Sunday, April 18, 2010


Various strategies and recommendations to treat patients with severe chronic obstructive pulmonary disease (COPD) are provided in a clinical review published in the April 15 issue of the New England Journal of Medicine.

"The sentinel clinical feature of severe ...COPD is dyspnea on exertion," writes Dennis E. Niewoehner, MD, from the Pulmonary Section, Veterans Affairs Medical Center in Minneapolis, Minnesota. "Its onset is usually insidious, and it may progress to severe disability over a period of years or decades. Other common symptoms include cough, sputum production, wheezing, and chest congestion."

The typical clinical manifestations of advanced COPD result from severe airflow obstruction, which can be confirmed by spirometry. Although physical findings may include a barrel-shaped chest, inspiratory retraction of the lower ribs (Hoover's sign), a prolonged expiratory phase, and use of the accessory muscles of respiration, these findings are sometimes absent even in patients with severe COPD.

Failure to confirm COPD with spirometry often leads to misdiagnosis. However, spirometry is a poor guide for decision making regarding treatment continuation or modification in an individual patient. Spirometric evidence of airflow obstruction is defined as a ratio of the postbronchodilator forced expiratory volume in 1 second (FEV1) to a forced vital capacity of less than 0.70. Overall severity of COPD can be classified based on FEV1 percentage of the predicted normal value, as well as on clinical criteria, such as the degree of breathlessness caused by specific tasks and the frequency of exacerbations.

Exacerbations often require medical visits and hospitalizations, causing a dramatic increase in healthcare costs. The relative risk for treatment failure (defined as no resolution or clinical deterioration) is lowered by approximately 50% when antibiotics are used for COPD exacerbations. Antibiotics are most effective in patients who have cough productive of purulent sputum.

Complications of severe COPD include pulmonary hypertension and cor pulmonale resulting from chronic hypoxemia and hypercapnia. Severe COPD is also associated with an elevated risk for cardiovascular disease, osteoporosis, lung cancer, depression, and other systemic diseases.

Management Strategies

Management should include patient education during the initial visit, which should focus on the signs and symptoms of a severe exacerbation and the need for prompt recognition and treatment. The most important aspect of management is smoking cessation, which should be addressed at every visit, as long as the patient continues smoking.

Pharmacotherapy may include an inhaled long-acting β2-agonist, an inhaled long-acting anticholinergic agent, and/or an inhaled corticosteroid. The long-acting β2-agonists salmeterol and formoterol offer at least 12 hours of sustained bronchodilation, whereas the inhaled long-acting anticholinergic agent tiotropium is effective for at least 24 hours.

Drugs from 2 of these 3 classes should be combined for patients with severe, exacerbation-prone COPD. Because they lower the relative risk for a severe exacerbation by 15% to 20%, these medications should be continued even if they do not provide symptomatic relief. Adverse events of long-acting bronchodilators are typically mild.

For rescue use, a short-acting bronchodilator should be given. Albuterol or other short-acting β2-adrenergic agonist and ipratropium bromide, a short-acting anticholinergic agent, may be used alone or combined. Patients should be instructed regarding proper inhaler technique. The faster onset of action of albuterol vs ipratropium bromide may give patients more rapid relief.

Long-term oxygen therapy should be prescribed and used for 18 hours or more each day if arterial oxygen saturation is 88% or lower at rest in a stable clinical state.

Patients with COPD should be vaccinated against influenza every autumn, and they should also receive pneumococcal vaccination, with revaccination as needed, unless there is a contraindication.

Patients with access to pulmonary rehabilitation should be offered this therapy, provided there are no medical contraindications.

The recommendations in this review are generally consistent with guidelines on the management of COPD published by the Global Initiative for Chronic Obstructive Lung Disease, the American Thoracic Society-European Respiratory Society, and the American College of Physicians.

Conclusion: Uncertainty Remains

"The role of disease-management programs for patients with COPD remains uncertain," Dr. Niewoehner concludes. "Randomized, controlled trials of case management for COPD have shown promise in reducing hospitalization rates, but the evidence is insufficient to make specific recommendations. Pulmonary rehabilitation improves health status and exercise capability for selected patients, but national surveys indicate that few patients complete such programs, and it is unclear how best to maintain the benefits achieved."

Dr. Niewoehner has received consulting fees from Boehringer Ingelheim, Adams Respiratory Therapeutics, GlaxoSmithKline, AstraZeneca, Nycomed, and Forest Research Institute and speaking fees from Boehringer Ingelheim, Pfizer, Sepracor, and Nycomed.

N Engl J Med. 2010;362:1407-1416.