Interstitial lung abnormalities are associated with decreased mean telomere length

Rachel K. Putman; Gisli Thor Axelsson; Samuel Y. Ash; Jason L. Sanders; Aravind A. Menon; Tetsuro Araki; Mizuki Nishino; Masahiro Yanagawa; Elías F. Gudmundsson; Dandi Qiao; Raúl San José Estépar; Josée Dupuis; George T. O'Connor; Ivan O. Rosas; George R. Washko; Souheil El-Chemaly; Benjamin A. Raby; Vilmundur Gudnason; Dawn L. DeMeo; Edwin K. Silverman; Hiroto Hatabu; Immaculata DeVivo; Michael H. Cho; Gunnar Gudmundsson; Gary M. Hunninghake

doi:10.1183/13993003.01814-2021

Interstitial lung abnormalities are associated with decreased mean telomere length

Rachel K. Putman, Gisli Thor Axelsson, Samuel Y. Ash, Jason L. Sanders, Aravind A. Menon, Tetsuro Araki, Mizuki Nishino, Masahiro Yanagawa, Elías F. Gudmundsson, Dandi Qiao, Raúl San José Estépar, Josée Dupuis, George T. O'Connor, Ivan O. Rosas, George R. Washko, Souheil El-Chemaly, Benjamin A. Raby, Vilmundur Gudnason, Dawn L. DeMeo, Edwin K. SilvermanHiroto Hatabu, Immaculata DeVivo, Michael H. Cho, Gunnar Gudmundsson, Gary M. Hunninghake

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

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.

Original language	English
Journal	The European respiratory journal
Volume	60
Issue number	2
DOIs	https://doi.org/10.1183/13993003.01814-2021
Publication status	Published - 1 Aug 2022

Bibliographical note

Copyright ©The authors 2022. For reproduction rights and permissions contact [email protected].

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.

Other keywords

Humans
Lung
Lung Diseases, Interstitial/epidemiology
Pulmonary Disease, Chronic Obstructive
Telomere/genetics
Tomography, X-Ray Computed

Access to Document

10.1183/13993003.01814-2021

Cite this

Putman, R. K., Axelsson, G. T., Ash, S. Y., Sanders, J. L., Menon, A. A., Araki, T., Nishino, M., Yanagawa, M., Gudmundsson, E. F., Qiao, D., San José Estépar, R., Dupuis, J., O'Connor, G. T., Rosas, I. O., Washko, G. R., El-Chemaly, S., Raby, B. A., Gudnason, V., DeMeo, D. L., ... Hunninghake, G. M. (2022). Interstitial lung abnormalities are associated with decreased mean telomere length. The European respiratory journal, 60(2). https://doi.org/10.1183/13993003.01814-2021

@article{1aa2cc11230f4c7caece5e40deb5371b,

title = "Interstitial lung abnormalities are associated with decreased mean telomere length",

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.",

keywords = "Humans, Lung, Lung Diseases, Interstitial/epidemiology, Pulmonary Disease, Chronic Obstructive, Telomere/genetics, Tomography, X-Ray Computed",

author = "Putman, {Rachel K.} and Axelsson, {Gisli Thor} and Ash, {Samuel Y.} and Sanders, {Jason L.} and Menon, {Aravind A.} and Tetsuro Araki and Mizuki Nishino and Masahiro Yanagawa and Gudmundsson, {El{\'i}as F.} and Dandi Qiao and {San Jos{\'e} Est{\'e}par}, Ra{\'u}l and Jos{\'e}e Dupuis and O'Connor, {George T.} and Rosas, {Ivan O.} and Washko, {George R.} and Souheil El-Chemaly and Raby, {Benjamin A.} and Vilmundur Gudnason and DeMeo, {Dawn L.} and Silverman, {Edwin K.} and Hiroto Hatabu and Immaculata DeVivo and Cho, {Michael H.} and Gunnar Gudmundsson and Hunninghake, {Gary M.}",

note = "Copyright {\textcopyright}The authors 2022. For reproduction rights and permissions contact [email protected]. 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 Jos{\'e} Est{\'e}par 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.",

year = "2022",

month = aug,

day = "1",

doi = "10.1183/13993003.01814-2021",

language = "English",

volume = "60",

journal = "The European respiratory journal",

issn = "0903-1936",

publisher = "European Respiratory Society",

number = "2",

}

Putman, RK, Axelsson, GT, Ash, SY, Sanders, JL, Menon, AA, Araki, T, Nishino, M, Yanagawa, M, Gudmundsson, EF, Qiao, D, San José Estépar, R, Dupuis, J, O'Connor, GT, Rosas, IO, Washko, GR, El-Chemaly, S, Raby, BA, Gudnason, V, DeMeo, DL, Silverman, EK, Hatabu, H, DeVivo, I, Cho, MH, Gudmundsson, G & Hunninghake, GM 2022, 'Interstitial lung abnormalities are associated with decreased mean telomere length', The European respiratory journal, vol. 60, no. 2. https://doi.org/10.1183/13993003.01814-2021

TY - JOUR

T1 - Interstitial lung abnormalities are associated with decreased mean telomere length

AU - Putman, Rachel K.

AU - Axelsson, Gisli Thor

AU - Ash, Samuel Y.

AU - Sanders, Jason L.

AU - Menon, Aravind A.

AU - Araki, Tetsuro

AU - Nishino, Mizuki

AU - Yanagawa, Masahiro

AU - Gudmundsson, Elías F.

AU - Qiao, Dandi

AU - San José Estépar, Raúl

AU - Dupuis, Josée

AU - O'Connor, George T.

AU - Rosas, Ivan O.

AU - Washko, George R.

AU - El-Chemaly, Souheil

AU - Raby, Benjamin A.

AU - Gudnason, Vilmundur

AU - DeMeo, Dawn L.

AU - Silverman, Edwin K.

AU - Hatabu, Hiroto

AU - DeVivo, Immaculata

AU - Cho, Michael H.

AU - Gudmundsson, Gunnar

AU - Hunninghake, Gary M.

N1 - Copyright ©The authors 2022. For reproduction rights and permissions contact [email protected]. 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.

PY - 2022/8/1

Y1 - 2022/8/1

N2 - 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.

AB - 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.

KW - Humans

KW - Lung

KW - Lung Diseases, Interstitial/epidemiology

KW - Pulmonary Disease, Chronic Obstructive

KW - Telomere/genetics

KW - Tomography, X-Ray Computed

UR - http://www.scopus.com/inward/record.url?scp=85137124741&partnerID=8YFLogxK

U2 - 10.1183/13993003.01814-2021

DO - 10.1183/13993003.01814-2021

M3 - Article

C2 - 35115336

AN - SCOPUS:85137124741

SN - 0903-1936

VL - 60

JO - The European respiratory journal

JF - The European respiratory journal

IS - 2

ER -

Interstitial lung abnormalities are associated with decreased mean telomere length

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