New research funded by NHLBI and published in JAMA reports that the size of a person’s airways may leave them at greater risk of developing COPD, even if they have never smoked. The condition, known as dysanapsis, causes underdeveloped bronchi and bronchioles, which reduces lung capacity and can make these patients more susceptible to COPD.
Smoking, asthma, or air pollution account for many COPD cases, but up to 30% of cases occur in people who never smoked, and only a minority of heavy smokers develop the disease, suggesting that there are other risk factors at play.
“This work, stemming from the careful analysis of lung images of COPD patients, shows that an abnormal lung development may account for a large proportion of COPD risk among older adults,” said James Kiley, PhD, director of the National Heart, Lung, and Blood Institute’s Division of Lung Diseases. “More research is needed to understand what drives this occurrence and to devise possible interventions.”
Previous research offered a clue about a possible cause, finding that about half of older adults with COPD appeared to have low lung function early in life. Benjamin Smith, M.D., a pulmonary physician in the Department of Medicine at Columbia University Irving Medical Center, New York City, who was involved in the new study, explained the phenomenon.
When people breathe, they move air through their airways, beginning with the windpipe or trachea, which branches out to smaller airways called bronchi and bronchioles. As people grow, their airways are thought to develop in proportion to their lungs, but in some people, the airways grow smaller or larger than expected—a condition called dysanapsis— for reasons that are not clear.
To find out if small airways might be the culprit for COPD in people who did not smoke or have other risk factors, a team led by Smith looked at records for more than 6,500 older adults participating in three studies that included smokers and nonsmokers with and without COPD. Each study—the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), and the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study—assessed dysanapsis using computed tomography (CT) scans of the lungs.
The MESA Lung study, based in six US cities, included white, African American, Hispanic, and Asian Americans who were age 69 on average. The participants from the CanCOLD study were age 67 on average and came from nine Canadian cities. SPIROMICS, based at 12 US medical centers, included people who were age 63 on average and reported 20 or more pack-years of smoking.
In the MESA Lung and CanCOLD studies, participants with smaller airways relative to lung size were much more likely to develop COPD compared with those with the larger airways relative to lung size. The association remained after considering standard COPD risk factors, including smoking, pollutants, and asthma.
The researchers then focused on participants from the CanCOLD study who never smoked and heavy smokers from the SPIROMICS study. Never smokers with COPD had much smaller airways relative to lung size, whereas the heavy smokers who did not have COPD had larger than normal airways.
“These results show that small airways relative to lung size are a very strong risk factor for COPD,” said Smith, the lead study author. “This helps us to understand why 30% of COPD can occur in people who never smoked.” With normal aging, lung function declines, so people who already have low lung function to begin with may develop COPD later in life, even if they don’t smoke, he explained.
Smith added that the findings may also help explain why some lifelong heavy smokers do not develop COPD. People with larger airways relative to lung size may be able to withstand lung damage from smoking and still have enough breathing reserve to prevent them from developing COPD. Still, given the multiple health problems caused by tobacco, Smith emphasized that smokers should do their best to quit.
The study, funded in part by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, will publish in the June 9 issue of JAMAexternal link.