Smaller Airways Set the Stage for Worse COPD Outcomes in Women

Smaller airways in women may explain their worse respiratory outcomes in chronic obstructive pulmonary disease (COPD), a large cohort study suggested.

For never-smokers and ever-smokers alike, CT imaging revealed that men had thicker airway walls than women, who also had smaller airway lumen dimensions after accounting for height and total lung capacity.

“It is plausible that the increased airway wall thickness associated with cigarette smoking disproportionately affects women who have smaller airways,” wrote study authors led by Surya Bhatt, MD, from the University of Alabama at Birmingham, in Radiology.

As for outcomes, a unit change in either segmental airway wall area percentage or segmental lumen diameter was associated with particularly worse forced expiratory volume in one second (FEV₁) to forced vital capacity (FVC) ratios, more dyspnea, poorer respiratory quality of life, lower 6-minute walk distance, and worse survival in women compared with men (all P<0.01).

“When airways narrow due to cigarette smoking, the impact on symptoms and survival is greater in women than in men,” Bhatt explained in a press release.

Historically, COPD has been more frequent in men, but changing factors in smoking behavior and urbanization have resulted in its prevalence becoming more similar between the sexes, according to the investigators.

Meanwhile, they noted that women experience worse COPD symptoms for a given degree of airflow obstruction. Age-adjusted rates of COPD-related deaths are on the decline in men, but not in women, who tend to have greater airflow obstruction and faster lung function decline after adjustment for smoking burden.

“The assumption that women have smaller airways is long standing and is on the basis of comparisons of the trachea and main stem bronchi, but few studies have compared distal airways in healthy individuals or accounted for differences in lung size,” Bhatt and colleagues wrote.

“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,” Bhatt said in the press release.

He and his group had performed a secondary analysis of the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease study. This was a multicenter, observational cohort study that had never, current, and former smokers enrolled from January 2008 to June 2011 and followed until November 2020.

Participants were 420 lifetime nonsmokers (mean age 60 years, 57% women, 81% non-Hispanic white) and 9,363 ever-smokers (mean age 60 years, 46% women, and 67% non-Hispanic white).

Least-squares mean values of airway metrics were calculated and adjusted for age, height, ethnicity, body mass index, pack-years of smoking, current smoking status, total long capacity, display field of view, and scanner type.

A major limitation of the study was the higher proportion of men among active smokers. The smallest airways also could not be examined due to CT resolution limitations, and medication was not included among the adjustments.

Bhatt’s group cautioned that the data do not answer the question of whether cigarette smoking causes the poor lung outcomes in women, and that cause of death was not analyzed.