The most appropriate treatment is to start short courses of antibiotics and prednisone. This patient has an acute exacerbation of COPD. In addition to short-acting bronchodilators and supplemental oxygen as needed, antibiotics and systemic glucocorticoids (such as prednisone) are indicated for treatment of acute COPD exacerbations. Acute exacerbations of COPD are mostly caused by bacterial or viral infections. The combination of cough, dyspnea, and sputum purulence that is increased from baseline generally indicates the need for antibiotics in the treatment of acute COPD exacerbations, especially in patients with severe and very severe COPD. The most common bacterial pathogens that cause exacerbations are Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Empiric antibiotic therapy should be chosen on the basis of local bacterial resistance patterns. Commonly used regimens include an advanced macrolide, a cephalosporin, or doxycycline. Systemic glucocorticoids decrease recovery time, improve lung function, improve arterial hypoxemia, and reduce the risk of early relapse. A prednisone dose of 40 mg/d for 5 days is recommended. Earlier studies suggested a 2-week course of prednisone, but a recent study showed that a 5-day course is sufficient. A prompt follow-up visit is necessary after discharge, and pulmonary rehabilitation should be recommended.

The benefits of glucocorticoids in acute COPD exacerbation have been documented with systemic treatment and not with inhaled agents such as fluticasone. Although adding a combination of a long-acting β₂-agonist (LABA) and inhaled glucocorticoid at the time of discharge may be appropriate, treating an acute exacerbation with antibiotics and an inhaled glucocorticoid would not be appropriate.

Short-acting β₂-agonists (albuterol) with or without short-acting anticholinergic agents are preferred for treatment of acute COPD exacerbations. Guidelines suggest adding a LABA or a combination of a LABA and an inhaled glucocorticoid at the time of discharge, in addition to the long-acting anticholinergic agent (tiotropium) that this patient was already taking. However, a combination of a LABA and an inhaled glucocorticoid (such as fluticasone/salmeterol) is not appropriate therapy during an acute COPD exacerbation.

Roflumilast is an oral phosphodiesterase-4 inhibitor that reduces airway inflammation. Roflumilast is indicated for patients with severe or very severe COPD with recurrent exacerbations; it is not indicated for use during acute exacerbations.