Airway Branch Variations Found That May Indicate Risk for COPD

Variations in the anatomy of airway branches may be used as indicators for people at higher risk of developing chronic obstructive pulmonary disease (COPD), a new study found.

The team of researchers, funded by the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH), discovered that a group of airway tree structural variants that  diverge from the common pattern were linked to a higher prevalence of lower lung function and a higher risk for COPD.

The work, “Human airway branch variation and chronic obstructive pulmonary disease,“ was published in the journal Proceedings of the National Academy of Sciences.

Cigarette smoking is known to be the most common cause of COPD, but not all smokers develop the disease. And nonsmokers have been know to develop COPD.

Genetic variants associated with COPD are known to regulate airway branch development, so researchers hypothesized that this could influence a person’s susceptibility to the disease.

The team first assessed the prevalence of airway branch variations on the general population in a large group of adult Americans — 3,169 participants, ages 40 to 84 — who were examined by chest computer tomography (CT).

Results revealed that central airway branch variations were present in about one-quarter (26.5 percent) of the total participants.

Then, a prospective analysis of 2,066 participants with COPD and 2,988 non-COPD controls showed that the most prevalent airway branch variant — an accessory subsuperior airway — was significantly associated with COPD patients, both smokers and nonsmokers, and in people with chronic bronchitis.

The second most common variant, absence of the right medial-basal airway, was associated with a higher risk for COPD only in smokers, and those with dyspnea (shortness of breath).

The associations found were not affected by gender, ethnicity, maternal smoking, presence of childhood asthma, or living with a smoker as a child.

“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,” Benjamin M. Smith, MD, an assistant professor at Columbia University Medical Center and the study’s first author, said in a NIH news release.

A comparison of CT scans over a 10-year gap in 300 participants also showed that branch variations did not change during that time, suggesting they were acquired before late adulthood (younger than age 40) and perhaps even inherited.

In fact, when researchers looked at the lungs of children from parents exhibiting a specific variant branch, the likelihood of those children having the same branch variation as their parents was higher, suggesting a genetic basis.

An analysis of gene candidates implicated in lung structure showed that no genetic variants were linked with the most common branch variant. However, the second most-prevalent variant was related to variations in the FGF10 gene.

According to the team, these findings suggest that “airway branch variation, which is common and easily identifiable, reflects widely altered lung structure and provides a genetically determined anatomical basis for COPD susceptibility.”

While cigarette smoking is the major COPD risk factor, these new results suggest that patient-specific determinants in lung structure, beyond smoking habits, also contribute to COPD.

“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,” said James Kiley, director of the NHLBI division of Lung Diseases.

“This novel study suggests that a CT scan, which is widely available, can be used to measure airway structure and predict who is at higher risk for smoke-induced lung injury,” Kiley added.

Even though the study puts forward the prospect of using central airway branch variants, easily detected by CT, as biomarkers of lower lung function and COPD susceptibility, the team emphasizes that additional research is needed to confirm that therapeutic decisions can be based on these indicators.

The team also notes that despite the new findings, quitting smoking remains the best antidote against developing COPD.