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Original Investigation
June 9, 2020

Association of Dysanapsis With Chronic Obstructive Pulmonary Disease Among Older Adults

Author Affiliations
  • 1Department of Medicine, Columbia University Medical Center, New York, New York
  • 2Department of Medicine, McGill University, Montreal, Quebec, Canada
  • 3Department of Physics, Ryerson University, Toronto, Ontario, Canada
  • 4Department of Radiology, University of Iowa, Iowa City
  • 5Department of Biomedical Engineering, University of Iowa, Iowa City
  • 6Department of Internal Medicine, University of Iowa, Iowa City
  • 7Department of Biostatistics, University of Washington, Seattle
  • 8Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
  • 9Department of Medicine, Northwestern University, Chicago, Illinois
  • 10Department of Medicine, Wake Forest University, Winston-Salem, North Carolina
  • 11Department of Radiology, University of British Columbia, Vancouver, Canada
  • 12Department of Medicine, University of California, Los Angeles
  • 13Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill
  • 14Department of Medicine, Temple University, Philadelphia, Pennsylvania
  • 15Department of Medicine, University of Alabama at Birmingham, Birmingham
  • 16Department of Medicine, University of Michigan, Ann Arbor
  • 17Department of Medicine, Johns Hopkins University, Baltimore, Maryland
  • 18Division of Epidemiology and Community Health School of Public Health, University of Minnesota, Minneapolis
  • 19Department of Epidemiology, University of Washington, Seattle
  • 20Department of Environmental and Occupational Health Sciences, University of Washington, Seattle
  • 21Department of Mechanical Engineering, University of Iowa, Iowa City
  • 22Department of Public Health Sciences, University of Virginia, Charlottesville
  • 23Department of Medicine, Cornell University, New York, New York
  • 24Department of Medicine, University of Utah, Salt Lake City
  • 25Department of Medicine, University of British Columbia, Vancouver, Canada
  • 26Department of Medicine, University of California, San Francisco
JAMA. 2020;323(22):2268-2280. doi:10.1001/jama.2020.6918
Key Points

Question  Is dysanapsis, a mismatch of airway tree caliber to lung size, associated with subsequent risk of chronic obstructive pulmonary disease (COPD)?

Findings  In this retrospective observational study involving 6529 older adults, a quantitative measure of dysanapsis (airway to lung ratio on computed tomography) was significantly associated with incident COPD (forced expiratory volume in the first second to forced vital capacity [FEV1:FVC], <0.70 with respiratory symptoms), after adjusting for tobacco exposures and other standard risk factors.

Meaning  Among older adults, dysanapsis appears to be a risk factor associated with COPD.

Abstract

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.

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