@article{e8e579ae85794d90ade7e01cb076d107,
title = "The relationship between the epigenetic aging biomarker “grimage” and lung function in both the airway and blood of people living with HIV: An observational cohort study",
abstract = "Background: Age-related comorbidities such as chronic obstructive pulmonary disease (COPD) are common in people living with human immunodeficiency virus (PLWH). We investigated the relationship between COPD and the epigenetic age of the airway epithelium and peripheral blood of PLWH. Methods: Airway epithelial brushings from 34 PLWH enrolled in the St. Paul's Hospital HIV Bronchoscopy cohort and peripheral blood from 378 PLWH enrolled in The Strategic Timing of Antiretroviral Treatment (START) study were profiled for DNA methylation. The DNA methylation biomarker of age and healthspan, GrimAge, was calculated in both tissue compartments. We tested the association of GrimAge with COPD in the airway epithelium and airflow obstruction as defined by an FEV1/FVC<0.70, and FEV1 decline over 6 years in blood. Findings: The airway epithelium of PLWH with COPD was associated with greater GrimAge residuals compared to PLWH without COPD (Beta=3.18, 95%CI=1.06-5.31, P=0.005). In blood, FEV1/FVC<LLN was associated with greater GrimAge residuals (Beta=1.74, 95%CI=0.37-3.24, P=0.019). FEV1 decline was inversely correlated with GrimAge residuals in blood (r=−0.13, P=0.012). PLWH who had normal lung function but who subsequently developed an FEV1/FVC<0.70 over the course of 6 years had higher GrimAge residuals at baseline (Beta=2.33, 95%CI=0.23-4.44, P=0.031). Interpretation: GrimAge may reflect lung and systemic epigenetic changes that occur with advanced airflow obstruction and may help to identify PLWH with a higher risk of developing COPD. Funding: Canadian Institutes of Health Research and the British Columbia Lung Association. The START substudy was funded by NIH grants: UM1-AI068641, UM1-AI120197, and RO1HL096453.",
keywords = "Airway, Blood, COPD, Epigenetic age, HIV",
author = "{INSIGHT START Pulmonary and Genomic Substudy Groups} and {Hern{\'a}ndez Cordero}, {Ana I.} and Yang, {Chen Xi} and Julia Yang and Xuan Li and Steve Horvath and Tawimas Shaipanich and Julia MacIsaac and David Lin and Lisa McEwen and Kobor, {Michael S.} and Silvia Guillemi and Marianne Harris and Wan Lam and Stephen Lam and Ma'en Obeidat and Novak, {Richard M.} and Fleur Hudson and Hartwig Klinker and Nila Dharan and Julio Montaner and Man, {S. F.Paul} and Ken Kunisaki and Sin, {Don D.} and Leung, {Janice M.} and Baker, {J. V.} and D. Duprez and A. Carr and J. Hoy and M. Dolan and A. Telenti and C. Grady and G. Matthews and J. Rockstroh and Belloso, {W. H.} and Kagan, {J. M.} and E. Wright and B. Brew and Price, {R. W.} and K. Robertson and L. Cysique and Connett, {J. E.} and Niewoehner, {D. E.} and {Endpoint Review Committee}, {Review Committee} and A. Lifson and Davey, {R. T.} and Gatell, {J. M.} and C. Pedersen and R. Prineas and J. Worley",
note = "Funding Information: We thank the participants of the START and bronchoscopy studies for their contribution to this work. This study was funded by the Canadian Institutes of Health Research and the British Columbia Lung Association. The START substudy was funded by NIH grants: UM1-AI068641, UM1-AI120197, and RO1HL096453. AIHC is supported by MITACS, the Providence Airway Centre, the St. Paul's Foundation, and the Michael Smith Foundation for Health Research trainee award. DDS holds a Canada Research Chair in COPD and the de Lazzari Family Chair at the Centre for Heart Lung Innovation. JML is supported by the Michael Smith Foundation for Health Research BC Health Professional Investigator Award and holds a Canada Research Chair in Translational Airway Biology. Funding Information: SH reports consulting fees from the non-profit organization, Epigenetic Clock Development Foundation, and royalty income from patents surrounding epigenetic clocks. HK reports consulting fees and payments from AbbVie, Janssen, MSD, ViiV, Gilead, and Intercept, outside of the submitted work. KK reports consulting fees and payments from Allergan and Nuvaira, outside of the submitted work. DS reports payments from AstraZeneca, GSK, and Boehringer Ingelheim, outside of the submitted work. MH reports consulting fees and payments from Gilead, Merck, and ViiV, outside of the submitted work. RMN reports payments from ViiV, Gilead, and Theratechnologies, outside of the submitted work. J Montaner reports grants from Gilead, Merck, ViiV, the Public Health Agency of Canada, and the BC Ministry of Health, outside of the submitted work. JML reports a grant from AstraZeneca, outside of the submitted work. The remaining authors report no competing interests. Funding Information: We thank the participants of the START and bronchoscopy studies for their contribution to this work. This study was funded by the Canadian Institutes of Health Research and the British Columbia Lung Association. The START substudy was funded by NIH grants: UM1-AI068641, UM1-AI120197, and RO1HL096453. AIHC is supported by MITACS, the Providence Airway Centre, the St. Paul's Foundation, and the Michael Smith Foundation for Health Research trainee award. DDS holds a Canada Research Chair in COPD and the de Lazzari Family Chair at the Centre for Heart Lung Innovation. JML is supported by the Michael Smith Foundation for Health Research BC Health Professional Investigator Award and holds a Canada Research Chair in Translational Airway Biology. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = sep,
doi = "10.1016/j.ebiom.2022.104206",
language = "English",
volume = "83",
journal = "eBioMedicine",
issn = "2352-3964",
}