Select Airway Specialized Pro-Resolving Mediators Are Associated with Recovery from Non-Viral COPD Exacerbations

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 which may be driven by Specialized Pro-resolving Mediators (SPMs). To characterize the temporal change in SPMs in the sputum of COPD patients during COPD exacerbations, their association with exacerbation triggers and exacerbation recovery. Participants were recruited from the London COPD Exacerbation Cohort between 01/11/2016 and 01/04/2018. Participants were reviewed at baseline, exacerbation onset, 1 week, 2 weeks and 6 weeks during their exacerbation recovery. Sputum, 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. There were 68 exacerbations during the study period. Median time to symptomatic recovery was 21 days for viral exacerbations compared to 13 days in non-viral exacerbations (P<0.001). There was a significant increase in Resolvin D1 (RvD1) at exacerbation onset in bacterial exacerbations but not 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. 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.