Why do some non-smokers get COPD while many heavy smokers don’t?

A new study highlights a strong risk factor for COPD related to lung development

Montreal, —Smoking is the best-known risk factor for chronic obstructive pulmonary disease (COPD), a debilitating lung condition that can severely limit a person’s day-to-day activities. But curiously, only a minority of lifelong smokers develops the disease, while non-smokers represent more than 25% of all COPD cases. A new study published today in The Journal of the American Medical Association suggests that a developmental mismatch between airway and lung size—a condition called dysanapsis—could answer why.


Dr. Benjamin Smith, scientist at the Research Institute of the McGill University Health Centre (RI-MUHC)

Dr. Benjamin Smith, a scientist at the Research Institute of the McGill University Health Centre (RI-MUHC), led a team of researchers from across Canada and the US, who analyzed data from more than 6,500 older adults participating in three studies that included smokers and nonsmokers with and without COPD —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. 

The team conducted detailed analysis of lung images and assessed standard COPD risk factors such as tobacco smoking, secondhand smoke, air pollution and occupational exposures. Their results show that dysanapsis appears to be a very strong risk factor for COPD, associated with twice as much of the variation in COPD risk when compared with cigarette smoking and other standard COPD risk factors.

According to the Canadian Centre for Health and Safety, COPD affects at least 4% of adults and is the fourth leading cause of death in Canada. It is characterized by insufficient flow from the lungs and is associated with symptoms like shortness of breath that gets worse over time, chronic coughing, and obstructed airways.

“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 do not get as large as expected,” says Dr. Smith, who is also an Associate Professor in the Department of Medicine at McGill University and the lead author of the study.

The researchers measured airway tree and lung size using state-of-the-art CT scans of the chest, and discovered that never smokers with COPD had much smaller airways relative to lung size, whereas the heavy smokers who did not have COPD had unusually large airways and thus found themselves at the opposite end of the dysanapsis spectrum (fig. 1). While the root cause for dysanapsis remains unknown, these findings help understand why COPD can occur in people who never smoked and do not have other risk factors.

“With normal aging, lung function declines,” explains Dr. Smith. “And because of that decline, people with smaller airways—who already have low lung function to begin with—may develop COPD later in life. On the other hand, smokers with larger airways might have some reserve to withstand the harmful effects of smoking. That said, given the multiple health problems caused by tobacco, quitting smoking remains of paramount importance.”

The team also looked at the prognosis of patients with COPD associated with smaller airway-to-lung ratio and found that they had much slower lung function decline when compared to those with larger airway-to-lung ratio.

“Amongst COPD patients who have dysanapsis, we observed that the rate of lung function decline is similar to that of healthy people, while COPD related to other causes, such as smoking, is associated with a faster decline,” says Dr. Smith.

Dr. Smith hopes that more research to understand what triggers dysanapsis may lead to interventions to promote the development of healthy lungs for life.

About the three cohort studies

The MESA Lung study, based in six U.S. cities, included white, African American, Hispanic, and Chinese American people 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 U.S. medical centers, included people who were age 63 on average and reported 20+ pack-years of smoking.

Figure 1. These CT scans of airways (red) and lungs (dark grey) show the spectrum of dysanapsis

Figure 1. These CT scans of airways (red) and lungs (dark grey) show the spectrum of dysanapsis, with smaller airways in proportion to lung size (left) compared with normal size airways (middle), and larger than normal airways (right).

About the study

The study Association of dysanapsis with chronic obstructive pulmonary disease among older adults was conducted by Benjamin M. Smith, Miranda Kirby, Eric A. Hoffman, Richard A. Kronmal, Shawn D. Aaron, Norrina B. Allen, Alain Bertoni, Harvey O. Coxson, Chris Cooper, David J. Couper, Gerard Criner, Mark T. Dransfield, MeiLan K. Han, Nadia N. Hansel, David R. Jacobs Jr., Joel D. Kaufman, Ching-Long Lin, Ani Manichaikul, Fernando J. Martinez, Erin D. Michos, Elizabeth C. Oelsner, Robert Paine III, Karol E. Watson, Andrea Benedetti, Wan C. Tan, Jean Bourbeau, Prescott G. Woodruff, R. Graham Barr, for the MESA Lung, CanCOLD and SPIROMICS investigators 

This work was made possible through funding from the National Institutes of Health (USA), the Canadian Institutes of Health Research, the Canadian Respiratory Research Network and the Fonds de recherche du Québec – Santé (FRQS).

About the RI-MUHC

The Research Institute of the McGill University Health Centre (RI-MUHC) is a world-renowned biomedical and healthcare research centre. The Institute, which is affiliated with the Faculty of Medicine of McGill University, is the research arm of the McGill University Health Centre (MUHC) – an academic health centre located in Montreal, Canada, that has a mandate to focus on complex care within its community. The RI-MUHC supports over 420 researchers and close to 1,200 research trainees devoted to a broad spectrum of fundamental, clinical and health outcomes research at the Glen and the Montreal General Hospital sites of the MUHC. Its research facilities offer a dynamic multidisciplinary environment that fosters collaboration and leverages discovery aimed at improving the health of individual patients across their lifespan. The RI-MUHC is supported in part by the Fonds de recherche du Québec – Santé (FRQS). www.rimuhc.ca

Media contact

Fabienne Landry
McGill University Health Centre
514 812-7722
[email protected]