Shorter Telomeres May Predict Poor Outcomes in COPD

Short telomeres may help predict poor outcomes in chronic obstructive pulmonary disease (COPD), according to the results of a study published in CHEST.

Some evidence suggests that COPD may be a disease of accelerated aging. Telomere length is an important biomarker of replicative senescence, but with each cycle of replication, telomeres shorten. COPD is associated with oxidative stress, which is intensified during exacerbations, and oxidative stress is known to increase telomere shortening.

Minhee Jin, MSc, of the Centre for Heart Lung Innovation at St. Paul’s Hospital, and Department of Medicine, University of British Columbia in Vancouver, Canada, and colleagues used quantitative polymerase chain reaction to measure the absolute telomere length (aTL) of DNA from peripheral blood leukocytes in 576 individuals with moderate to severe COPD treated with azithromycin or placebo for 12 months in the Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO) study. The investigators monitored the health status and exacerbations of participants who were followed for 13 months. They monitored patients for an additional 29 months for mortality.

Shorter telomere length was associated with worse health status as measured by St. George’s Respiratory Questionnaire (SGRQ; P =.034). In a multivariable model, SGRQ, age, and forced vital capacity percent predicted were significantly associated with aTL. The investigators found, however, that when the data were stratified by sex, the relationship between SGRQ and aTL was significant only among females (P =.012).  

Among patients randomly assigned to placebo, the rate of exacerbation (rate ratio, 1.50; 95% CI, 1.16-1.95; P =.002) and risk for mortality (hazard ratio, 9.45; 95% CI, 2.85-31.36; P =.015) were significantly higher in patients with shorter aTL than in those with longer aTL. However, they did not observe these differences in patients who received azithromycin (interaction P =.008 for exacerbation and interaction P =.017 for mortality).

Study limitations included the lack of a healthy control population and that the study measured peripheral leukocytes rather than those from lung tissue, which could have led to an underestimation of the effects of telomeres on health outcomes. The researchers, however, contended that the telomere lengths of peripheral leukocytes have been shown to correlate with those in lung tissue.

The authors argued that peripheral leukocyte telomeres are easy to obtain and measure and may represent a valid biomarker for patient risk stratification and identification of patients at increased risk for poor outcomes of COPD. However, they noted the necessity of more research before these biomarkers will be suitable for clinical application.

Reference

Jin M, Lee EC, Ra SW, et al. Relationship of absolute telomere length with quality of life, exacerbations, and mortality in COPD [published online July 12, 2018]. CHEST. doi:10.1016/j.chest.2018.05.022