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Genetic Lung Variants May Identify COPD Risk

Genetic Lung Variants May Identify COPD Risk

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Action Points

  • Genetic variations in the anatomy of the lungs could potentially identify smokers at high risk for developing chronic obstructive pulmonary disease (COPD).
  • Note that central airway branch variants, which are easily detected with standard clinical CT, were associated with higher odds of COPD later in life, suggesting that the central airway tree may be a useful biomarker to identify people at higher or lower COPD risk.

Genetic variations in the anatomy of the lungs could potentially identify smokers at high risk for developing chronic obstructive pulmonary disease (COPD), researchers reported.

Inherited lung central airway branch variants were identified in about a quarter of the study population using CT scanning, and the most commonly seen variant was associated with higher COPD and chronic bronchitis prevalence in smokers and nonsmokers, according to Benjamin M. Smith, MD, of Columbia University Medical Center in New York City, and McGill University in Montreal, and colleagues.

The second most common airway branch variant was associated with higher COPD risk among smokers, but not nonsmokers they wrote in the Proceedings of the National Academy of Sciences.

“The central airway tree develops early in life,” Smith told MedPage Today. “We found that central airway branch variants, which are easily detected with standard clinical CT, were associated with higher odds of COPD later in life. These findings suggest that the central airway tree may be a useful biomarker to identify people at higher or lower COPD risk.”

James Kiley, MD, director of the division of lung diseases at the National Heart Lung and Blood Institute, noted that the findings raise interesting questions for researchers.

“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,” Kiley noted in a press statement. “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.”

Other than smoking risk, susceptibility to COPD is poorly understood. “Cigarette smoking is the major COPD risk factor, but COPD is not rare among those who have never smoked cigarettes and many smokers do not develop COPD,” Smith’s group wrote. “Furthermore, approximately half of older adults with COPD exhibit low lung function early in life. These observations suggest that host factors beyond smoking may contribute to COPD risk and may create opportunities for personalized disease prevention and treatment.”

Genome-wide association studies (GWAS) have identified several genes that regulate tracheobronchial tree formation in utero, which may influence susceptibility to COPD and other lung diseases, they noted.

Smith’s demonstrated that lower-lobe segmental airway branch variants were common among participants in the large Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, which included both nonsmokers and current and former smokers.

Airway branch variation was seen in 26.5% (95% CI, 24.9-27.8%) of participants, with the most common variant being an accessory subsuperior airway (16%) followed by an absent right medial-basal airway (6.1%).

Accessory subsuperior segmental airway was more common among whites and less common among Asian Americans, while the absent right medial-basal airway was more common among Asian Americans and less common among African Americans.

In an effort to determine which airway branch variants were associated with COPD, the researchers compared 243 COPD cases and 2,065 controls without airflow limitation in the MESA cohort and 1,823 COPD cases and 923 controls in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS).

The accessory subsuperior segmental airway variant was associated with a 1.64 higher odds of COPD (95% CI 1.18-2.29, P=0.004) compared with standard anatomy in the MESA Lung Study and also SPIROMICS (pooled odds ratio for COPD in the two cohorts 1.40, 95% CI 1.19-1.64, P<0.001). The odds were similar for smokers and nonsmokers.

Absence of the right medial-basal segmental airway was not significantly associated with COPD in the MESA Lung Study, but there was evidence of an interaction by smoking status, with smokers with the variant having double the COPD risk (OR 2.04, 95% CI 1.13-3.71, P=0.019).

Among smokers in the SPIROMICS cohort, this variant was associated with a 1.71 higher odds of COPD (95% CI 1.19-2.47, P=0.004).

Smith said his group is currently studying whether identifying these central airway branch variants can help determine who will experience rapid lung function decline and who will have low but stable lung function.

He noted that identification of the variants could lead to personalized COPD management strategies, targeting patients most likely to benefit from interventions.

Study limitations included the cross-sectional design which may have introduced selection bias.

The study was funded by the National Heart Lung and Blood Institute.

Smith disclosed no relevant relationships with industry. One co-author disclosed relevant relationships with VIDA Diagnostics.

  • Reviewed by
    Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

1969-12-31T19:00:00-0500

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