Incidence of interstitial lung abnormalities: the MESA Lung Study

Claire F McGroder¹, Spencer Hansen², Karen Hinckley Stukovsky², David Zhang¹, P Hrudaya Nath³, Mary M Salvatore⁴, Sushilkumar K Sonavane⁵, Nina Terry³, Justin T Stowell⁵, Belinda M D'Souza⁴, Jay S Leb⁴, Shifali Dumeer⁴, Muhammad U Aziz³, Kiran Batra⁶, Eric A Hoffman⁷, Elana J Bernstein¹, John S Kim^{1

8}, Anna J Podolanczuk^{1

9}, Jerome I Rotter¹⁰, Ani W Manichaikul^{11

12}, Stephen S Rich^{11

12}, David J Lederer^{1

13}, R Graham Barr^{1

14}, Robyn L McClelland², Christine Kim Garcia^{15

16

17}

Affiliations

¹ Department of Medicine, Columbia University Medical Center, New York, NY, USA.
² Department of Biostatistics, University of Washington, Seattle, WA, USA.
³ Department of Radiology, University of Alabama, Birmingham, AL, USA.
⁴ Department of Radiology, Columbia University Medical Center, New York, NY, USA.
⁵ Department of Radiology, Mayo Clinic at Jacksonville, Jacksonville, FL, USA.
⁶ University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁷ Department of Radiology, University of Iowa, Iowa City, IA, USA.
⁸ Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.
⁹ Department of Medicine, Weill Medical College of Cornell University, New York, NY, USA.
¹⁰ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
¹¹ Department of Public Health Sciences, University of Virginia, Charlotte, VA, USA.
¹² Center for Public Health Genomics, University of Virginia, Charlotte, VA, USA.
¹³ Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
¹⁴ Department of Epidemiology, Columbia University Medical Center, New York, NY, USA.
¹⁵ Department of Medicine, Columbia University Medical Center, New York, NY, USA ckg2116@cumc.columbia.edu.
¹⁶ Institute for Genomic Medicine, Columbia University Medical Center, New York, NY, USA.
¹⁷ Center for Precision Medicine and Genomics, Columbia University Medical Center, New York, NY, USA.

PMID: 37202153
PMCID: PMC10773573
DOI: 10.1183/13993003.01950-2022

Incidence of interstitial lung abnormalities: the MESA Lung Study

Claire F McGroder et al. Eur Respir J. 2023.

. 2023 Jun 8;61(6):2201950.

doi: 10.1183/13993003.01950-2022. Print 2023 Jun.

Authors

Affiliations

¹ Department of Medicine, Columbia University Medical Center, New York, NY, USA.
² Department of Biostatistics, University of Washington, Seattle, WA, USA.
³ Department of Radiology, University of Alabama, Birmingham, AL, USA.
⁴ Department of Radiology, Columbia University Medical Center, New York, NY, USA.
⁵ Department of Radiology, Mayo Clinic at Jacksonville, Jacksonville, FL, USA.
⁶ University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁷ Department of Radiology, University of Iowa, Iowa City, IA, USA.
⁸ Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.
⁹ Department of Medicine, Weill Medical College of Cornell University, New York, NY, USA.
¹⁰ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
¹¹ Department of Public Health Sciences, University of Virginia, Charlotte, VA, USA.
¹² Center for Public Health Genomics, University of Virginia, Charlotte, VA, USA.
¹³ Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
¹⁴ Department of Epidemiology, Columbia University Medical Center, New York, NY, USA.
¹⁵ Department of Medicine, Columbia University Medical Center, New York, NY, USA ckg2116@cumc.columbia.edu.
¹⁶ Institute for Genomic Medicine, Columbia University Medical Center, New York, NY, USA.
¹⁷ Center for Precision Medicine and Genomics, Columbia University Medical Center, New York, NY, USA.

PMID: 37202153
PMCID: PMC10773573
DOI: 10.1183/13993003.01950-2022

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.

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Conflict of interest statement

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.

Figures

**FIGURE 1**
Study timeline with longitudinal cardiac scan imaging of Multi-Ethnic Study of Atherosclerosis (MESA) participants. At enrolment and during the subsequent four exams (2000–2012), participants had non-invasive assessment of cardiovascular status, including cardiac computed tomography (CT) scans. The number of cardiac CT scans included in this study’s incidence analysis are shown for each of the five different exam periods. By design, after Exam 1, all returning participants had a repeat cardiac CT scan at either Exam 2 (2955 participants) or at Exam 3 (2805 participants). Approximately 30% (1405 participants) had a cardiac CT scan at Exam 4. Only a subset of the Exam 5 cardiac CTs were analysed in this study.

**FIGURE 2**
Representative cardiac computed tomography scan imaging of Multi-Ethnic Study of Atherosclerosis participants. Example scans with a) no interstitial lung abnormalities (ILA), b) non-fibrotic ILA characterised by increased ground-glass opacities, and fibrotic ILA with c) bilateral peripheral reticulations and traction bronchiolectasis, and d) extensive bilateral peripheral reticulation, ground-glass opacities and honeycombing (arrows).

**FIGURE 3**
Kaplan–Meier curves of time to a, b) interstitial lung abnormalities (ILA) and c, d) fibrotic ILA for a, c) age and b, d) *MUC5B* minor allele. a, c) Proportion of participants who are ILA- or fibrotic ILA-free are shown for subjects of increasing decades of age: 45–54, 55–64, 65–74 and 75–84 years. b, d) Proportion of participants who are ILA- or fibrotic ILA-free of those without the *MUC5B* minor allele and those with at least one minor risk allele.

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Comment in

How does the MESA Lung Study sharpen blurry edges in interstitial lung abnormalities?
Brillet PY, Tran Ba S, Nunes H. Brillet PY, et al. Eur Respir J. 2023 Jun 8;61(6):2300397. doi: 10.1183/13993003.00397-2023. Print 2023 Jun. Eur Respir J. 2023. PMID: 37290811 No abstract available.

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Incidence of interstitial lung abnormalities: the MESA Lung Study

Affiliations

Incidence of interstitial lung abnormalities: the MESA Lung Study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

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