Smaller Airway Structures Raise Risk for COPD in Women, According to New Research

Lung airways were smaller in women than men, even among ever-smokers and never-smokers, according to large analysis.

Smaller airway structure found in women may explain the increase in chronic obstructive pulmonary disease (COPD) prevalence among this population, according to a large secondary analysis published in Radiology.

"The prevalence of COPD in women is fast approaching that seen in men, and airway disease may underlie some of the high COPD numbers in women that we are seeing,” said lead author, Surya P. Bhatt, MD, associate professor of medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama Lung Imaging Lab and Lung Health Center, Birmingham, in a press release. "When airways narrow due to cigarette smoking, the impact on symptoms and survival is greater in women than in men."

Bhatt and colleagues analyzed data from approximately 10 000 participants enrolled in the Genetic Epidemiology of COPD (COPDGene) clinical trial, a prospective multicenter observational cohort study of current and former smokers, as well as never-smokers, between the ages of 45 and 80 years, at 21 clinical centers in the US. Participants were enrolled in the COPDGene study from 2008 to 2011 and were followed until November 2020.

All participants underwent CT imaging to quantify airway disease using 7 metrics: airway wall thickness, wall area percent, and square root of the wall thickness of a hypothetical airway with internal perimeter of 10 mm (referred to as Pi10) for airway wall; and lumen diameter, airway volume, total airway count, and airway fractal dimension for airway lumen.

Least-squares mean (LSM) values for each airway metric was calculated and adjusted for age, height, race, body mass index, pack-years of smoking, current smoking status, and total lung capacity. In ever-smokers, investigators tested associations between each airway metric and postbronchodilator forced expiratory volume in 1 second (FEV1)-to–forced vital capacity (FVC) ratio, modified Medical Research Council dyspnea scale, St George’s Respiratory Questionnaire score, and 6-minute walk distance.

Findings

Among 420 never-smokers (mean age, 60 years; 57% women), CT imaging showed that men had thicker airway walls than women (LSM, 47.68 vs 45.78; P=.02), whereas airway lumen dimensions were lower in women than men after researchers accounted for height and total lung capacity (segmental lumen diameter, 8.05 mm vs 9.05 mm; P<.001).

Among 9393 ever-smokers (mean age, 60 years; 46% women), men had greater segmental airway wall area percentage compared with women (LSM 52.19 vs. 48.89; P<.001), whereas women had narrower segmental lumen diameter (7.8 mm vs 8.7 mm; P<.001), according to Bhatt et al.

The team reported that a unit change in each of the airway metrics (higher wall or lower lumen measure) resulted in lower FEV1-to-FVC ratio, more dyspnea, poorer respiratory quality of life, lower 6-minute walk distance, and worse survival in women compared with men (all P<.01).

"The differences in airway dimensions, even after adjusting for height and lung size, and the greater impact of changes in airway size on clinical outcomes in women was remarkable in that women appear to have a lower reserve against developing airway disease and COPD," said Bhatt in the press release.

One limitation that Bhatt and colleagues noted in the study was the fact that a higher proportion of men were active smokers compared with women and, despite adjusting for smoking status, some of the airway wall differences may have results from the impact of active cigarette smoking on airway wall thickness. Also, researchers did not adjust for medication use when analyzing outcomes and the smallest airways could not be examined due to CT resolution limitations.