Wan Emily, Yen Andrew, Elalami Rim, Grumley Scott, Nath Hrudaya P, Wang Wei, Brouha Sharon, Manapragada Padma P, Abozeed Mostafa, Aziz Muhammad Usman, Zahid Mohd, Ahmed Asmaa N, Terry Nina L, Nardelli Pietro, Ross James C, Kim Victor, Sonavane Sushilkumar, Kligerman Seth J, Vestbo Jørgen, Agusti Alvar, Kim Kangjin, San José Estépar Raul, Silverman Edwin K, Cho Michael H, Diaz Alejandro A
Brigham and Women's Hospital, Channing Division of Network Medicine, Boston, Massachusetts, United States.
VA Boston Health Care System Jamaica Plain Campus, Boston, Massachusetts, United States;
Am J Respir Crit Care Med. 2024 Oct 29;211(5):814-22. doi: 10.1164/rccm.202403-0632OC.
Rationale/Objective: Acute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) are associated with significant morbidity and mortality. Whether mucus plugs are associated with prospective exacerbations has not been examined extensively.
Mucus plugs were visually-identified on baseline chest computed tomography (CT) scans from smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 2-4 COPD enrolled in two multicenter cohort studies: Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) and COPDGene. Associations between ordinal mucus plug score categories (0/1-2/≥3) and prospectively-ascertained AEs, defined as worsening respiratory symptoms requiring systemic steroids and/or antibiotics (moderate-to-severe) and/or ER/hospitalization (severe), were assessed using multivariable-adjusted zero-inflated Poisson regression; subjects were exacerbation-free at enrollment.
Among 3,250 participants in COPDGene (mean±SD age 63.7±8.4 years, FEV1 50.6%±17.8% predicted, 45.1% female) and 1,716 participants in ECLIPSE (age 63.3±7.1 years, FEV1 48.3%±15.8% predicted, 36.2% female), 44.4% and 46.0% had mucus plugs, respectively. The incidence rates of AEs were 61.0 (COPDGene) and 125.7 (ECLIPSE) per 100 person-years. Relative to those without mucus plugs, the presence of 1-2 and ≥3 mucus plugs was associated with increased risk (adjusted rate ratio, aRR [95%CI]=1.07[1.05-1.09] and 1.15[1.1-1.2] in COPDGene; aRR=1.06[1.02-1.09] and 1.12[1.04-1.2] in ECLIPSE, respectively) for prospective moderate-to-severe AEs. The presence of 1-2 and ≥3 mucus plugs was also associated with increased risk for severe AEs during follow-up (aRR=1.05[1.01-1.08] and 1.09[1.02-1.18] in COPDGene; aRR=1.17[1.07-1.27] and 1.37[1.15-1.62] in ECLIPSE, respectively).
CT-based mucus plugs are associated with an increased risk for future COPD AEs.
原理/目的：慢性阻塞性肺疾病（COPD）急性加重（AE）与显著的发病率和死亡率相关。黏液栓是否与未来加重相关尚未得到广泛研究。
在两项多中心队列研究中，对慢性阻塞性肺疾病全球倡议（GOLD）2 - 4级COPD吸烟者的基线胸部计算机断层扫描（CT）图像进行肉眼识别黏液栓：纵向评估COPD以识别预测替代终点（ECLIPSE）研究和COPD基因研究。使用多变量调整的零膨胀泊松回归评估序数黏液栓评分类别（0/1 - 2/≥3）与前瞻性确定的AE之间的关联，AE定义为需要全身使用类固醇和/或抗生素（中度至重度）和/或急诊室就诊/住院（重度）的呼吸道症状恶化；入组时受试者无加重情况。
在COPD基因研究的3250名参与者（平均±标准差年龄63.7±8.4岁，FEV1为预测值的50.6%±17.8%，45.1%为女性）和ECLIPSE研究的1716名参与者（年龄63.3±7.1岁，FEV1为预测值的48.3%±15.8%，36.2%为女性）中，分别有44.4%和46.0%存在黏液栓。AE的发病率分别为每100人年61.0（COPD基因研究）和1125.7（ECLIPSE研究）。相对于无黏液栓者，存在1 - 2个和≥3个黏液栓与未来中度至重度AE风险增加相关（COPD基因研究中调整率比，aRR [95%CI]=1.07[1.05 - 1.09]和1.15[1.1 - 1.2]；ECLIPSE研究中aRR分别为1.06[1.02 - 1.09]和1.12[1.04 - 1.2]）。存在1 - 2个和≥3个黏液栓也与随访期间重度AE风险增加相关（COPD基因研究中aRR = 1.05[1.01 - 1.08]和1.09[1.02 - 1.18]；ECLIPSE研究中aRR分别为1.17[1.07 - 1.27]和1.37[1.15 - 1.62]）。
基于CT的黏液栓与未来COPD AE风险增加相关。
