Chronic Obstructive Pulmonary Disease

COPD is persistent, partially reversible airflow obstruction most commonly caused by an abnormal inflammatory response to toxins, often cigarette smoke. ₁-Antitrypsin deficiency and a variety of occupational exposures are less common causes in nonsmokers. Symptoms are productive cough and dyspnea that develop over years; common signs include decreased breath sounds and wheezing. Severe cases may be complicated by weight loss, pneumothorax, right heart failure, and respiratory failure. Diagnosis is based on history, physical examination, chest x-ray, and pulmonary function tests. Treatment is with bronchodilators, corticosteroids, and, when necessary, O₂ . About 50% of patients die within 10 yr of diagnosis.

Geriatric Essentials

• Aging itself results in a gradual decrease in FEV₁ (by 25 to 30 mL/yr), a slight increase in functional residual capacity (FRC), and a gradual decrease in resting PaO₂.
• Reduction in airflow accelerates with cumulative exposure to cigarette smoke in genetically susceptible people, and slows with smoking cessation, even after age 65. Clinically significant airflow obstruction typically takes decades to develop and makes COPD a disorder primarily of middle-aged and elderly people.
• Causes, symptoms, signs, diagnosis, and treatment are similar in younger adults and in the elderly. Guidelines for evaluation and treatment are available at the Global Initiative for Chronic Obstructive Pulmonary Disease web site and at the American Thoracic Society web site.
• Dry-powder inhaler forms of inhaled drugs (-agonists and anticholinergics) are usually best for the elderly because they reduce the need for coordination between activation and inhalation with metered-dose inhalers.
• Pulmonary rehabilitation programs may be particularly important for some elderly people with COPD because these programs can diminish the immobility, social isolation, anxiety, and depression that often accompany severe disease and can improve quality of life. However, they do not prolong life.
• Health care practitioners should initiate end-of-life discussions before hospitalization is needed to determine the wishes of patients with moderately severe disease, because patients with end-stage COPD often need assisted ventilation and may have difficulty being weaned from the ventilator.
• Unexplained weight loss in patients with end-stage COPD is a poor prognostic sign.
• Death in patients with COPD is typically due to acute respiratory failure, pneumonia, lung cancer, cardiac disease, or pulmonary embolism.

COPD comprises chronic obstructive bronchitis and emphysema. Many patients have features of both. In both variations, airflow obstruction may be partially reversible; a 15% improvement in FEV₁ after bronchodilator use defines reversibility.

The prevalence, incidence, and mortality rates of COPD increase with aging up to age 85 and then stabilize or decrease; up to 10% of people age 55 to 85 in North America have the disease. COPD ranks 2nd in frequency to coronary artery disease as a disability compensated by Social Security. COPD is the 4th leading cause of death in the US, and the number of deaths attributable to COPD is increasing. Incidence and mortality are generally higher in whites, blue-collar workers, and people with fewer years of formal education, partly because smoking is more prevalent among members of these groups. Prevalence is higher in men. Total mortality is similar in both sexes, although some recent evidence suggests mortality is leveling off among white men but increasing among the elderly, women, and blacks.

Chronic obstructive bronchitis is chronic bronchitis with airflow obstruction. Chronic bronchitis is defined as productive cough for most days of the week for at least 3 mo in 2 successive yr. Chronic bronchitis becomes chronic obstructive bronchitis if spirometric evidence of airflow obstruction develops. Only a minority of patients with chronic bronchitis develop airflow obstruction. Asthmatic bronchitis is a similar, overlapping condition characterized by chronic productive cough, wheezing, and partially reversible airflow obstruction in smokers with a history of asthma. In some cases, the distinction between chronic obstructive bronchitis and asthmatic bronchitis is unclear.

Emphysema is destruction of lung parenchyma leading to loss of elastic recoil and loss of alveolar septa and radial airway traction, which increases the tendency for airway collapse. Lung hyperinflation, airflow limitation, and air trapping follow. Airspaces enlarge and may eventually form bullae.

Etiology

A combination of genetic predisposition and environmental exposure leads to COPD. Cigarette smoking is the primary risk factor in > 80% of cases; an exposure history of >= 40 pack-years is especially predictive. Only about 15% of smokers develop clinically apparent COPD; those smokers who develop COPD probably do so because of genetic polymorphisms (eg, in microsomal epoxide hydrolase, vitamin D-binding protein, IL-1, IL-1 receptor antagonist, tumor necrosis factor [TNF]-, transforming growth factor- genes) that confer susceptibility to disease. Smokers with preexisting airway reactivity (defined by increased sensitivity to inhaled methacholine), even in the absence of clinical asthma, are at greater risk of developing COPD than are those without. Low body weight, childhood respiratory diseases, passive cigarette smoke exposure, air pollution, and occupational dust (eg, mineral or cotton dust) or chemical (eg, cadmium) exposure contribute to the risk of COPD but are of minor importance compared with cigarette smoking.

Pathophysiology

In genetically susceptible people, inhalational exposures trigger an inflammatory response in airways and alveoli that leads to disease. The process is thought to be mediated by an increase in protease activity and a decrease in antiprotease activity. In people with COPD, protease activity exceeds antiprotease activity, and tissue destruction and mucus hypersecretion result. Neutrophil-induced oxidative damage, release of profibrotic neuropeptides, and reduced levels of vascular endothelial growth factor may also play a role, as does infection.

Bacteria colonize the normally sterile lower airways of about 30% of patients with active COPD. Some experts postulate that smoking and airflow obstruction lead to impaired mucus clearance in lower airways, which predisposes to infection. The repeated bouts of infection lead to an increased inflammatory burden that may hasten disease progression. There is no evidence, however, that long-term use of antibiotics slows the progression of COPD in susceptible smokers.

The cardinal pathophysiologic feature of COPD is varying degrees of airflow limitation that occurs with emphysema (caused by parenchymal destruction) combined with airflow obstruction that occurs with chronic obstructive bronchitis (caused by mucus hypersecretion, airway wall thickening, ciliary dysfunction, mucus plugging, and bronchospasm). Increased airway resistance increases the work of respiration, as does lung hyperinflation. Increased work of breathing may lead to alveolar hypoventilation with hypoxia and hypercapnia, although hypoxia is also caused by ventilation/perfusion (V/Q) mismatch. Some patients with advanced disease develop chronic hypoxemia and hypercapnia. Chronic hypoxemia increases pulmonary vascular tone which, if diffuse, causes pulmonary hypertension and cor pulmonale. Excessive O₂ administration may then worsen hypercapnia in some patients by decreasing the hypoxic ventilatory drive, leading to alveolar hypoventilation.

Histologic changes of emphysema include airspace distortion due to loss of alveolar attachments and alveolar septal destruction. Enlarged alveolar spaces sometimes consolidate into bullae, defined as airspaces >= 1 cm in diameter. Bullae may be empty or have strands of lung tissue traversing them in areas of locally severe emphysema; they occasionally occupy half of or an entire hemithorax.

Histologic changes of chronic bronchitis include peribronchiolar inflammatory infiltrates, bronchial smooth muscle hypertrophy, an increased number of mucous glands, and goblet cell metaplasia.

Symptoms and Signs

The most common symptoms of COPD are productive cough and dyspnea. Productive cough is the initial symptom in most patients in their 40s and 50s who have smoked >= 20 cigarettes/day for > 20 yr. The sputum is usually opalescent and varies in volume from < 4.5 mL to > 15 mL. Color variations (eg, green, yellow) are a sign of sputum neutrophils and suggest bacterial infection or colonization, exacerbation, or, less commonly, bronchiectasis. Increase in sputum volume may also signify exacerbation.

Dyspnea that is progressive, persistent, exertional, or worse during respiratory infection appears by the time patients reach their late 50s or early 60s and usually progresses quickly in elderly patients who continue to smoke and who have higher lifetime tobacco exposure. Morning headache develops in more advanced disease and signals nocturnal hypercapnia or hypoxemia. Severe hypercapnia may cause confusion, lethargy, and increasing somnolence and is a sign of impending respiratory failure. Hypoxemia may impair cognition with symptoms such as an inability to concentrate and reduced short-term memory.

End-stage COPD is manifested by progressive weight loss that is not explained by other diseases; dyspnea with decreasing activity that ultimately leads to dyspnea at rest; rising resting Pco₂ over time; and chronic fatigue.

Signs of COPD include wheezing, lung hyperinflation manifesting as decreased heart and lung sounds, increased anteroposterior diameter of the thorax (barrel chest), and use of neck muscles during inspiration. Patients with advanced emphysema lose weight and experience muscle wasting because of immobility; hypoxia; release of systemic inflammatory mediators, such as TNF-; and increased metabolic rate. Signs of advanced disease include pursed-lip breathing, which delays airway closure so that a large tidal volume can be maintained and respiratory muscles can function more efficiently; breathing in the sitting position with elbows resting on the thighs or a table, which may make breathing more efficient by fixating the upper thorax and increasing the curvature of the diaphragm; use of accessory muscles with paradoxical indrawing of the lower intercostal interspaces (Hoover's sign); and cyanosis. Signs of cor pulmonale include neck vein distention; splitting of the 2nd heart sound with an accentuated pulmonic component; a right-sided S₃ gallop; tricuspid insufficiency murmur; and peripheral edema. Right ventricular heaves are uncommon in COPD because of hyperinflated lungs.

Acute exacerbations of COPD occur sporadically and are heralded by increased symptom severity. The specific cause of an exacerbation is almost always impossible to determine but is often attributed to viral URI or acute bacterial bronchitis. As COPD progresses, acute exacerbations tend to become more frequent, averaging about 3 episodes/yr. Patients who suffer acute exacerbations are much more likely to have recurrent exacerbations.

Spontaneous pneumothorax may occur as a result of rupture of bullae and should be suspected in any patient with COPD whose pulmonary status abruptly worsens.

Diagnosis

Diagnosis is suggested by history, physical examination, and chest imaging and is confirmed by pulmonary function tests.

Chest x-rays are insensitive for mild or moderate COPD, but patients with moderate or severe emphysema typically have hyperinflated lungs, a flattened diaphragm, a narrow heart, decreased peripheral vascular markings, and increased retrosternal airspace. Bullae (radiolucencies > 1 cm surrounded by arcuate hairline shadows) reflect locally severe disease. Emphysematous changes predominantly in the lung bases indicate ₁-antitrypsin deficiency. The chest x-rays of patients with chronic obstructive bronchitis may be normal or may demonstrate a bi-basilar increase in bronchovascular markings. Prominent hila may suggest large central pulmonary arteries, which commonly occur with pulmonary hypertension. Right ventricular enlargement that occurs in cor pulmonale may be masked by lung hyperinflation or may manifest as encroachment of the heart shadow on the retrosternal space or by widening of the transverse cardiac shadow in comparison with previous chest x-rays.

CT scans may clarify abnormalities seen on chest x-rays suggestive of coexisting or complicating diseases, such as pneumonia or lung cancer, and help assess the severity and distribution of emphysema, estimated either by visual scoring or by analyzing the distribution of lung density. These CT findings may be useful in preparation for lung volume reduction surgery.

Spirometry quantifies the severity and reversibility of suspected obstructive disease and is also useful for following disease progression and monitoring response to treatment. The primary diagnostic tests are FEV₁, which is the volume of air forcefully expired during the 1st second after a full breath; forced vital capacity (FVC), which is the total volume of air expired with maximal force; and flow-volume loops, which are simultaneous spirometric recordings of airflow and volume during forced maximal expiration and inspiration.

Pulmonary function test results must be interpreted in the context of changes attributed to aging and the duration of exposure to smoking. Aging itself results in a gradual reduction (25 to 30 mL/yr) of the FEV₁ beginning at about age 30 (see Figure 78-1) and a slight increase in FRC and residual volume (RV). FEV₁ declines more steeply (60 to 90 mL/yr) in smokers; in middle-aged smokers who already have a low FEV₁, the decline occurs at an even more rapid rate. A prolonged forced expiration (> 4 sec) is the initial clinically measurable sign of early or moderate COPD. Obstruction is present when the FEV₁ is < 80% of the FVC.

Flow-volume loops show a concave pattern in the expiratory tracing (see Figure 78-2).

Additional pulmonary function testing (eg, measurement of lung volumes and diffusing capacity) may be helpful to confirm the diagnosis or to plan treatment (eg, lung volume reduction surgery). Other test abnormalities may include an increased total lung capacity, FRC, and RV, which can help distinguish COPD from restrictive pulmonary disease, in which these measures are diminished; decreased vital capacity; and decreased single-breath diffusing capacity for carbon monoxide (DL_CO). Decreased DL_CO is nonspecific but can help distinguish COPD from asthma, in which DL_CO is normal or elevated.

The ECG, often performed to exclude cardiac causes of dyspnea, typically demonstrates diffusely low QRS voltage with a vertical heart axis caused by lung hyperinflation and increased P-wave voltage or rightward shifts of the P-wave vector caused by right atrial enlargement in patients with advanced emphysema. Findings of right ventricular hypertrophy include an R or R´ wave as tall as or taller than the S wave in lead V₁; an R wave smaller than the S wave in lead V₆; and/or right-axis deviation > 110° without right bundle branch block. Multifocal atrial tachycardia, an arrhythmia that can accompany COPD, manifests as a tachyarrhythmia with polymorphic P waves and variable PR intervals.

Echocardiography is occasionally useful for assessing right ventricular function, evaluating tricuspid regurgitation, and estimating pulmonary arterial pressure, although it may be technically difficult in COPD patients. It is most often indicated when coexistent left ventricular or valvular heart disease is suspected. A test for plasma levels of brain natriuretic peptide may be helpful in some cases for distinguishing dyspnea due to heart failure from dyspnea due to COPD.

CBC is of little diagnostic value in the evaluation of COPD but occasionally shows erythrocytosis (Hct > 48%) as a reflection of chronic hypoxemia.

ABGs should be measured in patients who display signs of exacerbation, such as increased work of breathing, somnolence, and low O₂ saturation on oximetry. Hypoxemia, when present, results from V/Q mismatching because of bronchospasm, intrabronchial mucus, premature airway collapse, and destruction of alveoli. Hypoxemia may also result from reduced PaO₂ with hypoventilation. When hypoventilation is present, hypercapnia also occurs. Chronic hypercapnia is confirmed by a near-normal blood pH and an elevated serum HCO₃ level. Care must be taken in diagnosing hypoxemia in the elderly because the normal PaO₂ of a 75-year-old is about 75 mm Hg, compared with 95 to 100 mm Hg in younger people.

Findings of PaO₂ < 50 mm Hg or PaCO₂ > 50 mm Hg in the setting of respiratory acidemia define acute respiratory failure. However, some patients with chronic COPD survive at such levels for prolonged periods.

Prognosis

Progression of COPD (manifesting as a decline in FEV₁ and appearance or worsening of symptoms) is accelerated by continued smoking. Aging itself can lead to a drop in FEV₁ of 250 to 300 mL over a period of 10 yr; thus, patients who have mild disease may progress to moderate disease and those who have moderate disease may progress to severe disease, even after they stop smoking and in the absence of other causes of disease progression.

Changes in severity of airflow obstruction predict symptoms, functional status, and survival. Patients are usually not dyspneic during usual activities until the FEV₁ decreases to about 1.5 to 1.75 L. When the FEV₁ falls below about 1 L, patients develop dyspnea during less physically demanding tasks, such as performing basic activities of daily living; when the FEV₁ falls below about 0.8 L, they are at risk of hypoxemia, hypercapnia, and cor pulmonale. An FEV₁ > 1.5 L is usually associated with a normal age-adjusted life span; if the FEV₁ is 0.75 to 1.25 L, 5-yr survival is about 40 to 60%; if < 0.75 L, about 30 to 40%. Combination of FEV₁ with measures of exercise capacity, dyspnea severity, and body mass index may be more predictive of mortality than FEV₁ alone. Cardiac disease, low body weight, resting tachycardia, ventricular arrhythmias, hypercapnia, and hypoxemia are also negatively correlated with survival, whereas a significant response to bronchodilators is associated with improved survival. Death in patients with COPD often results from intercurrent illnesses rather than from progression of the underlying disease; causes include acute respiratory failure, pneumonia, lung cancer, cardiac disease, and pulmonary embolism.

Hospitalization for a COPD exacerbation in elderly patients is associated with an average survival time of 5 yr, with women having a more favorable prognosis. In COPD patients, aging is associated with longer hospitalizations and a greater likelihood of discharge to institutional care. Therefore, assessment of likelihood of return to independent living and discharge planning should begin early in the hospitalization. Risk factors for death in patients with acute exacerbation requiring hospitalization include older age, higher PaCO₂, and use of maintenance oral corticosteroids.

The only treatment shown to decrease mortality is supplemental O₂ therapy for COPD patients whose PaO₂ is chronically < 55 mm Hg. However, pulmonary rehabilitation programs can improve patients' quality of life by improving their exercise capacity and independence.

End-of-life issues: All patients with moderate to severe COPD should be encouraged to discuss end-of-life care with their families and physicians, including issues of resuscitation and intubation. Ideally, the discussion should take place in the outpatient setting before either a life-threatening pulmonary infection develops or a comorbid illness is exacerbated. An advance directive in the form of a living will or durable power of attorney is the best way for patients to document their wishes. Families should ideally participate in the conversation to minimize conflicts that may arise during a critical illness when patients can no longer speak for themselves. A palliative care consultation should be considered for all patients with end-stage disease, and hospice care should be discussed with patients with end-stage disease who do not desire aggressive treatment for future exacerbations or acute illnesses.

In patients who are truly nearing the end of life, exercise is unwarranted and activities of daily living should be decreased to minimize dyspnea. Health care practitioners may suggest that patients live on a single level of their home, not wear shoes that require tying, avoid tight belts, and eat 5 or 6 small meals a day rather than 3 larger ones.

Patients with end-stage COPD who need assisted ventilation often have difficulty being weaned from ventilatory support. In some cases, it is more appropriate (with the patient's and family's consent) to forego artificial ventilation and instead use opioids and supportive measures to keep the patient comfortable.

Treatment

Guidelines for evaluation and treatment are available at the Global Initiative for Chronic Obstructive Pulmonary Disease web site and at the American Thoracic Society web site.

COPD management involves treatment of chronic stable disease and of exacerbations (see Table 78-1).

Chronic stable COPD: Treatment of chronic stable COPD aims to prevent exacerbations and provide long-term improvement in lung and physical function through drug and O₂ therapy, smoking cessation, exercise, enhancement of nutrition, and pulmonary rehabilitation. This approach limits functional impairment, loss of independence, depression, and social isolation that are often features of advanced disease.

Bronchodilators are the mainstay of management for the majority of patients with reversible airflow obstruction; drug classes include inhaled -agonists and anticholinergics. Any patient with symptomatic COPD should try taking a drug from 1 or both of these classes, which are equally effective. If the trial is beneficial (based on the patient's subjective response), the drugs should be continued; if the drugs have no apparent benefit, they can be stopped.

For initial therapy, the choice between short-acting -agonists, long-acting -agonists, anticholinergics (which have a greater bronchodilating effect), or combination -agonist and anticholinergic therapy is often a matter of tailoring cost and convenience to the patient's preferences, symptoms, and comorbid diseases (eg, anticholinergics may worsen symptomatic benign prostatic hypertrophy or glaucoma). There is no evidence that regular bronchodilator use slows deterioration of pulmonary function, but the drugs relieve acute symptoms and improve pulmonary function and exercise capacity.

In treatment of mild or moderate chronic stable disease, administration by metered-dose inhaler or dry-powder inhaler is preferred over nebulized home treatment; home nebulizers may be more helpful in patients with severe disease but are prone to contamination from inadequate cleaning and drying. Up to 1/3 of people > 65 yr using a metered-dose inhaler cannot synchronize drug aerosolization with inhalation; spacers help ensure optimal delivery of drug to the distal airways and reduce but do not eliminate the importance of coordinating activation of the inhaler with inhalation. Patients should be taught to exhale to FRC, inhale the aerosol slowly to total lung capacity, and hold the inhalation for 3 to 4 sec before exhaling. Some spacers alert patients if they are inhaling too rapidly. Patients should be advised to wash and dry their spacers after each use to prevent bacterial contamination. Dry-powder inhalers eliminate the need for coordination because drug is delivered only when the patient inhales, and they do not release fluorocarbon propellants into the environment.

-Agonists relax bronchial smooth muscle and increase mucociliary clearance. Albuterol aerosol, 2 puffs (90 µg/puff) inhaled from a metered-dose inhaler 4 to 6 times/day prn, is usually the drug of choice because of its low cost; regular dosing offers no advantages over as-needed use and causes more adverse effects. Long-acting -agonists are preferable for patients with nocturnal symptoms or for those who find frequent dosing inconvenient; options include salmeterol powder, 1 puff (50 µg) inhaled bid; or formoterol powder >= 1 puff (12 µg) inhaled bid (if any formoterol powder remains in the capsule after 1 puff and inhalation, patients are advised to repeat inhalations until capsule is empty). The dry-powder formulations may be more effective for patients who have trouble coordinating use of a metered-dose inhaler. Patients should be taught the difference between short- and long-acting drugs, because long-acting drugs that are used as needed or more than twice/day increase the risk of cardiac arrhythmias. Adverse effects commonly result from use of any -agonist and include tremor, anxiety, tachycardia, and mild hypokalemia.

Anticholinergics relax bronchial smooth muscle through competitive inhibition of muscarinic receptors (M₁, M₂, and M₃). Ipratropium is most commonly used because of its low cost and availability; dose is 2 to 4 puffs q 4 to 6 h (usual dose is 2 puffs q 6 h; patients should not exceed 12 puffs in 24 h). Ipratropium has a slow onset of action (within 30 min; peak effect in 1 to 2 h), so a ₂-agonist is often prescribed with it in a single combination inhaler or as a separate as-needed rescue drug. Tiotropium, a long-acting quaternary anticholinergic, is M₁ and M₃ selective and may therefore have an advantage over ipratropium because M₂ receptor blockade (as occurs with ipratropium) may limit bronchodilation. Dose is 18 µg once/day; once-daily dosing may make it attractive for many elderly patients, but the drug is not available worldwide, and additional studies are needed before its precise role can be clarified. Adverse effects of all anticholinergics are pupillary dilation, blurred vision, and dry mouth. Rarely, inhaled anticholinergics can exacerbate glaucoma or benign prostatic hypertrophy.

Inhaled corticosteroids inhibit airway inflammation, reverse -receptor down-regulation, and inhibit leukotriene and cytokine production. They do not alter the course of pulmonary function decline in COPD patients who continue to smoke, but they do improve short-term pulmonary function in some patients, are additive to the effect of bronchodilators, and may diminish the frequency of COPD exacerbations. Dose depends on the drug; examples include fluticasone 500 to 1000 µg bid and beclomethasone 80 to 320 µg bid. The long-term risks of inhaled corticosteroids in the elderly are not proven but probably include osteoporosis and cataract formation. Long-term users, therefore, should undergo periodic ophthalmologic and bone densitometry screening and should possibly receive supplemental Ca, vitamin D, and a bisphosphonate as indicated. Combinations of a long-acting -agonist (eg, salmeterol) and an inhaled corticosteroid (eg, fluticasone) are more effective than either drug alone in the treatment of chronic stable COPD.

Oral or systemic corticosteroids can be used to treat severe chronic stable COPD but seem to benefit only 10 to 20% of patients, and long-term risks may exceed benefits. Formal comparisons between oral and inhaled corticosteroids have not been performed. Oral dosing should start at about 30 mg prednisone once/day, and response to treatment should be monitored by spirometry. If the FEV₁ improves >= 20%, then the dose should be tapered at a rate of a 5-mg equivalent of prednisone per week to the lowest amount that maintains the improvement. If exacerbation occurs during tapering, inhaled corticosteroids may be helpful, but a resumption of higher dosing is likely to provide more rapid symptom relief and improvement in FEV₁. By contrast, if initial FEV₁ improvement is < 20%, then corticosteroids should be tapered rapidly and stopped. Alternate-day dosing is an option if it reduces adverse effects while sustaining daily improvement.

Theophylline plays a limited role in the treatment of chronic stable COPD now that safer, more effective drugs are available. Theophylline decreases smooth muscle spasm, enhances mucociliary clearance, improves right ventricular function, and decreases pulmonary vascular resistance and arterial pressure. Its mode of action is incompletely understood but appears to differ from that of ₂-agonists and anticholinergics. Its role in improving diaphragmatic function and dyspnea during exercise is controversial. Low-dose theophylline (300 to 400 mg/day) has anti-inflammatory properties and may enhance the effects of inhaled corticosteroids. Theophylline can be used for patients who have not adequately responded to inhaled agents and who have shown symptomatic benefit from a trial of the drug. Serum levels should be checked at least once after initial dosing or if the patient develops symptoms of toxicity or is questionably adherent; slowly absorbed oral theophylline preparations, which require less frequent dosing, enhance compliance. Adverse effects (eg, sleeplessness and GI upset) are common even at low blood levels. More serious adverse effects, such as supraventricular and ventricular arrhythmias and seizures, tend to occur at blood levels > 20 mg/L. Hepatic metabolism of theophylline varies greatly and is influenced by genetic factors, age, cigarette smoking, hepatic dysfunction, and some drugs, such as macrolide and fluoroquinolone antibiotics and nonsedating histamine₂ blockers. The half-life in elderly patients is prolonged, and proper dosage may be half the usual amount.

Oxygen therapy prolongs life in COPD patients whose PaO₂ is chronically < 55 mm Hg (SaO₂ < 88%) during treatment with an optimal medical regimen for at least 30 days. Additional criteria for use include a PaO₂ of 55 to 59 mm Hg or SaO₂ of 88 to 89% for patients with cor pulmonale or erythrocytosis (Hct > 55%) and possibly a PaO₂ >= 55 mm Hg or SaO₂ >= 88% for patients whose room-air PaO₂ is < 55 mm Hg or SaO₂ < 88% during exercise or sleep. Continual 24-h use is more effective than a 12-h nocturnal regimen in patients whose PaO₂ is persistently < 55 mm Hg. O₂ therapy brings Hct toward normal levels; moderately improves neuropsychologic factors, possibly by facilitating sleep; and ameliorates pulmonary hemodynamic abnormalities. O₂ therapy also increases exercise tolerance in many patients. O₂ is administered by nasal cannula at a flow rate sufficient to achieve a PaO₂ > 60 mm Hg (SaO₂ > 90%), usually <= 3 L/min at rest. O₂ is supplied by electrically driven O₂ concentrators, liquid O₂ systems, or cylinders of compressed gas. Concentrators, which limit mobility but are the least expensive, are preferable for patients who spend most of their time at home. Such patients require small O₂ tanks for backup and for portable use. Portable canisters of liquid O₂ are easier to carry and have more capacity than portable cylinders of compressed gas; a liquid system is preferable for patients who spend much time out of their homes. Large compressed-air cylinders are the most expensive way of providing O₂. Patients must be warned of the dangers of smoking during O₂ use. Various devices can conserve the amount of O₂ used, either by using a reservoir system or by permitting O₂ flow only during inspiration. In patients requiring lower O₂ flows, these devices correct hypoxemia as effectively as do continuous-flow systems.

Sleep studies should be considered for patients with advanced COPD who do not meet the criteria for long-term O₂ therapy but whose clinical assessment suggests pulmonary hypertension in the absence of daytime hypoxemia. Nocturnal O₂ may be prescribed if a sleep study shows episodic desaturation to <= 88%. Such treatment may prevent progression of pulmonary hypertension, but its effects on survival are unknown. Sleep apnea should be considered in COPD patients with unexplained pulmonary hypertension or in those with symptoms of daytime sleepiness, witnessed apneic events at night, or obesity.

Supplemental oxygen is needed by some patients during air travel, because flight cabin pressure in commercial airliners is low. Eucapnic COPD patients with a sea level PaO₂ > 68 mm Hg generally have an in-flight PaO₂ > 50 mm Hg and usually do not require supplemental O₂. All COPD patients with hypercapnia, significant anemia (Hct < 30), or coexisting cardiac or cerebrovascular disease should use supplemental O₂ during long flights and should notify the airline when making their reservation. Patients are not permitted to transport or use their own O₂. Airlines provide their own O₂ systems, and most require a minimum of 24 hours' notice, a physician's statement of necessity, and an O₂ prescription before the flight. Patients should bring their own nasal cannulas, because some airlines provide only face masks. Arrangements for O₂ equipment in the destination city, if required, should be made in advance so that the supplier can meet the traveler at the airport.

Smoking cessation slows but does not altogether halt the progression of airflow obstruction (see Figure 78-1). Simultaneous use of multiple strategies is most effective: establishment of a quit date, behavior modification techniques, group support sessions, nicotine replacement therapy (by gum, transdermal patch, inhaler, lozenge, or nasal spray), bupropion, and physician encouragement. Quit rates are about 30% at 1 yr even with bupropion combined with nicotine replacement, the most effective intervention.

Influenza vaccinations should be given annually to all patients with COPD. If a patient is unable to receive an influenza vaccination or if the prevailing influenza strain is not included in the annual vaccine formulation, prophylactic treatment (amantadine, rimantadine, oseltamivir, or zanamivir) is appropriate during community influenza outbreaks. Pneumococcal polysaccharide vaccine, although of unproven efficacy in COPD, has minimal adverse effects and should probably also be administered.

Physical activity should be maintained. Skeletal muscle deconditioning resulting from inactivity or prolonged hospitalization for respiratory failure can be ameliorated with a program of graded exercise. Specific training of respiratory muscles is less helpful than general aerobic conditioning. A typical training program begins with slow walking on a treadmill or unloaded cycling on an ergometer for a few minutes. Duration and exercise load are progressively increased over 4 to 6 wk until the patient can exercise for 20 to 30 min nonstop with manageable dyspnea. Patients with severe COPD can usually achieve an exercise regimen of walking for 30 min at 1 to 2 mph. Maintenance exercise should be performed 3 to 4 times/wk to maintain fitness levels. O₂ saturation is monitored and supplemental O₂ provided as needed. Upper extremity resistance training is helpful in allowing the patient to perform daily tasks such as bathing, dressing, and housecleaning. COPD patients should be taught ways to conserve energy during activities of daily living and to pace their activities. Difficulties in sexual function should be discussed and advice given on using energy-conserving techniques for sexual gratification, including scheduling activity for "best-breathing" time of day, using a bronchodilator 20 to 30 min beforehand, avoiding eating or drinking large amounts beforehand, and assuming a position that does not put pressure on the chest or abdomen or require arm support.

Nutrition also plays an important role in the treatment of COPD. COPD patients are at risk of weight loss and nutritional deficiencies because of a 15 to 25% increase in resting energy expenditure due to difficulty breathing; a larger postprandial increase in metabolism and heat production (ie, the thermal effect of feeding), perhaps because a distended stomach interferes with descent of the already flattened diaphragm and increases the work of breathing; a higher energy cost of daily activities; reduced caloric intake relative to need; and the catabolic effect of inflammatory cytokines such as TNF-. Generalized muscle strength and efficiency of O₂ use are impaired. Patients with poorer nutritional status have a worse prognosis, so it is prudent to recommend a balanced diet with adequate caloric intake in conjunction with exercise to prevent or reverse malnutrition and muscle atrophy. However, excessive weight gain should be avoided, and obese patients should strive to achieve a more normal body mass index. Studies of nutritional supplementation alone have not shown improvement in pulmonary function or exercise capacity. The roles of anabolic steroids (eg, megestrol, oxandrolone), growth hormone supplementation, and TNF antagonists in reversing malnutrition and improving functional status and prognosis in COPD are not well defined.

Pulmonary rehabilitation is a combination of exercise training, education, and psychosocial and behavioral intervention administered by a multidisciplinary team (eg, of physicians, nurses, respiratory therapists, physical and occupational therapists, psychologists, social workers) that may be particularly important for some elderly patents with COPD because it diminishes the immobility, social isolation, anxiety, and depression that often accompany severe disease and improves quality of life. However, it does not reduce mortality.

Surgery, specifically a procedure known as lung volume reduction surgery, may benefit a small number of patients. Whether or not patients benefit depends on their functional state, the severity and extent of their emphysema, and their general health. Evaluation should be done by a team experienced in performing this procedure.

Acute COPD exacerbation: Immediate objectives are to ensure adequate oxygenation, reverse airflow obstruction, and treat underlying causes. The cause is usually unknown, although some acute exacerbations result from bacterial or viral infections. Smoking, irritative inhalational exposure, and high levels of air pollution also contribute. Mild exacerbations often can be treated on an outpatient basis in patients with adequate home support. Elderly frail patients and those with comorbidities, a history of respiratory failure, or acute changes in ABG measurements should be admitted to the hospital for observation and treatment. Patients with life-threatening exacerbations manifesting as uncorrected hypoxemia, acute respiratory acidosis, new arrhythmias, or deteriorating respiratory function despite hospital treatment or those who require sedation for management should be admitted to the ICU and their respiratory status monitored frequently.

Ventilatory assistance should be given if agreed upon in end-of-life discussions. Noninvasive positive-pressure ventilation (eg, pressure support or bilevel positive airway pressure ventilation by face mask) is an alternative to full mechanical ventilation. Noninvasive ventilation appears to decrease the need for intubation, reduce hospital stay, and reduce mortality in some patients with severe exacerbations (defined as a pH < 7.3 in hemodynamically stable patients not at immediate risk of respiratory arrest). Noninvasive ventilation appears to have no effect in patients with less severe exacerbations. However, it may be indicated for patients in this group whose ABGs worsen despite initial drug therapy or who appear to be imminent candidates for full mechanical ventilation but who do not require intubation for control of the airway or sedation for agitation. Deterioration on noninvasive ventilation should prompt conversion to invasive mechanical ventilation.

Endotracheal intubation and mechanical ventilation are done if deteriorating ABG levels and mental status and progressive respiratory fatigue are present. Risk factors for ventilator dependence include an FEV₁ < 0.5 L, stable ABGs with a PaO₂ < 50 mm Hg and/or PaCO₂ > 60 mm Hg, severe exercise limitation, and poor nutritional status. Therefore, a discussion of the patient's wishes regarding intubation and mechanical ventilation should be initiated and documented in advance.

Tracheostomy is indicated to facilitate comfort, communication, and eating if a patient requires prolonged intubation (eg, > 2 wk). With a good multidisciplinary rehabilitation program, including nutritional and psychologic support, many patients requiring prolonged mechanical ventilation can be successfully weaned and can return to their former level of function.

Oxygen therapy is required by most hospitalized patients, even if they do not need it chronically. O₂ administration may worsen hypercapnia by attenuating hypoxic respiratory drive. After 30 days of recovery at home following hospital discharge, room-air PaO₂ should be reassessed to determine if the patient still requires supplemental O₂. -Agonists, anticholinergics, corticosteroids, or all 3 should be started concurrently with O₂ therapy (regardless of how O₂ is administered) with the aim of reversing airflow obstruction.

-Agonists are the cornerstone of drug therapy for acute exacerbations. The most widely used drug is albuterol, 2.5 mg by nebulizer or 2 to 4 inhalations (90 µg/puff) by metered-dose inhaler q 2 to 6 h. Inhalation using a metered-dose inhaler produces rapid bronchodilation; there are no data indicating that nebulizers are more effective than metered-dose inhalers.

Anticholinergics are effective in acute COPD exacerbation and should be given concurrently or alternating with -agonists using a metered-dose inhaler. Ipratropium is the most commonly used anticholinergic. Dosage is 0.5 mg by nebulizer q 6 to 8 h or 2 to 4 puffs by metered-dose inhaler q 4 to 6 h (patients should not exceed 12 puffs in 24 h). Ipratropium generally provides a bronchodilating effect similar to that of -agonists. The role of the longer-acting anticholinergic tiotropium in treating acute exacerbations has not been defined.

Corticosteroids should be begun immediately for all but mild exacerbations. Options include prednisone, 60 mg po once/day for 5 to 10 days then tapered over 7 to 14 days, and methylprednisolone, 125 mg IV q 6 h for 3 days then tapered over 7 to 14 days with the addition of an oral drug such as prednisone. These drugs are equivalent in their acute effects; inhaled corticosteroids have no role in the treatment of acute exacerbations. Short-term corticosteroid use is generally safe in the elderly, with the possible exception of those with diabetes.

Theophylline, once considered essential in treating acute COPD exacerbations, is no longer used routinely because adverse effects may exceed the benefits.

Antibiotics are recommended for exacerbations in patients with purulent sputum. Some health care practitioners give antibiotics empirically for change in sputum color or for nonspecific chest x-ray abnormalities. Routine cultures and Gram stains are not necessary before treatment unless an unusual or resistant organism is suspected. Trimethoprim-sulfamethoxazole 160 mg/800 mg bid, amoxicillin 250 to 500 mg tid, and doxycycline 50 to 100 bid given for 7 to 14 days are all effective and can be used as 1st-line drugs. The choice of drug should be dictated by local patterns of bacterial sensitivity and patient history. In most cases, treatment should be initiated with oral drugs if tolerated. If the patient is seriously ill or if clinical evidence suggests that the infectious organisms are resistant, 2nd-line drugs can be used. These drugs include amoxicillin-clavulanate 500 mg/125 mg tid or 875 mg/125 mg bid; fluoroquinolones, such as ciprofloxacin, levofloxacin, or gatifloxacin; 2nd-generation cephalosporins, such as cefuroxime or cefaclor; and extended-spectrum macrolides, such as azithromycin or clarithromycin. These drugs are effective against -lactamase-producing strains of H. influenzae and Moraxella catarrhalis but are not more effective than 1st-line drugs for most patients. Patients can be taught to recognize a change in sputum from normal to purulent as a sign of impending exacerbation and to start a 10- to 14-day course of antibiotic therapy. Long-term antibiotic prophylaxis is recommended only for patients with underlying structural changes in the lung, such as bronchiectasis or infected bullae.

Patient and caregiver issues: As COPD progresses and patient activity becomes more restricted, many patients become more dependent on family members and develop a sense of isolation, loss of control, and depression. It is important for the health care professional to give caregivers the tools to recognize these feelings and encourage the patient to talk about them; professional support from psychiatrists or psychologists may be helpful. Gentle encouragement to exercise regularly and recognition that activities must be carefully planned in advance will help ensure a better quality of life.

This topic was last updated December 2005.