Fisk Marie, Gomez Esteban A, Sun Yuan, Mickute Monika, McEniery Carmel, Cockcroft John R, Bolton Charlotte, Fuld Jonathan, Cheriyan Joseph, MacNee William, Tal-Singer Ruth, Polkey Michael, Wilkinson Ian, Dalli Jesmond
Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
University of Cambridge, Cambridge, UK.
ERJ Open Res. 2025 Mar 24;11(2). doi: 10.1183/23120541.00950-2023. eCollection 2025 Mar.
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) patients with frequent exacerbations.
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 for LMs, or mean±sd.
49 stable COPD patients had increased levels of pro-inflammatory mediators and some SPMs, compared with 28 controls (prostaglandin (PG)D: 13.97±2.44 0.53±0.13; p<0.001; lipoxins: 226.83±23.84 59.84±20.25; p<0.01, respectively). 52 patients with frequent exacerbations had lower levels of PGD (3.07±0.97 13.97±2.44; p<0.01) and SPMs (D-resolvins: 8.73±1.25 34.53±8.95; p<0.01; lipoxins: 53.93±9.23 226.83±23.84; p<0.01) than stable COPD patients, despite having a higher neutrophil count (5.28±2.16×10 L 4.28±1.60×10 L; 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.
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.
特殊促消退介质（SPM）是内源性产生的脂质介质（LM），可调节炎症的传播并促进组织修复。我们假设慢性阻塞性肺疾病（COPD）患者体内SPM的产生失调，且与疾病严重程度相关，疾病严重程度由稳定期COPD患者（无急性加重）和频繁急性加重患者来界定。
使用液相色谱 - 串联质谱法（LC - MS/MS），对COPD患者（稳定期患者和频繁急性加重患者）以及年龄、性别和体重指数相匹配的健康对照者的血浆样本中的LM进行测量。将对照组的LM谱与稳定期COPD患者的进行比较，将稳定期COPD患者的LM谱与频繁急性加重的COPD患者的进行比较。我们探讨了在4.1年的随访中，LM谱与曾发生严重COPD急性加重之间是否存在关联。数据以LM的pg·mL表示为平均值±标准误，或平均值±标准差。
与28名对照组相比，49名稳定期COPD患者的促炎介质和一些SPM水平升高（前列腺素（PG）D：13.97±2.44对0.53±0.13；p<0.001；脂氧素：226.83±23.84对59.84±20.25；p<0.01）。52名频繁急性加重患者的PGD（3.07±0.97对13.97±2.44；p<0.01）和SPM（D - 消退素：8.73±1.25对34.53±8.95；p<0.01；脂氧素：53.93±9.23对226.83±23.84；p<0.01）水平低于稳定期COPD患者，尽管其中性粒细胞计数更高（5.28±2.16×10⁹/L对4.28±1.60×10⁹/L；p = 0.004）。在频繁急性加重患者中，D - 消退素水平与随访期间严重急性加重的发生独立呈负相关（比值比0.88，95%置信区间（CI）0.79 - 0.97；p = 0.03）。
这些发现表明稳定期COPD患者和频繁急性加重患者具有不同的LM谱。在急性加重患者中，与稳定期COPD患者相比，D - 消退素下调，且与随访期间严重急性加重的未来风险相关。需要进一步开展工作来理解这些发现。
