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Pathophysiology

COPD is a combination of chronic airway inflammation and remodeling


(reorganization of tissue during healing) that results in airway narrowing,
parenchymal destruction, and pulmonary vascular thickening. Chronic
inflammation, characterized by an increase in neutrophils, macrophages,
and T lymphocytes, damages the endothelial lining of the airways. Airway
inflammation is made worse by an imbalance of proteases/antiproteases
and oxidants/antioxidants in patients with COPD.5 Airway damage results
in airway repair, leading to airway remodeling. These airway changes
appear to be most pronounced in the smaller peripheral airways
(bronchioles).5 The glands and goblet cells within the bronchial walls
hypertrophy producing excessive secretions, which either partially or
completely obstruct the airways. Decreases in ciliary function and
alterations in physiochemical characteristics of bronchial secretions
impair airway clearance and contribute to airway obstruction. Damaged
and inflamed mucosa shows an increased sensitivity of irritant receptors
within the bronchial walls, which in turn cause bronchial hyperreactivity.
During normal inspiration, the lungs and the airways are pulled open,
increasing the diameter of the airway lumen.
During normal exhalation, as the thorax returns to its resting position, the
airways decrease in size. In COPD, during inspiration, the airways are
pulled open wide by thoracic expansion, allowing air to enter. During
exhalation, the airways, already narrowed by inflammation, remodeling,
and excessive secretions, are prematurely closed, trapping air in the
distal airways and airspaces. This air trapping causes hyperinflation,
which is defined as an abnormal increase in the amount of air within the
lung tissue at the end of a tidal exhalation (increased FRC).
The most common parenchymal changes found in COPD are dilation and
destruction of the airspaces, which is thought to be due to an imbalance
of proteases and antiproteases in the lung.5 This change results in loss of
the normal elastic recoil properties of the lung tissue. The pulmonary
vasculature is also altered early in the development of COPD. Endothelial
changes result in thickening of the vessel walls. In advanced stages of the
disease, there is destruction of the pulmonary capillary bed.5
Ventilation in the alveoli and perfusion in the capillary membrane are no
longer matched. This results in hypoxemia, a condition in which a

decreased amount of oxygen is carried by the arterial blood to the


tissues. As the disease progresses and more areas of the lungs become
involved, hypoxemia will worsen and hypercapnea, a condition in which
there is an increased amount of carbon dioxide within the arterial blood,
will develop. Increased pulmonary vascular resistance secondary to
capillary wall damage and reflex vasoconstriction in the presence of
hypoxemia results in right ventricular hypertrophy, termed cor pulmonale.
Polycythemia, an increase in the amount of circulating red blood cells, is
another complication of advanced COPD.

Clinical Presentation
Patients with COPD will usually present with a history of cigarette smoking and
symptoms of chronic cough, expectoration, and exertional dyspnea. The intensity of
each symptom varies from patient to patient. Cough and expectoration appear
slowly and insidiously. Dyspnea is first evidenced during exertion. As the disease
progresses, symptoms worsen. Dyspnea occurs at progressively lower activity
levels. Severely involved patients may feel dyspneic even at rest. On physical
examination, the thorax appears enlarged owing to loss of lung elastic recoil and
hyperinflation. The anterior-posterior diameter of the chest increases and a dorsal
kyphosis results. These anatomical changes give the patient a barrel-chest
appearance (Fig. 12.4).
As the resting position of the thorax is now held in a more inspiratory mode,
the available range of thoracic motion is limited, that is, decreased thoracic
excursion. There are morphologic changes to the ventilatory muscles due to a
greater demand, both in frequency and in power needed for this altered thorax. The
muscles of ventilation hypertrophy as a result. Figure 12.5 shows many of the
accessory muscles of ventilation that may be recruited for breathing. In severe
disease, these muscles are recruited even at rest to aid in the work of breathing.
The lengthtension relationship of muscles of ventilation is altered as the thorax
increases in size with chronic hyperinflation. There are changes in the alignment of
fibers, especially the fibers of the diaphragm, with hyperinflation. The diaphragm
becomes flatter, or less domed. In severe disease, the diaphragm fiber alignment
may become more horizontal than vertical, resulting in an inward motion of the
lower ribs during a diaphragm muscle contraction of inhalation (Fig. 12.6).
Breath sounds and heart sounds may be distant and difficult to hear. Partially
obstructed bronchi and bronchioles may result in an expiratory wheeze, a musical,
whistling sound. Crackles, an intermittent bubbling or popping sound, may also be

present from secretions in the airways. Hypertrophy of accessory muscles of


ventilation, pursed-lip breathing, cyanosis, and digital clubbing may all be present in
the advanced stages of COPD. (See Examination in section titled Physical Therapy
Management for clarification of terms.)
Significant and progressive airway limitation is reflected in altered pulmonary
function tests. Lung volumes and capacities, especially RV and FRC, are increased
from the normal value due to air trapping. Figure 12.7 shows the changes in lung
volumes and capacities that occur in obstructive pulmonary disease.
Expiratory flow rates, especially FEV1, are decreased. The ratio of FEV1 to
FVC is also decreased (less than 70%).5 These changes in pulmonary function do
not show a major reversibility in response to pharmacological agents. Arterial blood
gas analyses may reflect hypoxemia (decreased oxygen in the arterial blood) in the
early stages of COPD. Hypercapnea (increased carbon dioxide in the arterial blood)
appears as the disease progresses. With disease progression, chest radiographs
show several characteristic findings. These include depressed and flattened
hemidiaphragms; alteration in pulmonary vascular markings; hyperinflation of the
thorax, evidenced by an increased anterior-posterior diameter of the chest; and an
increase in the size of the retrosternal airspace, hyperlucency reflecting a decreased
tissue density, elongation of the heart, and right ventricular hypertrophy.
The inflammatory reaction in the airways of patients with COPD can also
affect other organ systems.10 COPD is, therefore, not only a pulmonary disorder,
but also has extrapulmonary (i.e., systemic) effects, including changes to skeletal
muscle mass and function, cardiovascular disease, osteoporosis, and depression.

Asthma
Asthma is a common chronic pulmonary disease, affecting 300 million people
worldwide.16 The disease is characterized by chronic airway inflammation
associated with airway hyperresponsiveness (hyperreactivity) resulting in
bronchospasm. Wheezing, breathlessness, and coughing with sputum production
that is at least partially reversible in nature are characteristic symptoms of asthma.
Asthma exacerbations may improve spontaneously or with medical intervention and
are interspersed with symptom-free intervals.
Diagnosis
The diagnosis of asthma is clinically based on a history of episodic wheezing,
shortness of breath (SOB), tightness in the chest, and/or coughing, which may be
worse at night in the absence of any other obvious cause. The FEV1 during
exacerbations will be less than 80% of the predicted value. With the use of a rescue
drug (used to quickly relieve acute symptoms, e.g., inhaled short-acting beta-2

agonist), an improvement of at least 12% (or 200 mL) in FEV1 indicates reversibility
of the airway limitation consistent with a diagnosis of asthma. An improvement of
PEF of 60 L/min (or greater than 20%) following the use of a beta-2 agonist would
also suggest the diagnosis of asthma.
Etiology
The etiology of asthma is not completely understood. Historically, two types of
asthma have been described. Allergic (or extrinsic) asthma has an immunologic
(immunoglobulin E [IgE]mediated) response to certain environmental triggers (dust
mites, pollen, mold, animal dander). The resulting eosinophilic inflammatory
response (an increased number of eosinophils found in the airway mucosa)
produces the common symptoms and pathophysiological findings of asthma. Atopy,
or allergic sensitivity, is the strongest factor for the development of allergic asthma.
Nonallergic (or intrinsic) asthma is a less common form of asthma. There are no
clinical findings of atopy in nonallergic asthma; however, an inflammatory response
does result from exposure to an irritant such as smoke, fumes, infections, or cold air.
Literature in asthma has begun to consider that the two types of asthma are not all
that different: one has a known and widespread allergic response (extrinsic)
whereas the other has a more local inflammatory response (intrinsic).18 The Global
Initiative for Asthma (GINA) does not differentiate allergic from nonallergic asthma
in its guide to management and prevention.16 Viral infections have been suggested
to play a role in both the development and exacerbation of asthma.19 Symptoms of
asthma may begin at any age.
Pathophysiology
The major physiological manifestation of asthma is narrowing of the airways in
response to a trigger. The airway narrowing occurs as a result of eosinophilic
inflammation of the bronchial mucosa, bronchospasm, and increased bronchial
secretions. The narrowed airways increase the resistance to airflow and cause air
trapping, leading to hyperinflation. These narrowed airways provide an abnormal
distribution of ventilation to the alveoli. Even during periods of remission, some
degree of airway inflammation is present (Fig. 12.8).

Clinical Presentation

The clinical symptoms of asthma during an exacerbation may include cough,


dyspnea on exertion or at rest, and wheezing. The chest is usually held in an
expanded position, indicating that hyperinflation of the lungs has occurred.
Accessory muscles of ventilation may be used for breathing, even at rest.
Intercostal, supraclavicular, and substernal retractions (visible inward motion of the
soft tissue) may be present on inspiration. While expiratory wheezing is
characteristic of asthma, crackles may also be present. With severe airway
obstruction, breath sounds may be markedly decreased owing to poor air
movement and wheezing may be present not only during exhalation, but may also
become present on inspiration.
Chest radiographs taken during an asthmatic exacerbation usually
demonstrate hyperinflation, as evidenced by an increase in the anterior-posterior
diameter of the chest and hyperlucency of the lung fields. Less commonly, chest
radiographs may reveal areas of infiltrate or atelectasis from the bronchial
obstruction. Chest radiographs may be read as normal between asthmatic
exacerbations.
The most consistent change during an exacerbation of asthma is decreased
expiratory flow rates, both PEF and FEV1. RV and FRC are increased because of air
trapping at the expense of VC and IRV, which are reduced. The reversibility of these
pulmonary function test abnormalities is characteristic of asthma. During remission,
the patient with asthma may have normal or near-normal pulmonary function tests.
The most common arterial blood gas finding during an asthmatic
exacerbation is mild to moderate hypoxemia. Usually some degree of hypocapnea is
present secondary to an increased minute ventilation. With severe attacks,
hypoxemia will be more pronounced and hypercapnea may occur, indicating that
the patient is likely experiencing fatigue and respiratory failure may follow.

Clinical Course By the time adulthood is reached, many children with asthma
no longer have symptoms of the disease.19-21 When the onset of asthma
symptoms begins later in life, the clinical course is usually more progressive,
showing changes in pulmonary function tests even during periods of remission.
Airway remodeling in response to the chronic airway inflammation is thought to be
responsible for the progressive nature of the disease.

Cystic Fibrosis Cystic fibrosis (CF)


is a chronic disease that affects the excretory glands of the body. Secretions
made by these glands are thicker, more viscous than usual, and can affect a
number of systems of the body: pulmonary, pancreatic, hepatic, sinus, and

reproductive. Dysfunction of the pulmonary system is the most common cause of


morbidity and mortality in patients with CF. Thickened pulmonary secretions narrow
or obstruct airways leading to hyperinflation, infection, and tissue destruction. Other
presentations may occur due to the effect of this disease on other organ systems
such as failure to thrive, diabetes, sinusitis, biliary disorders, and infertility.
Etiology
CF is a genetic disease transmitted by an autosomal recessive trait (Fig. 12.9). The
incidence of disease in children is approximately 1 in 3,700 live births in the United
States.22 Caucasians make up the majority of all cases of CF in the United States.
CF is less common in the Hispanic population (white and black) and is rare in the
African American and native American populations. 22 The CF gene (cystic fibrosis
transmembrane conductance regulator [CFTR]) has been identified on the long arm
of chromosome 7. The CFTR functions to transport electrolytes and water in and out
of the epithelial cells of many organs in the body, including lungs, pancreas, and
digestive and reproductive tracts. Defective transport of sodium, potassium, and
water leaves the mucus made by excretory glands thickened and difficult to move,
and can often obstruct the lumen of its excretory gland. Over 1,400 mutations of
this gene have been described thus far.
Pathophysiology
The chronic pulmonary component of CF is related to the abnormally viscous
mucus secreted in the tracheobronchial tree. The altered secretions, resulting in
airway obstruction and hyperinflation, impair the function of the mucociliary
transport system. Exaggerated and sustained neutrophilic airway inflammation in
response to infection is also a feature of this disease.24 Partial or complete
obstruction of the airways reduces ventilation to the alveolar units. Ventilation and
perfusion within the lungs are not matched. Fibrotic changes are ultimately found in
the lung parenchyma.
Diagnosis
The diagnosis of CF may be suspected in patients who present with a positive family
history of the disease, in patients with recurrent respiratory infections from
Staphylococcus aureus and/or Pseudomonas aeruginosa, or with a diagnosis of
malnutrition and/or failure to thrive. A chloride concentration of greater than or
equal to 60 mEq/L found in the sweat of children is a positive test for the diagnosis
of CF. Genotyping for the most common CFTR mutations can also be done, but is
usually reserved for patients with borderline sweat chloride test results.
Clinical Presentation
The clinical presentation of CF can be related to any number of involved systems.
Failure to thrive due to gastrointestinal dysfunction, diabetes due to pancreatic

dysfunction, or frequent respiratory infections and chronic cough from pulmonary


dysfunction are all possible presentations of the disease. The severity of the
disease, while quite variable, has been linked to the classification of the CFTR
mutation.25 With pulmonary involvement, a patient presents with thick bronchial
secretions that may be difficult to clear. With advancing disease, the chest wall will
become barreled with an increased anterior-posterior (AP) diameter and an
increased dorsal kyphosis due to loss of elastic recoil of the underlying lungs and
hyperinflation. There is a resultant decrease in thoracic excursion. Breath sounds
may be decreased with adventitious sounds of crackles and wheezes. Hypertrophy
of accessory muscles of ventilation, pursed-lip breathing, cyanosis, and digital
clubbing may all be present. Pulmonary function studies show obstructive
impairments including decreased FEV1, decreased PEF, decreased FVC, increased
RV, and increased FRC. The abnormal ventilationperfusion relationship within the
lungs results in hypoxemia and hypercapnea, as shown by arterial blood gas
analysis. As the disease progresses, destruction of the alveolar capillary network
causes pulmonary hypertension and cor pulmonale. In advanced disease, chest
radiographs show diffuse hyperinflation, increased lung marking, and atelectasis.
Course and Prognosis
Seventy percent of new cases of CF are diagnosed when the child is less than 1
year of age, likely due to mandatory infant testing for CF within the United States.
Life expectancy continues to increase owing to advances in early diagnosis and
improved medical management. Although some patients unfortunately die in early
childhood, 45% of all patients diagnosed with CF are currently older than 18 years
of age.23 The predicted mean survival age of patients with CF was 37.4 years in
2008, a remarkable improvement from a mean survival age of 16 years in 1970.22
Respiratory failure is the most frequent cause of death in patients with CF.
Therefore, treatment of the pulmonary dysfunction including removal of the
abnormally thick secretions and prompt treatment of pulmonary infections is key to
the management of CF. Gastrointestinal dysfunction from CF can be aided by proper
diet, vitamin supplements, and replacement of pancreatic enzymes. Habitual
exercise has been linked to higher aerobic capacity, increased quality of life, and
improved survival.26 Nutritional status is also a powerful predictor of prognosis