Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Research Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA.
Sci Rep. 2023 May 22;13(1):8228. doi: 10.1038/s41598-023-32216-0.
Accelerated progression of chronic obstructive pulmonary disease (COPD) is associated with increased risks of hospitalization and death. Prognostic insights into mechanisms and markers of progression could facilitate development of disease-modifying therapies. Although individual biomarkers exhibit some predictive value, performance is modest and their univariate nature limits network-level insights. To overcome these limitations and gain insights into early pathways associated with rapid progression, we measured 1305 peripheral blood and 48 bronchoalveolar lavage proteins in individuals with COPD [n = 45, mean initial forced expiratory volume in one second (FEV) 75.6 ± 17.4% predicted]. We applied a data-driven analysis pipeline, which enabled identification of protein signatures that predicted individuals at-risk for accelerated lung function decline (FEV decline ≥ 70 mL/year) ~ 6 years later, with high accuracy. Progression signatures suggested that early dysregulation in elements of the complement cascade is associated with accelerated decline. Our results propose potential biomarkers and early aberrant signaling mechanisms driving rapid progression in COPD.
慢性阻塞性肺疾病（COPD）的加速进展与住院和死亡风险增加有关。对进展机制和标志物的预后见解可以促进疾病修饰治疗的发展。虽然个别生物标志物具有一定的预测价值，但性能适中，其单变量性质限制了网络层面的见解。为了克服这些限制并深入了解与快速进展相关的早期途径，我们测量了 45 名 COPD 患者的 1305 份外周血和 48 份支气管肺泡灌洗液中的蛋白质[平均初始用力呼气量（FEV）为预测值的 75.6±17.4%]。我们应用了一种数据驱动的分析管道，该管道能够识别出可预测 6 年后 FEV 下降（FEV 下降≥70ml/年）风险较高的个体的蛋白质特征，具有很高的准确性。进展特征表明，补体级联的早期失调与快速下降有关。我们的研究结果提出了潜在的生物标志物和早期异常信号机制，这些机制驱动了 COPD 的快速进展。
