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Chronic Obstructive Pulmonary Disease Riham

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COPD:
-Definition:
It is a preventable and treatable disease with some significant extra-pulmonary effects that
may contribute to the severity in individual patients. Its pulmonary component is characterized by
airflow limitation that is not fully reversible. The limitation is usually progressive and associated

with an abnormal inflammatory response of the lung to noxious particles or gases .

Chronic Bronchitis Emphysema


(Blue Bloater) (Pink Puffer)
Definition -Presence of cough &sputum - Permanent enlargement of
production for at least 3 Ms airspaces distal to terminal
in each of 2 consecutive yrs. bronchioles accompanied
with destruction of their walls
+/- fibrosis. (except in
-Not included in COPD compensatory, focal emphysema)
definitions - A pathological term that is
often (but incorrectly) used
clinically and describes only
one of several structural abn.
present in patients ‘e COPD.
Classification -Simple (mucoid): irritation -Ciba-Symposium class.:
‘e no infection. .Unselective compensatory
 Pan-acinar
-Muco-purulent chronic .Selective dist. Focal (dust)
 Centri-acinar
-Chronic obstructive (irrev.) .Irregular emphysema

-Leopold, Gough class.:


.Pan-acinar AAT (LL>UL)
.Centri-acinar Smoker,
CWP (UL>LL).
.Distal acinar  apical bullae
with pneumothorax.
C/P -History of freq. resp. infect. -Usually –ve past history.
.Dyspnea -Variable, mild -Severe, progressive
.Cough -Considerable -Negligible
.Sputum -Copious, purulent -Scanty, mucoid
.Built -Usually obese -Usually thin
.Cyanosis -Marked -Absent or mild

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.Breath sound -Normal -Distant


.Wheezes -Common -Rare
.Cor-pulmon. -Common + P++ -Rare
Investigations -Common polycythemia -Absent polycythemia
.CXR -Inc. BV markings (basal >) -Hyperinflation +/- Bullae
.PFT -Obstructive pattern, Low -m.b Mild obstruction, N VC,
VC, N or Low RV, N DLCo, High RV, Low DLCo, N or
Low PO2, High PCO2 mild dec. PO2, high TLC
-FEV1 >25%  CO2 -FEV1 <50%  exertional
retention + corpulmonale dyspnea
<25%  dyspnea at
rest + CO2 retention + corpul.
Death Usually cardio-respiratory -Frequently not related to
failure chest condition.
-Die of RF before
corpulmonale development.

-Epidemiology:
 Age: more in middle age and old age.
 Sex: Males > Females (due to smoking, exposure to pollution)
 Area: Urban areas > Rural areas
 Seasonal variation: more in winter
 Social class and occupation: more in low states (nutrition, pollution,
crowd, tobacco use)

-Risk Factors:
 Exposures to:
o Smoking: in cigarette > cigar and pipe, normally FEV1 declines

annually by 20-30 ml/yr but reaches 40ml/yr in smokers.

Smoking causes obstruction by:

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- Mucosal gland hypertrophy + inhibit ciliary blanket  stasis and


infection (edema, inflammation)  exacerbation.
- Reflex broncho-spasm through irritant receptors (may respond to
1cig.)  blocked with atropine.
- Release of neutrophil elastase (increase in BAL)  injury.
- Inactivation of alpha1 anti-trypsin by smoke itself (oxidation) and by
oxidants from neutrophils and MQs.
- Surfactant defect.

o Pollution: (smoke, coal miners, gold miners, asbestos miners,

cement workers)  FEV1 decrease in smokers of CWP but give


restrictive pattern in non-smokers, Evidenced effect by:
- Increased mortality, prevalence rates with urbanization in COPD Pts.
- Increased brochitic symptoms with high pollution levels.
- Increased prevalence of emphysema at autopsy in polluted areas.

o Infection:  in infants if much can turn to chronic bronchitis

later in life (especially if smoking family added).

 Host factors:
o Genes: (α1 anti-trypsin deficiency)  it’s a glycoprotein

responsible for serum anti-protease activation  inhibits neutrophil


elastase and its synthesis in the liver (defect transportation from liver
cells to blood)  PiMM (most common genotype), PiZZ (responsible
for c/p α1 anti-trypsin is 10% of normal value), PiMZ (alpha1 anti-
trypsin is 60% of N).

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o Airway hyper-responsiveness:  smokers have increased levels

of IgE and eosinophils but not to the extent of asthmatics.

o Lung growth:  infants with parental smokers have more

respiratory illnesses and pneumonias at that age  predispose to


chronic bronchitis later in life.

 Others:
o Socio-economic status

o Nutrition

o Oxidative stress: increased oxidants endogenously by phagocytes

and exogenously by smoke and pollution. (direct/ indirect) 


oxidants are H2O2, NO (increase in breath, BS in vitro), PG isomer or
iso-prostane F2a3 (increase in breath more with exacerbations, BS)
o Gender

o Asthma: (12 folds more than non-asthmatics)

-Overlap between COPD, BA:


COPD BA Mixed
-Neutrophils ++ -Eosinophils ++ -Neutrophils +
(inc. in smokers even
with no COPD)
Cells -MQs +++++ -MQs + -MQs
-CD8 cells -CD4 cells -CD4
-Eosinophils (occur -Mast cells -CD8
in exacerbations)
NO + Cotaxin IL8,5,13
IL8 (activates IL4,5,13 NO ++
Mediators neutrophils) , IL1,6 NO ++++
TNF (weight loss
& Cachexia  persist
inflammation)

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Oxid.stress +++ + +++


-Peripheral airway -Proximal airways -Proximal airways
Site -Lung parenchyma -Peripheral
-Pulmonary Vs airways
-Sq. metaplasia -Fragile
-Mucus “ epithelium
Consequence -Small AW fibros. -Mucus metaplasia
---------
s -Parench. Destruct. -Broncho-spasm
-Pul. vascular -Thick BM
remodeling.
-Small b/d -Large b/d -Smaller b/d
response. response. response.
Responsive ttt -Poor response to -Good response to -Dec. steroid
steroids. steroids (rev.>20%) response (partial
rev. 10-20%)

-Classification: (post-BD FEV1)


 According to GOLD 2007:
Mild Moderate Severe V. Severe
FEV1/FVC < 70% < 70% < 70% < 70%
FEV1 > 80% of < 30% or >
50-80% 30-50%
+/- ch. Sympt. predicted 50% with RF

 According to ATS:  Mild  50-80%


 Moderate  30-50%
 Severe  < 30%

 According to Crofton 2000:  Mild  60-80%


 Moderate  40-60%
 Severe  < 40%

-Pathogenesis:

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Noxious particles and gases


Anti Oxidants
Anti-protease
Lung Inflammation Deficiency
TNFa
IL8 -MQ
-CD8
Oxidative stress Protineases
(Imbalance bet.
-Neutrophils (Imbalance bet.

Oxidants /anti) P/anti)
*Mediators
Repair
Mechanisms
COPD
-Pathology

Central Peripheral Lung Vascular


Airway AW Parenchyma changes
-Trachea -Small -Respiratory -Pulmonary
-Bronchi bronchi bronchioles. vessels.
Site
-Bronchioles -Bronchioles
(> 2-4mm) (<2mm)
-Infl. Cells Chronic - Bronchiolar -Thick. Of
infilt. Surface inflammation dilatation, vessel wall
epithelium. (repeat. Infl, destruction. (early) (intima,
-Hypert. MS. then repair) -Pulmonary MS, wall infilt.
-Remodeling capillary bed with infl. cells)
-Hypertrophy
mucus glands of AW wall destruction. -Increased
-Inc. goblet (metaplasia). Gas exchange smooth MS
-Inc. collagen abn. (diffusion (‘e low o2) +
Mechanisms cell no. (thick proteoglycans
glandular layer content, scar defect)  dec.
tissue. + collagen 
in comp. to O2 only so inc.
bronchial wall -Lost ventil.  dysp., scaring (later)
 Reid cartilage no cyanosis.
index) Dec. elastic
recoil  dec.
traction forces
 inc. R in AW
-Path- -Mucus -AW fixed -P++  -P++ 

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Hypersecret. obstruction corpulmonale corpulmonale


or limitation
physiology -Ciliary  Increase -AW fixed -Systemic
dysfunction Alveolar pr. obstruction effects of
 P++ COPD
Symptoms .Ch. cough .Dyspnea .Hyperinflated .S of corpul.
(morning then (acute attacks chest (inc. .PE
(+ general
over day)  then in winter static FRC) .Pul. thromb.
weakness, then all year)
chest pain .Dyspnea inc. .Dec. work of
fatigue, .Wheezes
.Sputum (trial to maintain diaphragm
weight loss, .+/- Cyanosis O2, CO2)
.Inc. ‘e exac. (dec. muscle
anorexia, rel. .S of high .S of corpulm. weight)
social isolat., CO2 .LV++(25-60%)
mood swing) .S of low O2

*Mediators: LTB4, IL8, TNF (for persistent inflammation), MCP-1, MIP1,B,


GM-CSF (for neutrophil infl.), TGFb, EGF (last 2 for remodeling), substance-p,
VIP (last 2 for vascular changes), complement (neutrophil accumulation).
*Protineases like: elastase, cathepsin-G, and protinease-3

*Notes:
 Normal peripheral bronchial drainage is in left atrium, while central one
is drained in right atrium.

 Bronchial veins are distended in emphysema with more blood return


but with corpulmonale pressure inside SVC increases leading to reversed
blood flow  hypoxic bronchial venous blood (rt. to lt. shunt)  to
pulmonary veins  lt. atrium  aggravating hypoxia.

 Causes of chest pain in COPD:  Chronic cough  muscle strain


 Ruptured bullae  pneumothorax
 Ass. IHD, Pneumonia, infarction

 Causes of airway obstruction in COPD:


- Mucus in lumen

- Thickened bronchial mucus membrane (by hypertrophy of mucus


glands and inflammatory edema).

- Increased bronchial Ms tone (by irritation)

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- Increased collapsibility of peripheral airways (by lost elastic recoil


and cartilages)

- Invagination of soft posterior wall of large bronchi, trachea in


expiration by a steep gradient between extra-bronchial and
intraluminal pressure.

 Causes of Hyperinflated chest in COPD:


- Lost elastic recoil  increased static FRC (it’s the balancing
volume between inward recoil and outward recoil).

- Reflex  patient inspire before normal FRC is reached in attempt


to maintain patency of the narrowed airways  increased
dynamic FRC, RV, TLC and decreased VC.

- Air-trapping (if patency can’t be maintained)  occurs due to lost


elastic recoil  expiratory effort will be active  +ve pressure
increased outside the lung than Intrathoracic pressure 
collapsed bronchioles and alveoli before full expiration is
reached (it’s decreased by the patient by pursed lip breathing to
increase intra-bronchial pressure).

 Causes of P++ in COPD:


- Destruction of alveolar septa with lost capillary bed
- Vasoconstriction due to hypoxia
- Increased alveolar pressure 2ry to airway obstruction

 Causes of RVF in COPD:


- Chronic overload on right ventricle
- Disordered blood gases

 Causes of LVF in COPD:


- Hypoxia  impair myocardium and left ventricular performance
- Bohr’s effect  hypertrophy of rt. ventricle compresses on lt. side
- 2ry polycythemia  overload on lt. ventricle
- Rt. ventricular hypertrophy  increased coronary blood flow
- Increase blood flow in bronchial veins  overload on lt. side
- Co-incident
 Causes of Chronic Cough with Normal Chest X-ray:

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Intrathoracic
- Chronic obstructive pulmonary disease
- Bronchial asthma
- Central bronchial carcinoma
- Endobronchial tuberculosis
- Bronchiectasis
- Left heart failure
- Interstitial lung disease
- Cystic fibrosis

Extrathoracic
- Postnasal drip
- Gastroesophageal reflux
- Drug therapy (e.g., ACE inhibitors)

 Causes of low O2, high CO2 in COPD:


- V/Q mismatch
- Alveolar hypoventilation
- True shunts

-Signs of COPD:
 General:
oPuffiness of lower eyelids (by chronic cough)

oCentral cyanosis

oFlushed face (by polycythemia)

oClubbing (mild)  if inc. suggest carcinoma, bronchiectasis

oHigh intra-jugular pressure  expiratory filling (due to inc.


Intrathoracic pressure) > inspiratory filling (more with heart
failure and constrictive pericarditis).

o Bilateral lower limb edema  due to corpulmonale, CO2 retention


(high HCO3), amyloidosis kidney, hypo-proteinemia (by
expectoration), nutritional.

oPtosed liver or tender liver

oOf hypoxia

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oOf hyper-capnea  warm extremities (VD) except in P++


and low COP they become cold cyanotic
 Increased pulse pressure,
 Impaired drowsiness,
 Flapping tremors,
 Extensor planter response
 Depressed deep reflexes
 Fundus engorged vessels and
papilledema due to increased CSF pressure
 Confusion  coma (CO2 narcosis)
 Disturbed sleep rhythm

 Local:
o Inspection:  Hyperinflated chest  Inc. A-P diameter (barrel)
 Prominent sternal angle
 Horizontal ribs
 Wide sub-costal angle
 Kyphosis
 Hoover’s sign (decrease expansion of lower ribs,
later become paradoxical to pull the low flat diaphragm)
 Trill’s sign
 Short distance between cricothyroid &
supra-sternal notch (normal >3fingers)
 Indrawing of spaces due to low Intrathoracic pr.

o Palpation:  Low TVF all over in emphysema


 Palpable wheezes

oPercussion:  ± hyper-resonance

oAuscultation:  Harsh vesicular breathing


 Expiratory rhonchi
 Inspiratory crepitations

o Heart:  increased S2 (P++)


 Distant heart sounds
 Tricuspid incompetence (functional) with RVF
 S3 gallop on tricuspid area with RVF
-Factors affecting severity of COPD:

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 Severity of symptoms
 Severity of air flow limitation
 Frequency and severity of exacerbations
 Presence of respiratory failure
 Presence of co-morbid conditions
 General health status
 No. of medications needed to manage
 Presence of one or more complications:
o Pulmonary infections

o Corpulmonale  RVF

o LVF

o Pneumothorax (ruptures blebs or bullae)

o Bronchial obstruction  2ry collapse

o Peptic ulcer (20%)

o DVT  PE (by immobilization and polycythemia)

-D.D.:

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-Investigations:
[A] Laboratory investigations:
 Leucocytosis in acute exacerbations
 Polycythemia (HCT > 47% in females, > 52% in males)  degree is
related to amount of carboxy-Hb with smoke
 1-globulin by electrophoresis is dec. in AATD (qualitative test)
 Radial immuno-diffusion and Assessment of trypsin inhibiting
capacity are quantitative tests for AATD (=mg of trypsin
inhibited by ml of serum)  in ZZ (diseased)  <0.4mg/ml
 in MZ (diseased)  0.4-0.8mg/ml

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 in MM (normal)  0.8-1.4mg/ml
(also decreases in BAL with high neutrophil elastase in BAL)

[B] Sputum analysis: (not a routine because organisms are well known)
.Neuraminic acid is increased in purulent sputum

[C] Radiological investigations:


 CXR:
o P/A view: -Increased broncho-vascular markings

- Signs of hyperinflation
 Voluminous lungs
 Hyper-translucency
 Low flat diaphragm
 Transverse ribs
 Ribbon shaped heart
 Posterior portion of 11-12th ribs may be visible
 Bullae or tension cysts as fine hair like margins with
no vascular shadow (with infection they decrease in size
and may disappear)

- Enlarged proximal part of pulmonary artery with


thinned peripheral vascular shadows

- Persistent diffuse irregular shadows (scaring/infection)


- Broncho-pneumonia
- Cardiomegally and dilated proximal pul. Ar (corpul.)
o Lateral view: - Increased A-P diameter

- Increase in normal retro-sternal translucent area


- Increased horizontal distance from posterior surface of
aorta to sternum > 4.5cm below manubrium (N=3cm)

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 Fluoroscopy:  low flat diaphragm and decreased diaphragmatic


motility +/- slight paradoxical movement with inspiration
(due to upward drag of costal margins in inspiration).
 Bronchography:  not used now
 Shows irregular, narrowed, distorted bronchi,
 Pooling of dye to dilated bronchioles with pan-
acinar emphysema

 Apparent diverticulae in large bronchi (due to


entrance of contrast material in mouths of
hypertrophied glands).

 Screening:  Enlarged rt. ventricle and pulmonary Ar.


 Lung field may fail to darken normally on expiration.

 Skull x-ray: (rare) Erosion in lamina dura, floor of pituitary fossa


 Thinning of clinoid processes with high ICT
(due to high CO2)

 CT chest:  if doubting diagnosis or pre-operative

[D] Functional investigations:


 PFT:  VC: N or L, RV: N or L, MBC: L, FEV1: L or N, small AW:
L, DLCo: L or N, Breath condensate: H2O2, NO

 ABG:  hypoxia (<60 mmHg), +/- hypercapnea (>50 mmHg)

 Exercise test (treadmill cycle or 6 mins walk):  for rehabilitation,


 for surgery.
 Respiratory muscle function:  in poor nutrition
 in suspected steroid myopathy
 if dyspnea and hyper-capnea are
disproportionate with respect to FEV1

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[E] ECG:
 Clockwise rotation of the heart (rt. axis deviation, rt. BBB, RS
pattern in chest leads and V5-6, Poor R-wave progression, RS
pattern in AVL with QR pattern in AVF)

 P-pulmonale (leads 2, V1-2)  corpulmonale

 Arrhythmias: atrial and ventricular (mainly PVCs)

[F] Pulmonary vascular pressure and right ventricular function:


By echo (trans-esophageal) and right heart catheterization  for P++

[G] Sleep study:  when suspecting co-existing sleep apnea (overlap S)

-Management of COPD:
[A] Assess and Monitor the disease:  history, C/P, investigations.

[B] Reduce risk factors:


 Infection:  antibiotic therapy (preventive)  it’s not anymore used
this way except when there is an exacerbation indicating an
antibiotic treatment.
 Pollution  adequate ventilation, 1ry or 2ry prevention of
occupation, no vigorous exercise in pollution, if
exacerbations increased  prevent outdoor work.
 Smoking  improves lung function especially in early grades;
cough is improved whatever the grade is.

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o Smoking prevention:  Control policies and programs with clear

consistent, repeated non-smoking messages by:  health care


providers, schools, radio, TV, print media.
 National & local campaigns to decrease
exposure to tobacco smoke in public.
 Physicians and public health officials
should encourage smoke free homes.

o Smoking cessation: (most effective, cost effective way)

Current tobacco use


Yes No

Willing to Quit? (6% success rate) Former user?

Yes No Yes No

Initiate ttt Provide motivation Prevent relapse Encourage


Strategies Intervention
- Ask (users, status of smoking) -- Relevance (reasons to quit)
- Advice (by clear, personalized ways) -Risks (A.S, compl., child eff.)
- Assess (determine willingness) -Rewards (benefits of quit)
- Assist (aids: plans,ttt,suppl.,support) -Roadblocks (withd.S, fear
- Arrange (schedule 4 FU) fail, wt.gain, lack supp., dep.)
-Repetition (prol. remissions)
*Withdrawal symptoms of nicotine: (appear in 1st 8-12 wks of quit,
peak in 48 hours and subside in 6Ms)

-Headache, Anxiety, Mental confusion, Irritation, Restlessness, Lack of


concentration, Tingling in hands,
-Nausea, Cramps, Constipation,
-Craving to smoke, Sweating,
-Chemical dependency (needs certain amount and time),
-Cold symptoms (sore throat, coughing to clear nicotine from lungs),
-Tight Chest (from inc. needs & cough dt return of cilia movement),

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-Anger feeling  depression, Fatigue (as nicotine is stimulatory),


- Weight gain (5-10 pounds), Increased Appetite.

o Counseling:  high cessation rates (5-10%)  problem solving,

skill training, provision of intra ttt support  it needs good


group, good team to handle with skills, information about
quitting smoking.

o Pharmacotherapy: (if counseling is insufficient, quit rates double


with 1st line therapy)

-Nicotine replacement products: (10% success rate)


Forms: Gum (slowly chewed), Inhaler, Nasal spray,
Trans-dermal, Patch (for 24 hrs and some in the
morning only), Sub-lingual tab., Lozenges.

S.Es: irritations, cough (inhaler), sinusitis (nasal spray),


redness, itching (patches).

Contraindications: .Diseases IHD, untreated PU, recent


Stroke, MI, Convulsions, Hyper-tension.
.Adolescents, pregnant, light smokers<10
.Allergic people to patches.

Cautions: given for only 8 weeks with counseling and


behavioral therapy.

-Bupropion, Nortriptylline, Buspirone: increase long term quit


rates  anti-depressants mimic some withdrawal symptoms as
dry mouth, difficulty in sleeping so not to be taken with MAOI.

-Clonidine and Acupuncture: Under trial (20% success rate)

o Hypno-therapy: (success rate 60% in single session)  with no


weight gain

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Definition: Hypnosis is a state of deep relaxation in which the


subconscious mind is extraordinarily receptive to positive
thoughts and suggestions. It is not something a hypnotist does,
but it is something you give to yourself. Through hypnosis,
your behavior can be modified to benefit you.

How done? Relaxation is the first and most important step of


hypnosis. Eyes are closed, pt. breathe deeply at a
diaphragmatic, laggard pace, and be unfettered of any jewelry
or any other accessories that would cause uneasiness. When
he’s relaxed, tension is released in muscles, nerves, and blood
vessels. This also reduces the blood circulation which puts the
body at well-being. Relaxation is the key to overcome a fear,
habit, and many other symptoms.

o Follow UP: within a week of quitting day then after a month (the
more the follow up  the more the cessation rate).

o Harm reduction: (unproved to be beneficial) if unable to quit:

 Partial nicotine replacement,


 Substitute cigarettes for less harmful tobacco products.

*Smoking effects:
-Respiratory system:
a. Nicotine  high alertness, mental concentration (stimulate
synaptic transmission in brain)

b. Inhibits secretion of surfactant  respiratory distress


syndrome

c. Hot air  damage mucosal epithelial lining

d. Irritates lining and increase mucus secretion (thick and


tenacious)

e. Inhibits cilia motility with thickened secretions

f. Inhibits antibody secretions from plasma cells infections

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g. Pulmonary alveolar MQs are loaded with tar  burst in


alveoli  damage alveolar epithelial cells

h. Layer of tar interferes with gas exchange (Hb saturation with


O2 decreases)

i. Increased carboxy-Hb and Met-Hb  decreasing O2 carrying


capacity

j. Carcinogens increase  Bronchogenic carcinoma

k. Goza  increase TB susceptibility

-CVS:  tachycardia, arrhythmias, extrasystoles, IHD, HTN, PVD


(burger’s), atherosclerosis

-GIT:  PU, DU, IBS, abdominal distension, esophageal, gastric


cancer susceptibility.

-Others:  decrease glucose level, tobacco amblyopia, retardation


of fetal growth, urinary bladder and prostatic cancer.

[C] Treatment of Stable COPD: (Long term management)


 Education:  For all stages: advise to reduce risk factors.
 Stages 1, 2: the same + information about nature of
COPD, instructions on how to used inhalers and
methods of ttt, recognition of exacerbations, strategies
to decrease dyspnea.
 Stages 3, 4: the same + information about
complications and O2 therapy.

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 Pharmacological ttt:

*Bronchodilators: Medications that increase the FEV1 or change other spirometric


variables, usually by altering airway smooth muscle tone, since the improvements in
expiratory flow reflect widening of the airways rather than changes in lung elastic recoil.
Such drugs improve emptying of the lungs, tend to reduce dynamic hyperinflation at rest
and during exercise and improve exercise performance rather than predictable
improvement in FEV1 especially in advanced stages.
• Bronchodilator medications are central to symptom management in COPD.
• Inhaled therapy is preferred (anticholinergics reduce rate of exacerbations)
• The choice between B2-agonist, anticholinergic, theophylline (less used due to side
effects), or combination therapy depends on availability and individual response in terms
of symptom relief and side effects.
• Are prescribed on an as-needed or on a regular basis to prevent or reduce symptoms.

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• Long-acting inhaled bronchodilators are more effective and convenient.
• Combining BDs may improve efficacy and decrease the risk of side effects compared to
increasing the dose of a single bronchodilator.

*Steroids: -The effects of oral and inhaled steroids in COPD are much less dramatic than
in BA, & their role in the management of stable COPD is limited to specific indications.
-Based on the lack of evidence of benefit, and the large body of evidence on
side effects, long-term treatment with oral glucocorticosteroids is not recommended in
COPD, they are only used in exacerbations for 7-10 days.

*Others:  Vaccines: .Influenza vaccines can reduce serious illness, pneumonias and
death in COPD patients by about 50%.
.Vaccines containing killed or live, inactivated viruses are
recommended as they are more effective in elderly patients.

 Alpha-1 antitrypsin augmentation therapy: expensive, not easily available


(600mg/d for 3 days) used with danazol.

 Antibiotics: no current evidence that their use, other than for treating
infectious exacerbations of COPD and other bacterial infections, is helpful.

 Mucolytic (mucokinetic, mucoregulator) agents: (ambroxol, erdosteine,


carbocysteine, iodinated glycerol) few patients with viscous sputum may
benefit from mucolytics. (the best is a hot drink in the morning)

 Antioxidants: it was found that no effect of N-acetylcysteine on the


frequency of exacerbations, except in patients not treated with inhaled
steroids.

 Immunoregulators (immunostimulators, immunomodulators): a


decrease in the severity and frequency of exacerbations was detected.

 Antitussives: Cough, although sometimes a troublesome symptom in COPD,


has a significant protective role. Thus the regular use of antitussives is not
recommended in stable COPD.

 Vasodilators: The belief that P++ in COPD is associated with a poorer


prognosis has provoked many attempts to reduce right ventricular afterload,
increase cardiac output, and improve oxygen delivery and tissue oxygenation.
Many agents have been evaluated, including inhaled nitric oxide, but the
results have been uniformly disappointing. In patients with COPD, in whom
hypoxemia is caused primarily by ventilation-perfusion mismatching rather
than by increased intrapulmonary shunt (as in non-cardiogenic pulmonary
edema), inhaled nitric oxide can worsen gas exchange because of altered
hypoxic regulation of ventilation-perfusion balance. Therefore, nitric oxide is
contraindicated in stable COPD.

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 Narcotics (morphine): Oral and parenteral opioids are effective for treating
dyspnea in COPD patients with advanced disease.

 Others: .Nedocromil and leukotriene modifiers aren’t used.


.Anti-TNF-alpha antibody (infliximab) has no evidence of benefit -
and some evidence of harm (malignancy and pneumonia)- when
tested in moderate to severe COPD
.Herbal medicines have no evidence of the effectiveness.
.Alternative healing methods (acupuncture and homeopathy) have
not been adequately tested.

 Respiratory stimulants: (oral medroxy progesterone acetate (lost libido),


almitrine, dopram), they stimulate respiratory chemoreceptors increasing
ventilation so improve V/Q by modifying vasoconstrictive response to hypoxia
decreasing severity of COPD but not frequency of exacerbations.

 Non-pharmacological ttt:
a) Rehabilitation:
o The Cycle of Physical, Social, & Psychosocial Consequences:

o Benefits of Pulmonary Rehabilitation in COPD:

-Improves exercise capacity.


-Reduces the perceived intensity of breathlessness.
-Improves health-related quality of life.
-Reduces the number of hospitalizations & days in the hospital.
-Reduces anxiety and depression associated with COPD.
-Strength & endurance training of the upper limbs improves
arm function.

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-Benefits extend well beyond the immediate period of training.


- Improves survival: rehabilitation increases peak workload by
18%, peak O2 consumption by 11%, and endurance time by
87% of baseline. This translates into a 49 m improvement in
6-minute walking distance.
-Respiratory muscle training is beneficial, especially when
combined with general exercise training.
-Psychosocial intervention is helpful.

o Components of Pulmonary rehabilitation programs:

- Exercise training:
.Exercise tolerance can be assessed by:
 Bicycle ergometry or treadmill exercise with the
measurement of a number of physiological variables,
including maximum oxygen consumption, maximum
heart rate, and maximum work performed (aerobic)

 Self-paced, timed walking less complex test (e.g., 6-


minute walking distance).

. Ranges in frequency from daily to weekly (for > 6wks)


. Duration from 10-45 minutes per session, and in
intensity from 50% peak oxygen consumption (VO2 max) to
maximum tolerated.
.Forms of exercises:  Stretching exercises (Ms Preparation)
 Aerobic exercises (for large Ms, CB4)
 Strengthening exercises (repeat cont.)
 Breathe exercises (increase O2) as:
pursed lip & diaphragmatic breathing.
 Postural drainage after bronchodilator.
.Added approaches: use of oxygen during exercise, exercising

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while breathing heliox gas mixtures, unloading the ventilatory


muscles while exercising.
-Nutrition counseling:
.Nutritional state is an important determinant of symptoms,
disability, and prognosis in COPD; both overweight and
underweight can be a problem.

.Specific nutritional supplements (as creatine) may improve


body composition, Anabolic steroids in COPD patients with
weight loss increase body weight and lean body mass but have
little or no effect on exercise capacity.

-Education: must be included but effect isn’t clear yet.


-Psychological support
-Social support

o Assessment and Follow up:

- Detailed history and physical examination.

- Measurement of spirometry before and after a BD drug.

- Assessment of exercise capacity.

- Measurement of health status and impact of breathlessness.

- Assessment of inspiratory and expiratory muscle strength and


lower limb strength (e.g., quadriceps) in patients who suffer
from muscle wasting.

*The first 2 assessments are important for establishing entry


suitability and baseline status but are not used in outcome
assessment. Last 3 assessments are baseline and outcome measures

b) O2 therapy:
o Aim:

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- Increase PO2 to 60 mmHg at sea level and rest, and/or SaO2 at


least 90%  preserve vital organ function by ensuring adequate
delivery of oxygen.
- The long-term administration of oxygen (LTOT) (> 15
hours per day):  Increase survival.

 Have a beneficial impact on hemodynamics (prevents


progression of P++), hematologic characteristics, exercise
capacity, lung mechanics, and mental state.

o Used in:

- PO2 < 55 mm Hg or SaO2 < 88%, +/- hypercapnia.

- PO2 55-60 mm Hg, or SaO2 of 88%, if there is evidence of P+


+,peripheral edema suggesting congestive cardiac failure, or
polycythemia (hematocrit > 55%).

- Exercise induced hypoxia: improve dyspnea, exercise


intolerance at sub-maximal work load (determined by walk/
work).

- Air travel hypoxia: to give 1.2 liters more to keep PO2 >70

- Sleep hypoxia: to give 1 liter more than daily prescription.

o Advantages:

- Reserve 2ry polycythemia


- Increase body weight
- Alleviate RVF (decrease pulmonary vascular resistance)
- Increase neuropsychological function, improve exercise
performance and action.

c) Ventilatory support:
NIMV (NPV/NIPPV) IMV
Indications -Moderate to severe dyspnea -Severe dyspnea with accessory
with use of accessory Ms & Ms use & paradoxical

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abdominal motion.
-Severe acidosis (PH < 7.30,
PCO2 > 60)
-RR > 35 b/m
paradoxical abdominal -PO2 < 40, PO2/FIO2 <200
motion. -Respiratory arrest
-Moderate to severe acidosis -NIPPV failure or contraindic.
(PH> 7.30, PCO2 >45) -Cardiovascular complication.
-RR >25 b/m -Somnolence, impaired mental
status.
-Metabolic abnormality, sepsis,
pneumonia, PE, barotrauma,
massive pleural effusion.
-Long-term NIPPV can’t be recommended for the routine ttt of
patients with chronic RF due to COPD, the combination of
NIPPV with LTOT in some patients, particularly in those with
Contra-ind. daytime hypercapnia.
(For non- -Resp. arrest, CV instability (MI, arrhythmia, hypotension).
invasive) -High aspiration risk, somnolence, impaired mental status.
-Recent facial or GE surgery.
-Cranio-facial trauma, fixed nasopharyngeal abnormality.
-Burns, extreme obesity

d) Surgical intervention:
o Bullectomy: when bullae >50% of hemi thorax causing
displacement of the adjacent lung.

o Lung volume reduction surgery: when .FEV1 < 35%,


.PCO2 >45 mmHg
.RV > 200
.UL emphysema in CT
o Lung transplantation: when .FEV1 < 35%
.PO2 < 55-60 mmHg
.PCO2 > 50 mmHg
.2ry P++

[D] Treatment of Acute exacerbations: (Short term management)


 Definition of exacerbation:

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It’s an event in the natural course of the disease characterized by a


change in the patient’s baseline dyspnea, cough, and/or sputum that is
beyond normal day-to-day variations, is acute in onset, and may warrant a
change in regular medication in a patient with underlying COPD.

 Causes of exacerbation:
o Bacterial:  (more than 50%) H. influenza, Strept. Pneumonae,
Moraxella Catarrhalis, Mycoplasma Pneumonae.

o Viral:  (few) RSV, Rhinovirus, Influenza, Para influenza.

o Physical and chemical factors  2ry bacterial infection.

 Diagnosis and assessment of severity:


o Medical History:

- Severity of FEV1
- Duration of worsening or new symptoms

- Number of previous episodes (exacerbat./ hospitalizations)

- Comordibities

- Present treatment regimen

o Signs of Severity:

- Use of accessory respiratory muscles

- Paradoxical chest wall movements

- Worsening or new onset central cyanosis

- Development of peripheral edema

- Hemodynamic instability

- Signs of right heart failure

- Reduced alertness

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o PFT:

- PEF < 100 L/min.

- FEV1 < 1L (indicates severe exacerbation except if there’s


already a chronic severe airflow limitation).

o ABG:

- PO2 < 60, PCO2 > 50, SO2 < 90  life threatening if:
- PO2 < 50, PCO2 > 70, PH < 7.30

o Other laboratory: (can occur with associated co-morbidities)

- Hematocrit > 55%


- Leucocytosis (not very informative)
- Hyponatermia
- Hypokalemia
- Poor glucose control
- Metabolic acid-base disorder

 Home management:
Initiate or increase BD + Antibiotic  re-assess in hrs

resolution or improvement No resolution or improve.


continue step down manag. when possible + add oral steroids then
re-assess in hrs  if worsens
review long term management. Refer to hospital

 Hospital management:
The risk of dying from an exacerbation of COPD is closely related
to the development of respiratory acidosis, the presence of significant
comorbidities, and the need for ventilatory support.

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Indications of Ward Indications of ICU


• Marked increase in intensity of • Severe dyspnea that responds
symptoms, such as sudden inadequately to initial emergency ttt.
development of resting dyspnea. • Changes in mental status
• Severe underlying COPD. (confusion, lethargy, and coma).
• Onset of new physical signs (e.g., • Persistent or worsening hypoxemia
cyanosis, peripheral edema). (PaO2 < 5.3 kPa, 40 mmHg), and/or
• Failure of exacerbation to respond severe/worsening hypercapnia
to initial medical management. (PaCO2 > 8.0 kPa, 60 mmHg),
• Significant comorbidities. and/or severe/worsening
• Frequent exacerbations. respiratory acidosis (pH < 7.25)
• Newly occurring arrhythmias. despite supplemental oxygen and
• Diagnostic uncertainty. noninvasive ventilation (NIV).
• Older age. • Need for invasive mechanical
• Insufficient home support. ventilation (IMV).
• Hemodynamic instability (need for
vasopressors).

 Management of Severe but Not Life-Threatening Exacerbations of


COPD in the Emergency Department or the Hospital
 Assess severity of symptoms, blood gases, chest X-ray
 Administer controlled O2 therapy (it’s the cornerstone in
exacerbation management) and repeat ABG after 30-60 mins.

 Bronchodilators:
– Increase doses and/or frequency
– Combine B2-agonists and anticholinergics
– Use spacers or air-driven nebulizers
– Consider adding intravenous mehylxanthines, if needed
 Add oral or intravenous glucocorticosteroids
 Consider antibiotics (oral or IV) when signs of bacterial infection
 Consider noninvasive mechanical ventilation
 At all times:
– Monitor fluid balance and nutrition

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– Consider subcutaneous heparin


– Identify & treat associated conditions (HF, arrhythmias)
– Closely monitor condition of the patient

 Antibiotic ttt and stratification of COPD patients according:


Group A Group B Group C
Moderate Severe
Grade Mild exacerbation
exacerbation exacerbation
No risk Fs for poor -presence of For Pseud.
outcome comorbid diseases infection:
-severe COPD -recent hospit.
-frequent -frequent
exacerbations administ. of
(>3 /yr) antibiotics (4
-antimicrobial use courses in the last
within last 3 yr)
Risk Fs
months -severe COPD
AIE.
-isolation of
pseud. in a
previous exac. or
colonization
during a stable
period.
-H. influenza The same + Group B +
-S. Pneumonae resistant organisms pseudomonas
-M. catarrhalis (B-lactamase
-Chlamydia Pn. producing
Organisms -Viruses ,penicillin-resist.
S.pn.)
Enterobacteriaceae
(K.pn., E. coli,
Proteus, Enterobacter)
TTT .If 1 cardinal -B-lactam/B-lactamase -Fluoro-quinolones
symptom  No inhibitors. (Ciprofloxacin,
- Cephalosporin (2nd, Levofloxacin -
.If more:
3rd) high dose 750mg)

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-B-lactam (Penicillin,
Ampicillin/Amoxicillin)
-Tetracycline OR OR
-Trimethoprim/
Sulfamethoxazole -Fluoro-quinolones
OR (alternative) (Gemifloxacin, -B-lactam with
-B-lactam/B-lactamase Levofloxacin, P.aeruginosa
inhib. (Co-amoxiclav) Moxifloxacin) activity
-New Macrolides
-Cephalosporin(2nd, 3rd)
-Ketolide
(Telithromycin)
*Antibiotic must be given with BDs, and steroids.
*Cardinal symptoms are increased dyspnea, sputum volume, and
sputum purulence.
*Diuretic therapy for corpulmonale can worsen RF due to metabolic
alkalosis which depresses RC (no effect of digitalis in RVF).

 Discharge from hospital:


- Inhaled B2-agonist therapy is required not > every 4 hrs.
- Patient, if previously ambulatory, is able to walk across room.
- Patient is able to eat & sleep w/o frequent awakening by dyspnea.
- Patient has been clinically stable for 12-24 hrs.
- Arterial blood gases have been stable for 12-24 hrs.
- Patient fully understands correct use of medications.
- Follow-up and home care arrangements have been completed
(e.g., visiting nurse, oxygen delivery, meal provisions).

- Patient, family, and physician are confident patient can manage


successfully at home.

 Items to Assess at Follow-Up visit 4-6 Weeks after Discharge:


- Ability to cope in usual environment
- Measurement of FEV1
- Reassessment of inhaler technique
- Understanding of recommended treatment regimen

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- Need for LTOT +/- home nebulizer (for patients with Stage IV)

-Some important topics related to COPD:


[A] Infantile Lobar emphysema:
 Definition: It’s an obstructive distension of one lobe in an infant after
giving rise to severe dyspnea and necessitating surgical
removal.

 Etiology: Male > Female + congenital heart disease in 50% of cases


 Atresia of bronchial cartilage causing valve obstruction
 Obstruction by: inflammation, mucus, or flap of M.M.
 Gross increase in number of alveoli +/- emphysema
 Unknown sometimes

 Pathology: Site: Left UL and middle lobe (most common)


Shape: Gross distension of lobe with thin atrophic alveoli
Surround: Collapsed lung
Blood supply: its artery may be small

 C/P: Begin 1st 2Ms of life  dyspnea (main manifestation)


 Cough, stridor sometimes
 Bulge of chest wall
 Shift of mediastinum to other side

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 CXR:  Translucent left upper zone, hypoplastic (aerated with


collateral ventilation)

 Blind bronchus at hilum, may be patent peripherally (in


atresia)

 Ttt: Surgery only if acute case, as the cause of obstruction is rarely


identified (not done when asymptomatic)
[B] Mc Leod’s Syndrome
“Unilateral emphysema of a lung or lobe”:

 Cause: due to localized bronchiolitis or bronchitis (between birth- >8yrs


when the alveoli reach the adult size)

 Pathology: Size: normal or subnormal


Shape: pan-acinar emphysema + evidence of fewer alveoli
than normal

Site: patchy distributed obstruction, obliteration in small


bronchi, bronchioles

Pul. Ar.: .less hypoplastic than might be expected from the


angiogram, suggesting that the later appearance
may be functional and 2ry to local hypoxia.

.hypertrophy on pulmonary Ar. Walls with


decreased number of branches.

 Patho-physiology: .Airway obstruction  increased RV


.Low O2 uptake in affected lung (5-10%) of total of
both lungs

.Low V/Q (decreased both ventilation/perfusion)

 C/P:  Mostly asymptomatic.


 Co-incidental chronic bronchitis in older patients

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 2ry infection then bronchiectasis in larger bronchi

 Investigations:  CXR: unilateral hypertranslucency with decreased


shadows of BVs in hilum, lungs + shifted mediastinum to the
opposite side.

 Screening: air trapping with deviation of mediastinum

 Angiography: pul. Ar. Small with poor peripheral filling

 Bronchography: irregular dilatation of bronchi to 5th


order with failure to fill peripheral airways (characteristic to
bronchial obstruction) +/- features of bronchiectasis

 D.D: (X-ray picture)


 Unilateral changed in soft tissue cover (mastectomy, congenital
absence of pectoralis muscle)  differentiate with examination.

 Compensatory emphysema (collapsed lung seen, vessels increased


extending to the periphery seen in x-ray).

 Local accentuation of generalized emphysema (hilar Vs prominent)


 Congenital pulm. atresia on one side (no evidence of air trapping)
 Hypoplasia of one lung (small shrunken w/o hypertranslucency)

[C] Para-septal emphysema:


Site: around alveolar areas which lie against connective tissue septa,
especially at sharp edges of the lung such as the anterior edge of
upper and middle lobe, lingular and diaphragmatic rim.

C/P: asymptomatic or bulla (can rupture forming spontaneous


pneumothorax, or enlarge forming compression to the
neighboring lung and impaired functions).

[D] Bullous Lung diseases:

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 Definition:
It’s a large air containing space within the lung parenchyma
resulting from destruction, dilatation and confluence of airspaces distal to
terminal bronchioles (>1cm)

 Pathology:
- With emphysema  pan-acinar (1ry or with chronic bronchitis)
 para-septal (acinar)
- Infantile lobar emphysema
- Scar emphysema (traction on normal alveoli)
- Drug IV use
- Vanishing lung syndrome or 1ry emphysema (in end stages of
fibrotic sarcoid, pneumoconiosis, EAA)  die of RF without
cough or infections.

*Bullous lung disease: multiple bullae in otherwise normal lungs (its


pathogenesis is distinct from that of COPD complicated by bullae)

 Pathogenesis:  exaggerations of the mechanisms causing emphysema


 scar at the neck of type 1 bullae  obliteration of
bronchus and inflation of bulla by collateral ventilation
(ball-valve)

 C/P:  Asymptomatic
 Progressive dyspnea  can be marked if (spontaneous
pneumothorax, or sudden increase in size with air trapping)

 Chest pain, hemoptysis (BV rupture), cancer (on scar or due to


presence of carcinogens in the poorly ventilated air traps)

 Signs of underlying disease

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 Fatigue and increased cough and sputum when infected bulla

 Recurrence occur in 50% of cases

 D.D.:
Bulla Bleb Cyst
Epithelium lined
Accumulation of air
cavities that
Definition See before between layers of
resemble bullae
visceral pleura
radiologically
Lung parenchyma
Site With 2ry lobule In visceral pleura
or mediastinum
Size 1 cm 1-2 cm 2-10 cm
Connective tissue Elastic lamina of
Lining Epithelium
septa pleura
Spontaneous Respiratory
Association 2ry Pneumothorax
pneumothorax infections

 Reid classification:
- Type 1 (narrow necked): with pedicle attached to the lung and
protruding outwards.
- Type 2 (superficial broad based): pleura limiting its outside
lining and emphysematous lung lining from inside.
- Type 3 (deep broad based): as type 2 but with greater depth can
extend to hilum (any lobe can be affected).

 Investigations:
- Laboratory: leucocytosis (rare)

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- Microbiological: Gram stain  mixed flora w/o predicted org.


- Functional: obstructed pattern dt COPD & if patient is dyspneic
- Radiological:
.CXR:  Depends on size, degree of obscure by lung (some
are only seen by lateral view film)

 Hypertranslucent areas  well marked in type 1


 seen as fine lines with thin
line of compressed lung in type 2, 3.

 Marked compression can be seen, rarely displace


mediastinum.

 Sometimes it’s extended across the retro-sternal space


 convex line in the opposite lung.

 Can see air fluid level with infection that may


disappear and shrink after that because of obliteration
to the bronchial connections.

.CT: shows how much lung involved and before surgery.

.Fluoroscopy: large bullae in expiration that may show


deviation of mediastinum to the opposite side due to air
trapping.

.Bronchogram: define the bulla more precisely to see how


much lung involvement.

 Ttt:  Surgery
- Excision, Plication, Lung Resection  if large and
symptomatizing  show improvement of FEV1 from 50-200%

- Decompression (Mondali procedure)  if unfit due to severe ling


disease (small segment of rib resection and suction by cannula then
left inside the bullous space  shrinkage and obliteration in
weeks.

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