Telomeres could predict the progression of COPD

The shorter length of leukocyte telomeres may represent a clinically translatable biomarker to identify patients with COPD at increased risk for accelerated disease progression and poor outcomes, with secondary badysis of clinical trial data being indicated

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also suggest that treatment with the antibiotic azithromycin could help reverse the negative health impact of telomere length in patients with COPD

Minhee Jin, MSc, University of British Columbia in Vancouver. Total telomere length of DNA extracted blood samples taken from 576 patients with moderate to severe COPD who participated in the Macrolide Azithromycin Study for the Prevention of COPD Exacerbations (MACRO).

MACRO participants were treated with azithromycin or placebo. 12 months and all were followed for approximately 13 months, during which time their general health status and COPD exacerbations were recorded. They were followed for an additional 29 months to measure mortality.

The average age of participants in the reference visit was 66 ± 8.6 years, and 55.6% of the cohort were men. A total of 890 exacerbations occurred among the 576 patients during follow-up, with annualized rates of exacerbations showing no statistical difference between shorter and longer absolute telomeric length (aTL).

Jin and her colleagues found that the participants had a worse health status as defined by the high scores of the St. George's respiratory questionnaire.

Among participants enrolled in the placebo arm of the study, the rate of exacerbation (rate ratio 1.50, 95 IC: 1.16 to 1.95 P ] = 0.002) and the risk of death (hazard ratio 9.45, 95% CI 2.85 to 31.36, P = 0.015) was significantly higher in the shorter telomere group than in the telomere group longer

. Patients treated with azithromycin, there were smaller differences depending on telomere length that did not reach statistical significance (RR 0.89, P = 0.46 for exacerbation, HR 0.31, P = 0.181 for mortality) [196590] 02] "The most important finding of this study was that the short telomere lengths in peripheral leukocytes were badociated with a reduced quality of life and a higher risk of exacerbation and death in patients with moderate to severe COPD ". "Together, these data support the notion that COPD is a systemic disease of accelerated aging and that replicative senescence, denoted by peripheral blood telomeres, is badociated with poor health outcomes in COPD."

It is now well established that replicative senescence results in a change in the cellular phenotype to a pro-inflammatory state, a process which has been termed the secretory phenotype badociated with senescence. "

Jin and his colleagues wrote: "While it is beyond the scope of this study to determine the exact pathways by which reduced telomeres can contribute to the secretion of these proteins. to poor health outcomes, previous studies have suggested that a pro-inflammatory phenotype in COPD is badociated with increased risk A study strength cited by researchers included measurement of absolute telomeric length, rather than relative, peripheral leukocytes, which allowed cross-comparisons with other studies and may have increased the accuracy of the measurement.

limitation of the study was the absence of a healthy control group and the use of telomere peripheral leukocytes rather than lung tissue, which could have led to a sub- estimation of telomere effects on health outcomes

. the telomere length of peripheral leukocytes is significantly correlated with that of lung tissue, and most of the previously published studies on telomere length in COPD used peripheral leukocytes to mirror telomere lengths in other tissues. " .

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Last updated 07.19.2018