Microbiological Monitoring in Therapeutic Trials in Chronic Obstructive Pulmonary Disease
Background: Microbiological Monitoring in Therapeutic Trials in Chronic Obstructive Pulmonary Disease
Allinson and colleagues recently reported in the Journal that long-term treatment with doxycycline did not significantly reduce the exacerbation rate in patients with chronic obstructive pulmonary disease (COPD) (1). We would like to offer some comments to hopefully enrich the interpretation of these results.
Some comments to hopefully enrich the interpretation of these results
First, the characteristics of the study population are worth noting
All patients had frequent exacerbations (median of two exacerbations in the previous 1 yr), and 60% of them had chronic bronchitis.
This subgroup of patients with COPD frequently experience chronic bronchial infection (CBI) by potentially pathogenic microorganisms during times of clinical stability, including Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis (2). CBI in these patients is associated with higher incidences of exacerbations and pneumonia (3), which are often sensitive to doxycycline (4). Unfortunately, Allinson and colleagues did not report microbiological sputum data, so the influence of CBI on the potential preventive effect of doxycycline on exacerbations could not be analyzed.
Second, it is of note that long-term doxycycline treatment was actually effective in preventing exacerbations in the subgroups of patients with more severe COPD
Even though the overall results were negative, it is of note that long-term doxycycline treatment was actually effective in preventing exacerbations in the subgroups of patients with more severe COPD (rate ratio, 0.36; 95% confidence interval, 0.15–0.85; P = 0.019) and/or less peripheral eosinophilia (rate ratio, 0.50; 95% confidence interval, 0.29–0.84; P = 0.01).
Previous studies have shown that the prevalence of CBI is higher in patients with more severe COPD and in those with lower blood eosinophil levels (5).
Thus, it is possible that the significant effects seen in patients with more severe COPD and/or lower peripheral eosinophil counts can be due to the long-term effects of doxycycline on CBI without ruling out an additional antiinflammatory effect of doxycycline, as pointed out by the authors.
Conclusions
In summary, we think this study highlights the need for careful microbiological monitoring (and, if possible, analysis of potential pulmonary microbiome changes, i.e., dysbiosis) in future interventional trials in patients with COPD.
Authors
Miguel Angel Martinez-Garcia and Alvar Agusti.
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