Dysregulation of lipid mediators in patients with frequent exacerbations of COPD.

Abstract

Introduction: Specialised pro-resolving mediators (SPMs) are endogenously produced lipid mediators (LMs) that regulate the propagation of inflammation and promote tissue repair. We hypothesised that SPM production is dysregulated in COPD and is associated with disease severity, defined by patients with stable COPD (no exacerbations) versus patients with frequent exacerbations.

Methods: LMs were measured in plasma samples from patients with COPD (stable patients and patients with frequent exacerbations) and from healthy controls, matched for age, sex and body mass index, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The LM profiles of controls were compared with those of stable COPD patients, and the LM profiles of stable COPD patients were compared with those of COPD patients with frequent exacerbations. We explored whether or not there was an association between LM profile and ever having a severe COPD exacerbation over 4.1 years of follow-up. Data are presented as mean±sem in pg·mL^-1 for LMs, or mean±sd.

Results: 49 stable COPD patients had increased levels of pro-inflammatory mediators and some SPMs, compared with 28 controls (prostaglandin (PG)D₂: 13.97±2.44 versus 0.53±0.13; p<0.001; lipoxins: 226.83±23.84 versus 59.84±20.25; p<0.01, respectively). 52 patients with frequent exacerbations had lower levels of PGD₂ (3.07±0.97 versus 13.97±2.44; p<0.01) and SPMs (D-resolvins: 8.73±1.25 versus 34.53±8.95; p<0.01; lipoxins: 53.93±9.23 versus 226.83±23.84; p<0.01) than stable COPD patients, despite having a higher neutrophil count (5.28±2.16×10⁹ L^-1 versus 4.28±1.60×10⁹ L^-1; p=0.004). Among patients with frequent exacerbations, D-resolvin levels were independently inversely associated with occurrence of severe exacerbation (OR 0.88, 95% confidence interval (CI) 0.79-0.97; p=0.03) during follow-up.

Conclusion: These findings demonstrate distinct LM profiles of stable COPD patients and patients with frequent exacerbations. In those with exacerbations, D-resolvins were downregulated, compared with stable COPD patients, and associated with future risk of severe exacerbations during follow-up. Further work is needed to understand these findings.