Obstructive Lung Disease

Chronic Obstructive Pulmonary Disease (COPD), Asthma, and Related Diseases

Enrique Diaz-Guzman, Raed A. Dweik and James K. Stoller

Key Terms

acute exacerbation of COPD

airway hyperresponsiveness (AHR)

noninvasive ventilation

supplemental oxygen

The spectrum of obstructive lung diseases is broad and includes chronic obstructive pulmonary disease (COPD) and asthma as the most common components and less common entities such as bronchiectasis and cystic fibrosis. This chapter reviews the major obstructive lung diseases, emphasizing their defining features, epidemiology, pathophysiology, clinical signs and symptoms, prognosis, and management.

Chronic Obstructive Pulmonary Disease

Overview and Definitions

The term chronic obstructive pulmonary disease (COPD), or sometimes chronic obstructive lung disease (COLD), refers to a disease state characterized by the presence of incompletely reversible airflow obstruction. New guidelines by the American Thoracic Society (ATS) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend the use of the term COPD to encompass both chronic bronchitis and emphysema. The ATS guidelines statement regarding COPD define this entity as follows ¹:

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences.

The spectrum of COPD is shown in Figure 23-1, which presents a nonproportional Venn diagram representing the major components of COPD—chronic bronchitis and emphysema. Although asthma is no longer conventionally considered to be part of the spectrum of COPD, the diagram shows that considerable overlap between asthma and COPD exists. In actual practice, individuals with a history of asthma but with incompletely reversible airflow obstruction may be indistinguishable from patients with COPD.

FIGURE 23-1 Schema of COPD. This nonproportional Venn diagram shows subsets of patients with chronic bronchitis, emphysema, and asthma. The subsets constituting COPD are shaded. Subset areas are not proportional to actual relative subset sizes. Asthma is by definition associated with reversible airflow obstruction, although in variant asthma special maneuvers may be necessary to make the obstruction evident. Patients with asthma whose airflow obstruction is completely reversible *(subset 9)* are not considered to have COPD. Because in many cases it is virtually impossible to differentiate patients with asthma whose airflow obstruction does not remit completely from patients with chronic bronchitis and emphysema who have partially reversible airflow obstruction with airway hyperreactivity, patients with unremitting asthma are classified as having COPD (*subsets 6, 7,* and 8). Chronic bronchitis and emphysema with airflow obstruction usually occur together *(subset 5),* and some patients may have asthma associated with these two disorders *(subset 8).* Individuals with asthma who are exposed to chronic irritation, as from cigarette smoke, may develop a chronic, productive cough, a feature of chronic bronchitis *(subset 6).* Such patients are often referred to as having *asthmatic bronchitis* or the *asthmatic form of COPD*. Individuals with chronic bronchitis or emphysema without airflow obstruction (*subsets 1, 2,* and 11) are not classified as having COPD. Patients with airway obstruction caused by diseases with a known etiology or specific pathology, such as cystic fibrosis or obliterative bronchiolitis *(subset 10)*, are not included in this definition.

The two major entities constituting COPD—emphysema and chronic bronchitis—are defined in different ways. Emphysema is defined in anatomic terms as a condition characterized by abnormal, permanent enlargement of the airspaces beyond the terminal bronchiole, accompanied by destruction of the walls of the airspaces without fibrosis. Chronic bronchitis is defined in clinical terms as a condition in which chronic productive cough is present for at least 3 months per year for at least 2 consecutive years. The definition specifies further that other causes of chronic cough (e.g., gastroesophageal reflux, asthma, and postnasal drip) have been excluded. Figure 23-1 shows considerable overlap between chronic bronchitis and emphysema and some overlap with asthma—that is, when airflow obstruction is incompletely reversible. Figure 23-1 also shows that chronic bronchitis and emphysema can occur without airflow obstruction, although the clinical significance of these diseases usually stems from obstruction to airflow.

Epidemiology

COPD is one of the most frequent causes of morbidity and mortality worldwide.³ The World Health Organization predicts that COPD will become the fifth most prevalent disease in the world and the fourth leading cause of worldwide mortality by 2020. In the United States, COPD is currently the third leading cause of death; it was responsible for 145,075 deaths in 2008.⁴ Estimates suggest that 24 million Americans are affected.^4–6 Data from the National Health and Nutrition Examination Survey (NHANES) suggest that among adults 25 to 75 years old in the United States, mild COPD (defined as forced expiratory volume in 1 second [FEV₁]/forced vital capacity [FVC] <70%, and FEV₁ >80% predicted) occurs in 6.9% and moderate COPD (defined as FEV₁/FVC <79% and FEV₁ ≤80% predicted) occurs in 6.6%.³ COPD prevalence increases with aging, with a fivefold increased risk for adults older than 65 years compared with adults younger than 40 years, and some studies estimate a prevalence of 20% to 30% in adults older than 70 years.⁷

The growing health burden from COPD is caused in part by the aging of the population but mainly by the continued use of tobacco. The socioeconomic burden of COPD is also substantial. In 2000, COPD caused 726,000 hospitalizations (which accounted for 1.9% of all hospitalizations in the United States), 7,997,000 office visits to physicians, and 1,549,000 emergency department visits, and, in 2002, COPD resulted in a total health expenditure of $32.1 billion.³ In this regard, COPD is a problem that is a frequent challenge for the respiratory clinician.

Risk Factors and Pathophysiology

Although many risk factors exist for COPD (Box 23-1), the two most common are cigarette smoking (which has been estimated to account for 80% to 90% of all COPD-related deaths) and alpha₁-antitrypsin (AAT) deficiency.⁸ Evidence linking cigarette smoking to the development of COPD is strong and includes the following:

Box 23-1 Causes of Chronic Obstructive Pulmonary Disease *

Common Causes

• Cigarette smoking

• AAT deficiency

• Outdoor air pollution

• Long-standing asthma

• Biomass and occupational exposure

Less Common Causes

• Hypocomplementemic urticarial vasculitis

• Intravenous Ritalin abuse

• Ehlers-Danlos syndrome, Marfan syndrome

• Salla disease ^†

• Alpha₁-antichymotrypsin deficiency ^†

• HIV (emphysemalike illness)

^*Multiple causes (e.g., cigarette smoking and alpha₁-antitrypsin deficiency) may coexist in a single patient.

^†Putative cause; firm evidence is unavailable.

• Symptoms of COPD (e.g., chronic cough and phlegm production) are more common in smokers than in nonsmokers.

• Impaired lung function with evidence of an obstructive pattern of lung dysfunction is more common in smokers than in nonsmokers.

• Pathologic changes of airflow obstruction and chronic bronchitis are evident in the lungs of smokers.

• So-called susceptible smokers, who represent approximately 15% of all cigarette smokers, experience more rapid rates of decline of lung function than nonsmokers.

Information from the Lung Health Study (Figure 23-2) highlighted the accelerated rate of decrease of FEV₁ in smokers compared with former smokers who have achieved sustained quitting.^9,10 Overall, the strength of evidence implicating cigarette smoking as a cause of COPD has allowed the U.S. Surgeon General to conclude, “Cigarette smoking is the major cause of chronic obstructive lung disease in the United States for both men and women. The contribution of cigarette smoking to chronic obstructive lung disease morbidity and mortality far outweighs all other factors.”¹¹

FIGURE 23-2 Mean postbronchodilator FEV₁ for participants in the smoking intervention and placebo groups who were sustained quitters *(red circles)* and continuing smokers *(purple circles).* The two curves diverge sharply after baseline. (From Anthonisen SR, Connett JE, Kiley JP, et al: Effects of smoking intervention and the use of an anticholinergic bronchodilator on the rate of decline of FEV₁: the Lung Health Study. JAMA 272:1497–1504, 1994.)

As the second well-recognized cause of emphysema, AAT deficiency, sometimes called genetic emphysema, is a condition characterized by a deficient amount of the protein AAT, which may result in the early onset of emphysema and which is inherited as a so-called autosomal codominant condition. Accounting for 2% to 3% of all cases of COPD, AAT deficiency is severely underrecognized by health care providers but affects an estimated 100,000 Americans. In one 1995 survey, the mean interval between the first onset of pulmonary symptoms and initial diagnosis of AAT deficiency was 7.2 years, and 43% of individuals with severe deficiency of AAT reported seeing at least three physicians before the diagnosis of AAT deficiency was first made.¹² More recent studies suggested that underrecognition of AAT deficiency persisted as of 2003 and that the diagnostic delay interval had not decreased significantly.^12–14

The importance of early identification is emphasized by the need to test (by simply sending a serum level for AAT) first-degree relatives (e.g., siblings, parents, and children), by the favorable effect of primary prevention of smoking among individuals identified early, and by the availability of a specific therapy called intravenous augmentation therapy. The risk of developing emphysema for individuals with AAT deficiency increases as the serum AAT level decreases to less than 11 µmol/L, or less than approximately 57 mg/dl using nephelometry, and is enhanced by cigarette smoking.¹⁴

Study of AAT deficiency has helped formulate the protease-antiprotease hypothesis of emphysema.14,15 In this explanatory model (Figure 23-3), lung elastin, a major structural protein that supports the alveolar walls of the lung, is normally protected by AAT, a protein that opposes the degradative threat of neutrophil elastase. Neutrophil elastase is a protein contained within neutrophils that is released when neutrophils are attracted to the lung during inflammation or infection. Under normal circumstances of an adequate amount of AAT, neutrophil elastase is counteracted so as not to digest lung elastin. However, in the face of a severe deficiency of AAT (i.e., when serum levels decrease below a “protective threshold” value of 11 µmol/L, or 57 mg/dl), neutrophil elastase may go unchecked, causing breakdown of elastin and resulting in dissolution of alveolar walls. This protease-antiprotease model explains the pathogenesis of emphysema in AAT deficiency, but evidence suggesting its role in COPD in individuals with normal amounts of AAT is conflicting. Also, other proteases (e.g., matrix metalloproteinases and inflammation) are thought to contribute to the proteolysis that produces emphysema.¹⁶

FIGURE 23-3 Proposed biochemical links between cigarette smoking and the pathogenesis of emphysema. *(I)* Smoking recruits monocytes, macrophages, and (through macrophage chemotactic factors) polymorphonuclear neutrophils to the lung, elevating the connective tissue “burden” of elastolytic serine and metalloproteases. *(III)* At the same time, oxidants in smoke plus oxidants produced by smoke-stimulated lung phagocytes (and oxidizing products of chemical interactions between these two) inactivate bronchial mucus proteinase inhibitor and AAT, the latter representing the major antielastase “shield” of the respiratory units. *(II)* Other, unidentified water-soluble, gas-phase components of cigarette smoke (cyanide, copper chelators) inhibit lysyl oxidase–catalyzed oxidative deamination of epsilon-amino groups in tropoelastin and block formation of desmosine and presumably other cross-links during elastin synthesis, decreasing connective tissue repair. *(IV)* Antioxidants (ceruloplasmin, methionine-sulfoxide-reductase) may protect or reactivate elastase inhibitors, and other unidentified factors may modulate the chemical lesions induced in the lung by smoking to influence the risk of developing COPD. (Modified from Janoff A, Carp H, Laurent P, et al: The role of oxidative processes in emphysema. Am Rev Respir Dis 127[Suppl]:S31, 1983.)

COPD may occur in the absence of active cigarette smoking or AAT deficiency (see Box 23-1).^17,18 Factors such as passive smoking, air pollution, occupational exposure, and airway hyperresponsiveness may contribute to fixed airflow obstruction.

The mechanisms of airflow obstruction in COPD include inflammation and obstruction of small airways (<2 mm in diameter); loss of elasticity, which keeps small airways open when elastin is destroyed in emphysema; and active bronchospasm. Although traditionally considered to be characteristic of asthma, some reversibility of airflow obstruction has been observed in up to two-thirds of COPD patients when tested serially with inhaled bronchodilators.¹⁹

Clinical Signs and Symptoms

Common symptoms of COPD include cough, phlegm production, wheezing, and shortness of breath, typically on exertion. Dyspnea is often slow but progressive in onset and occurs later in the course of the disease, characteristically in the late sixth or seventh decade of life. One notable exception is AAT deficiency, in which dyspnea characteristically begins sooner (mean age approximately 45 years).⁸

Table 23-1 reviews the characteristic features of emphysema and chronic bronchitis and emphasizes traits that should suggest the possibility of AAT deficiency, including early onset of emphysema, emphysema in a nonsmoker, or a family history of emphysema. Suspicion of AAT deficiency should lead to a simple blood test by which the serum level can be established.^8,14

TABLE 23-1

Clinical Features of COPD: Distinctions Between Chronic Bronchitis and Emphysema, With Emphasis on Distinguishing Features of Alpha₁-Antitrypsin Deficiency

Features	Chronic Bronchitis	Emphysema	Severe Alpha₁-Antitrypsin Deficiency
Symptoms and Signs
Chronic cough, phlegm	Common	Less common	Less common, but may be present
Dyspnea on exertion	Less common	Common	Common
Cor pulmonale	Present (often with multiple exacerbations)	Present (but often in end-stage emphysema)	Present (but often in end-stage emphysema)
Age of patient at symptom onset	6th-7th decade	6th-7th decade	4th-5th decade (although late onset is possible)
Family history of COPD	Possible but not characteristic	Possible but not characteristic	Common in parents, children, and siblings
History of cigarette smoking	Present, often heavy	Present, often heavy	May be present, but COPD can occur in the absence of smoking
Physiologic Function
Airflow (FEV₁, FEV₁/FVC)	Decreased	Decreased	Decreased
Lung volumes, residual volume	Normal	Increased, suggesting air trapping	Increased
Gas exchange, diffusion PaO₂	Often decreased	Often preserved until advanced stage	Often preserved until advanced stage
PaCO₂	May be increased	Often preserved until advanced disease, then elevated	Often preserved until advanced disease, then elevated
Diffusion capacity	Often normal	Decreased	Decreased
Static lung compliance	Normal	Increased	Increased
Chest radiograph	“Dirty lungs” with peribronchial cuffing, suggesting thickened bronchial walls	Hyperinflation, with evidence of emphysema; greater at lung apex than at lung base	Hyperinflation, with evidence of emphysema; frequently greater at lung base than at lung apex (basilar hyperlucency)

Physical examination of the chest early on in a patient with COPD may show wheezing or diminished breath sounds. Later, signs of hyperinflation may be evident—that is, increased anteroposterior diameter (sometimes called a barrel chest), diaphragm flattening, and dimpling inward of the chest wall at the level of the diaphragm on inspiration (called Hoover sign). Other late signs of COPD include use of accessory muscles of respiration (e.g., sternocleidomastoid), edema from cor pulmonale, mental status changes caused by hypoxemia or hypercapnia (especially in acute exacerbations of chronic, severe disease), or asterixis (i.e., involuntary flapping of the hands when held in an extended position, as in “stopping traffic”).

Rule Of Thumb

In patients with COPD, PaCO₂ is usually preserved until airflow obstruction is severe (i.e., FEV₁ < 1 L), when PaCO₂ may increase.

Rule Of Thumb

Digital clubbing is not caused by COPD alone, even if hypoxemia is present. Clubbing in a patient with COPD warrants consideration of another cause (e.g., bronchogenic cancer, bronchiectasis).

Management

In managing patients with chronic, stable COPD, the following goals must guide the clinician 1,2:

• Establish the diagnosis of COPD.

• Optimize lung function.

• Maximize the patient’s functional status.

• Simplify the medical regimen as much as possible.

• Prolong survival whenever possible.

In managing an acute exacerbation of COPD, additional considerations are to reestablish the patient to baseline status as quickly and with as little incidence of morbidity and mortality as possible.20,21 Each of the treatments discussed in this section is considered in the context of these goals, recognizing differences in management between patients with chronic, stable COPD versus an acute exacerbation of COPD. In patients with COPD, PaCO₂ usually is generally preserved until airflow obstruction is severe (FEV₁ < 1 L), when the PaCO₂ level may increase.

Establishing the Diagnosis

Although a spectrum of diseases can give rise to obstructive lung disease, including some unusual entities such as chronic eosinophilic pneumonia, bronchiectasis, and allergic bronchopulmonary aspergillosis, the major challenge facing the clinician who encounters a patient with airflow obstruction is to distinguish COPD (i.e., emphysema or chronic bronchitis or both) from asthma. Distinguishing asthma from COPD may be very difficult in practice; features that tend to favor COPD include chronic daily phlegm production, which establishes the diagnosis of chronic bronchitis; diminished vascularity on chest radiograph; and a decreased diffusing capacity. The diagnosis of asthma is favored if the diminished FEV₁ obtained on spirometry can be normalized after use of an inhaled bronchodilator.

After the diagnosis of COPD is established, a secondary issue is for the clinician to consider whether the patient has an underlying predisposition to COPD, such as AAT deficiency or other cause listed in Box 23-1.^17,18 Underlying causes are present in fewer than 5% of patients with COPD, with AAT deficiency being the most common (2% to 3% of all patients with COPD).

Mini Clini

Determining the Severity of Chronic Obstructive Pulmonary Disease

Problem

You are called to see a patient with COPD (FEV₁ 40% predicted) and are asked to describe the severity of the patient’s illness to a colleague. How do you characterize the severity of COPD?

Discussion

The severity of COPD is described by the degree of airflow obstruction. Traditional descriptors such as hypoxemia and hypercapnia are useful for characterizing COPD. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has proposed a staging system for COPD.² According to this staging system, patients are categorized into one of the following four stages:

Stage	Description
I	Patients with FEV₁/FVC < 70% and FEV₁ > 80% predicted
II	Patients with FEV₁/FVC < 70% and FEV₁ 50%-79% predicted
III	Patients with FEV₁/FVC < 70% and FEV₁ 30%-49% predicted
IV	Patients with FEV₁/FVC < 70% and FEV₁ < 30% or FEV₁ < 50% predicted plus chronic respiratory failure

This patient would be described as having stage III COPD. The stages generally correspond to other physiologic features of COPD. Patients with stage I COPD do not usually have severe hypoxemia. Also, hypercapnia from airflow obstruction would not be expected in patients with stage I COPD, and an arterial blood gas analysis usually is not recommended. Patients with stage III or IV COPD may require supplemental O₂. A blood gas analysis may be helpful in assessment of these patients.

Optimizing Lung Function

Stable Chronic Obstructive Pulmonary Disease

Although airflow obstruction from emphysema itself is irreversible, most (up to two-thirds) patients with stable COPD exhibit a reversible component of airflow obstruction, defined as a 12% and 200-ml increase in postbronchodilator FEV₁ or FVC or both. For this reason, as indicated in an algorithm developed by GOLD (Figure 23-4),^2,22–24 bronchodilator therapy is recommended for patients with COPD.

FIGURE 23-4 COPD management algorithm. (From The Global Strategy for the Diagnosis, Management and Prevention of COPD. Global Initiative for Chronic Obstructive Lung Disease [GOLD], 2006. http://www.goldcopd.com.)

Bronchodilators produce smooth muscle relaxation resulting in improved airflow obstruction, improved symptoms and exercise tolerance, and decrease in the frequency and severity of exacerbations, but they do not enhance survival. The results of the Lung Health Study,⁹ which compared the effects of inhaled ipratropium bromide (two puffs four times daily) with placebo in patients with mild, stable COPD, showed that regular, long-term use of ipratropium did not change the rate of decline of lung function but offered a one-time, small increase in FEV₁.

Both anticholinergic and adrenergic (beta agonist) bronchodilators can improve airflow in patients with COPD, although some clinicians favor an inhaled anticholinergic medication (e.g., ipratropium bromide or tiotropium 22–24) as first-line therapy (Figure 23-5). More recent concerns about the possible adverse cardiovascular effects of anticholinergic therapy in patients with COPD²⁵ have been dismissed by the results of a multicenter trial (UPLIFT [Understanding Potential Long-Term Impacts on Function with Tiotropium]), which found a significantly lower rate of cardiac adverse events and cardiovascular death in patients who received tiotropium.²⁶

FIGURE 23-5 Cumulative percent survival of patients in the Nocturnal Oxygen Therapy Trial (NOTT) and Medical Research Council (MRC) controlled trials of long-term domiciliary O₂ therapy for men older than 70 years. MRC control subjects *(red line)* received no O₂. NOTT subjects *(purple line)* received O₂ for 12 hours in the 24-hour day, including the sleeping hours. MRC O₂ subjects *(blue line)* received O₂ for 15 hours in the 24-hour day, including the sleeping hours, and continuous O₂ therapy (COT) subjects *(green line)* received O₂ for 24 hours in the 24-hour day (on average, 19 hours). (Modified from Flenley DC: Long-term oxygen therapy. Chest 87:99–193, 1985.)

The GOLD guidelines ² recommend the use of short-acting beta-adrenergic agents (≤6 hours) for symptomatic management of all patients with COPD. Also, the use of a long-acting beta agonist (e.g., salmeterol) or a long-acting anticholinergic drug (e.g., tiotropium) can lessen the frequency of acute exacerbations of COPD.²⁵

Other treatment options to optimize lung function include administering corticosteroids and methylxanthines. Systemic corticosteroids can produce significant improvements in airflow in a few (6% to 29%) patients with stable COPD.²⁷ To assess whether airflow obstruction is completely reversible (i.e., the patient has asthma) and whether a patient with COPD is responsive to steroids, a brief course of corticosteroids (20 to 40 mg/day of prednisone or equivalent for 10 to 14 days) is often recommended. Patients with a significant clinical response often are treated with long-term inhaled corticosteroids or rarely with the smallest necessary dose of systemic corticosteroids, recognizing that long-term systemic steroid therapy has risks.²⁸ Also, results of several major clinical trials (e.g., Lung Health Study II, Euroscop, ISOLDE, and Copenhagen City Study but not TORCH) agree that inhaled corticosteroids do not change the rate of decline of FEV₁ in patients with COPD, although their use is associated with a decreased frequency of acute exacerbations.^29,30

Studies of combined salmeterol and fluticasone versus placebo in patients with COPD suggest that adding an inhaled corticosteroid (fluticasone) to the long-acting beta agonist (salmeterol) can improve FEV₁ and can reduce the frequency of acute exacerbations of COPD but does not improve survival.29,30 The finding of a higher rate of pneumonia in inhaled corticosteroid users is concerning. Overall, the GOLD guidelines² recommend use of inhaled corticosteroids in patients with FEV₁ less than 50% and history of recurrent exacerbations (three episodes in the last 3 years), whereas the ATS/European Respiratory Society (ERS) guidelines recommend use of inhaled corticosteroids in patients with FEV₁ less than 50% who have required use of oral corticosteroids or oral antibiotics at least once within the last year.³¹

Treatment with methylxanthines offers little additional bronchodilation in patients using inhaled bronchodilators and generally is reserved for patients with debilitating symptoms from stable COPD despite optimal inhaled bronchodilator therapy. Controlled trials show lessened dyspnea in methylxanthine recipients despite a lack of measurable increases in airflow.³² Side effects of methylxanthines include anxiety, tremulousness, nausea, cardiac arrhythmias, and seizures. To minimize the chance of toxicity, current recommendations suggest maintaining serum theophylline levels at 8 to 10 mcg/ml.

Acute Exacerbations

Strategies for improving lung function during acute exacerbations of COPD generally include inhaled bronchodilators (especially beta-2 agonists), antibiotics, and systemic corticosteroids. Because of their rapid onset of action and efficacy, short-acting beta-2 agonists are first-line therapy for patients with COPD exacerbation. Inhaled beta-2 agonists are frequently administered through a nebulizer, although metered dose inhaler devices may have equal efficacy if administered appropriately.² A common practice is to administer 2.5 mg of albuterol by nebulizer every 1 to 4 hours as needed. Higher doses of albuterol (i.e., 5 mg) do not produce further improvement in pulmonary function and may cause cardiac side effects.³³ Similarly, continuous nebulization of short-acting beta-2 agonists in patients with COPD exacerbation is not recommended.

In addition to inhaled bronchodilator therapy, short-term systemic corticosteroids are recommended to reduce inflammation and improve lung function. An early randomized, controlled trial of intravenous methylprednisolone for patients with acute exacerbations showed accelerated improvement in FEV₁ within 72 hours.³⁴ Larger, more recent trials have confirmed the benefits of systemic corticosteroids in acute exacerbations and have shown that short-term oral courses (i.e., approximately 2 weeks) are as effective as longer courses (i.e., 8 weeks) with fewer adverse steroid effects.³⁵ For patients with acute exacerbations characterized by purulent phlegm, oral antibiotics (e.g., trimethoprim-sulfamethoxazole, amoxicillin, or doxycycline) administered for 7 to 10 days have produced accelerated improvement of peak flow rates compared with placebo recipients.^20,36,37

Finally, intravenous methylxanthines offer little benefit in the setting of acute exacerbations of COPD and have fallen into disfavor.38,39 Taken together, important elements of managing an acute exacerbation of COPD caused by purulent bronchitis include supplemental oxygen (O₂) to maintain arterial saturation at greater than 90%, inhaled bronchodilators, oral antibiotics, and a brief course of systemic corticosteroids.²⁰

For patients with hypercapnia and acute respiratory acidemia, the clinician also must decide whether to institute ventilatory assistance. Although intubation and mechanical ventilation historically have been the preferred approach, more recent studies suggest that noninvasive positive pressure ventilation can be an appealing alternative for patients with acute exacerbations of COPD, especially with severe exacerbations characterized by pH less than 7.30.⁴⁰ Specifically, based on available randomized, controlled clinical trials showing that noninvasive positive pressure ventilation can shorten intensive care unit (ICU) stay and avert the need for intubation, the American Association for Respiratory Care consensus conference and guidelines on noninvasive ventilation from other official societies have endorsed this approach.^41,42 Criteria defining candidacy for noninvasive ventilation include acute respiratory acidosis (without frank respiratory arrest); hemodynamic stability; ability to tolerate the interface needed for noninvasive ventilation; ability to protect the airway; and lack of craniofacial trauma or burns, copious secretions, or massive obesity.⁴¹

Maximizing Functional Status

In symptomatic patients with stable COPD, maximizing their ability to perform daily activities is a priority (see Figure 23-4). Pharmacologic treatments to maximize functional status include administration of bronchodilators to enhance lung function as much as possible and consideration of methylxanthine therapy, based on data that such drugs can lessen dyspnea and improve functional status ratings even in the absence of improved airflow.³²

Comprehensive pulmonary rehabilitation is a multidisciplinary intervention that consists of lower and upper extremity exercise conditioning, breathing retraining, education, and psychosocial support. Pulmonary rehabilitation is an additional important strategy for improving functional status.⁴³ Randomized, controlled trials show that although pulmonary rehabilitation does not improve lung function or survival, this strategy results in decreased dyspnea perception, improved health-related quality of life, fewer days of hospitalization, and decreased health care usage.^44,45

Finally, transcutaneous neuromuscular electrical stimulation is a new experimental therapy that has been successfully used to stimulate peripheral muscles in patients with COPD. Studies have shown significant improvements in quadriceps muscle function, exercise tolerance (including walk distance), and health status in patients with severe COPD.⁴⁶

Mini Clini

Recognizing and Managing an Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Problem

A 70-year-old man with long-standing COPD is admitted to the hospital with an acute exacerbation. On physical examination, he is not dehydrated, and examination shows diminished breath sounds bilaterally without wheezing. Pertinent laboratory values show a hematocrit of 54% (normal is 40%-47%). An arterial blood gas analysis taken on room air revealed the following:

How do you describe his current status, what do his current laboratory values suggest about his long-term gas exchange status, and what treatment should be considered?

Solution

The patient has an acute exacerbation of COPD. The acidemia (pH 7.30) on his arterial blood gas analysis suggests an acute increase in PCO₂ superimposed on chronic hypercapnia, which is suggested by the elevated serum bicarbonate (HCO₃⁻), indicating renal compensation for chronic respiratory acidosis. Although his current hypoxemia may be due to worsened gas exchange accompanying the current flare-up of COPD, his elevated hematocrit, in the absence of dehydration, suggests chronic hypoxemia and secondary erythrocytosis. The goal of therapy is to restore his gas exchange to baseline and to avoid invasive or high-risk interventions, while optimizing survival.

To achieve these goals, treatment would consist of aggressive use of bronchodilators, intravenous corticosteroids, supplemental O₂, and antibiotics (if there is evidence of acute lung infection, either bronchitis or pneumonia). In view of the patient’s acute chronic respiratory acidemia, ventilatory support should be implemented. As indicated by several randomized, controlled trials, noninvasive positive pressure ventilation is an effective alternative to intubation.

Preventing Progression of Chronic Obstructive Pulmonary Disease and Enhancing Survival

Cigarette smoking is widely recognized as the major risk factor for accelerating airflow obstruction in smokers who are “susceptible.” For these individuals, smoking cessation can slow the rate of decline of FEV₁ and restore the rate of lung decline to that seen in healthy, age-matched nonsmokers.

Follow-up data from the Lung Health Study ⁹ confirm that a comprehensive smoking cessation program (including instruction, group counseling, and nicotine replacement therapy) can achieve sustained smoking cessation in 22% of participants and that the rate of annual FEV₁ decline in these sustained nonsmokers was significantly less than it was for continuing smokers, even over 11 years of follow-up.¹⁰ Participation in aggressive smoking cessation can enhance survival rates in patients with COPD.¹⁰

Critical elements in achieving successful abstinence from smoking include identifying “teachable moments” (i.e., during episodes of illness where smoking can be identified as a contributing factor ⁴⁷), identifying the role of smoking in adverse health outcomes, negotiating a “quit date,” and providing frequent follow-up reminders from health care providers.⁴⁸ A helpful strategy during counseling is to use the five A’s of smoking cessation²:

Ask if they are smoking

Advise to quit

Assess willingness to quit

Assist by providing a plan

Arrange a follow up

In this regard, the respiratory therapist (RT), who sees the patient frequently, has a special responsibility to provide frequent, constructive reminders about the advisability of smoking cessation.⁴⁹

Among available treatments for COPD, supplemental oxygen is important because, similar to smoking cessation and lung volume reduction surgery in selected individuals (see later), it can prolong survival.50–53 Box 23-2 reviews the indications for supplemental O₂, and Figure 23-5 shows the results of the American Nocturnal Oxygen Therapy Trial⁵⁰ and the British Medical Research Council trial of domiciliary O₂ (1980-1981).^51,52