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.