Researchers Make COPD Genetic Discovery That Could Identify At-Risk Patients Earlier

January 16, 2018

Cigarette smoking is the most common cause of chronic obstructive pulmonary disease (COPD), but not all smokers develop the condition, and many non-smokers do. Why that is has remained a mystery until now, as a research team, funded by the National Institutes of Health, has discovered genetic variations in the anatomy of the lungs could serve as early-warning indicators.

Cigarette smoking is the most common cause of chronic obstructive pulmonary disease (COPD), but not all smokers develop the condition, and many non-smokers do. Why that is has remained a mystery until now, as a research team, funded by the National Institutes of Health, has discovered genetic variations in the anatomy of the lungs could serve as early-warning indicators.

This genetic variation could identify patients who have low, but stable, lung function early in life, and those who are particularly at risk for COPD because of smoke-induced decline in lung function, according to a team of researchers that found that a genetically programmed airway tree variation is linked to the higher prevalence of COPD among older adults.

The results of the study appear this week in the journal Proceedings of the National Academy of Sciences.

“Understanding precisely why these genes influence the development of COPD may lead to entirely new and more effective ways of preventing or treating this disease,” James Kiley, MD, director of the National Heart, Lung, and Blood Institute’s Division of Lung Diseases, said in a statement. “This novel study suggests that a [computated tomography] scan, which is widely available, can be used to measure airway structure and predict who is at higher risk for smoke-induced lung injury.”

COPD, a progressive disease that makes it hard to breathe, is the fourth-leading cause of death in the United States. An estimated 16 million people are currently diagnosed with COPD. Millions more are believed to have the condition.

Until recently, researchers believed that COPD developed later in life as a result of prolonged exposure to cigarette smoke or air pollution. However, recent studies have shown that many older adults with COPD had low lung function early in life and experienced the normal lung function decline associated with aging, not an accelerated decline.

“In the current study, we found that central airway branches of the lungs, which are believed to form early in life, do not follow the textbook pattern in one quarter of the adult population and these non-textbook variations in airway branches are associated with higher COPD prevalence among older adults,” said the study’s first author Benjamin M. Smith, MD, MS, assistant professor at Columbia University Medical Center. “Interestingly, one of the airway branch variants was associated with COPD among smokers and non-smokers. The other was associated with COPD, but only among smokers.”

These airway tree variations are identifiable on low-dose screening lung CT scans, which are currently indicated clinically for lung cancer screening in older patients with a history of heavy smoking in the prior 15 years.

Before CT scans are used outside of this group for the identification of airway variants in clinical practice, the study authors say more research will be needed to confirm that preventive or therapeutic interventions based on the presence of airway tree variations can improve outcomes.

In the meantime, the researchers say they will be investigating another important finding—this one around family history.

Their study identified a common airway branch variation that occurs within families and is associated with COPD among non-smokers. Smith said while other developmental events that occur within families may be involved, his research team is looking into whether there is a genetic basis for this variant. “If proven,” he said, “this would represent a novel mechanism of COPD among non-smokers.”

The researcher emphasized that for all the new findings, quitting smoking remains the best antidote to COPD, and smokers trying to quit should seek professional help, if necessary, to succeed.