Abstract
Background Interstitial lung abnormalities (ILA) share many features with idiopathic pulmonary fibrosis; however, it is not known if ILA are associated with decreased mean telomere length (MTL).
Methods Telomere length was measured with quantitative PCR in the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) and Age Gene/Environment Susceptibility Reykjavik (AGES-Reykjavik) cohorts and Southern blot analysis was used in the Framingham Heart Study (FHS). Logistic and linear regression were used to assess the association between ILA and MTL; Cox proportional hazards models were used to assess the association between MTL and mortality.
Results In all three cohorts, ILA were associated with decreased MTL. In the COPDGene and AGES-Reykjavik cohorts, after adjustment there was greater than twofold increase in the odds of ILA when comparing the shortest quartile of telomere length to the longest quartile (OR 2.2, 95% CI 1.5–3.4, p=0.0001, and OR 2.6, 95% CI 1.4–4.9, p=0.003, respectively). In the FHS, those with ILA had shorter telomeres than those without ILA (−767 bp, 95% CI 76–1584 bp, p=0.03). Although decreased MTL was associated with chronic obstructive pulmonary disease (OR 1.3, 95% CI 1.1–1.6, p=0.01) in COPDGene, the effect estimate was less than that noted with ILA. There was no consistent association between MTL and risk of death when comparing the shortest quartile of telomere length in COPDGene and AGES-Reykjavik (HR 0.82, 95% CI 0.4–1.7, p=0.6, and HR 1.2, 95% CI 0.6–2.2, p=0.5, respectively).
Conclusion ILA are associated with decreased MTL.
Abstract
Interstitial lung abnormalities are associated with decreased telomere length https://bit.ly/3qo5pV3
Footnotes
Author contributions: Study design: G. Gudmundsson, G.M. Hunninghake and R.K. Putman; acquisition, analysis or interpretation of the data: R.K. Putman, H. Hatabu, T. Araki, M. Nishino, M. Yanagawa, E.F. Gudmundsson, J. Dupuis, I. DeVivo and G.M. Hunninghake; critical revision of the manuscript for important intellectual content: R.K. Putman, G.T. Axelsson, J.L. Sanders, S.Y. Ash, A.A. Menon, T. Araki, M. Yanagawa, E.F. Gudmundsson, D. Qiao, J. Dupuis, G.T. O'Connor, I.O. Rosas, G.R. Washko, S. El-Chemaly, B.A. Raby, V. Gudnason, D.L. DeMeo, E.K. Silverman, I. DeVivo, M.H. Cho, G. Gudmundsson, G.M. Hunninghake and R. San José Estépar; statistical analysis: R.K. Putman, J. Dupuis and G.M. Hunninghake; obtained funding: G.M. Hunninghake, M.H. Cho, R.K. Putman and G. Gudmundsson.
Conflict of interest: R.K. Putman reports grants from NIH/NHLBI, during the conduct of the study.
Conflict of interest: G.T. Axelsson has nothing to disclose.
Conflict of interest: S.Y. Ash reports grants from NHLBI (K08HL145118) and Pulmonary Fibrosis Foundation, during the conduct of the study; and is the owner of Quantitative Imaging Solutions, outside the submitted work.
Conflict of interest: J.L. Sanders has commenced employment at Vertex Pharmaceuticals Inc. since the study was completed.
Conflict of interest: A.A. Menon has nothing to disclose.
Conflict of interest: T. Araki has nothing to disclose.
Conflict of interest: M. Nishino reports personal fees for consultancy from Daiichi Sankyo and AstraZeneca, and grants from the Merck investigator studies programme, Canon Medical Systems, AstraZeneca and Daiichi Sankyo, outside the submitted work.
Conflict of interest: M. Yanagawa reports travel expenses from Canon Medical Systems, outside the submitted work.
Conflict of interest: E.F. Gudmundsson has nothing to disclose.
Conflict of interest: D. Qiao has nothing to disclose.
Conflict of interest: R. San José Estépar reports grants from Boehringer Ingelheim, Lung Biotechnology and Insmed, payment for lectures and travel expenses from Chiesi, and stock and/or stock options from Quantitative Imaging Solutions, outside the submitted work.
Conflict of interest: J. Dupuis reports grants from NIH, during the conduct of the study.
Conflict of interest: G.T. O'Connor reports grants from NIH, during the conduct of the study.
Conflict of interest: I.O. Rosas has a patent 62/849,644 pending.
Conflict of interest: G.R. Washko reports grants from Boehringer Ingelheim, consultancy for Pulmonx, Janssen Pharmaceuticals, Novartis and Vertex, and is founder and co-owner of Quantitative Imaging Solutions, outside the submitted work.
Conflict of interest: S. El-Chemaly has nothing to disclose.
Conflict of interest: B.A. Raby reports grants from NIH, outside the submitted work.
Conflict of interest: V. Gudnason has nothing to disclose.
Conflict of interest: D.L. DeMeo reports grants from Novartis and Bayer, during the conduct of the study.
Conflict of interest: E.K. Silverman reports grants from GlaxoSmithKline and Bayer, during the conduct of the study.
Conflict of interest: H. Hatabu reports grants from Canon Medical Systems Inc. and Konica-Minolta Inc., and personal fees for consultancy from Mitsubishi Chemical Inc. and Canon Medical Systems Inc., outside the submitted work.
Conflict of interest: I. DeVivo has nothing to disclose.
Conflict of interest: M.H. Cho reports grants from GlaxoSmithKline and Bayer, and consultancy and/or speaker fees from Genentech, AstraZeneca and Illumina, outside the submitted work.
Conflict of interest: G. Gudmundsson has nothing to disclose.
Conflict of interest: G.M. Hunninghake reports personal fees from Gerson Lehrman Group and Boehringer Ingelheim, outside the submitted work.
Support statement: The COPDGene project was supported by Award Number U01 HL089897 and Award Number U01 HL089856 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. COPDGene is also supported by the COPD Foundation through contributions made to an Industry Advisory Board comprising AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, Siemens and Sunovion. R.K. Putman is supported by NIH grant K08 HL140087. J.L. Sanders is supported by NIH grant T32 HL007633. S.Y. Ash is supported by NIH grant K08 HL145118. G. Gudmundsson is supported by project grant 141513-051 from the Icelandic Research Fund and Landspitali Scientific Fund A-2019-029 and A-2018-024. M. Nishino is supported by NIH grant R01 CA203636. D. Qiao is supported by NIH grant K01 HL129039. R. San José Estépar is supported by NIH grants R21HL140422 and R01HL149877. I.O. Rosas is supported by NIH grants U01 HL133232 and R01 HL130974. G.R. Washko is supported by NIH grants R01 HL116473 and R01 HL122464. The Age, Gene/Environment Susceptibility Reykjavik Study was supported by NIH contracts N01-AG-1-2100 and HHSN27120120022C, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament). V. Gudnason is supported by NIA grant 27120120022C and project grant 141513-051 from the Icelandic Research Fund. D.L. DeMeo is supported by NIH grant P01 HL132825. H. Hatabu is supported by NIH grant 5U01CA209414-03. M.H. Cho is supported by NIH grants HL137927, HL147148, HL149861 and HL135142. G.M. Hunninghake and this work were supported by NIH grants R01 HL111024, R01 HL130974 and R01 135142, and project grant 141513-051 from the Icelandic Research Fund. The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with Boston University (contract numbers N01-HC-25195, HHSN268201500001I and 75N92019D00031). The COPDGene study is supported by NIH grants U01 HL089897 and U01 HL089856. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received June 27, 2021.
- Accepted December 29, 2021.
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