADOWING Tuberose sclerosis
Neurofibromatosis
Bronchoalveolar lavage Lymphangitis carcinomatosa
Lympocytic: e.g. sarcoidosis ALVEOLITIS
Neutrophilic: e.g. cryptogenic (inflammation)
fibrosing alveolitis
Idiopathic
Histology Cryptogenic fibrosing alveolitis
Transbronchial biopsy LUNG FIBROSIS Sarcoidosis
Surgical biopsy (honeycomb lung) Crytogenic organizing pneumonitis
Fig. 14.2 Summary of the clinical investigations whereas others show a rapid progression.
and differential diagnosis of interstitial lung Overall about 50% of patients die within
disease.
3 years of diagnosis. High-dose corticos-
teroids (e.g. prednisolone 60mg/day) are the
show a better response to corticosteroids and main treatment but only about 2030% of
have a better survival than those with UIP. patients show a good response. Usually, any
The clinical course of cryptogenic fibrosing response will be apparent within 12 months
alveolitis is very variable with some patients at which stage the benefits and side-effects of
following an indolent course over many years prolonged steroid treatment must be carefully
Connective tissue diseases 139
RHE U MATO ID DI SE A SE
Cricoarytenoid
arthritis
Obliterative disease
of airways
Diffuse pulmonary
fibrosis
Pleurisy and pleural
effusion
Fig. 14.4 Summary of pulmonary complications when no pathogen is identified and the patient
of rheumatoid disease. fails to respond to antibiotics. A range of chest
X-ray abnormalities occur including fleeting
shadows, localised alveolar infiltrates and
suppressive treatments predispose to oppor- diffuse reticular shadowing. As the same his-
tunistic infections (e.g. Pneumocystis carinii). tological pattern is found as a result of a variety
of insults to the lung, BOOP/COP is probably
not a single entity but one pattern of response
Cryptogenic organising of the lungs to injury. Characteristically, there is
pneumonitis a dramatic response to corticosteroids
although relapse may occur as the dose is
Cryptogenic organising pneumonitis (COP) (or reduced.
bronchiolitis obliterans organising pneumonia
(BOOP)) is an uncommon condition charac-
terised by the occurrence of intra-alveolar Extrinsic allergic alveolitis
buds of organising fibrosis with obliteration
of bronchioles on lung biopsy. It seems to be a Extrinsic allergic alveolitis (hypersensitivity
pattern of response in the lungs to a variety pneumonitis) is an immunologically medi-
of insults. It particularly occurs in association ated lung disease in which a hypersensitivity
with some drugs (e.g. amiodarone, sul- response occurs in a sensitised individual to
fasalazine, gold), connective tissue diseases an inhaled antigen. Typical examples of this
(e.g. rheumatoid disease) or ulcerative colitis, disease are farmers lung and bird fanciers
but often no cause is identifiable. Clinically, lung.When hay is harvested and stored in damp
patients often have cough, malaise, fever, dysp- conditions it becomes mouldy, generating heat
noea with chest X-ray infiltrates and elevated which encourages growth of fungi such as Ther-
erythrocyte sedimentation rate (ESR). Often moactinomyces vulgaris or Micropolyspora faeni.
the patient is thought to have infective pneumo- When the hay is subsequently used for fodder-
nia but the differential diagnosis is widened ing cattle, fungal spores may be inhaled. Avian
Sarcoidosis 141
antigens are inhaled by people who participate fungal antigens can be detected in serum but are
in the sport of pigeon racing or who keep pet also found in many asymptomatic subjects so
birds such as budgerigars. The inhalation of that they are not diagnostic.
these antigens provokes a complex immune Complete cessation of exposure to the
response in susceptible subjects involving provoking antigen is the main treatment.
antibody reactions, immune-complex forma- However, pigeon fanciers, for example, are very
tion, complement activation and cellular re- committed to their sport and will often wish to
sponses, resulting in alveolitis. Strangely these continue keeping pigeons.They can reduce anti-
diseases are less common in smokers. gen contact by wearing a mask and a loft-coat
In the acute form of the disease the patient and hat (so as to avoid carrying antigen on their
typically experiences recurrent episodes of dys- clothing or hair). Steroids (e.g. prednisolone
pnoea, dry cough, pyrexia, myalgia and a flu-like 40 mg/day) hasten the resolution of the alveoli-
sensation, occurring about 48 hours after anti- tis and are often used during severe acute
gen exposure. During such an episode lung episodes. The immune response in extrinsic
function tests may show a reduction in lung allergic alveolitis is complex and a variety of
volumes and gas diffusion, and chest X-ray may modulating factors influence the interaction of
show diffuse shadowing. Sometimes the chest antigenic stimulus and host response so that the
X-ray may be normal and CT is more sensitive longitudinal course of the disease is variable
in detecting the changes of extrinsic allergic with some patients developing lung fibrosis and
alveolitis (Fig 14.5). The acute illness is often others showing spontaneous improvement
misdiagnosed as a pneumonia. The chronic despite continued antigen exposure.
form is characterised by the insidious develop-
ment of dyspnoea and lung fibrosis. Lung biop-
sies show features of fibrosis, alveolitis and Sarcoidosis
granuloma formation. Bronchoalveolar lavage
typically shows evidence of a lymphocytic alve- Sarcoidosis is a mysterious multisystem
olitis with a predominance of T-suppressor lym- disease characterised by the occurrence in
phocytes. Precipitating antibodies to avian or affected organs of non-caseating granulo-
142 Chapter 14: Interstitial Lung Disease
S ARCO ID O S IS
MAJOR COMPLICATIONS
CNS, meninges
Acute VII palsy OCULAR
uveitis Parotitis Uveitiscataract
Lupus pernio glaucoma
Nasal and sinus
BHL PULMONARY
Skin infiltrations Fibrosis
Liver Cor pulmonale
Endobronchial
Splenomegaly
disease
Renal stones
HYPERCALCAEMIA
Nephrocalcinosis
Bone cysts
Erythema
nodosum
Acute
arthritis
Acute Chronic
Fig. 14.6 Principal clinical features of sarcoidosis. immunoglobulin levels are usually elevated and
BHL, bilateral hilar lymphadenopathy. immune complexes are often present in acute
sarcoidosis.
The clinical features of sarcoidosis are very
matous lesions which may progress to cause varied but it is useful to consider two broad cat-
fibrosis.The aetiology is unknown but the accu- egories of disease: an acute form which is usual-
mulation of T4-helper lymphocytes at disease ly transient and often resolves spontaneously;
sites is suggestive of an immunological reaction and a chronic form which is persistent and may
to an unidentified poorly degradable antigen. cause fibrosis (Fig. 14.6).
The frequent involvement of the lungs raises the
possibility that such a putative antigen enters Acute sarcoidosis
the body via the lungs. The compartmentalisa- The acute form typically develops abruptly in
tion of T4 lymphocytes in affected tissues is as- young adults with erythema nodosum and
sociated with a corresponding depletion of T4 bilateral hilar lymphadenopathy, some-
cells in other tissues and depression of some de- times with uveitis, arthritis and parotitis.
layed-type hypersensitivity responses such that
patients with sarcoidosis often demonstrate Erythema nodosum
negative reactions to tuberculin (i.e. negative This appears as round red raised nodules,
Heaf or Mantoux tests despite previous bacillus typically over the shins. It is a manifestation of
CalmetteGurin (BCG) vaccination). Serum hypersensitivity and is also found in other
Sarcoidosis 143
diseases such as streptococcal infection, tuber- group, with involvement of many tissues of the
culosis, ulcerative colitis and Crohns disease, body.
and with drugs (e.g. sulphonamides, contracep-
tive pill), but in many cases no cause is identified. Chronic pulmonary sarcoidosis
This involves the lung parenchyma with reticu-
Bilateral hilar lymphadenopathy lar shadowing often distributed in a perihilar
Bilateral hilar lymphadenopathy (BHL) is not as- fashion on chest X-ray (Fig. 14.8). There are
sociated with any signs on examination of the often remarkably few signs on examination of
chest or with any loss of lung function and is the chest, and lung function may be well main-
often found incidentally on a chest X-ray, but tained but the disease may progress in some pa-
often the X-ray was taken in a patient with other tients causing progressive fibrosis and loss of
features suggestive of sarcoidosis (Fig. 14.7). lung function with impairment of gas diffusion,
Although sarcoidosis is the most important reduction in lung volumes and sometimes air-
cause of BHL, other causes include lymphoma, ways obstruction with air trapping and bulla
metastatic carcinoma, tuberculosis, fungal formation.
infections such as coccidioidomycosis and
histoplasmosis in endemic areas (e.g. North Chronic extrapulmonary sarcoidosis
America); and, in the past, berylliosis (e.g. beryl- Sarcoidosis may affect virtually any organ in the
lium used in fluorescent lighting). body. Ocular sarcoidosis often presents as
pain and redness of the eye as a result of ante-
Chronic sarcoidosis rior uveitis. Chorioretinitis, keratoconjunctivi-
The chronic form of sarcoidosis pursues a tis sicca and lacrimal gland enlargement may
more indolent course, often in an older age complicate chronic sarcoidosis. Parotid gland
144 Chapter 14: Interstitial Lung Disease
Fig. 14.8 This 60-year-old woman presented with reticular shadowing.Transbronchial lung biopsy
cough and progressive breathlessness.There showed non-caseating granulomas and lung
were no crackles on auscultation of her chest but fibrosis.Tests for tuberculosis were negative.
transfer factor for carbon monoxide and transfer She was treated with prednisolone with some
coefficient were reduced to 60% of the predicted improvement in lung function.
values.The chest X-ray shows extensive perihilar
tients with active sarcoidosis but this test lacks evidence of efficacy is lacking. In chronic
sensitivity and specificity and is therefore of sarcoidosis deciding who to treat and when
limited value in diagnosis or in monitoring the to treat requires careful judgement to
course of the disease. balance the benefit and risks of chronic
steroid therapy.
Treatment
In most patients sarcoidosis is a self-limiting
disease which resolves spontaneously Further reading
without treatment. However, a minority of
patients with chronic sarcoidosis develop Bourke SJ, Boyd G. Pigeon fanciers lung. BMJ 1997;
progressive fibrosis. Because the cause of 315: 701.
sarcoidosis is unknown no specific treatment is British Thoracic Society. The diagnosis, assessment
and treatment of diffuse parenchymal lung disease
available but corticosteroids suppress inflam-
in adults. Thorax 1999; 54 (suppl. 1): 130.
mation in the affected organs, frequently im- Evans CC. Rheumatic and connective tissue diseases.
proving local and systemic symptoms. Their In: Brewis RAL, Corrin B, Geddes DM, Gibson GJ,
effect on the long-term natural history of eds. Respiratory Medicine. London: WB Saunders
sarcoidosis is less clear.They are usually used in Co, 1995: 167385.
patients with progressive disease and studies Geddes DM. BOOP and COP. Thorax 1991; 46:
suggest some benefit from steroid therapy 5457.
Johnston IDA, Prescott RJ, Chalmers JC, Rudd RM.
at the cost of side-effects (e.g. osteoporosis,
British Thoracic Society Study of cryptogenic fi-
Cushings syndrome). A short course of pred- brosing alveolitis: current presentation and initial
nisolone is sometimes used for particularly management. Thorax 1997; 52: 3844.
troublesome acute symptoms such as parotitis, OConnor CM, Fitzgerald MX. Speculations on
arthritis or erythema nodosum if non-steroidal sarcoidosis. Respir Med 1992; 86: 27782.
anti-inflammatory drugs are not sufficient. Riha RL, Duhig EE, Clarke BE, Steele RH, Slaughter RE,
Simmerman PV. Survival of patients with bio-
Uveitis may be treated by topical steroids, and
psy-proven usual interstitial pneumonia and non-
skin manifestations may be amenable to steroid specific interstitial pneumonia. Eur Respir J 2002;
creams or steroid injections. Inhaled steroids 19: 111418.
have been tried for pulmonary disease but
CHAPTER 15
Occupational Lung Disease
146
Occupational asthma 147
Table 15.1 Common causes of occupational ing morning. Initially, symptoms improve away
asthma. from work on holidays or at weekends and de-
teriorate on return to work. Once asthma
becomes established symptoms may persist
Diagnosis even when away from the work environment
To establish a diagnosis of occupational asthma and are also triggered by other factors such as
it is first necessary to confirm the presence exercise or cold air. Sometimes the sensitising
of asthma and, secondly, to show a causal agent also causes rhinitis and dermatitis. Occu-
relationship between the asthma and the pational asthma may develop in workers with
work environment.Although the suspicion of pre-existing asthma and this may lead to a delay
occupational asthma is often based upon the in diagnosis if the relationship of symptoms to
patients history, the diagnosis should be con- the work environment is not recognised. The
firmed by objective tests wherever possible patient may be exposed to a known inducer of
because of the importance of the diagnosis asthma (e.g. paint sprayers using isocyanates)
in terms of managing the patient, identifying but doctors need to be constantly alert to new
the causative agent, reducing the risk to other causes of occupational asthma.
workers and addressing the medicolegal and Serial measurement of peak expiratory
compensation aspects of the diagnosis. flow or spirometry over several days at work
Characteristically, there is an initial latent in- and away from work will usually show evidence
terval of asymptomatic exposure to the agent of variable airways obstruction (the hallmark of
before symptoms develop. This latent inter- asthma) and may demonstrate a relationship be-
val varies from a few weeks to several years. tween symptoms, airways obstruction and the
Once the worker has developed sensitisation to work environment. Lung function tests may be
the agent further exposure may provoke an normal when the patient is seen away from the
early asthmatic response (reaching a peak work environment. Assessment and manage-
within 30 minutes), a late asthmatic re- ment of occupational asthma is notoriously
sponse (occurring 4 12 hours later) or a dual difficult as some workers may be reluctant to
response. If an early response occurs, the rela- admit to symptoms in case this jeopardises their
tionship of symptoms to the work environment employment. Conversely, others may exag-
is usually apparent. Late responses typically gerate symptoms in an attempt to gain compen-
develop the evening after exposure, disturbing sation. Patients with suspected occupational
sleep and causing cough and wheeze the follow- asthma should therefore be referred for special-
148 Chapter 15: Occupational Lung Disease
CH A L L EN G E S T UDY I N
OC CU P ATIO NA L A ST H M A
5.0
4.0
3.0
FEV1
2.0
Fig. 15.1 Workplace challenge
Mean of control days study showing the mean forced
Work day 1 expiratory volume in 1 second
1.0 (FEV1) on control days away
Work day 2
Work day 3 from the workplace and
progressive falls in FEV1 over 3
0 days at work indicating late
07.00 11.00 15.00 19.00 23.00 asthmatic reactions of
09.00 13.00 17.00 21.00 increasing severity occurring in
Time relation to exposure to a biocide
in the workplace.
ist assessment. One of the best ways of showing assessment of the materials used. However,
a relationship between asthma and the work en- workers may be exposed to many agents and it
vironment is to perform a carefully supervised may be difficult to know which agent is causing
workplace challenge study. In this the pa- asthma. Laboratory challenge studies in-
tient is removed from the work environment volve the patient inhaling the specific suspect
for about 2 weeks and then returned to work agent under double-blind, carefully controlled
under supervision. Serial measurements of circumstances with serial measurements of
spirometry or peak expiratory flow are per- spirometry and airway responsiveness. These
formed on control days away from work and studies are particularly useful in identifying
then over about 3 days on return to the patients previously unrecognised causes of occupational
normal work environment. Serial measure- asthma but they should only be undertaken in
ments of airway responsiveness to metha- specialist units as they are potentially haz-
choline or histamine (see Chapter 11) typically ardous. In some cases of occupational asthma it
show sequential improvement away from work is possible to demonstrate a positive skin prick
and rapid deterioration on return to work. test or circulating antibodies to the agent but
Figure 15.1 shows a typical late asthmatic reac- such immunological reactions are often present
tion occurring during a workplace challenge in asymptomatic workers also.
study in a worker in a biocide manufacturing
plant. The agent inducing the patients asthma Management
can often be identified with reasonable confi- Treatment of occupational asthma involves
dence by a visit to the workplace and an management of both the affected individual
Pneumoconiosis 149
with increased use of alternative sources of not appreciated and there is often a tendency
energy. In the UK the number of coalminers to attribute any respiratory symptoms to the
has fallen from about 750 000 to 10 000 over the pneumoconiosis, whereas alternative explana-
last 50 years. Coal dust inhaled into the alveoli tions such as chronic obstructive pulmonary
is taken up by macrophages which are then disease (COPD), asthma or heart disease
cleared via the lymphatic drainage system or via are more likely to account for the patients
the mucociliary escalator of the bronchial tree. symptoms.
If there is heavy prolonged exposure to dust the Complicated coalworkers pneumoconiosis (pro-
clearance mechanisms are overwhelmed and gressive massive fibrosis) is characterised by the
dust macules arise particularly in the region of occurrence of large black fibrotic masses in the
the respiratory bronchioles. Release of dust lung parenchyma, consisting of coal dust and
from dying macrophages induces fibroblast bundles of collagen.These are typically situated
proliferation and fibrosis.There is an important in the upper zones and appear as rather
distinction to be made between the two major bizarre opacities on chest X-ray against the
categories of coalworkers pneumoconiosis. background of simple pneumoconiosis (Fig.
Simple coalworkers pneumoconiosis consists of 15.2). Cavitation of these lesions may occur
the accumulation, within the lung tissue, of small and may result in the expectoration of black
(<5 mm) aggregations of coal particles which sputum (melanoptysis). Complicated pneumo-
are uniformly dispersed and evident on chest X- coniosis often results in dyspnoea, a restric-
ray as a delicate micronodular mottling. Simple tive ventilatory defect (reduced lung
pneumoconiosis is not associated with volumes) and impaired gas diffusion (re-
any significant symptoms, signs, impair- duced transfer factor for carbon monoxide),
ment of lung function or alteration to and reduced life expectancy.
prognosis, e.g. life expectancy.The size and
extent of the nodules can be categorised for re- Caplans syndrome (rheumatoid
search and classification purposes by comparing pneumoconiosis)
the patients X-ray with standard films published Coalworkers with rheumatoid arthritis may
by the International Labour Office. The benign develop multiple nodules of about 0.52 cm
nature of simple pneumoconiosis is sometimes in diameter in the lungs.These lung nodules are
Asbestos-related lung disease 151
often accompanied by the occurrence of subcu- lobes. The nodules are usually denser and
taneous rheumatoid nodules. larger than those seen in simple coalworkers
pneumoconiosis. Eggshell calcification of
Coalworkers bronchitis hilar lymph nodes is a particularly character-
and emphysema istic feature (Fig. 15.3). Pleural thickening
Coalminers have a high prevalence of bronchi- may also occur.
tis, airways obstruction and emphysema.
This may often relate to cigarette smok-
ing but studies suggest that coal dust also Siderosis
contributes directly to the development of
bronchitis and emphysema, and in 1993 the Dust containing iron and its oxides is encoun-
Department of Social Security in the UK tered at various stages in the iron and steel in-
decided that coalminers who had spent 20 years dustry and in welding. It gives rise to a simple
or more in underground work and who had re- pneumoconiosis (siderosis) which produces
duced FEV1 were entitled to compensation. a striking mottled appearance on the chest X-
ray because of the high radiodensity of iron,
but which is not accompanied by symptoms,
Silicosis signs or any physiological defect. Other metals
such as antimony and tin may produce a similar
This is a form of pneumoconiosis resulting from picture.
the inhalation of free silica (silicon dioxide). It is
now uncommon in developed countries be-
cause of widespread recognition and control of Asbestos-related lung disease
the hazards of respirable silica dust, but it still
occurs in developing countries.There is a risk of Asbestos is a collective term for a number of
silicosis in workers involved in: quarrying, naturally occurring fibrous mineral silicates
grinding and dressing of sandstone, granite and which are widely used because of their fire-
slate; developing tunnels and sinking shafts resistant and insulation properties. Asbestos fi-
(e.g. coalmines); boiler scaling; sandblasting bres are of two main types which have different
of castings in iron and steel foundries; and the physical and chemical properties: serpentine as-
pottery industry where silica may be used in bestos fibres (chrysotile white asbestos)
the lining of kilns and the dry-grinding of cer- are wispy, flexible and relatively long, such that
amic products. they are less easily inhaled to the periphery of
Simple nodular silicosis, like simple coal- the lung. Amphibole asbestos fibres (e.g. crocido-
workers pneumoconiosis, causes no symptoms lite blue asbestos, amosite brown as-
and is an X-ray phenomenon. Complicated sili- bestos, tremolite) are straighter, stiffer and
cosis, however, results in progressive fibro- more brittle, and penetrate more deeply into
sis, loss of lung function and dyspnoea. The the lung.They are also more resistant to break-
silicotic nodule consists of concentric layers of down within the lung.
collagen surrounding a central area of dust in- Workers may be exposed to asbestos in
cluding quartz crystals and dying macrophages. many different settings so that it is important to
There is a significantly increased risk of tuber- take a detailed history of all the patients occu-
culosis in patients with silicosis as silica inter- pations over the years and of the tasks under-
feres with the ability of macrophages to kill taken. Pipe laggers and industrial plumbers
tubercle bacilli. Patients with silicosis are also at often have had heavy exposure to asbestos be-
increased risk of developing lung cancer. cause it is widely used for thermal insulation
A chest X-ray typically shows nodular in ships, power stations and factories. Many
opacities particularly affecting the upper workers in the shipbuilding industry were
152 Chapter 15: Occupational Lung Disease
heavily exposed to asbestos when they worked bestos exposure (Fig. 15.4) as they each have
alongside pipe laggers in confined spaces such as very different manifestations and prognosis.
the engine rooms of ships. Sometimes house- Asbestosis: asbestosis is a pneumoconiosis
wives washing their husbands work overalls in- in which diffuse parenchymal lung fibrosis
haled significant amounts of asbestos. Workers develops as a result of heavy prolonged expo-
in the insulation industry and those produc- sure to asbestos.The lag interval between expo-
ing asbestos products may have been heavily sure and the onset of the disease is typically
exposed. Chrysotile asbestos is used in brake- 1025 years, and is shorter the more intense
pad linings, in cement products, in pipes, the exposure. The clinical features are similar
tiles and roofing materials. In many circum- to those of other interstitial lung diseases such
stances the asbestos is safely bound within com- as cryptogenic fibrosing alveolitis, with cough,
posite materials but respirable dust may be progressive dyspnoea, bibasal crackles,
produced by the cutting of asbestos sheets, frequently clubbing, and a restrictive ven-
or in demolition work involving the removal, tilatory defect (reduced lung volumes) with
or stripping-off, of asbestos insulation from impaired gas diffusion (reduced transfer fac-
pipes or boilers. tor for carbon monoxide). Chest X-ray shows
Strict precautions were eventually widely in- bilateral reticulonodular shadowing. Com-
troduced in the 1970s to restrict exposure to puted tomography (CT) is more sensitive in de-
asbestos with the use of protective respirators tecting early changes. Fibrosis is usually first
and exhaust ventilation, and the substitution of evident around the respiratory bronchioles at
other materials where possible. However, the the lung bases, becoming more diffuse as the
long lag interval between the inhalation of as- disease progresses. Asbestos bodies, consist-
bestos and the development of disease means ing of an asbestos fibre coated with an iron-
that asbestos-related lung disease is still all too containing protein, are usually seen within areas
common. It is important to have a clear under- of fibrosis on light or electron microscopy. The
standing of the different diseases related to as- disease is usually slowly progressive even after
Asbestos-related lung disease 153
E F F E C T S O F A SBE S TOS
Light Heavy
exposure exposure
Pleural
calcification Asbestosis
ASBESTOS +
2040 yrs Carcinoma
?
2040 yrs + Cigarettes
Mesothelioma Bronchial
carcinoma
exposure has ceased, and is not usually respon- Acute asbestos pleurisy and pleural effusions:
sive to corticosteroids. Patients with asbestosis many years after first exposure to asbestos,
are at substantial risk of developing lung cancer. patients may develop episodes of pleurisy
It seems likely that some individuals have an in- with pleuritic pain and pleural effusions.
creased susceptibility to developing asbestosis, The pleural fluid is an exudate which is often
although the nature of this susceptibility is bloodstained even in the absence of mali-
unknown. gnancy.There is sometimes associated elevation
Pleural plaques: pleural plaques are often visi- of erythrocyte sedimentation rate (ESR). Other
ble as an incidental finding on chest X-rays of causes of pleural effusion need to be excluded.
workers who have been exposed to asbestos. Pleural biopsy shows evidence of inflammation
They are often calcified and appear as dense and fibrosis without any specific diagnostic fea-
white lines on the pleura of the chest wall, di- tures. There is usually spontaneous resolution
aphragm, pericardium and mediastinum. When but recurrent episodes affecting both sides may
seen face-on they form an irregular holly leaf occur and may lead to pleural thickening.
pattern (Fig. 15.5). They consist of white Pleural thickening: localised or diffuse thicken-
fibrous tissue usually situated on the parietal ing and fibrosis of the pleura may develop as
pleura.They do not give rise to any impair- a result of asbestos exposure. There may be a
ment of lung function or disability. history of recurrent episodes of acute pleurisy
154 Chapter 15: Occupational Lung Disease
malignant mesothelial changes, and between who may wish to undertake a post-mortem
secondary adenocarcinoma of the pleura and examination.
mesothelioma. The tumour has a tendency to
spread along needle biopsy tracks giving rise to
cutaneous nodules. Local radiotherapy is there- Further reading
fore often given to the site of biopsy to reduce
this risk. Prognosis is poor, with most patients British Thoracic Society. Statement on malignant
dying within 2 years of diagnosis. Unfortu- mesothelioma in the United Kingdom. Thorax 2001;
nately, there is no effective treatment and man- 56: 25065.
Cartier A. Definition and diagnosis of occupational
agement focuses on palliation of symptoms
asthma. Eur Respir J 1994; 7: 15360.
(e.g. high-dose opiate analgesia) and support of Craighead JE, Mossman BT. The pathogenesis of
the patient. asbestos-associated diseases. N Engl J Med 1982;
306: 144655.
Patients who have suffered disability as a result Edge JR. Mesothelioma. Br J Hosp Med 1983; 29:
of occupational lung disease have a statutory 52136.
right to receive compensation from govern- Hendrick DJ. Management of occupational asthma.
Eur Respir J 1994; 7: 9618.
mental agencies such as the Department of
Hendrick DJ, Sherwood Burge P, Beckett WS, Churg
Social Security in the UK. In some cases they A. Occupational Disorders of the Lung: Recognition,
may wish to pursue litigation against their em- Managment and Prevention. London: Harcourt Pub-
ployer. The death of a patient with a suspected lishers Limited, 2002.
occupational lung disease should be reported to McLaren W, Soutar CA. Progressive massive fibrosis
the relevant authority, such as the coroner, and simple pneumoconiosis in ex-miners. Br J Ind
Med 1985; 42: 73440.
CHAPTER 16
Pulmonary Vascular
Disease
material outlines thrombus, ultrasound pnoea, tachypnoea (respiratory rate > 20/min)
techniques (e.g. compression ultrasound and and pleuritic pain are the three cardinal features
colour flow Doppler), and 125I-fibrinogen iso- of pulmonary embolism. The absence of any of
tope scan which demonstrates incorporation these clinical features makes a diagnosis of pul-
of radiolabelled fibrinogen into the thrombus. monary embolism very unlikely.
PUL MO NA RY E M B O L I SM
Subacute
> 50% occlusion of circulation
Progressive severe dyspnoea over few weeks without
obvious cause. Dyspnoea even at rest
(a)
Raised jugular vein pulse, sometimes loud P2
ECG: may show right ventricular hypertrophy (RVH)
CXR: may show infarcts
Angiography and scan: always severe perfusion defects
Without infarction
May be 'silent'
? Dyspnoea, hyperventilation
? Fever
(b) CXR: may be normal
ECG: unhelpful
Angiography: usually shows obstruction if early
Scan: shows perfusion defects
Fig. 16.1 Synopsis of pulmonary embolism. Blood tests: there may be evidence of intrav-
ascular thrombosis (thrombinanti-thrombin III
complex assay) and fibrinolysis (fibrin degrada-
tion products). D -dimer is a breakdown product
Pulmonary embolism 159
of cross-linked fibrin and levels are elevated in usually decreased in the same areas resulting in
patients with thromboembolism. However, lev- matched defects in ventilation and perfusion
els are also often elevated in other hospitalised scans. The classic pattern seen in pulmonary
patients so that D -dimer assays can be used embolism consists of multiple areas of perfusion
to exclude, but not to confirm venous throm- defects that are not matched with defects in
boembolism. A normal D -dimer level can be ventilation. A V/Q scan may therefore show
particularly useful in certain clinical settings. For normal perfusion, in which case pulmonary em-
example, a young woman on oral contraception bolism is unlikely (low probability), areas of
who presents with isolated pleuritic pain is very perfusion defects not matched with ventilation
unlikely to have pulmonary embolism if the res- defects in the presence of a normal chest X-ray
piratory rate is below 20/min and chest X-ray, which indicates a high probability of pul-
arterial blood gases and D -dimer are normal. monary embolism, or it may show matched
She can be reassured without the need for ventilation and perfusion defects in which
admission to hospital or further investigation. case interpretation is difficult and the scan is
regarded as indeterminate. Patients with
Specific investigations a suspected pulmonary embolism but an inde-
Pulmonary angiography is the definitive test terminate scan require further imaging.
for diagnosing pulmonary embolism but it is an Computed tomography (CT) angiography (Fig.
invasive test requiring specialist expertise and 16.3). Improvements in CT technology now
equipment which are not widely available, and allow very rapid spiral images to be obtained
it is associated with a small risk, particularly in during the injection of iodinated contrast
critically ill patients. A catheter is passed from medium into a peripheral vein.This technique is
a peripheral vein (e.g. femoral vein), through being increasingly used as a definitive non-
the right side of the heart into the pulmonary invasive test for pulmonary emboli, with a high
arteries, and radiocontrast material is injected level of accuracy in diagnosing emboli in the
and a rapid sequence of X-rays is taken.The an- central pulmonary arteries. CT angiography
giographic features of embolism are intralumi- typically involves a radiation dose of about 8mSv
nal filling defects, abrupt cut-off of vessels, compared to about 1.5mSv for a V/Q scan.V/Q
peripheral pruning of vessels and areas of re- scanning is therefore still used if the chest X-ray
duced perfusion. is normal, when it is likely to give a definitive
Ventilation/perfusion (V/Q) lung scan (Fig. 16.2): result. However, if the chest X-ray is diffusely
macroaggregrated particles or microspheres of abnormal or if the patient has significant
human albumin, labelled with a gamma-emitting emphysema,V/Q scans are likely to be indeter-
radioisotope, technetium-99m, are injected in- minate and CT angiography may be the best
travenously. These particles impact in the pul- investigation.
monary capillaries and the radioactivity emitted Imaging of peripheral veins: demonstration of
from the lung fields is detected by a gamma cam- thrombus in the peripheral veins by venography,
era, thus outlining the distribution of pulmonary Doppler ultrasound or 125I-fibrinogen isotope
perfusion. The distribution of ventilation in the scan provides support for the decision to anti-
lungs is similarly outlined after the patient has coagulate a patient who has clinical features of
inhaled radiolabelled xenon. A completely nor- pulmonary embolism but an indeterminate V/Q
mal pattern of pulmonary perfusion is strong scan.
evidence against pulmonary embolism. Cold
areas are evident on the scan where there is de- Treatment
fective blood flow and these may occur in asso- Anti-coagulant therapy
ciation with localised abnormalities apparent on When a clinical diagnosis of suspected pul-
a chest X-ray (e.g. pleural effusion, carcinoma, monary embolism or DVT has been made, anti-
bulla). In these circumstances ventilation is coagulants should be started at once unless
160 Chapter 16: Pulmonary Vascular Disease
CH ES T X - RAY A N D V / Q SC A N
CXR V Q
(a)
(b)
(c)
Fig. 16.2 Diagrammatic representation of the chest X-ray shows only trivial changes at the right
chest X-ray (CXR) appearances, together with base.Ventilation is uniformly distributed but
. .
ventilation (V ) and perfusion (Q ) images obtained there are several major defects in the distribution
with a gamma camera in three patients. Only of perfusion these are non-matching defects.
anterior projections are shown. In practice Such defects are typical of pulmonary embolism
posterior, lateral and oblique projections would and the appearances shown are diagnostic of
be obtained for perfusion images (and, less multiple pulmonary embolism. Radiological
commonly, ventilation images). In the diagram, shadowing in the lung fields, of whatever cause, is
ventilation images are shown at a stage before almost inevitably accompanied by abnormality of
complete equilibrium is established. ventilation and/or perfusion at that site.The
(a) Large right pleural effusion.Ventilation is interest, as in case (b), then centres on the other
reduced on the right as expected. Perfusion is also radiologically normal areas of lung.
reduced as expected. Even though perfusion (c) Severe airways obstruction. It is common for
seems proportionately more reduced than quite marked regional defects of ventilation and
ventilation, the diversion of blood flow is in perfusion to accompany severe airways
keeping with that commonly seen in pleural obstruction.The chest X-ray may show only
effusion and the overall distribution of perfusion overinflation. Usually, the distribution of
resembles that of ventilation there is a perfusion and that of ventilation are broadly
matching defect. similar (matching defects) as in (c).
(b) Pulmonary embolism. In this particular case, the
Pulmonary embolism 161
there is a strong contraindication (e.g. active ratio (INR) is measured and the dosage adjusted
haemorrhage).The decision as to whether anti- to maintain a ratio of about 1.53.0. Warfarin
coagulants should be continued in the long term takes at least 4872 hours to establish its anti-
is made later based upon the results of sub- coagulant effect so that heparin needs to be con-
sequent investigations. Rapid onset of anti- tinued for this period. The optimal duration of
coagulanteffectisachievedusingheparin,which warfarin treatment is uncertain but it is usually
may be given intravenously or subcutaneously. continued for 6 weeks to 3 months after a first
Usually, an intravenous loading dose of episode of DVT or pulmonary embolism where
500010 000 units of heparin is given as a this has occurred in association with a recog-
bolus, followed by a continuous infusion of nised transient risk factor (e.g. surgery, immobil-
400600 units/kg. The activated partial throm- ity, etc.). Patients with recurrent or unexplained
boplastin time (APPT) is measured after 6 hours thromboembolic disease should have investiga-
and the dose is adjusted to maintain the APPT at tions for hypercoagulable states performed (e.g.
1.52.5 times the control value. High dose anti-thrombin III, protein S or C deficiencies;
low-molecular-weight heparin given sub- anti-cardiolipin antibody disease) and may
cutaneously (e.g. tinzaparin 175 units/kg once require long-term anti-coagulation.
daily) is now the standard treatment of DVT and The patient should be given an anti-coagu-
there is increasing evidence of its effectiveness in lant information booklet which explains the
treating pulmonary emboli also. It has the advan- nature and side-effects of treatment, states the
tages of predictable rapid anti-coagulation, indication for and proposed duration of treat-
a simple subcutaneous dosing regimen and no ment, contact numbers for obtaining advice,
need for laboratory monitoring. Side-effects and instructions on avoiding medications which
of heparin include haemorrhage, bruising and interfere with therapy. Many drugs enhance
thrombocytopenia. Once the clinical suspicion the effect of warfarin (e.g. non-steroidal anti-
of pulmonary embolism or DVT has been sup- inflammatory drugs, aspirin, ciprofloxacin, ery-
ported by subsequent investigations oral anti- thromycin, etc.) and others reduce the effect
coagulation is commenced using warfarin. (e.g. carbamazepine, barbiturates, rifampicin,
Usually, 10 mg is given on the first day as a loading etc.). Warfarin is teratogenic and women of
dose, and then the international normalised child-bearing age should be warned of this
162 Chapter 16: Pulmonary Vascular Disease
Thrombolytic therapy
The aim of thrombolytic therapy is to actively
dissolve clot, but its use is reserved mainly for
those patients with acute massive pulmonary
embolism who remain in severe haemodynamic
collapse (e.g. hypotensive, poorly perfused,
hypoxaemic). These patients have survived the
immediate impact of the pulmonary embolism
but remain critically ill. If all the clinical features
and bedside tests (e.g. ECG, chest X-ray) sug-
gest a massive pulmonary embolism and ex-
clude alternative diagnoses (pneumothorax,
post-operative haemorrhage, etc.), a decision
may have to be taken that the circumstances jus-
tify the use of thrombolytic therapy. Contraindi-
cations to thrombolytic therapy include active
haemorrhage, recent major surgery or trauma.
Typically, streptokinase 250 000 units is in-
fused over 20 minutes, followed by 100 000
units/hour for 24 hours or recombinant tissue
plasminogen activator (rtPA) 100 mg is given in-
travenously over 2 hours. Thereafter heparin
anti-coagulation is commenced. Fig. 16.4 Inferior vena caval filter. Most
Patients with acute pulmonary embolism pulmonary emboli arise from thrombi in the deep
require high-flow oxygen to correct hypox- veins of the leg. An inferior vena caval filter can be
aemia, and analgesia (e.g. diamorphine) to re- used to prevent emboli from reaching the lungs.
lieve pain and distress. In patients with active They are used in patients who have suffered
haemorrhage contraindicating the use of anti- recurrent pulmonary emboli despite adequate
anti-coagulation and in those in whom anti-
coagulant, or recurrent pulmonary emboli
coagulant therapy is contraindicated.This 64-
despite adequate anti-coagulation, a venous year-old woman had had major pulmonary
filter procedure may be useful.This involves the emboli from a deep vein thrombosis in her right
passing of a specially designed filter into the infe- femoral vein. She then suffered major
rior vena cava to prevent further emboli from haemorrhage from a gastric ulcer while on
reaching the lungs from DVT in the pelvis or heparin therapy, which was discontinued. A filter
device was passed through the venous system
lower limbs (Fig. 16.4).
from the internal jugular vein to be placed in the
inferior vena cava.
Deep vein thrombosis prophylaxis
A variety of measures are directed against
Virchows triad of factors predisposing to
DVT. Early ambulation, use of graded elastic
Pulmonary hypertension 163
compression stockings and leg exercises monary emboli, pulmonary artery stenosis),
reduce venous stasis. Prophylactic low-dose increased blood flow (e.g. left-to-right in-
heparin is now widely used to reduce the risk tracardiac shunts atrial and ventricular septal
for patients on surgical, obstetric and medical defects) and loss of pulmonary vascular
wards. Typically, tinzaparin 3500 units/day is bed (e.g. fibrotic lung disease, emphysema).
given subcutaneously. For patients undergoing The clinical features of cor pulmonale are
surgery with a higher risk of DVT (e.g. hip re- elevation of jugular venous pressure, he-
placement) the dosage may be increased to patomegaly (as a result of congestion) periph-
4500 units given 12 hours before surgery and eral oedema, a prominent left parasternal
then daily until the patient is mobile again. heave, a loud pulmonary secondary sound
Other materials which may occasionally em- and a systolic murmur of tricuspid regurgita-
bolise to the lungs include fat (after fracture of tion. A chest X-ray may show large pulmonary
long bones), amniotic fluid (post-partum), air arteries with pruning of the vessels in the lung
(e.g. from disconnected central venous lines), fields. ECG typically shows p pulmonale (tall p
tumour (from tumour invasion of venous sys- wave in leads II III AVF) with a tall R wave inV1 and
tem), infected vegetations (from tricuspid ST segment depression with T-wave inversion in
endocarditis) and foreign materials (from V1V3. Echocardiography can assess the struc-
contamination of drugs injected by drug ture and dimension of the right heart chambers
misusers). and the pulmonary artery pressure can be esti-
mated from the velocity of the tricuspid regurgi-
tation jet.
Pulmonary hypertension
Idiopathic primary pulmonary
In normal lungs the pulmonary arterial pressure hypertension
is about 20/8 mmHg (compared with typical This is a rare disease, affecting about two per
systemic artery systolic/diastolic pressures of million of the population per annum, in which
120/80 mmHg) and the mean pulmonary artery pulmonary hypertension occurs without a
pressure is 1215 mmHg. Pulmonary hyperten- demonstrable cause. It particularly affects
sion is defined as a mean pulmonary artery young women. A small number of cases are
pressure >25 mmHg at rest. Hypertension oc- inherited as an autosomal dominant trait and
curs as a result of hypoxaemia and chronic lung some cases are associated with human immun-
disease, when it is often referred to as cor pul- odeficiency virus (HIV) infection or with use of
monale, but in some cases there is no demon- appetite-suppressant drugs (e.g. aminorex,
strable cause and this is termed primary fenfluramine) but in most cases no cause is ap-
pulmonary hypertension. parent. Pulmonary hypertension also occurs as
a complication of collagen vascular diseases
Cor pulmonale such as systemic sclerosis (scleroderma), mixed
Some confusion arises from the differing ways in connective tissue disease and systemic lupus
which this term is used but it essentially refers erythematosus (SLE). Some patients with gen-
to the development of pulmonary hypertension eralised systemic sclerosis develop severe pul-
and right ventricular hypertrophy secondary to monary fibrosis (see Chapter 14) but there
disease of the lungs. Hypoxaemia is a power- is also a limited cutaneous variant of systemic
ful stimulus for pulmonary vasoconstriction and sclerosis characterised by subcutaneous calci-
this is the most common mechanism giving rise nosis, Raynauds phenomenon, oesophageal in-
to cor pulmonale (e.g. chronic hypercapnic res- volvement, and sclerodactyly and telangiectasia
piratory failure in COPD). Other mechanisms (CREST syndrome). Patients with the CREST
giving rise to pulmonary hypertension in- syndrome usually have anti-centromere anti-
clude vascular obstruction (e.g. chronic pul- bodies and may develop pulmonary hyperten-
164 Chapter 16: Pulmonary Vascular Disease
sion as a primary vascular phenomenon, often in myocarditis, myositis, neuritis, rashes and
the absence of significant pulmonary fibrosis. glomerulonephritis. It usually responds rapidly
Patients present with dyspnoea, fatigue, angina to corticosteroids.
and syncope on exertion. Investigations (e.g.
echocardiography, V/Q scans, pulmonary artery Polyarteritis nodosa
catheterisation) are particularly directed to- This consists of a vasculitis of medium and small
wards excluding other causes of pulmonary arteries resulting in aneurysm formation,
hypertension such as left-to-right cardiac glomerulonephritis and vasculitic lesions
shunts and chronic thromboembolic disease. in various organs. Pulmonary involvement is un-
The pathophysiology of the disease involves pul- usual but may result in haemoptysis, pulmonary
monary artery vasoconstriction, vascular wall haemorrhage, fibrosis and pleurisy. There is
remodelling and thrombosis in situ. Treatment often considerable overlap in the clinical fea-
involves vasodilators (e.g. oral nifedipine, nebu- tures of the various vasculitic syndromes.
lised iloprost or intravenous prostacycline in-
fused continuously via a central venous cannula) Goodpastures syndrome
and anti-coagulants, but heartlung or lung This consists of a combination of glomeru-
transplantation need to be considered as the lonephritis and alveolar haemorrhage in
disease is usually relentlessly progressive. association with circulating anti-basement
membrane antibody which binds to lung and
renal tissue. Pulmonary involvement is more
Pulmonary vasculitis common in smokers and may cause severe pul-
monary haemorrhage resulting in haemoptysis,
When pulmonary vasculitis occurs it is usually infiltrates on chest X-ray, hypoxaemia and
as part of a more widespread systemic vasculitis anaemia. Transfer factor may be elevated be-
such as Wegeners granulomatosis, polyarteritis cause of binding of the inhaled carbon mono-
nodosa, ChurgStrauss syndrome, Good- xide to haemoglobin in the alveoli. Treatment
pastures disease or collagen vascular diseases consists of corticosteroids and cyclophos-
(e.g. scleroderma, SLE; see also Chapter 14). phamide, with plasmapheresis to remove circu-
lating antibodies.
Wegeners granulomatosis
This is characterised by necrotising granuloma-
tous inflammation and vasculitis affecting in Further reading
particular the upper airways (rhinitis, sinu-
sitis, bloodstained nasal discharge), the lungs Burns A. Pulmonary vasculitis. Br J Hosp Med 1997; 58:
(cavitating nodules, endobronchial disease) and 38992.
kidneys (glomerulonephritis). Anti-neu- Corris P, Ellis D, Foley N, Miller A. Suspected acute
pulmonary embolism: a practical approach. Thorax
trophil cytoplasmic antibodies (ANCA)
1997; 52 (suppl. 4): 124.
are usually present in the serum. It is treated Gibbs JSR, Higenbottam TW. Recommendations on
with a combination of corticosteroids and the management of pulmonary hypertension in
cyclophosphamide. clinical practice. Heart 2001; 86 (suppl 1): 113.
Ginsberg JS. Management of venous thromboem-
ChurgStrauss syndrome bolism. N Engl J Med 1996; 335: 181627.
This is an unusual disease consisting of allergic Rubin LJ. Primary pulmonary hypertension. N Engl J
Med 1997; 336: 11117.
granulomatosis and angiitis. It consists of an ini-
Stein PD, Henry JW. Prevalence of acute pulmonary
tial phase of asthma followed by marked pe- embolism among patients in a general hospital and
ripheral blood eosinophilia and eosinophilic at autopsy. Chest 1995; 108: 97881.
vasculitis giving rise to pulmonary infiltrates,
CHAPTER 17
Pneumothorax and
Pleural Effusion
open and the air leak will then continue until the
Pneumothorax
pressure equalises. Occasionally, the opening
from the lung to the pleural space functions as a
Pneumothorax is the presence of air in the
valve allowing air to leak into the pleural space
pleural space. Usually the air enters the pleural
during inspiration but not to re-enter the lung
space as the result of a leak from a hole in the un-
on expiration. This is a potentially lethal situa-
derlying lung, but rarely it enters from outside as
tion as the air accumulates in the pleural space
a result of chest injury. Pneumothoraces may be
under increasing pressure giving a tension
classified as spontaneous or traumatic, and
pneumothorax in which the lung is pushed
spontaneous pneumothoraces may be pri-
down, the mediastinum is shifted to the oppo-
mary, without evidence of other lung disease,
site side and the venous return to the heart and
or occur secondary to underlying lung disease
cardiac output are impaired.
(e.g. chronic obstructive pulmonary disease
There is an increased risk of pneumothorax
(COPD)).
in association with virtually all lung diseases.
Pathogenesis These spontaneous secondary pneumotho-
Spontaneous primary pneumothorax typically races are particularly common in patients with
occurs in a previously healthy young adult and is COPD and bullous emphysema. A pneumotho-
most common in tall thin men. Most seem to rax resulting from rupture of a bulla may render
arise from the rupture of subpleural blebs or an already disabled patient critically ill. Pneu-
bullae at the apex of an otherwise normal lung. mothorax is a well-recognised complication of
The aetiology of these blebs is uncertain but positive pressure endotracheal ventilation on
they may represent congenital lesions aggrav- intensive therapy units (ITUs) of patients with
ated by the more negative pleural space pres- underlying lung disease.Traumatic pneumotho-
sure at the apex of the lung. Smoking increases rax usually arises from puncture of the lung by a
the risk of a first spontaneous pneumothorax by fractured rib but air may enter the pleural space
approximately ninefold in women and 22-fold in from outside via a penetrating injury or from
men.The intrapleural pressure is normally nega- rupture of alveoli, oesophagus, trachea or
tive because of the retractive force of lung elas- bronchi. Iatrogenic (doctor-induced) pneu-
tic recoil so that when a communication is mothorax may arise as a complication of inva-
established between the atmosphere and the sive chest procedures such as the insertion of a
pleural space air is sucked in and the lung de- catheter into the subclavian vein, percutaneous
flates.A small hole in the lung often closes off as needle aspiration of a lung lesion or trans-
the lung deflates. Sometimes the hole remains bronchial lung biopsy.
165
166 Chapter 17: Pneumothorax and Pleural Effusion
PLE U RAL FL U ID D Y N A M I C S
expedite the removal of air. High-pressure suc- mothorax on both sides, because of the risk of
tion may succeed in bringing the pleural surfaces catastrophic simultaneous bilateral pneumoth-
into apposition thereby sealing off the leak. oraces. Particular thought must be given to the
Surgical intervention: surgical treatment is re- best procedure for young adults with compli-
quired for persistent or recurrent pneumotho- cated pneumothoraces secondary to diseases
races. Failure of re-expansion of the lung with such as cystic fibrosis so as not to compromise
profuse bubbling of air through the underwater potential future lung transplantion. A limited
drain suggests a bronchopleural fistula (i.e. a apicolateral surgical abrasion pleurodesis may
persistent communication between the lung be the best option in these circumstances.
and pleural space). Surgical closure of the
hole with pleurodesis is usually necessary and
may be performed via a thoracotomy or via tho- Pleural effusion
racoscopy. The hole is oversewn and blebs on
the surface of the lung are excised. Pleurode- A pleural effusion is a collection of fluid in the
sis involves the obliteration of the pleural space pleural space.
and can be achieved by instilling tetracycline or
talc which provokes adhesions between the vis- Pleural fluid dynamics
ceral and parietal pleura. Pleurectomy in- The parietal and visceral pleural surfaces are
volves the removal of the parietal pleural. normally in close contact and the potential
Usually, an apicolateral pleurectomy (leaving the space between them contains only a very thin
posterobasal pleura intact) prevents recur- layer of fluid. Pleural fluid dynamics are complex
rence without compromising lung function. and incompletely understood but Fig. 17.3
There is a risk of recurrence of approximately shows, in a simplified form, some of the main
20% after a first spontaneous pneumothorax factors governing fluid filtration and absorption.
and a 50% risk after a second pneumothorax. The parietal pleura is perfused by the systemic
Surgical intervention is therefore usually rec- circulation, and the high systemic capillary pres-
ommended after a second pneumothorax.This sure, negative intrapleural pressure and pleural
is also the case if the patient has suffered a pneu- oncotic pressure overcome the plasma oncotic
Pleural effusion 169
pressure resulting in fluid filtration into the suspected by haziness on the affected side. A
pleural space. The visceral pleura is mainly per- lateral decubitus film may be useful in
fused by the pulmonary circulation with its low demonstrating mobility of the fluid, distinguish-
pulmonary capillary pressure so that the bal- ing the features from pleural thickening. Ultra-
ance of forces results in movement of fluid out- sound imaging is helpful in localising loculated
ward from the pleural space to the veins and effusions and in positioning chest tubes. Com-
lymphatics. The balance between fluid filtra- puted tomography (CT) may be helpful in
tion by the parietal pleura and fluid absorp- detecting pleural tumours (e.g. mesothelioma)
tion by the visceral pleura is such that fluid does and in assessing the underlying lung and
not normally collect in the pleural space. Pleur- mediastinum.
al effusions may develop from increased capil- Pleural fluid aspiration (thoracocentesis) is the
lary pressure (e.g. left ventricular failure), key initial investigation. A protein level >30g/L
reduced plasma oncotic pressure (e.g. and lactate dehydrogenase (LDH) level
hypoalbuminaemia), increased capillary >200iu/L indicate that the effusion is an exudate
permeability (e.g. disease of pleura) or and that further investigations for pleural dis-
obstruction of lymphatic drainage (e.g. ease are indicated. Both transudates and exu-
carcinoma of lymphatics). dates are typically a yellow, straw colour.
Bloodstained fluid points towards malignancy,
Clinical features pulmonary infarction or severe inflammation.
Patients with pleural effusions typically present Pus indicates an empyema, milky white fluid
with dyspnoea, sometimes with pleuritic pain, suggests a chylothorax and frank blood sug-
and often with features of associated diseases gests a haemothorax (e.g. as a result of trauma).
(e.g. cardiac failure, carcinoma, etc.). The signs A low glucose content points towards infec-
of pleural effusion are decreased expansion tion or a connective tissue disease as a cause of
on the side of the effusion, stony dullness, di- the effusion.A high amylase content is charac-
minished breath sounds and reduced tac- teristic of pleural effusion associated with pan-
tile vocal fremitus. Sometimes bronchial creatitis but also sometimes occurs with
breathing is heard at the upper level of the adenocarcinoma. Neutrophils are the pre-
fluid. In taking the patients history it is impor- dominant cells in acute inflammation or infec-
tant to enquire about clues to possible causes of tion and lymphocytes in chronic effusions
pleural effusion such as asbestos exposure, con- particularly caused by tuberculosis or malignan-
tact with tuberculosis, smoking, drugs (e.g. cy. Cytology may show malignant cells (e.g.
dantrolene, bromocriptine) or systemic dis- mesothelioma or metastatic carcinoma).
ease.A full careful physical examination is essen- Microbiology examination of the fluid may
tial to detect signs of underlying disease (e.g. identify tuberculosis or bacterial infection, for
cardiac failure, breast lump, lymphadenopathy, example.
etc.). Pleural biopsy may be performed using a spe-
cially designed needle such as the Abrams
Investigations (Fig. 17.4) needle. After injection of local anaesthetic, in-
Radiology: chest X-ray characteristically cision of the skin and blunt dissection of the in-
shows a dense white shadow with a concave tercostal muscles, the needle is passed into the
upper edge (Fig. 17.5). Small effusions cause no pleural space.The Abrams needle is in two parts
more than blunting of a costophrenic angle which can be rotated on each other; pleural
whereas very large effusions cause white out of fluid can be aspirated when the window of the
an entire hemithorax with shift of the medi- needle is rotated to the open position.The nee-
astinum to the opposite side. Pleural fluid can be dle is then pulled back until some parietal pleur-
difficult to detect if the chest X-ray is performed al tissue is caught in the notch of the needle.The
with the patient lying supine, and may only be inner cylinder of the needle has a sharp cutting
170 Chapter 17: Pneumothorax and Pleural Effusion
INVESTIGATION CAUSES
CLINICAL EXAMINATION
Pleural fluid aspiration Exudates
APPEARANCE (protein > 30g/L, LDH > 200 iu/L)
Staw coloured MALIGNANCY
Bloodstained Metastatic carcinoma
Pus (empyema) Mesothelioma
Blood (haemothorax) INFECTION
BIOCHEMISTRY TB
Protein > 30g/L (exudate) Parapneumonic
LDH > 200 iu/L (exudate) Empyema (pus)
Amylase (pancreatitis)
INFLAMMATION
Glucose (infection) PLEURAL FLUID ASPIRATION SLE
CYTOLOGY Rheumatoid arthritis
Lymphocytes (TB, tumour) Dressler's syndrome
Neutrophils (infection, Benign asbestos effusion
inflammation) Drugs (e.g. dantrolene)
Malignant cells
SUBDIAPHRAGMATIC DISEASE
MICROBIOLOGY Subphrenic abscess
TB, bacteria Ascites
Pancreatitis
Pleural biopsy
(Abram's needle; thoracoscopy)
HISTOLOGY
Carcinoma, mesothelioma,
TB
MICROBIOLOGY ABRAM'S NEEDLE BIOPSY
TB
Fig. 17.5 This 68-year-old man presented with a the left side of the chest.The pleural fluid was
6-week history of progressive breathlessness and bloodstained and showed metastatic
left pleuritic pain. On examination there was adenocarcinoma on cytology. Bronchoscopy
stony dullness and diminished breath sounds showed the primary tumour partly occluding the
over the left hemithorax.The chest X-ray shows left lower lobe bronchus. An intercostal drain was
features of a large pleural effusion with a dense inserted to evacuate the fluid and tetracycline
white shadow with a concave upper border over was instilled to achieve pleurodesis.
which may recur producing diffuse pleural thick- caused by mucosal tears from protracted vom-
ening (see Chapter 15). Small pleural effusions iting. Characteristically, vomiting is followed by
may complicate pulmonary embolism and chest pain and subcutaneous emphysema (pal-
infarction (see Chapter 16). Dresslers syn- pable air in skin) as air and gastric contents leak
drome consists of inflammatory pericarditis into the mediastinum. A few hours later the
and pleurisy of uncertain aetiology following a pleural membrane gives way and air and food
myocardial infarction or cardiac surgery. debris pass into the pleural cavity pro-
Subdiaphragmatic disease: pancreatitis may ducing pleuritic pain, pleural effusion and
be associated with pleural effusions probably as empyema. Chest X-ray typically shows an initial
a result of diaphragmatic inflammation. Such ef- pneumomediastinum (a rim of air around
fusions are usually left-sided and characterised mediastinal structures) followed by a hydrop-
by a high amylase content. Ascites may tra- neumothorax. The diagnosis is notoriously
verse the diaphragm through pleuroperitoneal difficult to make and a radiocontrast oesopha-
communications causing a pleural effusion. gogram is the key investigation. Thoracotomy
Spread of infection or inflammation from a sub- with repair of the oesophagus is usually the best
phrenic abscess or intrahepatic abscess treatment.
may also cause a pleural effusion.
Further reading
Oesophageal rupture
Antony VB, Loddenkemper R, Astoul P, et al. Manage-
Oesophageal rupture may give rise to a pyop- ment of malignant pleural effusions. Eur Resp J 2001;
neumothorax (air and pus in the pleural cavity). 18: 40219.
Dhillon DP, Spiro SG. Malignant pleural effusions. Br J
This may result from external trauma or be ia-
Hosp Med 1983; 29: 50610.
trogenic (e.g. perforation during endoscopy). Ferguson AD, Prescott RJ, Selkon JB, Watson D,
Spontaneous rupture of the oesophagus Swinburn CR.The clinical course and management
(Boerhaaves syndrome) is a rare but cata- of thoracic empyema. Q J Med 1996; 89: 2859.
strophic condition which typically occurs when Hamm H, Light RW. Parapneumonic effusion and
the patient attempts to suppress vomiting by empyema. Eur Respir J 1997; 10: 11506.
closure of the pharyngeal sphincter. Intra- Miller AC, Harvey JE. Guidelines for the management
of spontaneous pneumothorax. BMJ 1993; 307:
oesophageal pressure rises steeply and rupture
11416.
typically occurs in the lowest third of the Miller KS, Sahan SA. Chest tubes: indications, tech-
oesophagus. It is a more severe form of the nique, management and complications. Chest 1987;
MalloryWeiss syndrome of haematemesis 91: 25864.
CHAPTER 18
Acute Respiratory
Distress Syndrome
Introduction Pathogenesis
The acute respiratory distress syndrome In most situations pulmonary oedema arises as
(ARDS) is a form of acute respiratory fail- a result of increased pulmonary capillary pres-
ure caused by permeability pulmonary sure (e.g. left ventricular failure) but in ARDS it
oedema resulting from endothelial damage arises because of increased alveolar capillary
developing in response to an initiating injury permeability.
or illness.
It had long been recognised that soldiers Pressure pulmonary oedema
wounded in battle often died of respiratory (Fig. 18.1)
failure some days later. During World Wars I and In the normal situation the hydrostatic pressure
II it was thought that this was because of infec- and the osmotic pressure exerted by the plasma
tion or excessive fluid administration. Further proteins are in a state of equilibrium between
experience of the condition during the Vietnam the pulmonary capillaries and lung alveoli.An in-
War showed that despite successful surgical crease in hydrostatic pressure is the most
management of wounds and optimal fluid re- common cause of pulmonary oedema and this
placement soldiers were still dying of pul- typically occurs secondary to elevated left atrial
monary dysfunction some days later and that pressure from left ventricular failure (e.g. after
the lungs showed features such as oedema, at- myocardial infarction) or from mitral valve dis-
electasis, haemorrhage and hyaline membrane ease (e.g. mitral stenosis). Volume overload
formation. It was not until 1967 that this condi- may also increase pulmonary capillary pressure
tion was recognised as a specific clinical entity and this may arise from excessive intravenous
separate from the precipitating injury, and that it fluid administration or fluid retention (e.g. renal
could also arise from civilian injuries and illness- failure). Reduced osmotic pressure may
es. The term adult respiratory distress syn- contribute to pulmonary oedema and this
drome was used because of the superficial occurs in hypoproteinaemic states (e.g. severe-
similarity of the pathology of the disease, show- ly ill, malnourished patients; nephrotic syn-
ing hyaline membranes, to the infant respiratory drome with renal protein loss). In the early
distress syndrome (caused by surfactant defi- stages of pulmonary oedema there is an in-
ciency in premature babies), although the term crease in the fluid content of the interstitial
acute respiratory distress syndrome may be space between the capillaries and alveoli but as
more appropriate. the condition deteriorates flooding of the alve-
oli occurs.
174
Clinical features 175
H Y DR O ST A T I C AND C OLLOI D
P R E SSU R E S
Lymphatic
Alveolus
Fig. 18.1 Diagram illustrating channels
approximate values for
hydrostatic and colloid
pressures in millimetres of 15
Su n
mercury (mmHg) between the rf a
ce t e n sio
pulmonary capillary and (21)
15
alveolus. Pulmonary oedema
may arise from increased
hydrostatic pressure (e.g. 28
cardiogenic pulmonary +7
oedema), from reduced colloid (21)
Capillary
pressure (e.g.
hypoalbuminaemia), or from 6
15 (21)
increased capillary
Hydrostatic pressure Colloid pressure
permeability (e.g. acute
respiratory distress syndrome).
fractional inspired oxygen concentration mation about gas exchange and the metabolic
(FiO 2/100% oxygen = FiO 2 of 1). In ARDS state of the patient.
PO 2/FiO 2 is <26 kPa (200 mmHg).
Bilateral diffuse infiltrates on chest X-ray
(Fig. 18.2). Treatment
No evidence of cardiogenic pulmonary
oedema (e.g. pulmonary capillary wedge The treatment of ARDS consists of optimal
pressure 18 mmHg). management of the initiating illness or injury
combined with supportive care directed at
preserving adequate oxygenation, maintaining
Recognition of critically optimal haemodynamic function and com-
ill patients pensating for multiorgan failure which often
supervenes.
Patients who subsequently develop ARDS may
appear deceptively well in the initial stages of Treatment of initiating illness
their illness. Early recognition and careful ob- Prompt and complete treatment of the initiating
servation of at-risk patients is of crucial impor- injury or illness is essential. This includes rapid
tance in detecting the signs of deterioration and resuscitation with correction of hypotension in
in identifying the need for intensive therapy unit patients with multiple trauma for example, and
(ITU) care. Certain warning signs are applicable eradication of any source of sepsis (e.g. intra-
in a wide variety of clinical circumstances be- abdominal abscess or ischaemic bowel post-
cause there is often a common physiological surgery).
pathway of deterioration in the severely ill
which can be detected by simple observations Respiratory support
of the pulse rate, respiratory rate, blood Characteristically, the hypoxaemia of ARDS is
pressure, urine output and level of con- refractory to oxygen therapy because of
sciousness (Table 18.2). Arterial blood gas shunting of blood through areas of lung which
measurements provides useful additional infor- are not being ventilated as a result of the alveoli
Treatment 177
Fig. 18.2 This 21-year-old diabetic patient was pressure (PEEP) of 7.5 cmH2O. Electrocardiogram
admitted to the intensive therapy unit (ITU) monitor leads are visible and a central venous line
having vomited and inhaled gastric contents has been inserted via the right internal jugular
while unconscious with severe ketoacidosis. vein. A SwanGanz catheter has been passed from
Despite antibiotics and treatment of ketoacidosis the right subclavian vein and can be seen, looped
she developed acute respiratory distress around through the right side of the heart into the
syndrome (ARDS) with progressive respiratory pulmonary artery. Pulmonary capillary wedge
distress and severe hypoxaemia refractory to pressure was low at 8 mmHg indicating that the
oxygen therapy.The chest X-ray shows diffuse lung shadowing was not caused by cardiogenic
bilateral shadowing with air bronchograms (black pulmonary oedema, but by increased capillary
tubes of air against the white background of permeability of ARDS. Despite requiring
consolidated lung). An endotracheal tube is in prolonged ventilation and support on ITU the
place and the patient is being mechanically patient made a full recovery.
ventilated, with a positive end-expiratory
being filled with a proteinaceous exudate and the lungs, delivering oxygen-enriched air at a set
undergoing atelectasis. Continuous positive tidal volume and rate. Adjustments in the
airway pressure (CPAP) can be applied via volume, inflation pressure, rate and percentage
a tight-fitting nasal mask to prevent alveolar oxygen are made to achieve adequate ventila-
atelectasis and thereby reduce ventilation/per- tion. A positive end-expiratory pressure
fusion mismatch and the work of breathing. (PEEP) of 515 cmH2O is usually applied at the
However, endotracheal intubation and end of the expiratory cycle to prevent collapse
mechanical ventilation rapidly become nec- of the alveoli. High airway pressures may be
essary and the patient may need to be trans- generated in ventilating the non-compliant stiff
ferred to a specialist ITU with expertise and lungs in ARDS and this can reduce cardiac out-
facilities for treating ARDS. Intermittent posi- put and carries the risk of barotrauma (e.g.
tive pressure ventilation mechanically inflates pneumothorax). High ventilation pressures
178 Chapter 18: Acute Respiratory Distress Syndrome
RECOGNITION OF CRITICALLY
ILL PATIENTS
Respiratory rate <8 or >30/min
Pulse rate <40 or >130/min
Blood pressure <90 mmHg
Urine output <30 mL/h for 3 hours Table 18.2 Features indicating
Level of consciousness Not responding to commands a critically ill patient. A patient
Oxygenation O2 sat. <90% ir. PaO 2 <8 kPa (60 mmHg) demonstrating any of these
despite 60% inspired oxygen warning signs needs urgent
Acidosis pH <7.2; bicarbonate <20mmol/L attention and consideration for
ITU care.
combined with high oxygen concentrations may lary leak. This is achieved by avoiding excessive
themselves result in microvascular damage fluid administration, by judicious use of diuret-
which perpetuates the problem of permeability ics and by use of drugs which act as vasodila-
pulmonary oedema (ventilator lung/oxygen tors of the pulmonary arteries. Treatment is
toxicity). A variety of ventilatory techniques often guided by use of a balloon-tipped pul-
have been developed to overcome these prob- monary artery catheter (SwanGanz) which
lems. Permissive hypercapnea is a technique measures pulmonary artery pressures, pul-
which allows the patient to have a high PaC O 2 monary capillary wedge pressure (reflecting left
level (e.g. 10 kPa; 75 mmHg) in order to reduce atrial pressure) and cardiac output (using a ther-
the alveolar ventilation and to avoid excessive mal dilution technique). Haemodynamic man-
airway pressure. Inverse ratio ventilation agement essentially consists of achieving an
prolongs the inspiratory phase of ventilation optimal balance between a low pulmonary
such that it is longer than the expiratory phase artery pressure to reduce fluid leak to the
allowing the tidal volume to be delivered alveoli, an adequate systemic blood pres-
over a longer time at a lower pressure. How- sure to maintain perfusion of tissues and organs
ever, this may cause progressive air trapping. (e.g. kidneys) with a satisfactory cardiac out-
High-frequency jet ventilation is a tech- put and optimal oxygen delivery to tissues
nique whereby small volumes are delivered as (oxygen delivery is a function of the haemoglo-
an injected jet of gas at high frequencies (e.g. bin level, oxygen saturation of blood and cardiac
100300/minute). Ventilation of the patient in output). Most drugs used to vasodilate the pul-
the prone posture may be beneficial as it monary arteries, such as nitrates or calcium
reduces gravity-dependent fluid deposition and antagonists, also cause systemic vasodilatation
atelectasis. Extra corporeal membrane with hypotension and impaired organ perfusion.
oxygenation (ECMO) involves the diversion Inotropes and vasopressor agents, such as
of the patients circulation through an artificial dobutamine or norepinephrine (noradren-
external membrane to provide oxygen and aline) may be needed to maintain systemic
remove carbon dioxide. None of these ventila- blood pressure and cardiac output particularly
tory strategies has yet achieved a major im- in patients with the sepsis syndrome (caused
provement in the overall prognosis of ARDS but by septicaemia or peritonitis, for example) in
each may be useful in individual circumstances. which sepsis is associated with systemic vasodi-
latation. Recently, inhaled nitric oxide (NO)
Optimising haemodynamic has been used as a selective pulmonary artery
function vasodilator. Because it is given by inhalation it is
Reducing the pulmonary artery pressure may selectively distributed to ventilated regions of
help to reduce the degree of pulmonary capil- the lung where it produces vasodilatation. This
Further reading 179
180
Oxygen desaturation during sleep in respiratory disease 181
changes during sleep may aggravate pre-existing bon dioxide retention because in many of these
respiratory disease, and specific breathing patients respiratory drive is partly dependent
disorders may arise during sleep. on the stimulant effect of hypoxaemia. Pro-
triptyline, a non-sedative tricyclic antidepres-
sant, may have a beneficial effect by reducing the
Oxygen desaturation during time spent in REM sleep, but anti-cholinergic
sleep in respiratory disease side-effects (e.g. dry mouth, urinary retention)
are common.
During sleep the respiratory centre in the There are very few drugs that have respira-
medulla receives less stimulation from higher tory stimulant effects but an intravenous infu-
cortical centres and becomes less responsive to sion of doxapram may be useful for a short
chemical (e.g. hypercapnia) and mechanical (e.g. period during a crisis. Ventilatory support
from chest wall and airway receptors) stimuli. can be delivered in the short term by endotra-
Minute ventilation (tidal volume and respiratory cheal ventilation in an intensive therapy unit
rate), falls, PCO2 rises, functional residual capac- (ITU) to tide the patient over a crisis. However,
ity decreases and there is diminished activity of long-term ventilatory support is often required
the intercostal and accessory respiratory mus- and this is nowadays usually given as domiciliary
cles. These changes are most marked during nocturnal non-invasive positive pressure
REM sleep. Although they are not associated ventilation (NIPPV). A tight-fitting mask is
with any adverse effects in normal individuals strapped in place over the nose and connected
they may produce profound nocturnal hypox- to a specifically designed ventilating machine.
aemia and hypercapnia in patients with underly- The spontaneous respiratory efforts of the pa-
ing respiratory disease, who are dependent on tient trigger the ventilator to deliver additional
accessory respiratory muscle activity and who tidal volume under positive pressure. Despite
are already hypoxic when awake and on the the cumbersome nature of this form of ventila-
steep part of the oxyhaemoglobin dissociation tory support it is very well tolerated by patients
curve. Sleep-related oxygen desaturation is who usually can manage to sleep while receiving
most important in diseases associated with nasal ventilation after a few nights of acclimatisa-
hypercapnic (type 2) respiratory failure such as tion. Control of nocturnal desaturation by
chronic obstructive pulmonary disease NIPPV not only improves the quality of their
(COPD), neuromuscular disease (e.g. sleep and nocturnal symptoms but also im-
muscular dystrophy, motor neurone disease) proves daytime symptoms and gas exchange. It
and thoracic cage disorders (e.g. kyphoscol- seems that improvement of arterial blood gas
iosis). The nocturnal oxygen desaturation in levels during ventilation, resting fatigued respi-
these disorders results from the deleterious ratory muscles, recruiting atelectatic alveoli, re-
effect of sleep physiology on pre-existing respi- lief of sleep deprivation and control of nocturnal
ratory insufficiency and is quite distinct from hypoventilation by NIPPV all result in some re-
obstructive sleep apnoea syndrome (see calibration of ventilatory responses with sus-
below). tained improvement which ameliorates daytime
arterial blood gas levels also. NIPPV represents
Treatment an important advance in the treatment of
Optimising the management of the underlying patients with ventilatory failure caused by
respiratory disease is the first priority (e.g. kyphoscoliosis, for example (Fig. 19.1).
bronchodilators in COPD). Avoidance of ag-
gravating factors, such as use of alcohol or
sedative medication is important. Supplemental
oxygen may alleviate oxygen desaturation but
may provoke further hypoventilation and car-
182 Chapter 19: Sleep-Related Breathing Disorders
Fig. 19.1 This 39-year-old woman with severe because of deteriorating hypercapnia. Nocturnal
kyphoscoliosis developed sleep disturbance, ventilatory support was commenced using non-
tiredness, headaches and oedema. She was invasive positive pressure ventilation (NIPPV)
erroneously treated with sedatives for insomnia. delivered via a tight nasal mask. She has now
Spirometry showed a severe restrictive defect been using NIPPV for about 8 hours at night at
with forced expiratory volume in 1 second (FEV1) home for 2 years. She works as a secretary and
of 0.4 and forced vital capacity (FVC) of 0.5L. PO2 can do housework but is dyspnoeic on walking
was 5.6 kPa (42 mmHg) and PCO2 10.2 kPa 150 metres. NIPPV is an effective means of
(76 mmHg). Her sleep was fragmented with ventilatory support for patients with hypercapnic
multiple arousals and profound oxygen respiratory failure caused by thoracic cage
desaturation. She was unable to tolerate oxygen disorders or neuromuscular disease.
Pathogenesis
Obstructive sleep apnoea
The oropharyngeal dilator muscles play an im-
syndrome (Fig. 19.2)
portant part in maintaining patency of the upper
airway. During deep sleep there is reduced
Obstructive sleep apnoea syndrome is a condi-
muscle tone so that the pharyngeal airway is
tion in which recurrent episodes of upper air-
most vulnerable to collapse during REM sleep.
way occlusion occur during sleep causing
Use of sedatives or alcohol may cause a further
diminution (hypopnoea) or cessation of airflow
loss of muscle tone. Narrowing of the upper air-
(apnoea) in the pharynx provoking arousals
way predisposes to occlusion and this is usually
and sleep fragmentation, resulting in day-
a result of fat deposition in the neck from obesi-
time sleepiness.
Obstructive sleep apnoea syndrome 183
O B S TRU CTIV E SL E E P A P N O E A
PATHOGENESIS TREATMENT
Fig. 19.2 Apnoea results from occlusion of the sucks in the pharyngeal airway. Nasal
pharyngeal airway in patients with narrowed continuous positive airway pressure (CPAP) acts
airways when there is loss of pharyngeal dilator as a splint preventing collapse of the airway and is
muscle tone in sleep. Increased inspiratory effort, the main treatment used for sleep apnoea.
when there is increased upper airway resistance,
ty, but other factors such as bone morphology be important, the main factors involved in
(e.g. micrognathia), soft tissue deposition (e.g. upper airway patency are the calibre of the
hypothyroidism, acromegaly) or enlargement of pharyngeal airway, the action of oropha-
tonsils or adenoids in children may be impor- ryngeal dilator muscles and the inspir-
tant. Contraction of the diaphragm and inter- atory effort needed to overcome upper
costal muscles during inspiration creates a airway resistance.
negative pressure in the airways drawing air into OSAS is characterised by recurrent episodes
the lungs. The negative pressure in the airway, of pharyngeal airway obstruction during sleep
however, also acts as a force sucking in or col- with apnoea, arousal and sleep fragmentation.
lapsing the upper airway. An increase in upper As the patient with a compromised pharyngeal
airway resistance such as occurs in nasal ob- airway (e.g. narrowed by obesity) enters deep
struction (e.g. deviated nasal septum, polyps) or sleep the reduction in oropharyngeal dilator
in enlargement of tonsils and adenoids, requires muscle tone results in collapse of the airway
a greater inspiratory effort to overcome it, and causing apnoea (cessation of airflow) or hypop-
thus increases the forces sucking in the pharyn- noea (reduction of airflow) with a fall in oxygen
geal airway. Although upper airway reflexes and saturation. Inspiratory effort increases as the
neuromuscular control of respiration may also diaphragm and intercostal muscles try to over-
184 Chapter 19: Sleep-Related Breathing Disorders
come the closed upper airway. The apnoea is Cardiovascular complications associ-
terminated by a brief arousal from sleep and this ated with OSAS include hypertension, myocar-
is associated with a burst of sympathetic nerve dial infarction, stroke, cardiac arrhythmias,
activity, release of catecholamines and fluctua- structural cardiac changes and cardiac failure.
tions in pulse rate and blood pressure. Resump- Although some of these associations may be ex-
tion of pharyngeal airflow is accompanied by plained by confounding variables such as obesi-
loud snoring which is an inspiratory noise aris- ty, evidence is accumulating of an independent
ing from vibration of the soft tissues of the direct relationship between OSAS and cardio-
oropharynx.Arousals are often associated with vascular disease which may be caused by a com-
generalised body movement. Hundreds of bination of factors such as hypoxaemia, changes
episodes of apnoea and arousal throughout in blood pressure and sympathetic nervous
the night disrupt sleep, resulting in daytime system activation during apnoeas and arousals.
sleepiness. It is important to reduce cardiovascular risk fac-
tors in these patients by checking smoking his-
Clinical features tory, blood pressure, and cholesterol and
Patients with OSAS may have no detectable res- glucose levels, and intervening as appropriate. In
piratory abnormality when awake but daytime addition to catecholamine release, OSAS is as-
symptoms include excessive sleepiness, sociated with other hormonal changes in-
poor concentration, irritability, morning cluding reduced testosterone and growth
headaches and loss of libido. Sleepiness is hormone levels. Although hypoxaemia, hyper-
usually a prominent feature and may result in the capnia and elevation of pulmonary artery pres-
patient falling asleep inappropriately when read- sure occur during apnoeas, cor pulmonale is
ing, watching television, listening to a lecture, unusual unless there is concomitant lung dis-
travelling on a bus or driving a car, for example. ease (e.g. COPD). The long-term prognosis of
It is important to recognise the importance of OSAS is not fully understood but some studies
such symptoms and their relationship to sleep- have shown a significantly higher mortality in pa-
disordered breathing as such symptoms may be tients who refused treatment than in those
erroneously dismissed as laziness. Patients with whose sleep apnoea was controlled by continu-
OSAS have a high rate of accidents at home, at ous positive airway pressure (CPAP).
work and when driving. It is estimated that
about 5% of commercial drivers have OSAS and Polysomnography
that sleep-related road traffic accidents Although OSAS may sometimes be diagnosed
comprise 1520% of all crashes, resulting in on the basis of clinical features and overnight
many serious injuries and deaths. Patients with oximetry, definitive assessment requires
OSAS should be advised to notify their driving polysomnography. This involves the recording
licence authority of their condition and to avoid of signals relating to oxygenation, airflow, chest
driving until their sleepiness has been con- wall movement and stage of sleep. An elec-
trolled by treatment. The patient may be un- troencephalogram (EEG) records the stage
aware of night-time symptoms but the bed of sleep. An electrooculogram (EOG) de-
partner may report loud snoring, witnessed tects rapid eye movement.A thermistor detects
apnoeas and restless sleep. It is important to airflow at the nose and mouth, and ribcage
enquire about use of sedatives or alcohol which and abdominal movements are measured
may aggravate OSAS. Examination focuses on using magnetometers or impedance plethys-
risk factors for OSAS such as obesity, in- mography. Oximetry detects oxygen desatu-
creased neck circumference, anatomical ration and an electrocardiogram (ECG)
abnormalities reducing pharyngeal calibre records heart rate. These tracings are often
(e.g. micrognathia, enlarged tonsils), and nasal combined with a video recording of the patient
obstruction (e.g. polyps, deviated septum). during sleep which permits observation of the
Central sleep apnoea 185
the respiratory centres by brain stem infarcts De Backer WA. Central sleep apnoea, pathogenesis
or syringobulbia, for example. Most of these and treatment. Eur Respir J 1995; 8: 137283.
patients also have hypercapnic respiratory Griffths CJ, Cooper BG, Gibson GJ. A video system
for investigating breathing disorders during sleep.
failure when awake, and non-invasive positive
Thorax 1991; 46: 13640.
pressure ventilation is the main form of treat- Hudgel DW. Treatment of obstructive sleep apnoea.
ment used. Chest 1996; 109: 134658.
McNicholas WT. Impact of sleep in respiratory failure.
Eur Respir J 1997; 10: 92033.
Further reading Strohl KP, Redline S. Recognition of obstructive sleep
apnoea. Am J Respir Crit Care Med 1996; 154:
27989.
Bradley TD, Leung RST. Sleep anoea and cardiovascu-
Suratt PM, Findley LJ. Serious motor vehicle crashes :
lar disease. Am J Respir Crit Care Med 2001; 164:
the cost of untreated sleep apnoea. Thorax 2001;
214765.
56: 505.
CHAPTER 20
Lung Transplantation
who are then diagnosed as having suffered brain needs time to understand the severity of the
stem death. There are strict guidelines govern- disease, the predicted prognosis and what is in-
ing the diagnosis of brain stem death and the volved in lung transplantation.Addressing these
process of organ donation. Because of the vul- issues is traumatic for the patient and his or her
nerability of the lungs to injury and infection family. Some patients with advanced lung dis-
only about 20% of suitable heart donors will ease want to try all available treatment options,
also be potential lung donors.There must be no whereas other patients fear high-intensity un-
history of significant respiratory disease and no pleasant interventions and would prefer to take
major chest trauma. Chest X-ray must be a palliative approach to the terminal stages of
clear and gas exchange adequate (PO2 >12 kPa their disease. Contraindications to lung
(90 mmHg) on <35% inspired oxygen). Tech- transplantation include hepatic or renal dis-
niques have been developed to preserve the ease, uncontrolled infection, the presence
donor lungs for up to 68 hours allowing of an aspergilloma and poor nutritional
emergency transport (e.g. by plane) of donor status. The success of lung transplantation pro-
organs to the recipient. The donor and re- grammes is based upon careful selection of the
cipient are matched for ABO blood group, small number of patients who can benefit from
cytomegalovirus status and chest size. the procedure and who can be supported long
enough to have a realistic chance of getting a
donor organ.
Indications for transplantation
Fig. 20.1 This 29-year-old woman developed lungs. Her hypercapnic respiratory failure
respiratory failure (PO2 6kPa (45mmHg), PCO2 8kPa deteriorated and she was bridged to
(60mmHg)) as a result of advanced cystic fibrosis transplantation by domiciliary intermittent
lung disease (forced expiratory volume in 1 positive pressure ventilation delivered via a tight-
second (FEV1) 0.5L). (a) Her chest X-ray shows fitting nasal mask. (b) Bilateral sequential single-
hyperinflated lungs with diffuse bronchiectasis lung transplantations were performed 14 months
and peribronchial fibrosis. She was accepted onto after being accepted onto the waiting list. She
a lung transplantation waiting list and supported subsequently died 5 years post-transplantation of
by oxygen therapy, antibiotics, physiotherapy and obliterative bronchiolitis.
nutritional supplements while awaiting donor
4500
4000 Men
Women
Number of manufactured
3500
cigarettes per person
3000
2500
2000
1500
1000
500
0 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85
Year
60
Prevalence (%)
50
40
30
20
10
0
48 50 52 54 56 58 60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96
Year
Fig. 21.2 Prevalence of smoking in the UK, component linked to the development of lung
194896. (Reproduced with permission from the cancer. Carbon monoxide is associated with
Lung and Asthma Information Agency Factsheet
the cardiovascular risks of smoking and nico-
98/2.)
tine has addictive properties. Both the gas and
particulate components of cigarette smoke are
tobacco smoke at home have an increased risk implicated in the development of COPD. From
of bronchitis, lower respiratory infections and the 1950s onward, when filtered cigarettes
exacerbations of asthma. began to replace unfiltered varieties, the tar
yield fell by about half and the nicotine yield fell
by about one-third, but the carbon monoxide
Composition of smoke yield remained stable. However, changes in the
contents of cigarettes cause many smokers to
Cigarette smoke has a very complex composi- inhale more deeply or to smoke more ciga-
tion, with gas and particulate phase compo- rettes, and it is not possible to produce a safe
nents.The smoke emitted from the burning end cigarette because smoking involves the burning
of the cigarette is known as sidestream of complex hydrocarbons that will always pro-
smoke and emerges directly into the environ- duce toxic products.
ment, whereas the mainstream smoke is
inhaled directly by the smoker. Many toxic con-
stituents are present in higher concentrations in Smoking cessation
sidestream smoke, and this may be important in
assessing the risks of passive smoking. Tar con- The process of smoking cessation may be
sists of a mixture of aromatic hydrocarbons divided into five stages:
including carcinogens such as nitrosamines, Precontemplation (contented smoker not
aromatic amines and benzopyrene, and is the considering cessation)
194 Chapter 21: Smoking and Smoking Cessation
Contemplation (concerned smoker who breaks at work). Enlist the support of family and
would like to stop) friends. Encourage them not to rely solely on
Preparation (smoker planning practical will power but to consider using nicotine
ways of stopping) replacement therapy. Adopt a positive
Action (setting a quit date) attitude: I know you can do it, and we will
Maintenance (supporting cessation and help. Provide a booklet giving advice and practi-
preventing relapse). cal tips for smoking cessation.
People who smoke need help,not hostility Arrange follow-up and support. Offer a fol-
from health-care workers in stopping smoking low-up visit with the doctor or nurse about 1
and it is important to develop a therapeutic week after the quit date. Applaud success and
partnership which provides support and prac- warn about preventing relapse.
tical advice. Smoking is such an important More intensive smoking cessation sup-
health issue that all health-care workers should port can help smokers who are motivated to
routinely ask patients about their smoking sta- stop but who have repeatedly failed. Group ses-
tus and advise them appropriately All the sions with other smokers provide additional
As. support and encouragement, and can be used to
Ask about smoking at every opportunity and develop coping skills, training in dealing with
document the smoking status of all patients. cravings and social support.
Applaud those who are non-smokers. Assess
the attitude of smokers to smoking cessation.
Some say that they do not intend to quit and Pharmacotherapy (Table 21.1)
these should be advised to contemplate the
health risk. Such advice should be individu- Small doses of nicotine produce predominantly
alised to their current health issues (e.g. asthma, stimulant effects such as arousal, whereas larger
respiratory infections) or social circumstances doses produce mainly depressant effects such as
(e.g. plans to become pregnant). Young people relaxation and relief of stress. Nicotine with-
often erroneously think that they will have time drawal can cause irritability, restlessness,
to stop smoking later if diseases develop. Some- anxiety, insomnia and a craving for cigarettes.
times shock tactics may help them contem- Nicotine replacement therapy approximately
plate the future (e.g. when your daughter is doubles the success rates of attempts at smok-
getting married in 20 years time who will walk ing cessation and smokers should be encour-
her down the aisle if you get lung cancer?). aged to use it to avoid withdrawal symptoms.
About 70% of smokers say that they would like Typically, a heavy smoker is given transdermal
to quit and these need to be encouraged to nicotine patches 21 mg/day for 4 weeks,
move from contemplation of stopping to taking reducing to 14 mg/day for 2 weeks and then
action to stop.
Advise all smokers on the value of stopping,
the risks to health of continuing and the support
PHARMACOTHERAPY
available in helping them to stop (e.g. nicotine
replacement therapy). Assure them that Its Nicotine replacement therapy
never too late to stop and encourage them to Transdermal patch
Chewing gum
Never stop trying to stop.
Lozenges
Assist patients who have decided to stop
Inhalator
with practical personalised advice and support. Nasal spray
Set a quit date and stop completely on that Bupropion (amfebutamone)
day. Plan ahead by identifying problems and
situations where the temptation to smoke aris- Table 21.1 Pharmacotherapy in smoking
es (e.g. after meals, in the pub, during coffee cessation.
Further reading 195
7 mg/day for 2 weeks. Most withdrawal symp- smoking and disease but they feel healthy, young
toms have resolved within that period of time. and immortal and do not relate well to con-
The patch is applied to the skin each morning and cepts of ageing and disease. Counteracting this
delivers a constant dose over 1624 hours, but normal rebellious youth culture is difficult, but
the onset of action is quite slow. Patients who involves the promotion of a positive image of
experience marked cravings for cigarettes may a healthy lifestyle and emphasising the unat-
benefit from using nicotine chewing gum, tractiveness of the smoker, whose clothes,
lozenges, inhalator, or nasal spray which hands and breath reek of tobacco (Its like kiss-
provide more rapid peak blood levels from ing an ashtray). In teenagers sporting activities
absorption of the nicotine through the buccal or are inversely related to smoking because
nasal mucosa. Nicotine replacement therapy is sports seem to promote self-confidence, en-
safe, but is not recommended in pregnancy. courage a healthy lifestyle and reduce peer influ-
Addiction to nicotine replacement therapy can ences about smoking. Mass media intervention,
occur in a few patients who use it in the long with advertisements promoting the anti-
term, but most patients can be weaned off treat- smoking message targeted at the young, also ap-
ment over a few weeks. Bupropion (amfebu- pear to be effective in preventing the uptake of
tamone) is a newer antidepressant drug which smoking. Outright prohibition of smoking is not
significantly improves the success of attempts at likely to be feasible or successful but the exam-
smoking cessation, although its mode of action is ples of parents, teachers, sports people and
uncertain. It has some significant side-effects, society in general are crucial.
most notably a 1 in 1000 risk of epileptic seizures Tackling the epidemic of smoking-related
such that it is contraindicated in patients with mortality and morbidity requires action by all
convulsive disorders, central nervous system levels of society. There is a crucial role for all
disease, bulimia or anorexia nervosa, and in health-care workers in providing leadership and
patients experiencing symptoms of withdrawal example in creating a tobacco-free society.
from alcohol or benzodiazepines.
Further reading
Primary prevention
Anderson JE, Jorenby DE, Scott WJ, Fiore MC. Treat-
Many long-term smokers were introduced to ing tobacco use and dependence. Chest 2002; 121:
the habit as teenagers when they were vulnera- 93241.
Britton J, Jarvis MJ. Bupropion: a new treatment for
ble to cigarette advertising and when smoking
smokers. BMJ 2000; 321: 656.
may have been seen as a symbol of forbidden Davis RM. Passive smoking: history repeats itself. BMJ
adult behaviour. Measures designed to discour- 1997; 315: 9612.
age smoking among young people are particu- Lung and Asthma Information Agency. Trends in Smok-
larly important in the primary prevention of ing. Factsheet 98/2.
smoking-related diseases. Most young people Raw M, McNeill A, West R. Smoking cessation guide-
are fully aware of the causal relationship of lines for health professionals. Thorax 1998; 53
(suppl. 5): 138.
Index
Note: page numbers in italics refer to figures and those in bold refer to tables.
abdominal paradox 13 airborne particulates 93, 94 pneumonia 51
Abrams needle biopsy 16970 airflow obstruction in COPD 111 anatomical dead-space 3
accessory muscles of respiration 11 airway(s) angiotensin-converting enzyme
acetazolamide 185 disease in HIV infection 68 (ACE) 144
acid- and alcohol-fast bacilli (AAFB) remodelling in asthma 96 anorexia 10
staining 58 resistance 3 anti-basement membrane antibody
acidbase balance 289 responsiveness in asthma 163
acinar glands, bronchi 3 98100 anti-centromere antibodies 163
acquired immune deficiency airways obstruction 111, 113 anti-inflammatory drugs
syndrome seeAIDS asthma 91 ARDS 179
actinomycosis 172 coalworkers 151 asthma 102, 103, 104, 1056
activated partial thromboplastin cystic fibrosis 82 cystic fibrosis 90
time (APPT) 160 diffuse 20 anti-neutrophil cytoplasmic
acute respiratory distress syndrome irreversible 119 antibodies (ANCA) 163
(ARDS) 174 pulmonary embolism 160 anti-protease enzyme deficiency
anti-inflammatory therapy 179 reversibility 113 114
blood transfusion 179 severe 23, 25, 26 anti-retroviral drugs 667
clinical features 1756 alcohol 185 pulmonary hypersensitivity
diabetes 177 misuse 48, 58 reactions 71
haemodynamic function 1789 allergens 92, 94 antibiotics 88
inflammatory cascade 175 avoidance 103 bronchiectasis 789
initiating illness 176 pet-derived 93, 96, 103 COPD 119
multi-organ failure 179 alveolar capillary membrane 1 intravenous treatment 88
nutritional support 179 alveolar capillary permeability 175 lung abscess 80
pathogenesis 1745 alveolar cell carcinoma 30, 34, 135 nebulised 88
prognosis 179 alveolar haemorrhage 163 pleural effusion 172
respiratory support 1767 alveoli pneumonia treatment 512
treatment 1769 structure 3 resistance 48, 52
ventilation 1778 ventilation 1, 34, 5, 28 anticholinergic drugs 118
adenovirus 70 alveolitis anticoagulant therapy 159, 1612
adherence, bacterial 73, 81 cryptogenic fibrosing 13740 anticoagulation, oral 161
advertisements, anti-smoking 195 extrinsic allergic 1401 antigen
aegophony 17 lymphocytic 67 detection tests 51
aeroallergens 92 amfebutamone 195 inhaled 140
AIDS 55, 65 aminoglycosides 51, 53 interstitial lung disease 136
atypical mycobacteria 64 aminorex 163 antigenic drift/shift 43
B-cell lymphoma 70 amiodarone 140 antimony 151
diagnosis 66, 68 amniotic fluid embolism 163 a1-antitrypsin deficiency 1011
fungal infections 70 amosite 151 aorta, aneurysmal enlargement 33
neoplastic diseases 68 amoxicillin 52 apex beat 13
perinatal transmission 65 COPD 119 apex of lung, fibrosis 1314
pneumonia 70 cystic fibrosis 88 apnoea 180, 1826
viral infections 70 pneumonia 51 central sleep 1856
AIDS-defining illness 68 cAMP 104 apnoeahypopnoea index 185
air amyloidosis 86 appetite-suppressant drugs 163
bronchogram 31 anaemia 12 aromatic hydrocarbons 193
embolism 163 anaerobic bacteria 42, 79 arterial blood gas 245, 27
pollution 93, 94 analgesia COPD 117, 121, 1223
trapping 98 lung carcinoma 1345 pulmonary embolism 157
197
198 Index
bronchial breathing 17, 169 car exhaust emissions 93, 94 challenge studies in occupational
bronchial carcinoma 9, 30, 74 carbon dioxide asthma 148
cavitation 323 dissociation curve 6 chemotherapy
clubbing 12 exchange 1 anti-neoplastic 72
smoking 125 partial pressure 5, 7, 28, 98 lung carcinoma 131, 134
bronchial tree 1, 2, 3 carbon monoxide chest
bronchiectasis 10, 739 cigarette smoke 193 deformity in asthma 97, 98
aetiology 747 diffusing capacity 21 examination 1315, 17
allergic bronchopulmonary mean alveolar level 23 movement palpation 13
aspergillosis 75 transfer coefficient (Kco) 21, 23, pain 10
bronchial obstruction 74 24 tightness in asthma 96
ciliary dyskinesia 756 transfer factor 21, 23, 27 trauma and lung abscess 80
clinical features 77 carcinogens 146, 193 chest X-ray 303, 34, 35, 36
cystic fibrosis 81, 82 carcinoid syndrome 135 asbestosis 152
disease associations 77 carcinoma of the lung 125 asthma 100
HIV infection 68, 74 adenocarcinoma 127 bronchiectasis 77
inflammatory response 73 aetiology 1259 COPD 117
investigations 778 analgesics 1345 cryptogenic fibrosing alveolitis
measles 74 asbestos-related 154 137
pathogenesis 73 asbestosis 153 cryptogenic organising
pertussis 74 chemotherapy 132, 133, 134 pneumonitis 140
pneumonia 74 diagnosis 127, 130 immigrants 63
surgery 79 diet 126 interstitial lung disease 136
treatment 789 large-cell 127 lung carcinoma 1292
tuberculosis 56, 74 mortality 125, 126 pleural effusion 169
bronchioles 12 non-small-cell carcinoma 127 pneumonia 50, 50
bronchiolitis, obliterative 139, 189, management 132 pneumothorax 166
189 staging 1334 pulmonary embolism 157, 160
bronchitis 47 surgical resection 133 sarcoidosis 143
airflow obstruction 111 pain control 1345 total lung capacity 21
chronic 9, 111, 114 palliative care 1345 tuberculosis 58
coalworkers 151 Pancoast tumour 129 contact screening 63
history 10 pathology 127 childhood
HIV infection 68 percutaneous needle biopsy 129 factors in COPD development
infective exacerbations 11415 presentations 128 114
bronchoalveolar lavage 136 radiotherapy 134 lung disease 10
bronchodilators risk 11 pneumonia 47
airways obstruction reversibility silicosis 151 vaccination programme 88
98 small-cell carcinoma 127 Chlamydia pneumoniae 40, 41, 534,
anti-cholinergic 104 management 132 115
asthma 102, 103, 1045 treatment 1301, 133 Chlamydia psittaci 45, 53
bronchiectasis 79 smoking 192 Chlamydia trachomatis 47, 54
COPD 11819 social support 135 chloride channel 81
cystic fibrosis 88 staging 39 chlorofluorocarbons (CFCs) 106
nebulised 1089, 110 treatment 1301, 132, 1335, chronic obstructive pulmonary
bronchopneumonia 47, 52, 115 1345 disease (COPD) 111
bronchopulmonary segments 2 cardiac apex beat 13 acute exacerbation 115
bronchopulmonary sequestration cardiac failure 171 aetiology 114
80 cardiac sarcoid 144 arterial blood gases 117, 121,
bronchorrhoea 9, 135 cardiorespiratory disease 48 1223
bronchoscopy cardiovascular disease 184 artificial ventilation 121
asthma 100 cavitation 323, 36, 53 breathing control techniques
bronchiectasis 78 CD4 lymphocyte count 66, 67, 68 120
lung carcinoma 129, 131 CD4 receptor 66 chest physiotherapy 51
bulbar palsy 9 cefuroxime 51 childhood factors 114
bullae, subpleural 165 central airways obstruction 21 clinical features 11416
bullectomy, COPD 1201 central nervous system sarcoidosis cor pulmonale 13, 11516
Burkholderia cepacia 82, 84, 88 144 definition 111
byssinosis 149 central sleep apnoea 1856 drug nebulisation 1223
cepacia syndrome 82, 84 drug treatment 11819
Candida albicans,AIDS 70 cephalosporins, third generation dyspnoea 8
capillary permeability/pressure 51, 53 exacerbations 52, 118, 120
169 cervical adenopathy 80 exercise training 120
Caplans syndrome 139, 1501 CFTR dysfunction 81 genetic factors 114
200 Index