Undersized Airways May Explain Why Some Nonsmokers Develop COPD

Having small airways compared to lung size may contribute to the development of chronic obstructive pulmonary disease (COPD) in many non-smokers, a retrospective study has found.

The finding broadens understanding of the risk factors involved in COPD, say  Columbia University Irving Medical Center researchers, whose work, “Association of Dysanapsis With Chronic Obstructive Pulmonary Disease Among Older Adults,” was published in the Journal of the American Medical Association.

COPD is the third leading cause of death in the U.S. The disease is thought to result from long-term exposure to irritants such as cigarette smoke, air pollution, and dust that can damage the lungs.

Smoking is a known major risk factor for COPD, although nearly one in four patients with the disease have never smoked.

Past research has shown that some adults with COPD had poor lung function early in life, which led researchers to suspect that dysanapsis — a mismatch of airway-to-lung size — might influence COPD risk.

Although one’s airways typically develop in proportion to their lungs, the airways of some people grow smaller than expected, resulting in dysanapsis. The reasons for this have eluded scientists.

Now researchers reviewed medical records, including computed tomography scans, of 6,529 older adults looking for instances in which dysanapsis occurred with COPD.

Records came from three major lung studies in the U.S. and Canada. Two were community-based samples: the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, drawing from six sites across the U.S.; and the Canadian Cohort of Obstructive Lung Disease (CanCOLD), which involved nine sites across Canada. The third was a case-control study of COPD — the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which drew participants from 12 U.S. sites.

The average age in the three groups ranged from 63 to 69 years, and all included both smokers and non-smokers of diverse ethnicities.

Researchers found a strong association between COPD and dysanapsis. The lower the ratio of airway to lung size, the greater the risk of COPD. This was regardless of patients’ smoking habits.

“Our study shows that having an undersized airway tree compromises breathing and leaves you vulnerable to COPD later in life,” Benjamin M. Smith, MD, the study’s lead author, said in a Columbia press release.

Results showed that individuals with smaller airways relative to lung size were eight times more likely to develop COPD.

“A quantitative measure of dysanapsis (airway to lung ratio on computed tomography) was significantly associated with incident COPD … after adjusting for tobacco exposures and other standard risk factors,” the researchers wrote.

Notably, heavy smokers who did not develop COPD had larger than normal airways. But this is no guarantee that they would stay healthy over the course of their lives.

“This suggests that people at the opposite end of the dysanapsis spectrum, i.e. those with larger than expected airways, may be able to incur considerable damage from smoking while maintaining enough reserve to avoid COPD,” Smith said. “Of course, the harmful effects of smoking are legion, including lung cancer, heart disease, and stroke. So anyone who smokes should do their best to quit.”

Taken together, “our findings suggest that dysanapsis is a major COPD risk factor — on par with cigarette smoking,” Smith said. “Dysanapsis is believed to arise early in life. Understanding the biological basis of dysanapsis may one day lead to early life interventions to promote healthy and resilient lung development.”