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MKSAP Quiz: 3-year history of dyspnea, cough

A 69-year-old man is evaluated for a three-year history of dyspnea and chronic productive cough. He was diagnosed with chronic obstructive pulmonary disease (COPD) two years ago and has been treated for three exacerbations in the past year. He is taking tiotropium, fluticasone/salmeterol, and albuterol inhalers. Which long-term treatment is most likely to reduce exacerbations?


A 69-year-old man is evaluated for a 3-year history of dyspnea and chronic productive cough. He was diagnosed with chronic obstructive pulmonary disease (COPD) 2 years ago after spirometry confirmed severe airflow obstruction. He discontinued smoking at that time but in the past year he was treated for three COPD exacerbations, one requiring hospitalization. Medications are tiotropium, fluticasone/salmeterol, and albuterol inhalers.

On physical examination, vital signs are normal; oxygen saturation is 92% on ambient air. He intermittently coughs during the examination. He has a prolonged expiratory phase. The remainder of the examination is unremarkable.

Chest radiograph shows the lungs to be clear.

Spirometry demonstrates a postbronchodilator FEV1 of 45% of predicted.

Which of the following long-term treatments is most likely to reduce this patient's exacerbations of COPD?

A. Prednisone
B. Roflumilast
C. Theophylline
D. Trimethoprim-sulfamethoxazole

Reveal the Answer

MKSAP Answer and Critique

The correct answer is B. Roflumilast. This content is available to MKSAP 18 subscribers as Question 3 in the Pulmonology & Critical Care section. More information about MKSAP is available online.

Roflumilast is the most appropriate treatment. It is used primarily as add-on therapy in severe COPD associated with chronic bronchitis and a history of recurrent exacerbations despite other therapies; it has been shown to improve lung function and reduce risk and frequency of exacerbations in these individuals. However, it is not a bronchodilator, is expensive, and has not been shown to be effective in other groups of patients with COPD. Common side effects include diarrhea, nausea, weight loss, and headache. Recently the FDA has raised concerns regarding psychiatric adverse events with roflumilast (anxiety, depression, insomnia). Roflumilast is contraindicated in patients with liver impairment and has significant drug interactions.

Oral glucocorticoids, such as prednisone, are reserved for limited periodic use in treating exacerbations of COPD and may provide some benefit in decreasing hospital readmission rates after exacerbation. Long-term oral glucocorticoid therapy has limited, if any, benefit in COPD and carries a high risk for other significant side effects (such as muscle weakness and decreased functional status) and is generally not recommended.

Methylxanthines such as theophylline have shown modest treatment benefit in COPD, likely due to a bronchodilating effect mediated by nonselective inhibition of phosphodiesterase. However, the potential toxicity of this class of drugs coupled with their reduced efficacy has led to increasingly limited use. Although they may be helpful in any classification of COPD, they tend to be used in selected patients with late-stage disease or for patients in whom other preferred therapies have proved ineffective for symptomatic relief; they may also be used when other medications are not available or affordable.

Clinical trials have demonstrated that chronic macrolide therapy is associated with a reduction in the rate of exacerbation in patients with moderate to severe COPD despite optimal maintenance inhaler therapy. Macrolide antibiotic therapy and roflumilast have not been directly compared in patients with frequent exacerbations of COPD and the choice among the two is informed by benefits and risks on an individual patient basis. Trimethoprim-sulfamethoxazole has not been shown to prevent exacerbations of COPD.

Key Point

  • Roflumilast, a selective phosphodiesterase-4 inhibitor, is used as add-on therapy in severe COPD associated with chronic bronchitis and a history of recurrent exacerbations to reduce risk and frequency of exacerbations.