Azithromycin and COPD Exacerbations in the Presence or Absence of Symptoms or Active Treatment for Gastroesophageal Reflux

: Introduction: Gastroesophageal reflux disease (GERD) is common in chronic obstructive pulmonary disease (COPD) and is associated with COPD exacerbations. Since macrolides have prokinetic effects and consequently may decrease GERD, we hypothesized that azithromycin may decrease exacerbations by decreasing GERD. Methods: We conducted a retrospective review of data collected in a prospective, randomized, controlled trial of azithromycin for preventing COPD exacerbations. Participants were classified as having GERD on the basis of having a history of GERD or having a history or being treated for GERD. Results: We analyzed 1116 participants, 478 (43%) and 568 (51%) had GERD on the basis of history and history or treatment respectively. Individuals with GERD developed exacerbations sooner and more frequently, and were more likely to be hospitalized than those without GERD but the difference only reached significance when GERD was defined by history or treatment (P = 0.02, 0.02, and 0.03, respectively). Azithromycin reduced exacerbations regardless of the presence of GERD, but had a greater effect in those without GERD. Conclusions: GERD is associated with more frequent and severe COPD exacerbations. Azithromycin reduces COPD exacerbations regardless of the presence or absence of GERD but does so to a greater degree in individuals without GERD.