The problems of meta-analysis for antibiotic treatment of chronic obstructive pulmonary disease, a heterogeneous disease: a commentary on Puhan et al

Bronchitis is among the most common reasons for antibiotic prescription worldwide. This diagnosis includes two distinct entities, acute bronchitis in the absence of underlying lung disease and acute exacerbations of chronic bronchitis or chronic obstructive pulmonary disease (COPD). Acute bronchitis is predominantly a viral disease with good evidence that antibiotics are not of benefit in its management. Exacerbations of COPD, on the other hand, can be of bacterial, viral or mixed etiology, with bacterial infection currently estimated to contribute up to 50% of exacerbations. Furthermore, in contrast to acute bronchitis, these exacerbation episodes are not benign events, as they have consequences ranging from days lost from work, deterioration of health status, progression of airflow obstruction and even death. Therefore, appropriate management of COPD exacerbations is crucial.Antibiotics are often used in the management of COPD exacerbations. It is estimated that more than 80% of COPD exacerbations are treated on an outpatient basis, which can be regarded as mild to moderate exacerbations. The article published by Puhan et al this month in BMC Medicine makes the argument that there is a lack of evidence for antibiotic benefit in mild to moderate exacerbations of COPD and that additional placebo-controlled trials are required [1]. Their argument is based on a meta-analytic approach where they identified five placebo-controlled randomized trials in the literature, which were confined to 'mild to moderate' exacerbations of COPD. With this approach, although all but one of the trials favor antibiotics, the combined odds ratio is not statistically significant.Although their conclusions based on the analysis are not erroneous, their approach to this question highlights a number of issues that make it difficult to resolve this argument; these include the heterogeneity of exacerbations, patients and antibiotics in these trials. Another major issue is the acceptance of the