Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking has not been fully determined, although several genetic variants associated with COPD are known to regulate airway branch development.

For a study published in Proceedings of the National Academy of Sciences of the United States of America, Benjamin Smith, MD, MSc, FRCPC, and colleagues sought to determine whether central airway branch variation, readily detected by computed tomography, is a biomarker of widely altered lung structure with a genetic basis and represents a COPD susceptibility factor.

“The classical thinking about COPD pathogenesis was that heavy smoking over many years caused lung function to decline, resulting in COPD later in life,” Dr. Smith says. “But more recent studies suggest that some people with COPD later in life actually had low lung function early in life.”

Dr. Smith and colleagues demonstrated that in vivo central airway branch variants were present in 26.5% of the general population, unchanged over 10 years, and exhibited strong familial aggregation. The most common airway branch variant was associated with COPD in two cohorts, with greater central airway bifurcation density and with emphysema throughout the lung. The second most common airway branch variant was associated with COPD among smokers, with narrower airway lumens in all lobes and with genetic polymorphisms within the FGF10 gene.

“Our study shows that variations in airway tree structure, which are believed to form in utero, are associated with higher odds of COPD later in life,” Dr. Smith says. “Furthermore, these airway variants are easy to detect on CT, cluster within families, and have a genetic basis. Together, these findings suggest that variations in airway tree development may contribute to the COPD that we see later in life. Our study suggests that early life events (eg, central airway development) may be an easily detected biomarker of increased COPD susceptibility.”

References

Smith B, Traboulsi H, Austin J, et al. Human airway branch variation and chronic obstructive pulmonary disease. Proc Natl Acad Sci U S A. 2018;115(5):E974-E981. Available at www.pnas.org/content/early/2018/01/09/1715564115.