Atherosclerosis is triggered by trauma to the intima of the arterial wall. The trauma may be related to various primary cardiac risk factors, such as high blood pressure and cigarette smoking. Oxidative stress has been identified as the common denominator for atherogenesis, acute myocardial infarction (MI), and heart failure.¹³ Healthy endothelium is central to optimal vascular control. High blood pressure has been identified as a trauma inducer because increased pressure and turbulence can damage the endothelial cells of the intima of the blood vessel wall, thus exposing the media to the circulation. The media, which consists primarily of smooth muscle, is thought to be the origin of the atherosclerotic lesion.

Cigarette smoking has also been identified as a potential inducer of trauma in the blood vessel wall. The hypothesized mode of injury appears to be different from that observed with increased blood pressure. Cigarette smoke is high in carbon monoxide and hydrocarbons that are carried by the red blood cells and the plasma. The hydrocarbons and carbon monoxide are thought to bind to the endothelial cells, causing damage to and possibly death of these cells.

Diabetes is another risk factor for cardiovascular disease of the myocardium and of the peripheral arteries.¹⁴ The reduced contractility of the heart in people with diabetes is attributed to reduced calcium handling in the sarcoplasmic reticulum of muscle.

Once the media is exposed to the circulation, the process of atherosclerosis is initiated and this predisposes an individual to thromboembolic events, in even mild cases. Platelets aggregate at the injury site and release substances that induce endothelial and smooth muscle cell replication. It is at this site that fatty streaks and fibrous plaques develop. The cause of fatty-streak development is the deposition of low-density lipoproteins (LDLs) into the smooth muscle of the media. Why this occurs is unknown, but it appears to be related to smooth muscle cell proliferation and perhaps to increased energy demands. The initial fatty streaks are generally raised only slightly and do not impede circulation. When a fibrous plaque develops, however, impingement on the vessel lumen occurs. The plaque is relatively hard and consists of connective scar-like tissue, smooth muscle, and fat. Finally, the plaque may undergo calcification or may lead to hemorrhaging if the vessel wall necroses. The result is decreased blood flow (ischemia) and oxygenation (hypoxia) or complete lack of blood flow and oxygen (anoxia) to the target organ.

Atherothrombosis is a generalized and diffuse progressive process affecting multiple vascular beds.15,16 The clinical consequences include the acute coronary syndromes, ischemic stroke, and peripheral arterial disease. Thus these conditions can be viewed as diverse manifestations of a common underlying pathology. The time course of these conditions is unpredictable; yet they can be life-threatening.

Thyroid is an important regulator of cardiac function and cardiovascular hemodynamics.¹⁷ The effects of the physiologically active form of thyroid hormone triiodothyronine (T₃) on the systemic vasculature include relaxation of the vascular smooth muscle, hence reduced resistance and diastolic blood pressure. In hypothyroidism, cardiac contractility and cardiac output are decreased and systemic vascular resistance is increased, whereas the opposite occurs in hyperthyroidism. Cardiac dysfunction is associated with low levels of T₃.

Because of the current appreciation and understanding of the involvement of inflammation and endothelial injury in cardiovascular dysfunction, endothelial function biomarkers have been proposed as a sensitive means of evaluating cardiovascular disease.18,19

Angina Pectoris

Angina pectoris is defined as chest pain that is related to ischemia of the myocardium. Ischemic pain, however, may be referred to the left shoulder, neck, jaw, or between the shoulder blades. In fact, pain anywhere above the umbilicus could be related to coronary ischemia. Angina can be classified as stable, unstable, or variant. People with chest pain but normal coronary arteries on angiography tend to be women, and this presentation is not as benign as previously believed.³⁰ With the advent of the ability to assess endothelial function, those at risk may be more readily identified and managed.

Obstructive Sleep Apnea Syndrome

Obstructive sleep apnea (OSA) has a greater incidence in individuals with atherosclerosis, cardiac dysrhythmias, and hypertension than in those without.³⁴ This has been explained in part by the presence of proinflammatory and prothrombotic factors.³⁵ OSA is characterized by the repetitive closing and opening of the posterior pharynx that are synchronized with breathing while sleeping, usually when recumbent. Apneic periods and arterial desaturation are also common to the syndrome. Additional pathologies common to OSA and atherosclerosis include endothelial dysfunction, increased C-reactive protein, fibrinogen, reduced fibrinolytic activities, and increased platelet activity and aggregation. OSA is now considered a risk factor for cardiovascular disease. The complications of sleep apnea syndrome are exacerbated by autonomic dysfunction as well. Sleep apnea often coexists undiagnosed in people with cardiovascular disease, activates mechanisms known to aggravate and advance cardiovascular injury, and contributes to resistance to therapeutic interventions.³⁴

Myocardial Infarction

MI is defined as necrosis of a portion of the myocardium. The death of the myocardium occurs as a result of ischemia and anoxia. The vessels affected by occlusion are the right and left coronary arteries and their anterior and posterior descending branches. The right coronary artery supplies the posterior section and portions of the inferior section of the left ventricle. The left coronary artery branches and forms the circumflex and anterior descending arteries. The circumflex supplies the lateral portion of the left ventricle, and the anterior descending artery supplies the anterior portion. In addition, the right coronary artery supplies the right atrium atrioventricular bundle and the right ventricle. The left coronary artery supplies the left atrium and the primary portion of the conduction pathway. Generally, the clinical symptoms are similar to those of angina, with emphasis on extreme pressure as well as tightness over the sternal region. In addition, pain can radiate to the jaw, upper back, and shoulders (on the left more often than on the right).

MIs are categorized by location, size, and degree of involvement of the myocardial wall. The terms small and large are often used to describe MIs. Degrees of complication are also used in conjunction with size. MIs can be described as uncomplicated and complicated, based on the size of the MI and the patient’s recovery. Location indicates the area of the heart involved and the coronary artery or branches that are involved. The anatomic areas of the heart are differentiated as anterior, posterior, lateral, and inferior. Finally, MIs are classified by the extent of damage to the wall. A transmural (or full-wall) infarct extends from the endocardium to the epicardium, whereas only some involvement of the ventricle wall may occur, for example, just beneath the epicardium (subepicardial) or just beneath the endocardium (subendocardial).

Silent ischemia is particularly prevalent in patients with high cardiac risk and is associated with a poor outcome.³⁶ Silent MIs can be detected when a patient has undergone ECG investigation or imaging for other problems.

Congestive Heart Failure

Congestive heart failure (CHF) is a leading cause of hospitalization and death. It is characterized by the inability of the heart to maintain adequate cardiac output. The incidence of congestive heart failure appears to be increasing because of the prevalence of injurious lifestyle behaviors, aging, and improved survival after acute cardiac episodes.⁵⁸

Almost half of all patients with congestive heart failure are women.⁵⁹ Smoking, diabetes, and high blood pressure are stronger risk factors for CHF in women than in men. Peripartum cardiomyopathy, which is unique to women in their childbearing years, occurs either in the late stages of pregnancy or within several months after giving birth.

The causative factors of heart failure are usually ischemia and MI secondary to ischemic heart disease. For the heart to maintain optimal blood flow to the pulmonary and systemic circulations, heart rate and stroke volume must be adequate. If heart rate is regular and within an acceptable range, stroke volume is the critical factor for maintaining adequate cardiac output. Stroke volume is a function of the amount of blood in the left ventricle at the end of diastole (preload); the amount of pressure and resistance the heart must overcome to eject blood into the systemic circulation (afterload); and myocardial contractility, which is the amount of force the left ventricle can apply to the blood within the chamber. If any one of these three variables is adversely affected, cardiac output is reduced. Progressive deterioration of myocardial contractility and dilation and fluid overload precipitate heart failure.

Dyspnea is the primary complaint of people with congestive heart failure. It can be challenging to distinguish between dyspnea resulting from CHF and dyspnea resulting from pulmonary causes. B-type natriuretic peptide (BNP) is synthesized, stored, and released in the ventricular myocardium, and it is stimulated by changes in ventricular wall tension and stretch.⁶⁰ The use of BNP holds some promise as a marker for congestive heart failure and a guide to clinical management.

Congestive heart failure is a major contributor to progressive renal dysfunction and anemia.⁶¹ Anemia is observed in one-third of all patients with CHF. Conversely, chronic renal dysfunction can cause severe cardiac injury and is often associated with anemia. Thus congestive heart failure, chronic renal insufficiency, and anemia create a vicious circle that warrants aggressive medical management to attenuate the progression of the three conditions.

Chronic Bronchitis

Chronic bronchitis is a condition associated with chronic swelling and inflammation of the bronchi and bronchioles. The diagnosis is based on report of a cough producing sputum on most days for 3 months during 2 consecutive years when other conditions have been ruled out.⁹⁴ The degree of airway narrowing is assessed with spirometry.

Pathologically, an increase in the size of the tracheobronchial mucous glands (increased Reid index) occurs, along with goblet cell hyperplasia.⁹⁵ Mucous cell metaplasia of bronchial epithelium results in a decreased number of cilia. Ciliary dysfunction and disruption of the continuity of the mucous blanket are common. In the peripheral airways, bronchiolitis, bronchiolar narrowing, and increased amounts of mucus are observed.⁹⁶

Chronic bronchitis results from long-term irritation of the tracheobronchial tree. The most common cause of irritation is cigarette smoking.⁹⁷ Regular exposure to the inhaled toxic particles and gases in cigarette smoke causes inflammation in the epithelium of the central airways (larger than 4 mm in internal diameter). This inflammatory process is associated with an increased production of mucus by the goblet cells and mucous glands. Smoking inhibits ciliary action and destroys cilia. The hypersecretion of mucus and the loss and impairment of cilia lead to a chronic productive cough. The fact that smokers secrete an abnormal amount of mucus predisposes them to respiratory infection and prolonged recovery from such infection. The irritation of smoke in the tracheobronchial tree causes bronchoconstriction. Although smoking is the most common cause of chronic bronchitis, other triggers include air pollution, bronchial infections, and occupations in which air quality is affected.

Patients with chronic bronchitis often appear blue as a result of hypoxemia. Although many patients have a high arterial partial pressure of carbon dioxide (PaCO₂), the pH is normalized by renal retention of bicarbonate (HCO₃). The bone marrow compensates for chronic hypoxemia by increasing the production of red blood cells, leading to polycythemia.⁹⁰ Polycythemia increases blood viscosity and the work required by the heart to pump and circulate the blood through the lungs and systemic vasculature. Long-term hypoxemia leads to hypoxic pulmonary vasoconstriction, increased pulmonary artery pressure and, potentially, right ventricular hypertrophy.

Individuals with bronchitis often expectorate mucoid sputum. In an exacerbation, usually from infection, they have an even greater amount of purulent sputum. Ventilation-perfusion abnormalities are common, and they increase hypoxemia and PaCO₂ retention. The respiratory rate increases, as does the use of accessory muscles. Oxygen demand by these muscles and production of carbon dioxide (CO₂) increase beyond the capacity of the ventilatory system. The work of breathing increases disproportionately. This contributes to a further decrease in the arterial partial pressure of oxygen (PaO₂) and an increase in PaCO₂. The hypoxemia and respiratory acidemia increase pulmonary artery constriction, which further increases pulmonary artery pressure and right ventricular strain. During an exacerbation, these patients are usually treated with intravenous fluids, antibiotics, bronchodilators, and low-flow oxygen. Corticosteroids may be administered. Diuretics and digitalis are used to treat right ventricular failure.

Emphysema

Emphysema is defined as “a condition of the lung characterized by abnormal permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by destruction of their walls.”⁹⁸ There are two main types of emphysema: centrilobular and panlobular.⁹⁹ Centrilobular emphysema is 20 times more common than panlobular emphysema, although both types often coexist in the same patient.

Centrilobular emphysema is characterized by inflammation, edema, thickened bronchiolar walls, and destruction of the respiratory bronchioles. These changes are common and are marked in the upper lobes and the superior segments of the lower lobes.¹⁰⁰ Centrilobular emphysema is more common in men than in women, is rare in nonsmokers, and is common in patients with chronic bronchitis.

Panlobular emphysema, characterized by destructive enlargement of the alveoli, affects primarily the lower lobes (Fig. 5-1). This type of emphysema is characteristic of alpha₁-antitripsin deficiency, which involves an imbalance between the elastin and elastase in the lung parenchyma. The emphysematous lung develops secondary to loss of radial traction on the bronchioles and loss of the elastic recoil of the alveoli. When individuals without pulmonary dysfunction inhale, the airways are stretched open by the enlarging elastic lung. In exhalation, the airways are narrowed as a result of the decreasing stretch of the lung. The lungs of people with panlobular emphysema have decreased elasticity because of the destruction of surrounding alveolar walls. Thus the bronchioles lack tethering and support, which exposes them to collapse even during normal exhalation.

Bullae, emphysematous spaces larger than 1 cm in diameter, are commonly present in patients with emphysema (Fig. 5-2).^101,102 Bullae develop from a coalescence of adjacent areas of emphysematous lung or because of an obstruction of the conducting airways that permits the flow of air into the alveoli during inspiration but impedes the outflow of air during expiration. The alveoli become hyperinflated and eventually the walls are damaged, leading to an enlarged air space in the lung parenchyma. These bullae can exceed 10 cm in diameter and they compromise the function of the remaining lung tissue (Fig. 5-3). Surgical intervention to remove bullae may be indicated. Pneumothorax, a serious complication, can result from their rupture.

There are several long-term structural and functional changes in the lungs of people with emphysema. The diagnosis is based on these changes. Chronic airflow obstruction reflects both the effect of chronic inflammation of the small airways (contributing to obstructive bronchiolitis) and parenchymal destruction (emphysema). The latter contributes to the loss of alveolar tethering and attachment, resulting in increased lung compliance (reduced elastic recoil) of the affected lung regions. The airways lose their ability to remain open during expiration, which contributes to dynamic airway closure.

Shortness of breath is the most common complaint of a person with emphysema, and it reflects psychological factors, as well as pulmonary impairment.¹⁰³ Dyspnea is persistent (present daily) and worsens with exertion and during respiratory infections. These patients appear thin and have elevated shoulders and an increased anteroposterior chest diameter. They tend to breathe with the accessory muscles of respiration. These patients tend to lean forward when distressed, resting their forearms on their knees or sitting with their arms extended at their sides and pushing down against the bed or chair, to elevate their shoulders and improve the efficiency of the accessory muscles to support breathing. They may breathe through pursed lips during the expiratory phase of breathing.

On auscultation, breath sounds are reduced throughout most or all lung fields. Radiographs show overinflated lungs, flattened hemidiaphragms, and elongated hearts (Fig. 5-4). Pulmonary function tests show decreased vital capacity, FEV₁, maximum voluntary ventilation, and diffusing capacity. The total lung capacity increases as a result of greater anatomic dead space caused by hyperinflation, whereas the residual volume and functional residual capacity increase even more. Arterial blood gases reflect a mildly or moderately low PaO₂, a normal or slightly elevated PaCO₂, and a normal pH. At the end stage of disease, these patients develop heart failure (Fig. 5-5).

COPD is often associated with sodium retention, leading to massive edema and the development of right-sided heart failure.¹⁰⁴ Cardiac output can remain remarkably normal, suggesting that the pathology is related to fluid overload. Underfilling of the arterial side of the circulation has been proposed for stimulating the sodium-retaining mechanism in right-sided heart failure.

Exacerbations of the disease are more frequent and severe with increased severity of lung pathology and impairment of baseline pulmonary function.¹⁰⁵ The principal cause of an acute exacerbation of COPD is infection, which may be of viral or bacterial origin. The infection causes an inflammatory response, which causes an increased production of mucus and airflow obstruction. If hospitalization is required, treatment usually includes IV fluids, antibiotics, and low-flow oxygen.⁹⁰ Some patients may receive bronchodilators, corticosteroids, diuretics, and digitalis. Theophylline is often prescribed as a bronchodilator in COPD, but it also has other important benefits. Theophylline has been shown to improve respiratory muscle strength and endurance, mucociliary clearance, respiratory drive, and cardiac function.^106,107 Pursed-lip breathing can relieve dyspnea and improve arterial blood gases in some people with COPD.¹⁰⁸ The majority of people with COPD report symptoms consistent with asthma, bronchitis, or both, which explains why inhaled corticosteroids reduce symptoms and improve survival in some patients.^106,109,110

Individuals with COPD who are hypoxemic when awake become more hypoxemic during sleep, with desaturation most marked during REM sleep.¹¹¹ The mechanism is thought to reflect alveolar hypoventilation and ventilation-perfusion mismatch. Diminished ventilation during sleep also increases the risk for cardiac dysrhythmias.⁹³ If COPD is associated with obstructive sleep apnea, patients have increased risk for respiratory insufficiency and failure. During acute exacerbations, these effects can be augmented, thus contributing to nocturnal death.

Risk factors for emphysema include smoking, a history of chronic bronchitis, and increasing age.⁹⁴ The risk for developing COPD is 30 times greater in smokers than in nonsmokers.^99,100 The relatively rare form of inherited emphysema, alpha₁-antitrypsin deficiency, develops fairly early in life and is unrelated to smoking history. Repeated lower respiratory tract infections can play a role.

COPD is associated with clinically important extrapulmonary effects, including peripheral skeletal muscle dysfunction, muscle wasting, and osteoporosis.⁹¹ Recent literature supports the theory that chronic lung and heart conditions share a common myopathy (see Chapters 24 and 31).^112–114 Both muscle wasting and altered muscle protein metabolism have been implicated in the muscle adaptation to COPD.¹¹⁵ This finding has important implications for rehabilitation.

Respiratory muscle weakness and fatigue are associated with the severity of COPD.¹¹⁶ Muscle weakness results from structural ventilatory impairments, adaptations to the chronic mechanical load imposed by the underlying pathology, and deconditioning. A delicate balance exists between respiratory muscle overload and adaptation. Respiratory muscle strength and endurance are fundamental to assessment, evaluation, treatment prescription, and prognosis.

Venous thromboembolism poses major risk to individuals with COPD, particularly during acute exacerbations, when blood volume may be relatively reduced in the presence of normally elevated hematocrit and, during an exacerbation, these patients are less active.¹¹⁷ Even though pharmacologic prophylaxis has been advocated for high-risk patients, the physical therapist should institute prophylactic measures for all patients.

For comprehensive evaluation of the functional status of individuals with chronic lung disease, exercise testing provides an integrated perspective of organ-system function and can be used to prescribe physical activity and a structured exercise program (see Chapter 24). Exercise testing data provide supplemental information in the assessment because resting pulmonary function is not necessarily closely associated with functional capacity.

COPD progresses from respiratory insufficiency to failure. The two categories of failure are lung failure, resulting in hypoxemia, and pump failure, resulting in alveolar ventilation and hypercapnia.¹¹⁸ These two conditions are managed differently based on their underlying pathophysiological mechanisms and varying clinical manifestations.

Asthma

Asthma is a chronic inflammatory condition of the airways that is characterized by an increased responsiveness of the airway smooth muscle to various stimuli (due to a lowering of the threshold of airway smooth muscle reactivity). It is manifested by widespread narrowing of the airways that reverses either spontaneously or as a result of treatment.125–127 During an asthma attack, the lumens of the airways are narrowed or occluded by a combination of bronchial smooth muscle spasm, inflammation of the mucosa, and overproduction of viscous mucus.^128–130 Specifically, eosinophilic inflammation is prevalent, and airway remodeling of the bronchial airways occurs over time.^131,132 Clinically, peak expiratory flow rates are sensitive to subtle changes in airway status, which may be detected before the onset of symptoms.¹³³ This early objective sign can be useful in anticipating an asthma attack.

Asthma is a widespread condition that affects 5% to 10% of the population of the United States.¹³⁴ Asthma is prevalent in individuals under 25 years of age, where estimates of prevalence vary from 5% to 15%.¹³⁵ Approximately 80% of children with asthma do not have asthma after 10 years of age.

Asthma that begins before the age of 35 is usually allergic or extrinsic. Asthma attacks are precipitated when an individual comes into contact with a substance to which she or he is sensitive, such as pollens or household dust (Box 5-1). Commonly, people with asthma are allergic to multiple allergens.¹²⁶

Prognosis of Bronchiectasis

Before the era of antibiotics, the prognosis for individuals with bronchiectasis was poor. Infection was usually the precipitating cause of death. Today, with advances in medical management, the prognosis for patients is much better.¹⁴⁴ Most patients can lead relatively normal lives. Right-sided heart failure, a complication of diffuse, long-standing bronchiectasis, can lead to death. Pneumonia and hemorrhage are less common causes of death. Repeated bronchopulmonary infections can contribute to worsening pulmonary function and an earlier death. Before the antimicrobial era, most patients with untreated, widespread, severe bronchiectasis died within 25 years. Prognosis depends on the extent of the disease process at the time of diagnosis and on optimal medical management. Patients with moderate, localized disease, with timely intervention, can expect a relatively normal life expectancy.

Diffuse Interstitial Pulmonary Fibrosis

Pulmonary fibrosis is a common response to various types of lung injuries.¹⁴⁸ Numerous acute and chronic lung conditions are associated with fibroproliferation, inflammation, or both, predisposing an individual to fibrosis. These are collectively known as interstitial lung disease.

The hypothesis that inflammation causes the development of interstitial pulmonary fibrosis is being challenged by a growing body of evidence suggesting that an abnormal wound-healing response to multiple microscopic sites of acute alveolar injury occurs, progressing to fibrosis.135,149 The resolution of the fibroproliferation response to irritation and injury is essential to patient survival. More than 130 types of interstitial lung disease have been described. Diffuse interstitial pulmonary fibrosis represents a common histological response to a wide variety of insults.¹⁵⁰ Initially, an insult or injury to the pulmonary parenchyma causes an influx of inflammatory and immune cells, resulting in a diffuse inflammatory process distal to the terminal bronchiole (alveolitis).¹⁵¹ This can progress to subacute interstitial disease with the presence of acute and chronic inflammatory cells. Chronic disease is manifest by thickened alveolar walls and progression to fibrosis and scarring. A role for circulating cells of hematopoietic origin has been proposed as a causal factor.¹⁵⁰ In addition, apoptosis has been implicated in the pathophysiology of pulmonary fibrosis.¹⁵²

The known causes of pulmonary fibrosis include occupational or environmental exposure to inorganic dusts (e.g., silica and coal), toxic gases, and certain drugs or poisons.153,154 In addition, interstitial lung disease is associated with rheumatoid arthritis and systemic sclerosis.¹⁵⁵ Twins, siblings, and other family members have been reported to have a higher incidence of diffuse interstitial pulmonary fibrosis, which supports the idea that there is a genetic link. Less commonly, interstitial pulmonary fibrosis has been reported in individuals with Raynaud’s phenomenon and ulcerative colitis.

Idiopathic pulmonary fibrosis (IPF), or cryptogenic fibrosing alveolitis, is a chronic, progressive, irreversible disease of unknown cause.148,149 The median survival time after diagnosis is approximately 3 years. Idiopathic interstitial pneumonia is associated with idiopathic pulmonary fibrosis and is a type of chronic fibrosing interstitial pneumonia with the histiologic appearance of usual interstitial pneumonia (UIP).⁸⁷ It is a condition that occurs primarily in individuals over 50 years of age. Risk factors include cigarette smoking, use of antidepressants, chronic aspiration, and exposure to metal and wood dusts.

The most common early symptoms of IPF are fatigue, dyspnea on exertion, and chronic unproductive cough. As the disease progresses, the patient becomes more dyspneic and cyanotic. On auscultation, crackles are noted, chest expansion is reduced, and clubbing of the fingers may be present.

Chest radiograph usually indicates diffuse reticular markings that show prominently in the lower lung fields. High-resolution computerized tomography is often used because it is more sensitive than a radiograph; it usually reveals patchy, predominantly peripheral reticular abnormalities in the bases. It is used to evaluate the extent of parenchymal involvement and to monitor disease progression.

Pulmonary function tests show reduced lung volumes and capacities, maintained flows, and abnormal gas exchange.¹⁵⁶ Compliance is markedly reduced to less than half of the predicted value. Reduced diffusing capacity is the earliest and most consistent change. Initially, arterial PaO₂ may be normal at rest but may decrease markedly with exercise. PaCO₂ is reduced as a result of hyperventilation, and pH is maintained by renal compensation. Later, the PaO₂ is greatly reduced because of the thickened alveolar membrane and ventilation-perfusion mismatching.

Bronchoalveolar lavage (BAL) may be used to assess the amount of inflammation and the accumulation of immune effector cells and proteins in the alveoli.¹⁵⁷ The technique consists of wedging a fiberoptic bronchoscope into a sublobar airway, then infusing 20 to 50 mL aliquots of saline into the peripheral airway. The saline is immediately aspirated by syringe. A total of 150 to 300 mL is instilled and recovered. The fluid and cells are analyzed. High-intensity alveolitis is defined by the presence of 10% or more polymorphonuclear granulocytes (PMNs) in BAL cell differential counts; low-intensity alveolitis consists of 10% PMNs or less.¹⁵⁸

Lung biopsies that demonstrate an abundance of inflammatory cells suggest early disease, whereas a prevalence of fibrosis is indicative of advanced disease. A distinct category of IPF has been described and may be clinically useful.¹⁵⁴ Desquamous interstitial pneumonitis (DIP) is characterized by the intraalveolar accumulation of mononuclear cells, relatively intact alveolar walls without destruction or fibrinous exudates (numerous inflammatory cells with little or no fibrosis). This pattern has correlated with a more benign course and a better response to corticosteroids. Because a pattern of DIP is commonly seen with UIP and IPF, DIP may represent an earlier, more easily reversible stage of IPF.

Corticosteroids are the mainstay of treatment for diffuse interstitial pulmonary fibrosis,154,159 although their efficacy is being questioned for treatment of IPF because the favorable response rate is only 25% to 30% and there is a high incidence of adverse effects.^160,161 Regardless, a trial of immunosuppressive therapy is usually prescribed for a short period. Objective measures such as blood counts, erythrocyte sedimentation rate, pulmonary function testing, exercise tests with measurement of arterial oxygen desaturation and diffusing capacity, BAL fluid analysis, and the patient’s symptoms should demonstrate improvement; otherwise, the medication is likely to be discontinued. Individuals who are not responsive to corticosteroids may be placed on antiinflammatory medications such as colchicines¹⁶⁰ or immunosuppressive drugs such as cyclophosphamide, azathioprine, or penicillamine.^148,161,162 Penicillamine is more effective in patients with connective tissue diseases and interstitial fibrosis other than IPF.

Patients should stop smoking. Supplemental oxygen is important, along with exercise, because there is a characteristic significant fall in arterial oxygen tension (PaO₂).¹⁶² Individuals who require more than a 4-L flow per minute by nasal prongs may prefer direct administration of oxygen into the trachea. In addition to supplying higher concentrations of oxygen to the lungs, many patients prefer not to wear conspicuous nasal prongs.

Patients who have refractory restrictive lung disease may be candidates for single or double lung transplantation. Outcomes of transplantation surgery have been improving (see Chapter 40).

Most individuals with acute interstitial pneumonia and diffuse alveolar damage die within 6 months.¹⁴⁸ Patients with the chronic form who are treated with steroids can survive for years. Untreated, these patients commonly die within 1 to 4 years. The cause of death is usually related to respiratory or heart failure, although some die of adenocarcinoma and undifferentiated or alveolar cell carcinoma of the lung.

Pulmonary Infiltrates with Eosinophilia

Eosinophils are commonly present in lung tissue as part of the body’s cellular response to a variety of agents and systemic immunological diseases.⁹⁵ They are present in the airways and lung tissue of patients with idiopathic pulmonary fibrosis. In interstitial lung disease that appears to have an allergic component (e.g., hypersensitivity pneumonitis, drug-induced lung syndromes, and sarcoidosis), eosinophils are minor components of the tissue reaction. In certain primary or systemic diseases, however, eosinophils can be the most conspicuous inflammatory cell present in the lung. These conditions can be grouped together and referred to as eosinophilic syndromes. Considerable overlapping exists among these syndromes because their causes and pathogenesis remain poorly understood.¹⁶²

Pulmonary Alveolar Proteinosis

Pulmonary alveolar proteinosis (PAP) is an uncommon condition of unknown origin that is characterized by alveoli filled with lipid-rich “proteinaceous” material (i.e., surfactant phospholipids) in the absence of defects of the alveolar wall, interstitial spaces, conducting airways, or pleural surfaces. Most commonly, men between the ages of 30 and 50 are affected, although people of all ages and both sexes can be affected. There are three clinical types of PAP. The most common type (>90%) is acquired PAP, which is considered an autoimmune response. Hematopoietic growth factor (granulocyte-macrophage colony-stimulating factor [GM-CSF]) is essential for local regulation of surfactant homeostasis in the lungs. People with acquired PAP have a circulating, neutralizing GM-CSF antibody. The remaining two types are congenital PAP and secondary PAP; the latter is associated with environmental factors, immunological disorders, malignancies, and hematopoietic disorders.¹⁶³

The most common symptoms are progressive dyspnea and weight loss, with cough; hemoptysis and chest pain are reported less frequently. Chest radiographs reveal diffuse bilateral (commonly perihilar) opacities (Fig. 5-10). Physical findings may include fine inspiratory crackles, dullness to percussion, and in the later stages, cyanosis and finger clubbing. Pulmonary function studies show reduced vital capacity, functional residual capacity, and diffusing capacity. Arterial blood gases indicate a low PaO₂, especially during exercise, with normal PaCO₂, and pH.⁹⁵

The treatment of choice for patients with moderate to severe dyspnea on exertion due to alveolar proteinosis is whole-lung lavage.¹⁶⁴ In the operating room, after general anesthesia and the placement of a double-lumen tube (which isolates each lung), the patient is positioned in the lateral decubitus position, with the lung that is to be lavaged in the lowermost position. The double-lumen tube enables the patient to be ventilated to functional residual capacity by the uppermost lung while the lower lung is filled with saline. An additional 300 to 500 mL saline is alternately allowed to run in and out of the lung in response to gravity. As the saline flows out, manual percussion is performed over the lavaged lung, which increases the amount of proteinaceous material washed from the affected lung. The effectiveness of mechanical percussion, manual vibration, and manual percussion in removing material from involved lungs has been compared, and manual percussion has been found to be superior.^165,166 In this procedure the affected lung is lavaged with 20 to 70 L saline. The patient may be positioned prone during the administration of the final 10 to 15 L of the lavage. After the procedure, the patient is transported to the recovery room and, once stabilized, to the ward. After a few days, the procedure may be repeated in the opposite lung.

Most patients show significant clinical improvement after whole-lung lavage, including improved PaO₂, diffusing capacity, and vital capacity.164,166 Many also show an improved radiograph. After lavage, patients must be followed up, because the material may reaccumulate over time. Some patients do have spontaneous remissions without undergoing lavage.

The use of limited lobar lavage through a bronchoscope has shown some benefit.¹⁶⁷ Half of patients who have acquired PAP with subcutaneous GM-CSF show improvement, but they show a lower rate of improvement than is seen after whole-lung lavage.¹⁶⁴

Before whole-lung lavage became standard treatment, almost all children with alveolar proteinosis died and 20% to 25% of adults died within a few years, usually because of respiratory failure, right-sided heart failure, or uncontrolled infection. The majority of patients now improve greatly or recover.¹⁶⁴

Sarcoidosis

Sarcoidosis is one of the most common causes of interstitial pulmonary disease.95,168 It is a granulomatous disorder of unknown origin that can affect multiple organ systems.¹⁶⁹ Initial findings can include bilateral hilar adenopathy, pulmonary infiltration, and skin or eye lesions.¹⁷⁰ The lungs are the organs most often involved, and in such cases, 20% to 50% of patients seek medical attention because of respiratory symptoms. African Americans are affected 10 to 20 times more often than Caucasians, and women are affected twice as often as men. It usually occurs in the third or fourth decade of life.

The intrathoracic changes can be classified into four stages.⁹⁵ In the first stage, the patient is asymptomatic, with the chest radiograph showing bilateral hilar adenopathy and right paratracheal adenopathy (Fig. 5-11, A). In the second stage, a diffuse pulmonary infiltration is found, along with the bilateral hilar adenopathy. Interstitial infiltration or fibrosis, without hilar adenopathy, characterizes the third stage (Fig. 5-11, B). In the fourth stage, emphysematous changes, cysts, and bullae occur.

About one-third of people with sarcoidosis involving the lungs have spontaneous regressions with some residual fibrosis. The remaining two-thirds have progressive pulmonary impairment, along with a variable degree of impairment to the heart, liver, spleen, lymph nodes, muscles, bones, and central nervous system. Most people with sarcoidosis need no treatment. Corticosteroids, although controversial, have shown benefit.

Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic disease that involves the joints but can affect the lungs, pleurae, and heart. The most common thoracic complication in RA is pleuritis, with or without pleural effusions. Although RA occurs twice as often in women, pleuritis has a striking predilection for men.¹⁶² Pleural disease is one manifestation of RA, occasionally causing fibrothorax and restrictive lung disease that requires decortication.

Interstitial lung disease, indicated by abnormal pulmonary function tests demonstrating a restrictive ventilatory impairment and a reduced ventilatory capacity, is evident in about 40% of people with RA. It is also more prevalent in men. The chest radiograph shows diffuse interstitial infiltrates, especially in the lung bases. Pulmonary nodules, which are pathologically identical to the subcutaneous nodules found in RA, may also occur and may cavitate.¹⁵⁵

Coal miners with RA may have chest radiographs that demonstrate rounded densities that evolve rapidly and undergo cavitation (Caplan syndrome) in contrast to the massive fibrosis found in coal miners’ pneumoconiosis.

Systemic Lupus Erythematosus

Although systemic lupus erythematosus (SLE) is a systemic collagen vascular disease, 50% to 90% of patients have pleural or pulmonary involvement. Pleuritic chest pain often signals polyserositis associated with SLE. Pleural effusions are a manifestation of polyserositis and are present in 40% to 60% of individuals with SLE. Often they are bilateral.

Chronic interstitial pneumonitis is found in 3% to 13% of people with SLE, and acute lupus pneumonitis occurs in 1% to 4%.¹⁷¹ Patients with pulmonary involvement have dyspnea on exertion and a cough productive of mucoid sputum.¹⁵⁵ Although rare, complaints of supine dyspnea suggest diaphragmatic paresis or a diffuse myopathy of the diaphragm.¹⁷¹ The chest radiograph usually indicates patchy, nonspecific densities, basilar linear or plate-like atelectasis, or both. Pleural effusions and pulmonary infiltrates are common, whereas diffuse interstitial fibrosis is rare. Pulmonary function tests often indicate a restrictive pattern with a decreased diffusing capacity and reduced arterial oxygen saturation.

Progressive Systemic Sclerosis (Scleroderma)

Progressive systemic sclerosis, also called scleroderma, is an uncommon condition that causes thickening and fibrosis of the connective tissue throughout the body and replacement of many elements of the connective tissue by colloidal collagen. Although the skin is most often involved, the lungs, heart, kidney, bones, and other parts of the body can also be affected. Approximately two-thirds of people with progressive systemic sclerosis have pulmonary involvement.155,162

Many of these patients with pulmonary involvement are asymptomatic, although symptoms can include weight loss, progressive dyspnea, low-grade fever, and cough (sometimes producing mucoid sputum). Chest radiographs show a characteristic fibrosis of the middle and lower lung fields. Auscultation often reveals bibasilar crackles. Pulmonary function tests reveal a restrictive defect with impaired diffusion.

The form of treatment for pulmonary involvement in patients with progressive systemic sclerosis is controversial, but usually involves corticosteroids, cyclophosphamide, or both.¹⁵⁵

The prognosis for patients with only skin and joint involvement is much better than for those with involvement of the heart, lungs, and kidneys. Those with kidney involvement have a poor prognosis and a survival rate of only several years. Women have a poorer prognosis than men.

Tuberculosis

Tuberculosis (TB), a highly infectious bacterial disease, was prominent in the first half of the 1900s. With improved sanitation and medical care, TB was largely controlled. A recent resurgence of the disease has been documented, however, probably resulting from the migration patterns of people globally and the poor becoming poorer in high-income countries. TB affects many organ systems, including the lungs, and is more prevalent in people living in poor sanitary conditions with poor health. Mycobacterium tuberculosis is highly contagious but responds well to medication.87,172 The resurgence of tuberculosis in high-income countries has become a significant public health concern.

Lung Cancer

Lung cancer is by far the leading cause of death due to cancer in both men and women.¹⁷³ The growth and division of cells is regulated by the DNA within every cell. When the DNA is damaged, which is estimated to be the result of lifestyle behaviors and environmental factors at least 50% of the time, cell division becomes uncontrolled. Cancer-causing agents, or carcinogens, related to lung disease include oxygen radicals and toxins in cigarette smoke. Although lung cancer is associated primarily with smoking, the occurrence of many other cancers is also higher in smokers. Thus the risk for cancer in general is increased in smokers. A physical therapist needs to understand the pathophysiology of all cancers, particularly lung cancer, and their medical and surgical management, as well as the impact of the natural history of a given cancer and the stage of a particular cancer on an individual’s health-related quality of life. Lung cancer, as all cancers, tends to have multisystem consequences that must be understood by the physical therapist and considered during management. The physical therapist has a primary role in cancer prevention, in its early detection (by recognizing the seven warning signs of cancer), and in its management during conservative and surgical phases of care and over the long term.

End-Stage Lung Disease

Lung transplantation may be indicated in end-stage lung disease. Bronchiolitis obliterans syndrome is a serious complication of lung transplantation, but its cause is uncertain.¹⁷⁴