Obstructive Sleep Apnea and Subclinical Interstitial Lung Disease in the Multi-Ethnic Study of Atherosclerosis (MESA)

John S Kim; Anna J Podolanczuk; Priya Borker; Steven M Kawut; Ganesh Raghu; Joel D Kaufman; Karen D Hinckley Stukovsky; Eric A Hoffman; R Graham Barr; Daniel J Gottlieb; Susan S Redline; David J Lederer

doi:10.1513/AnnalsATS.201701-091OC

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Obstructive Sleep Apnea and Subclinical Interstitial Lung Disease in the Multi-Ethnic Study of Atherosclerosis (MESA)

Journal article

Open access

Peer reviewed

Obstructive Sleep Apnea and Subclinical Interstitial Lung Disease in the Multi-Ethnic Study of Atherosclerosis (MESA)

John S Kim, Anna J Podolanczuk, Priya Borker, Steven M Kawut, Ganesh Raghu, Joel D Kaufman, Karen D Hinckley Stukovsky, Eric A Hoffman, R Graham Barr, Daniel J Gottlieb, …

Annals of the American Thoracic Society, Vol.14(12), pp.1786-1795

12/2017

DOI: 10.1513/AnnalsATS.201701-091OC

PMCID: PMC5711259

PMID: 28613935

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Abstract

Obstructive sleep apnea (OSA) has been postulated to contribute to idiopathic pulmonary fibrosis by promoting alveolar epithelial injury via tractional forces and intermittent hypoxia. To determine whether OSA is associated with subclinical interstitial lung disease (ILD) and with biomarkers of alveolar epithelial injury and remodeling. We performed cross-sectional analyses of 1,690 community-dwelling adults who underwent 15-channel in-home polysomnography and thoracic computed tomographic imaging in the Multi-Ethnic Study of Atherosclerosis. We measured the obstructive apnea-hypopnea index (oAHI) by polysomnography and high-attenuation areas (HAAs) and interstitial lung abnormalities (ILAs) by computed tomography. Serum matrix metalloproteinase-7 (MMP-7) and surfactant protein-A (SP-A) were measured by ELISA in 99 participants. We used generalized linear models to adjust for potential confounders. The mean age was 68 years, and the mean forced vital capacity was 97% predicted. The median oAHI was 8.4 events/h, and 32% had an oAHI greater than 15. After adjusting for demographics, smoking, and center, an oAHI greater than 15 was associated with a 4.0% HAA increment (95% confidence interval [CI], 1.4-6.8%; P = 0.003) and 35% increased odds of ILA (95% CI, 13-61%; P = 0.001). However, there was evidence that these associations varied by body mass index (BMI) (P for interaction = 0.08 and 0.04, respectively). Among those with a BMI less than 25 kg/m , an oAHI greater than 15 was associated with a 6.1% HAA increment (95% CI, 0.5-12%; P = 0.03) and 2.3-fold increased odds of ILA (95% CI, 1.3-4.1; P = 0.005). Among those with a BMI greater than 30 kg/m , an oAHI greater than 15 was associated with 1.8-fold greater odds of ILA (95% CI, 1.1-2.9; P = 0.01) but was not associated with HAA. There were no meaningful associations detected among those with a BMI of 25-30 kg/m . Greater oAHI was associated higher serum SP-A and MMP-7 levels, particularly among those with a BMI less than 25 kg/m . Moderate to severe OSA is associated with subclinical ILD and with evidence of alveolar epithelial injury and extracellular matrix remodeling in community-dwelling adults, an association that is strongest among normal-weight individuals. These findings support the hypothesis that OSA might contribute to early ILD.

Body Mass Index

Severity of Illness Index

United States - epidemiology

Matrix Metalloproteinase 7 - blood

Prospective Studies

Cross-Sectional Studies

Humans

Middle Aged

Linear Models

Male

Sleep Apnea, Obstructive - complications

Tomography, X-Ray Computed

Biomarkers - blood

Polysomnography

Lung Diseases, Interstitial - diagnostic imaging

Pulmonary Surfactant-Associated Protein A - blood

Female

Aged

Lung Diseases, Interstitial - epidemiology

Details

Title: Subtitle: Obstructive Sleep Apnea and Subclinical Interstitial Lung Disease in the Multi-Ethnic Study of Atherosclerosis (MESA)
Creators: John S Kim - 1 Department of Medicine, Columbia University Medical Center, New York, New York
Anna J Podolanczuk - 1 Department of Medicine, Columbia University Medical Center, New York, New York
Priya Borker - 2 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
Steven M Kawut - 3 Department of Medicine and the Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
Ganesh Raghu - 4 Department of Medicine
Joel D Kaufman - 5 Department of Environmental and Occupational Health Sciences and Department of Epidemiology, and
Karen D Hinckley Stukovsky - 6 Department of Biostatistics, University of Washington, Seattle, Washington
Eric A Hoffman - 7 Departments of Radiology, Medicine, and Biomedical Engineering, University of Iowa Carver College of Medicine, Iowa City, Iowa
R Graham Barr - 8 Department of Epidemiology, Mailman School of Public Health, Columbia University Medical Center, New York, New York
Daniel J Gottlieb - 10 Department of Medicine, VA Boston Healthcare System, Boston, Massachusetts
Susan S Redline - 9 Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and
David J Lederer - 8 Department of Epidemiology, Mailman School of Public Health, Columbia University Medical Center, New York, New York
Resource Type: Journal article
Publication Details: Annals of the American Thoracic Society, Vol.14(12), pp.1786-1795
DOI: 10.1513/AnnalsATS.201701-091OC
PMID: 28613935
PMCID: PMC5711259
NLM abbreviation: Ann Am Thorac Soc
ISSN: 2325-6621
eISSN: 2325-6621
Publisher: American Thoracic Society; United States
Grant note: R01 HL098433 / NHLBI NIH HHS P30 ES005605 / NIEHS NIH HHS N01HC95169 / NHLBI NIH HHS N01HC95161 / NHLBI NIH HHS T32 HL105323 / NHLBI NIH HHS R01 HL093081 / NHLBI NIH HHS N01HC95164 / NHLBI NIH HHS HHSN268201500003C / NHLBI NIH HHS N01HC95160 / NHLBI NIH HHS R01 HL112986 / NHLBI NIH HHS N01HC95167 / NHLBI NIH HHS N01HC95159 / NHLBI NIH HHS R01 HL103676 / NHLBI NIH HHS N01HC95163 / NHLBI NIH HHS R01 HL077612 / NHLBI NIH HHS N01HC95166 / NHLBI NIH HHS K24 HL103844 / NHLBI NIH HHS UL1 TR000040 / NCATS NIH HHS N01HC95168 / NHLBI NIH HHS UL1 TR001079 / NCATS NIH HHS K24 HL131937 / NHLBI NIH HHS N01HC95165 / NHLBI NIH HHS N01HC95162 / NHLBI NIH HHS
Language: English
Date published: 12/2017
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
Record Identifier: 9984051726002771

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