Abstract
Some have suggested that chronic obstructive pulmonary disease (COPD) is a disease of accelerated aging. Aging is characterized by shortening of telomeres. The relationship of telomere length to important clinical outcomes such as mortality, disease progression and cancer in COPD is unknown. Using quantitative polymerase chain reaction (qPCR), we measured telomere length of peripheral leukocytes in 4,271 subjects with mild to moderate COPD who participated in the Lung Health Study (LHS). The subjects were followed for approximately 7.5 years during which time their vital status, FEV1 and smoking status were ascertained. Using multiple regression methods, we determined the relationship of telomere length to cancer and total mortality in these subjects. We also measured telomere length in healthy “mid-life” volunteers and patients with more severe COPD. The LHS subjects had significantly shorter telomeres than those of healthy “mid-life” volunteers (p<.001). Compared to individuals in the 4th quartile of relative telomere length (i.e. longest telomere group), the remaining participants had significantly higher risk of cancer mortality (Hazard ratio, HR, 1.48; p = 0.0324) and total mortality (HR, 1.29; p = 0.0425). Smoking status did not make a significant difference in peripheral blood cells telomere length. In conclusion, COPD patients have short leukocyte telomeres, which are in turn associated increased risk of total and cancer mortality. Accelerated aging is of particular relevance to cancer mortality in COPD.
Highlights
The pathogenesis of chronic obstructive pulmonary disease (COPD) is obscure
There were no significant differences in age, sex, body mass index (BMI), race or cumulative smoking exposure across the quartiles of the reference single copy gene (T/S) ratio (Table 1)
Telomere Length and Smoking Status Because cigarette smoke is suggested to accelerate telomere attrition, we evaluated the effect of smoking status on leukocyte
Summary
The pathogenesis of chronic obstructive pulmonary disease (COPD) is obscure. What is well known is that COPD is rare before 40 years of age even among heavy smokers and its incidence increases exponentially with aging. COPD frequently aggregates with other age-related co-morbidities such as osteoporosis, cardiovascular disease and dementia [1,2]. Together, these data suggest that COPD is likely related to the aging process [3]. Owing to the end-replication problem in mature somatic cells, telomere repeats are lost with each replicative cycle, until a critical length is reached at which point cells undergo apoptosis or other disruptive events [8] This entire process is accelerated by the presence of reactive oxygen species (ROS) or inflammation [9,10,11], leading to short telomeres. We hypothesized that COPD patients with longer telomeres would have a lower mortality rate than those with shorter telomeres and that telomere length serves as a predictor of mortality among COPD patients
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have