Short Telomeres May Signal Worse Outcomes in COPD

Patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) who have short telomeres, a biomarker of aging, are more likely to have a worse quality of life and have a higher risk of exacerbations and death, according to a recent study.

Researchers publishing in the journal CHEST wrote that measuring blood telomeres can be used to predict future risk of the disease. The antibiotic azithromycin may help these patients, the study said.

“Previous studies have suggested that COPD may be a disease of accelerated aging for a variety of reasons including a close relation to senescence-related disorders, such as osteoporosis and dementia, and its exponential increase in prevalence beyond 50 years of age,” the researchers wrote.

Lead investigator Don D. Sin, MD, FCCP, of the Centre for Heart Lung Innovation, St. Paul’s Hospital, and the Department of Medicine (Respiratory Division) of the University of British Columbia, Vancouver, BC, Canada, said in a statement that “it is known that short telomeres are associated with common comorbidities of COPD, such as cardiovascular disease and cancer, but it was not known if there is a relationship between blood telomeres and patient-related outcomes in COPD.”

Telomeres are specific repetitive DNA sequences found on the ends of chromosomes. They prevent harmful DNA events including abnormal genetic recombinations or deletions. Each time a cell replicates, the telomeres become shorter and shorter until they stop dividing, a process known as cellular aging, or senescence.

Researchers used data from the Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO) study, which included participants from 17 sites across 12 academic health centers in the United States.

A total of 1142 participants with COPD were randomized to azithromycin or placebo in addition to standard care for 12 months.

Patients were included in the study if they were aged 40 or more years; had a clinical diagnosis of COPD; had a smoking history of at least 10 pack-years; a ratio of postbronchodilator pulmonary function as measured by mean forced expiratory volume in 1 second (FEV₁)/FVC <70% with a postbronchodilator FEV₁ of <80%, being admitted to the hospital; arrived at the emergency department for acute exacerbation of COPD; continuous usage of supplemental oxygen; or were treated with systemic glucocorticoids within the past year.

After 545 of the 1142 were excluded from the study, the blood of 597 participants who agreed to participate in DNA biobanking was collected and analyzed. Of those, 576 blood samples were analyzed. Absolute telomere length was measured to determine the age of the cells in the blood samples.

The researchers divided the group into individuals with shorter and longer telomere lengths, using the median value of absolute telomere length as the cutoff. Patients were followed for up to 3.5 years.

Researchers found that patients with short telomeres, indicating more rapidly aging blood cells, were 50% more likely to have exacerbations and 9 times more likely to die than those with normal blood telomeres.

Patients with short telomeres also experienced worse health status and poorer quality of life. Health status was measured using the St. George’s Respiratory Questionnaire (SGRQ), which assesses daily activities, respiratory symptoms, and perceived psychological impact.

However, the differences were not seen when patients with short telomeres were treated with daily azithromycin.

“This suggests that this blood biomarker may help select those patients with COPD who will benefit most from azithromycin treatment,” said Sin. “Peripheral leukocyte telomeres are readily accessible and easy to measure; thus, they may represent a clinically translatable biomarker for patient risk-stratification and identifying individuals at increased risk of poor patient-centered outcomes in COPD.”

This study was funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, and the National, Heart, Lung, and Blood Institute.

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: org/10.1016/j.chest.2018.05.022.