The association between leukocyte telomere length and chronic obstructive pulmonary disease is partially mediated by inflammation: a meta-analysis and population-based mediation study

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is one of the major health issues worldwide. Pathophysiological changes in COPD are mainly reflected in the deterioration of lung function with aging.

Methods: Considering that telomere length is a hallmark of biological aging, we first performed a meta-analysis to summarize the current knowledge about the relationship between telomere length and COPD and then employed individual-level data from the continuous National Health and Nutrition Examination Survey (NHANES) to investigate whether telomere length could reflect accelerated aging in COPD and serve as an independent predictor. A mediation study was further performed to examine whether the association between telomeres and COPD could be mediated by inflammation, as one of the most important etiologies and characteristics of COPD.

Results: The four studies included in our meta-analysis were with high heterogeneity (I² = 95.7%, P_het < 0.001), and the pooled relative risk for COPD comparing the shortest tertile versus the longest tertile was 4.06 (95% CI = 1.38 to 11.96). Of the 6,378 subjects in the individual-level data analyses using NHANES, 455 were diagnosed with COPD, and multivariable-adjusted logistic regression also indicated that short telomere length was associated with COPD. Consistently, cubic regression spline analyses showed that long telomeres exhibited a significant association with a decreased risk of COPD. In the subsequent mediation analyses, C-reactive protein concentration, white blood cells count and blood neutrophil count, as inflammatory biomarkers, showed a significant indirect effect on the relationship between telomere length and COPD.

Conclusion: Accelerated aging in COPD could be characterized by excessive telomere shortening, and inflammatory response might be involved in the underlying mechanisms of COPD pathogenesis promoted by short telomere length. Telomere length measurement may facilitate clinical translational research and targeted therapy of COPD.

Keywords: COPD; Inflammation; Mediation study; NHANES; Telomere length.