Short telomere length, lung function and chronic obstructive pulmonary disease in 46 396 individuals

Background A previous case-control study of 100 individuals found that short telomere length was associated with a 28-fold increased risk of chronic obstructive pulmonary disease (COPD). Objectives To test the hypothesis that short telomere length is associated with reduced lung function and an increased risk of COPD. Methods Observational study of 46 396 individuals from the Danish general population. Measurements Leucocyte telomere length and spirometry were measured. COPD was defined using either fixed forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.70 as suggested by the Global initiative for chronic Obstructive Lung Disease (GOLD) or FEV1/FVC below the lower limit of normal (LLN). Results Telomere length decreased significantly with increasing age (p<10(-300)). FEV1, FVC and FEV1/FVC decreased with decreasing telomere length quartiles (p trend: 5x10(-51), 5x10(-35) and 6x10(-137), respectively), but the associations attenuated after age and multivariable adjustment. The risk of COPD increased with decreasing telomere length quartile (p trend: p=7x10(-92) for GOLD; p=8x10(-44) for FEV1/FVC below LLN), but associations also attenuated after adjustment. Unadjusted and multivariable adjusted OR for shortest versus longest telomere length quartiles were 2.06 (95% CI 1.91 to 2.22) and 1.15 (95% CI 1.06 to 1.25) for GOLD and 1.73 (95% CI 1.60 to 1.88) and 1.19 (95% CI 1.09 to 1.30) for FEV1/FVC below LLN, respectively. Per 1000 base pairs decrease in telomere length, the multivariable adjusted OR was 1.07 (95% CI 1.03 to 1.10) for GOLD and 1.07 (95% CI 1.03 to 1.11) for FEV1/FVC below LLN. Conclusions Short telomere length is associated with decreased lung function and with increased risk of COPD, but the associations are markedly attenuated after adjustment. Our data support a modest correlation between telomere length and the lung function indices examined.