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.
Design, Setting and Participants
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
Main Outcome(s) and Measure(s)
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).
Conclusions and Relevance
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