Select Airway Specialized Proresolving Mediators Are Associated with Recovery from Nonviral Chronic Obstructive Pulmonary Disease Exacerbations

Rationale: Recovery from chronic obstructive pulmonary disease (COPD) exacerbations is heterogeneous and has a profound impact on disease trajectories. Resolution of airway inflammation is an active process that may be driven by specialized proresolving mediators (SPMs). Objectives: We sought to characterize the temporal change in SPMs in the sputum of patients with COPD during exacerbations, their association with exacerbation triggers, and exacerbation recovery. Methods: Participants were recruited from the London COPD Exacerbation Cohort between January 11, 2016, and April 30, 2018. Participants were reviewed at baseline, exacerbation onset, 1 week, 2 weeks, and 6 weeks during their exacerbation recovery. Sputum collection, nasopharyngeal swabs, phlebotomy, quality-of-life questionnaires, and spirometry were performed at each visit. SPMs were measured in sputum by liquid chromatography–tandem mass spectrometry. Respiratory viruses were measured by quantitative PCR and bacteria by microbiological culture. Measurements and Main Results: There were 68 exacerbations during the study period. Median time to symptomatic recovery was 21 days for viral exacerbations, compared with 13 days in nonviral exacerbations (P, 0.001). There was a significant increase in resolvin D1 (RvD1) at exacerbation onset in bacterial exacerbations but not in viral exacerbations. Lower levels of RvD1 were associated with prolonged respiratory symptoms during the 1-week and 2-week recovery time points. Exogenous RvD1 significantly reduced IL-6 and CXCL8 response to rhinovirus infection in COPD bronchial epithelial cells. Conclusions: There is a dynamic temporal change in airway SPMs during COPD exacerbations. Reduced levels of RvD1 were associated with prolonged respiratory symptoms. SPMs may be a potential therapeutic approach to promote exacerbation recovery.