Importance: Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD), yet much of COPD risk remains unexplained. Objective: To determine whether dysanapsis, a mismatch of airway tree caliber to lung size, assessed by computed tomography (CT), is associated with incident COPD among older adults and lung function decline in COPD. Design, Setting, and Participants: A retrospective cohort study of 2 community-based samples: the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, which involved 2531 participants (6 US sites, 2010-2018) and the Canadian Cohort of Obstructive Lung Disease (CanCOLD), which involved 1272 participants (9 Canadian sites, 2010-2018), and a case-control study of COPD: the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which involved 2726 participants (12 US sites, 2011-2016). Exposures: Dysanapsis was quantified on CT as the geometric mean of airway lumen diameters measured at 19 standard anatomic locations divided by the cube root of lung volume (airway to lung ratio). Main Outcomes and Measures: Primary outcome was COPD defined by postbronchodilator ratio of forced expired volume in the first second to vital capacity (FEV1:FVC) less than 0.70 with respiratory symptoms. Secondary outcome was longitudinal lung function. All analyses were adjusted for demographics and standard COPD risk factors (primary and secondhand tobacco smoke exposures, occupational and environmental pollutants, and asthma). Results: In the MESA Lung sample (mean [SD] age, 69 years [9 years]; 1334 women [52.7%]), 237 of 2531 participants (9.4%) had prevalent COPD, the mean (SD) airway to lung ratio was 0.033 (0.004), and the mean (SD) FEV1 decline was -33 mL/y (31 mL/y). Of 2294 MESA Lung participants without prevalent COPD, 98 (4.3%) had incident COPD at a median of 6.2 years. Compared with participants in the highest quartile of airway to lung ratio, those in the lowest had a significantly higher COPD incidence (9.8 vs 1.2 cases per 1000 person-years; rate ratio [RR], 8.12; 95% CI, 3.81 to 17.27; rate difference, 8.6 cases per 1000 person-years; 95% CI, 7.1 to 9.2; P <.001) but no significant difference in FEV1 decline (-31 vs -33 mL/y; difference, 2 mL/y; 95% CI, -2 to 5; P =.30). Among CanCOLD participants (mean [SD] age, 67 years [10 years]; 564 women [44.3%]), 113 of 752 (15.0%) had incident COPD at a median of 3.1 years and the mean (SD) FEV1 decline was -36 mL/y (75 mL/y). The COPD incidence in the lowest airway to lung quartile was significantly higher than in the highest quartile (80.6 vs 24.2 cases per 1000 person-years; RR, 3.33; 95% CI, 1.89 to 5.85; rate difference, 56.4 cases per 1000 person-years; 95% CI, 38.0 to 66.8; P<.001), but the FEV1 decline did not differ significantly (-34 vs -36 mL/y; difference, 1 mL/y; 95% CI, -15 to 16; P=.97). Among 1206 SPIROMICS participants (mean [SD] age, 65 years [8 years]; 542 women [44.9%]) with COPD who were followed up for a median 2.1 years, those in the lowest airway to lung ratio quartile had a mean FEV1 decline of -37 mL/y (15 mL/y), which did not differ significantly from the decline in MESA Lung participants (P =.98), whereas those in highest quartile had significantly faster decline than participants in MESA Lung (-55 mL/y [16 mL/y]; difference, -17 mL/y; 95% CI, -32 to -3; P =.004). Conclusions and Relevance: Among older adults, dysanapsis was significantly associated with COPD, with lower airway tree caliber relative to lung size associated with greater COPD risk. Dysanapsis appears to be a risk factor associated with COPD..
|Original language||English (US)|
|Number of pages||13|
|Journal||JAMA - Journal of the American Medical Association|
|State||Published - Jun 9 2020|
Bibliographical noteFunding Information:
receiving grants from the National Institutes of Health (NIH), Canadian Institutes of Health Research (CIHR), Fonds de la recherche en santé du Québec (FRQS), the Research Institute of the McGill University Health Centre, and the Quebec Lung Association and winning an investigator-initiated operating grant from AstraZeneca. Dr Kirby reports serving as a consultant for VIDA Diagnostics Inc as a consultant. Dr Kronmal reports receiving a grant from the NIH. Dr Hoffman reports receiving grants from the NIH; being a founder and shareholder of VIDA Diagnostics; and holding patents for an apparatus for analyzing CT images to determine the presence of pulmonary tissue pathology, an apparatus for image display and analysis, and a method for multiscale meshing of branching biological structures. Dr Allen reports receiving grants from the American Heart Association and the National Heart, Lung, and Blood Institute (NHLBI). Dr Cooper reports receiving personal fees from GlaxoSmithKline. Dr Couper reports receiving grants from NHLBI and COPD Foundation. Dr Dransfield reports receiving a grant from the NHLBI and personal fees from AstraZeneca, GlaxoSmithKline, Pulmonx, PneumRx/BTG, and Quark. Dr Han reports consulting for GlaxoSmithKline, AstraZeneca and Boehringer Ingelheim receiving research support from Novartis and Sunovion. Dr Hansel reports receiving grants from the NIH, Boehringer Ingelheim, and the COPD Foundation. Dr Kaufman reports receiving grants from US Environmental Protection Agency and the NIH. Dr Manichaikul reports receiving a grant from NHLBI. Dr Martinez reports serving on COPD advisory boards for AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Sunovion, and Teva; serving as a consultant for ProterixBio and Verona; serving on the steering committees of studies sponsored by the NHLBI, AstraZeneca, and GlaxoSmithKline; having served on data safety and monitoring boards of COPD studies supported by Genentech and GlaxoSmithKline. Dr Oelsner reports receiving grants from the NIH and NHLBI. Dr Paine III reports receiving grants from the NHLBI, the COPD Foundation, and the Department of Veterans Affairs. Dr Tan reports receiving grants from the CIHR/Rx&D Collaborative Research Program Operating Grants with industry partners AstraZeneca Canada, Boehringer-Ingelheim Canada, GlaxoSmithKline Canada, Merck, Novartis Pharma Canada Inc, Nycomed Canada Inc, Pfizer Canada. Dr Bourbeau reports receiving grants from the CIHR/Rx&D Collaborative Research Program Operating Grants with industry partners AstraZeneca Canada, Boehringer Ingelheim Canada, GlaxoSmithKline Canada, Merck, Novartis Pharma Canada, Nycomed Canada, and Pfizer Canada. Dr Woodruff reports receiving personal fees for consultancy from Theravance, AstraZeneca, Regeneron, Sanofi, Genentech, Roche, and Janssen. Dr Barr reports receiving grants from the COPD Foundation, the Alpha1 Foundation, the US Environmental Protection Agency (EPA), and the NIH. No other disclosures were reported.
ProterixBio, Regeneron Pharmaceuticals, Sanofi, Sunovion, Takeda, and Theravance Biopharma and Mylan. The corresponding author was also supported by the CIHR (PJT-162335), the Respiratory Health Research Network of the Quebec Health Research Fund, and the Quebec Lung Association.
funded by grants R01-1 HL130506, R01-HL077612, R01-HL093081, and R01-HL121270 from the NIH/ NHLBI. MESA was funded by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from the NHLBI; and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences (NCATS). This publication was developed under the Science to Achieve Results (STAR) research assistance agreements, Nos. RD831697 (MESA Air) and RD-83830001 (MESA Air Next Stage), awarded by the EPA. CanCOLD was supported by the Canadian Respiratory Research Network; industry partners: Astra Zeneca Canada, Boehringer Ingelheim Canada, GlaxoSmithKline Canada, and Novartis. Researchers at RI-MUHC (Montreal) and Icapture Centre (Vancouver) led the project. Previous funding partners are the CIHR (CIHR/Rx&D Collaborative Research Program Operating Grants 93326); the Respiratory Health Network of the FRSQ; industry partners: Almirall; Merck Nycomed; Pfizer Canada; and Theratechnologies. SPIROMICS was supported by contracts HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, HHSN268200900020C from the NIH/NHLBI; grants U01 HL137880 and U24 HL141762 from the NIH/NHLBI, and supplemented by contributions made through the Foundation for the NIH and the COPD Foundation from AstraZeneca/MedImmune, Bayer, Bellerophon Therapeutics, Boehringer Ingelheim Pharmaceuticals, Chiesi Farmaceutici SpA, Forest Research Institute Inc, GlaxoSmithKline, Grifols Therapeutics, Ikaria, Novartis, Nycomed GmbH,
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