ABSTRACT
BACKGROUND: Simple viral respiratory infections (the common cold) often predispose patients with COPD to lower respiratory infections and subsequent exacerbations. Low-dose, long-term erythromycin therapy has been reported to treat diffuse panbronchiolitis and bronchiectasis by anti-inflammatory mechanisms rather than through its inherent antibacterial mechanisms. Macrolide antibiotics have also been reported to have antiviral protective mechanisms. This study investigated the frequency of common colds and COPD exacerbations in patients treated with low-dose, long-term erythromycin.
POPULATION STUDIED: This Japanese study included 109 patients with COPD as defined by the American Thoracic Society. Subjects could be treated with sustained-released theophylline and inhaled anticholinergic agents, but not corticosteroids. The investigators excluded patients with diffuse panbronchiolitis or bronchiectasis.
STUDY DESIGN AND VALIDITY: This was a randomized, nonblinded study conducted over 12 months. One group of 55 patients received erythromycin (200-400 mg daily); the control group of 54 patients received 10 mg riboflavin daily. The investigators were unaware which treatments would be given before enrolling patients into the study (ie, allocation was concealed). The groups were similar in age, sex, and baseline lung function. Patients self-reported daily symptoms, including sneezing, nasal discharge, malaise, headache, chills, fever, sore throat, hoarseness, and cough, and rated each for severity on a scale of 0 to 3. An episode of common cold was defined as a quantitative symptom score of >5. COPD exacerbations were defined as a worsening in symptoms requiring changes to the regular pharmacologic regimen, including the need for antimicrobial or systemic steroid therapy. Exacerbations were graded based on need for hospitalization: mild and moderate, if treatment did not require hospitalization; severe, if hospitalization was required. Physicians evaluated their patients every 2 weeks. Patients who had cold symptoms were encouraged to visit the hospital for investigator-initiated checks.
OUTCOMES MEASURED: The investigators measured the number of common colds and the frequency and severity of COPD exacerbations.
RESULTS: The number of common colds was significantly lower in the erythromycin group than in the control group (1.24 vs 4.54 episodes per person; P = .002). Over a 12-month period, 76% of the control group subjects experienced more than one cold, compared with 13% in the erythromycin group (relative risk = 9.26; 95% CI, 3.92-31.74, number needed to treat [NNT] = 1.6). The percentage of patients having one or more COPD exacerbations was significantly higher in the control group (54% vs 11%; RR = 4.71; 95% CI, 1.53-14.5; NNT = 2.2). The control group experienced 11 severe exacerbations; the erythromycin group had none. The total number and severity of COPD exacerbations were also significantly lower in the erythromycin group than in the control group. No deaths were reported during the study period. One patient in the erythromycin group was excluded because of adverse effects of treatment (diarrhea and anorexia).
The frequency of common colds and of subsequent COPD exacerbations was significantly lowered in patients taking a low-dose of erythromycin daily for 1 year. This effect may be a result of the anti-inflammatory and antiviral mechanisms of macrolide antibiotics. Unfortunately, because neither the investigators nor the study subjects were blinded, the reported magnitude of this benefit may not be accurate. Additionally, these patients were not using corticosteroid therapy, which would have provided an anti-inflammatory benefit. The potential risk of emerging erythromycin/macrolide–resistant pathogens should restrict liberal prophylactic use. Considering the limitations of the study design and the risk of antibiotic resistance, we do not recommend prophylactic erythromycin treatment for common cold prevention in COPD patients.