Association Between Expiratory Central Airway Collapse and Respiratory Outcomes Among Smokers.
Association Between Expiratory Central Airway Collapse and Respiratory Outcomes Among Smokers.
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DOI：
10.1001/jama.2015.19431
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发表时间：
2016-02-02
影响因子：
120.7
通讯作者：
Dransfield, Mark T.
中科院分区：
文献类型：
--
作者：
Bhatt, Surya P.;Terry, Nina L. J.;Nath, Hrudaya;Zach, Jordan A.;Tschirren, Juerg;Bolding, Mark S.;Stinson, Douglas S.;Wilson, Carla G.;Curran-Everett, Douglas;Lynch, David A.;Putcha, Nirupama;Soler, Xavi;Wise, Robert A.;Washko, George R.;Hoffman, Eric A.;Foreman, Marilyn G.;Dransfield, Mark T.
在呼气期间中心气道塌陷大于管腔面积的50%（呼气中心气道塌陷，ECAC）与吸烟和慢性阻塞性肺疾病（COPD）相关。然而，其患病率和临床意义尚不清楚。确定ECAC是否与吸烟者的呼吸系统发病率相关，而不依赖于潜在的肺部疾病。我们分析了一项大型多中心研究（COPDGene）中45-80岁吸烟者和既往吸烟者的成对吸气-呼气计算机断层扫描（CT）图像。参与者于2008年1月至2011年6月入组，并纵向随访至2014年10月。使用定量方法筛选图像，以检测从吸气到呼气末短轴气管直径至少减少30%。从该筛选阳性扫描样本中，手动测量气管的横截面积，以确认吸气-呼气扫描中三个预定水平（主动脉弓、隆突和中间支气管）处的ECAC。横截面积减少≥50%的参与者被诊断为ECAC。主要结局为基线呼吸生活质量[St乔治呼吸问卷（SGRQ）量表0 - 100，100代表最差健康状况，最小临床重要差异MCID 4个单位]，次要结局为呼吸困难[改良医学研究理事会（mMRC）量表0 - 4，4代表呼吸困难恶化，入组时的MCID 0.7单位]和6分钟步行距离[MCID 30 m]以及纵向随访时的急性加重频率（事件/100人-年）。纳入了8820名患有和不患有COPD的当前和既往吸烟者。ECAC的患病率为5%。在多变量分析中，ECAC与年龄较大相关[65.0 vs.59.4岁，绝对差异= 5.6，95%CI 4.8 - 6.4，调整后比值比，OR每增加1年为1.06，95%CI 1.04-1.07; P<0.001]，女性[297（67%）vs 3856（46%），绝对差异= 21.0%，95%CI 16.4 - 25.4，OR 2.08，95%CI 1.63-2.63; p<0.001]，白色人种与非裔美国人相比[374（84.4%）与5654（67.5%），绝对差异= 16.9%，95%CI 13.1 ~ 20.2，OR 1.85，95%CI 1.38-2.48; P<0.001]，BMI升高[31.2 vs. 28.7，绝对差= 2.5，95%CI 1.9 - 3.1，OR每增加1个单位1.07，95%CI 1.06-1.09; p<0.001]和FEV 1降低[1.82 vs. 2.28 L，绝对差异=-0.46，95%CI-0.54 to-0.38，OR每1 L降低0.74，95%CI 0.62-0.89;p<0.001]。ECAC与更差的SGRQ评分[30.9 vs. 26.5单位，p<0.001，绝对差异=4.4，95%CI 2.2 - 6.6]和mMRC [中位数2，四分位距IQR 0-3 vs. 1，IQR 0-3，p<0.001]相关，与年龄、性别、种族、BMI、FEV 1、吸烟负担和肺气肿无关。在随访中，没有COPD但患有ECAC的参与者的总频率增加，（每100人-年54对35起事件，IRR 2.19; 95%CI 1.78 - 2.71;p<0.001）和需要住院治疗的严重呼吸道事件（每100人-年16对10起事件，IRR 2.95; 95%CI 2.20 - 3.95;p<0.001）。在一项对当前和既往吸烟者的横断面分析中，呼气中心气道塌陷的存在与呼吸生活质量较差相关。需要进一步的研究来评估对临床结果的长期影响。ClinicalTrials.gov：标识符：NCT 00608764 https://clinicaltrials.gov/ct2/show/NCT00608764? term=copdgene&rank=1第1阶段方案可在此处获得：http://www.copdgene.org/sites/default/files/COPDGeneProtocol-5-0_06-19-2009.pdf第2阶段方案可在此处获得：http://www.copdgene.org/sites/default/files/CentralStudyProtocol_06%20Oct%202014_Clean.pd
Central airway collapse greater than 50% of luminal area during exhalation (Expiratory Central Airway Collapse, ECAC) is associated with cigarette smoking and chronic obstructive pulmonary disease (COPD). However, its prevalence and clinical significance are unknown. To determine whether ECAC is associated with respiratory morbidity in smokers independent of underlying lung disease. We analyzed paired inspiratory-expiratory computerized tomography (CT) images from a large multicenter study (COPDGene) of current and former smokers aged 45–80 years. Participants were enrolled from January 2008 to June 2011, and followed longitudinally till October 2014. Images were screened using a quantitative method to detect at least a 30% reduction in minor axis tracheal diameter from inspiration to end-expiration. From this sample of screen positive scans, cross-sectional area of the trachea was measured manually for confirmation of ECAC at three predetermined levels (aortic arch, carina and bronchus intermedius) in the inspiratory-expiratory scans. Participants with ≥50% reduction in cross-sectional area were diagnosed with ECAC. Expiratory Central Airway Collapse Primary outcome was baseline respiratory quality of life [St George’s Respiratory Questionnaire (SGRQ) scale 0 to 100, 100 represents worst health status, minimum clinically important difference MCID 4 units] and secondary outcomes were dyspnea [modified Medical Research Council (mMRC) scale 0 to 4, 4 represents worse dyspnea, MCID 0.7 units] and six minute walk distance [MCID 30 m] at enrollment and exacerbation frequency (events per 100 person-years) on longitudinal follow-up. 8820 current and former smokers with and without COPD were included. The prevalence of ECAC was 5%. On multivariable analyses, ECAC was associated with older age [65.0 vs. 59.4 years, absolute difference = 5.6, 95%CI 4.8 to 6.4, adjusted Odds Ratio, OR for every 1-year increase 1.06,95%CI 1.04–1.07;p<0.001], female sex [297 (67%) vs. 3856 (46%), absolute difference = 21.0%, 95%CI 16.4 to 25.4, OR 2.08,95%CI 1.63–2.63;p<0.001], white race compared to African American [374 (84.4%) vs. 5654 (67.5%), absolute difference = 16.9%, 95%CI 13.1 to 20.2, OR 1.85,95%CI 1.38–2.48;p<0.001], higher BMI [31.2 vs. 28.7, absolute difference = 2.5, 95%CI 1.9 to 3.1, OR for every 1 unit increase 1.07,95%CI 1.06–1.09;p<0.001] and lower FEV1 [1.82 vs. 2.28 L, absolute difference = −0.46, 95%CI −0.54 to −0.38, OR for every 1L decrease 0.74,95%CI 0.62–0.89;p<0.001]. ECAC was associated with worse SGRQ scores [30.9 vs. 26.5 units, p<0.001, absolute difference =4.4, 95%CI 2.2 to 6.6)] and mMRC [median 2, Interquartile range IQR 0–3 vs. 1, IQR 0–3, p<0.001] and independent of age, sex, race, BMI, FEV1, smoking burden and emphysema. On follow-up, participants without COPD but with ECAC had increased frequency of total (54 vs. 35 events per 100 person-years, IRR 2.19; 95%CI 1.78 to 2.71;p<0.001) and severe respiratory events requiring hospitalization (16 vs. 10 events per 100 person-years, IRR 2.95; 95%CI 2.20 to 3.95;p<0.001). In a cross-sectional analysis of current and former smokers, the presence of expiratory central airway collapse was associated with worse respiratory quality of life. Further studies are needed to assess long-term effects on clinical outcomes. ClinicalTrials.gov: Identifier: NCT00608764 https://clinicaltrials.gov/ct2/show/NCT00608764?term=copdgene&rank=1 Phase 1 protocol available here: http://www.copdgene.org/sites/default/files/COPDGeneProtocol-5-0_06-19-2009.pdf Phase 2 protocol available here: http://www.copdgene.org/sites/default/files/CentralStudyProtocol_06%20Oct%202014_Clean.pd
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