老年慢性阻塞性肺疾病合并肺动脉高压患者外周血NLRP3炎症小体水平变化及意义

Changes in levels of peripheral blood NLRP3 inflammasome and its significance in elderly patients with chronic obstructive pulmonary disease complicated with pulmonary arterial hypertension

中文关键词: 老年  慢性阻塞性肺疾病  肺动脉高压  NLRP3炎症小体  疗效评估

英文关键词: elderly  chronic obstructive pulmonary disease  pulmonary arterial hypertension  NLRP3 inflammasome  treatment efficacy evaluation

中文摘要:

      目的 研究老年慢性阻塞性肺疾病(COPD)合并肺动脉高压(PAH)患者外周血NOD样受体家族蛋白3(NLRP3)炎症小体水平变化及意义.方法 前瞻性选取2019年6月—2024年6月于上海市奉贤区中心医院采用气道激素雾化吸入治疗的老年COPD合并PAH患者150例,根据疗效评估标准分为治疗有效组(n=119)和治疗无效组(n=31).入组后检测所有受试者实验室血液指标值、外周血NLRP3炎性小体及其下游炎症因子白细胞介素(IL-1 β、IL-18)水平,分析其与老年COPD合并PAH患者整体治疗效果的关系,同时绘制受试者工作特征曲线(ROC)评价外周血NLRP3、凋亡相关斑点样蛋白(ASC)、半胱氨酸蛋白酶-1(caspase-1)、IL-1β、IL-18水平在患者疗效评估中的价值.结果 治疗有效组NLR、PLR、NLRP3、caspase-1、ASC、IL-1β、IL-18水平均低于治疗无效组(P＜0.05),而ALB、LYM水平则高于治疗无效组(P＜0.05);经LASSO回归筛选后Logistic回归分析显示,NLRP3、caspase-1、IL-1β水平升高均是造成患者整体治疗效果较差的独立危险因素(P＜0.05);ROC曲线结果显示,外周血NLRP3+caspase-1+ASC+IL-1 β+IL-18联合预测效能均高于单个指标(P＜0.05).结论 老年COPD合并PAH患者采用气道激素雾化吸入治疗失败与外周血NLRP3炎症小体高水平有关,治疗前检测NLRP3炎症小体可能预测老年COPD合并PAH患者治疗失败风险.

英文摘要:

      Objective To investigate the changes in the levels of the peripheral blood NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome and its significance in elderly patients with chronic obstructive pulmonary disease(COPD)complicated with pulmonary arterial hypertension(PAH).Methods 150 elderly COPD patients with PAH treated with inhaled corticosteroids in Central Hospital of Fengxian District,Shanghai,between June 2019 and June 2024 were prospec-tively selected.They were divided into effective treatment group(n=119)and ineffective treatment group(n=31)based on therapeutic efficacy evaluation criteria.Laboratory blood parameters,peripheral blood levels of the NLRP3 inflammasome and its downstream inflammatory cytokines[interleukin(IL)-1β and IL-18]were measured in all subjects after enrollment.The relationship between these factors and the overall treatment efficacy in elderly COPD patients with PAH was analyzed.The re-ceiver operating characteristic curve(ROC)was drawn to determine the value of the levels of peripheral blood NLRP3,apopto-sis-associated speck-like protein(ASC),caspase-1,IL-1β and IL-18 in the evaluation of treatment efficacy.Results The levels of ALB,LYM,NLRP3,caspase-1,ASC,IL-1β and IL-18 in the effective treatment group were significantly lower than those in the ineffective treatment group(P＜0.05),while the levels of neutrophil-to-lymphocyte ratio(NLR)and PLR were higher than those in the ineffective treatment group(P＜0.05).After screening by LASSO regression,Logistic regression analysis showed that elevated levels of NLRP3,caspase-1,and IL-1 β were independent risk factors for poor overall treatment efficacy in patients(P＜0.05).ROC curve results showed that the combined predictive efficacy of peripheral blood NLRP3+caspase-1+ASC+IL-1β+IL-18 was significantly higher than that of any single indicator(P＜0.05).Conclusion The fail-ure of airway hormone nebulized inhalation treatment in elderly COPD patients with PAH is related to the high level of NLRP3 inflammasome in peripheral blood.The detection of NLRP3 inflammasome before treatment may predict the risk of treatment failure in elderly these patients.