Fawzy Ashraf, Putcha Nirupama, Raju Sarath, Woo Han, Lin Cheng Ting, Brown Robert H, Williams Marlene S, Faraday Nauder, McCormack Meredith C, Hansel Nadia
Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, Maryland, United States.
Department of Radiology, Johns Hopkins University, Baltimore, Maryland, United States.
Chronic Obstr Pulm Dis. 2023 Jan 25;10(1):22-32. doi: 10.15326/jcopdf.2022.0326.
Antiplatelet therapy has been associated with fewer exacerbations and reduced respiratory symptoms in chronic obstructive pulmonary disease (COPD). Whether platelet activation is associated with respiratory symptoms in COPD is unknown.
Former smokers with spirometry-confirmed COPD had urine 11-dehydro-thromboxane B2 (11dTxB2), plasma soluble CD40L (sCD40L), and soluble P-selectin (sP-selectin) repeatedly measured during a 6- to 9-month study period. Multivariate mixed-effects models adjusted for demographics, clinical characteristics, and medication use evaluated the association of each biomarker with respiratory symptoms, health status, and quality of life.
Among 169 participants (average age 66.5±8.2 years, 51.5% female, 47.5±31 pack years, forced expiratory volume in 1 second percent predicted 53.8±17.1), a 100% increase in 11dTxB2 was associated with worse respiratory symptoms reflected by higher scores on the COPD Assessment Test (β 0.77, 95% confidence interval [CI]: 0.11-1.4) and Ease of Cough and Sputum Clearance Questionnaire β 0.77, 95%CI: 0.38-1.2, worse health status (Clinical COPD Questionnaire β 0.13, 95%CI: 0.03-0.23) and worse quality of life (St George's Respiratory Questionnaire β 1.9, 95%CI: 0.39-3.4). No statistically significant associations were observed for sCD40L or sP-selectin. There was no consistent statistically significant effect modification of the relationship between urine 11dTxB2 and respiratory outcomes by history of cardiovascular disease, subclinical coronary artery disease, antiplatelet therapy, or COPD severity.
In stable moderate-severe COPD, elevated urinary11dTxB2, a metabolite of the platelet activation product thromboxane A2, was associated with worse respiratory symptoms, health status, and quality of life.
抗血小板治疗与慢性阻塞性肺疾病(COPD)加重次数减少及呼吸道症状减轻有关。COPD中血小板活化是否与呼吸道症状相关尚不清楚。
在6至9个月的研究期间,对通过肺活量测定确诊为COPD的既往吸烟者多次测量尿11-脱氢血栓素B2(11dTxB2)、血浆可溶性CD40配体(sCD40L)和可溶性P-选择素(sP-选择素)。多变量混合效应模型对人口统计学、临床特征和药物使用进行了调整,评估了每种生物标志物与呼吸道症状、健康状况和生活质量之间的关联。
在169名参与者中(平均年龄66.5±8.2岁,女性占51.5%,吸烟量47.5±31包年,1秒用力呼气容积占预计值百分比为53.8±17.1),11dTxB2增加100%与更差的呼吸道症状相关,这表现为慢性阻塞性肺疾病评估测试得分更高(β 0.77,95%置信区间[CI]:0.11-1.4)以及咳嗽与痰液清除问卷得分更高(β 0.77,95%CI:0.38-1.2),健康状况更差(临床慢性阻塞性肺疾病问卷β 0.13,95%CI:0.03-0.23)和生活质量更差(圣乔治呼吸问卷β 1.9,95%CI:0.39-3.4)。未观察到sCD40L或sP-选择素存在统计学显著关联。心血管疾病史、亚临床冠状动脉疾病、抗血小板治疗或COPD严重程度对尿11dTxB2与呼吸道结局之间的关系没有一致的统计学显著效应修饰作用。
在稳定的中重度COPD中,尿11dTxB2(血小板活化产物血栓素A2的一种代谢产物)升高与更差的呼吸道症状、健康状况和生活质量相关。