Abstract
Background The incidence of newly developed interstitial lung abnormalities (ILA) and fibrotic ILA has not been previously reported.
Methods Trained thoracic radiologists evaluated 13 944 cardiac computed tomography scans for the presence of ILA in 6197 Multi-Ethnic Study of Atherosclerosis (MESA) longitudinal cohort study participants >45 years of age from 2000 to 2012. Five percent of the scans were re-read by the same or a different observer in a blinded fashion. After exclusion of participants with ILA at baseline, incidence rates and incidence rate ratios for ILA and fibrotic ILA were calculated.
Results The intra-reader agreement of ILA was 92.0% (Gwet's AC1 0.912, intraclass correlation coefficient (ICC) 0.982) and the inter-reader agreement of ILA was 83.5% (Gwet's AC1 0.814, ICC 0.969). Incidence of ILA and fibrotic ILA was estimated to be 13.1 and 3.5 cases per 1000 person-years, respectively. In multivariable analyses, age (hazard ratio (HR) 1.06 (95% CI 1.05–1.08); p<0.001 and HR 1.08 (95% CI 1.06–1.11); p<0.001), high attenuation area at baseline (HR 1.05 (95% CI 1.03–1.07); p<0.001 and HR 1.06 (95% CI 1.02–1.10); p=0.002) and the MUC5B promoter single nucleotide polymorphism (HR 1.73 (95% CI 1.17–2.56); p=0.01 and HR 4.96 (95% CI 2.68–9.15); p<0.001) were associated with incident ILA and fibrotic ILA, respectively. Ever-smoking (HR 2.31 (95% CI 1.34–3.96); p=0.002) and an idiopathic pulmonary fibrosis polygenic risk score (HR 2.09 (95% CI 1.61–2.71); p<0.001) were associated only with incident fibrotic ILA.
Conclusions Incident ILA and fibrotic ILA were estimated by review of cardiac imaging studies. These findings may lead to wider application of a screening tool for atherosclerosis to identify pre-clinical lung disease.
Abstract
Incidence rates of ILA and fibrotic ILA were calculated from single-reader evaluations of cardiac CT scans, with good inter-reader correlation. ILA incidence was found to be associated with age, baseline lung attenuation and polygenic risk scores. https://bit.ly/3ZUAM9v
Footnotes
Conflict of interest: All authors report support for the present work from the National Institutes of Health. C.F. McGroder, S. Hansen, K. Hinckley Stukovsky, P.H. Nath, S.K. Sonavone, J.T. Stowell, B.M. D'Souza, J.S. Leb, S. Dumeer, M.U. Aziz, K. Batra, J.I. Rotter, A.W. Manichaikul, S.S. Rich and R.L. McClelland report no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. D. Zhang reports support for the present manuscript from Stony Wold-Herbert Fund and consulting fees from Boehringer Ingelheim, outside of this work. M.M. Salvatore reports grants, lecture honoraria, travel support and advisory board membership for Genentech and Boehringer Ingelheim, outside of this work. N. Terry reports travel support from Alabama Academy of Radiology, and acts as Treasurer, Foundation Board Member, is ACR Councillor and also reports equity in Johnson & Johnson, Kimberly-Clark Corp., Microsoft Corp., Amgen, Bristol-Myers Squibb, Cisco Systems, Medtronic, Merck, Proctor & Gamble, Crisper Therapeutics, Nvidia, Texas Instruments, Hewlett Packard, United Health, Abbott Labs, Eli Lilly and Co., AbbVie Inc. and LyondellBasell Industries. E.A. Hoffman is founder and shareholder of VIDA Diagnostics, outside of this work. E.J. Bernstein reports grants from Boehringer Ingelheim and Pfizer, and consulting fees and travel support from Boehringer Ingelheim, outside of this work. J.S. Kim reports grants from the Pulmonary Fibrosis Foundation and participation on a data safety monitoring board for the University of Virginia, outside of this work. A.J. Podolanczuk reports grants from the American Lung Association, consulting fees from Regeneron, Roche and Imvaria, lecture honoraria from the National Association for Continuing Education and EBSCO/DynaMed, and participation on an advisory board with Boehringer Ingelheim, outside of this work. D.J. Lederer reports employment and equity in Regeneron Pharmaceuticals. R.G. Barr reports grants from the American Lung Association and the COPD Foundation, and advisory board participation from the COPD Foundation, outside of this work. C.K. Garcia reports grants from the Department of Defense, NIH, Boehringer Ingelheim and AstraZeneca, and lecture honoraria from the Three Lakes Foundation, Stanford, UPenn, UCSF and Cedar Sinai, outside of this work.
This article has an editorial commentary: https://doi.org/10.1183/13993003.00397-2023
Support statement: TOPMed funding/acknowledgements: molecular data for the Trans-Omics in Precision Medicine (TOPMed) programme was supported by the National Heart, Lung, and Blood Institute (NHLBI). Genome sequencing for “NHLBI TOPMed: Multi-Ethnic Study of Atherosclerosis (MESA)” (phs001416) was performed at Broad Genomics (3U54HG003067-13S1, contract HHSN268201600034I). Core support including centralised genomic read mapping and genotype calling, along with variant quality metrics and filtering were provided by the TOPMed Informatics Research Center (3R01HL-117626-02S1; contract HHSN268201800002I). Core support including phenotype harmonisation, data management, sample-identity quality control and general programme coordination were provided by the TOPMed Data Coordinating Center (R01-HL120393, U01-HL120393; contract HHSN268201800001I). We gratefully acknowledge the studies and participants who provided biological samples and data for TOPMed. MESA funding/acknowledgements: the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study was supported by grants R01-HL077612 and RC1-HL100543 from the NHLBI. The MESA Lung Fibrosis Study was funded by grants R01-HL103676 from the NHLBI. MESA projects are conducted and supported by the NHLBI in collaboration with MESA investigators. Support for MESA is provided by contracts 75N92020D00001, HHSN268201500003I, N01-HC95159, 75N92020D00005, N01-HC95160, 75N92020D00002, N01-HC95161, 75N92020D00003, N01-HC95162, 75N92020D00006, N01-HC95163, 75N92020D00004, N01-HC95164, 75N92020D00007, N01-HC95165, N01-HC95166, N01-HC95167, N01-HC95168, N01-HC95169, UL1-TR000040, UL1-TR001079, UL1-TR001420, UL1TR001881, P30-DK063491 and R01-HL105756. E.J. Bernstein's work was supported by K23-AR075112 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. J.S. Kim was supported by grant K23-HL150301 from the NHLBI. C.F. McGroder was supported by grant T32-HL105323. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received October 11, 2022.
- Accepted January 19, 2023.
- Copyright ©The authors 2023. For reproduction rights and permissions contact permissions{at}ersnet.org
LIBRARY USERS
Log in through your institution
Purchase access
