Abstract
The objective of this study was to examine whether shorter leukocyte telomere length (LTL) is associated with more rapid pulmonary function decline in a longitudinal study of World Trade Center (WTC) responders. WTC responders (N = 284) participating in a monitoring study underwent blood sampling and were followed prospectively for spirometric outcomes. A single blood sample was taken to measure LTL using southern blotting. Outcomes included percent-predicted one-second forced expiratory volume (FEV1%), forced vital capacity (FVC%), and the FEV1/FVC ratio. In a subset, percent-predicted diffusing capacity (DLCO%) was also measured. Longitudinal modeling examined prospectively collected information over five years since blood was banked was used to examine the rate of change in pulmonary functioning over time. Severity of WTC exposure was assessed. Shorter LTL was associated with lower FEV1% and FVC% at baseline. For example, 29.9% of those with LTL <6.5 kbps had FEV1% <80% whereas only 12.4% of those with LTL ≥6.5 had FEV1% <80% (RR = 2.53, 95%CI = [1.70–3.76]). Lower DLCO% was also significantly associated with shorter LTL. Longitudinal models identified a prospective association between shorter LTL and greater yearly rates of decline in FEV1% (0.46%/year, 95%CI = [0.05–0.87]) and in the FEV1/FVC ratio (0.19%/year, 95%CI = [0.03–0.36]). There were no associations between severity of exposure and either LTL or pulmonary function. Longitudinal analyses revealed that shorter LTL, but not severity of WTC exposures, was associated with poorer pulmonary functioning and with greater subsequent decline in pulmonary functioning over time. These findings are consistent with the idea that shortened LTL may act as a biomarker for enhanced pulmonary vulnerability in the face of acute severe toxic inhalation exposures.
Highlights
Telomeres are nucleoprotein complexes, consisting of repetition of the TTAGGG nucleotide sequences forming the end of human chromosomes, that maintain chromosomal stability and control cellular senescence[1]
Comparing the sample of those whose blood was assayed for leukocyte telomere length (LTL) to those without the LTL measure who were followed up in the same year (N = 4,290) we find that those with LTL data were not older (P = 0.595) and did not differ in terms of FVC% (P = 0.420), FEV1% (P = 0.714), or occupation (P = 0.484) compared to those who were not selected for the study
Nor have prior studies examined the prospective association between LTL changes in pulmonary functioning over time, or the distribution of LTL among responders to the tragic events at the www.nature.com/scientificreports
Summary
Telomeres are nucleoprotein complexes, consisting of repetition of the TTAGGG nucleotide sequences forming the end of human chromosomes, that maintain chromosomal stability and control cellular senescence[1]. One systematic review and meta-analysis of 12,595 individuals identified a consistent association between LTL and one-second forced expiratory volume (FEV1)[3]. Together, these studies have revealed associations between shorter LTL and several measures of poorer lung function and increased risk of emphysema[4,5,6,7]. To date, nothing is known about the association between LTL and pulmonary function in the context of an acute but severe exposure to fine airborne particulate matter. The objective of the current study was to understand the association between LTL and pulmonary function in the face of severe exposures to inhaled particulate matter. The ability to follow pulmonary function over time after the acute exposure gave us the unique opportunity to test whether LTL was associated with subsequent rate of decline in pulmonary functioning
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