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Ann Am Thorac Soc. 2017 Jun 14. doi: 10.1513/AnnalsATS.201701-091OC. [Epub ahead of print]

Obstructive Sleep Apnea and Subclinical Interstitial Lung Disease in MESA.

Author information

1
Columbia University Medical Center, 21611, Department of Medicine, Division of Pulmonology, New York, New York, United States ; jk3862@cumc.columbia.edu.
2
Columbia University, Department of Medicine, New York, New York, United States ; ajp2158@cumc.columbia.edu.
3
Brigham and Women's Hospital, 1861, Boston, Massachusetts, United States ; pborker@bidmc.harvard.edu.
4
University of Pennsylvania, Department of Medicine, Perelman School of Medicine, Philadelphia, Pennsylvania, United States ; kawut@exchange.upenn.edu.
5
University of Washington Medical Center, 21617, Division of Pulmonary and Critical Care Medicine, Seattle, Washington, United States ; graghu@uw.edu.
6
University of Washington, 12Departments of Environmental & Occupational Health Sciences, Medicine, and Epidemiology, Seattle, Washington, United States ; joelk@u.washington.edu.
7
University of Washington, Department of Biostatistics, Seattle, Washington, United States ; hincklek@u.washington.edu.
8
University of Iowa Carver College of Medicine, Radiology , Department of Radiology , 200 Hawkins Drive , Iowa City, Iowa, United States , 52242 ; eric-hoffman@uiowa.edu.
9
Columbia University, Epidemiology, New York, New York, United States ; rgb9@cumc.columbia.edu.
10
Harvard Medical School, Boston, Massachusetts, United States ; DJGOTTLIEB@PARTNERS.ORG.
11
Brigham and Women's Hospital and Harvard Medical School, Division of Sleep and Circadian Disorders , Boston, Massachusetts, United States.
12
Beth Israel Deaconess Medical Center, Department of Medicine, Boston, Massachusetts, United States ; sredline1@rics.bwh.harvard.edu.
13
Columbia University, Divison of Pulmonary, Allergy, and Critical Care Medicine , 161 Fort Washington Ave , Room 3-321A , New York, New York, United States , 10032 ; dl427@cumc.columbia.edu.

Abstract

RATIONALE:

Obstructive sleep apnea (OSA) has been postulated to contribute to idiopathic pulmonary fibrosis by promoting alveolar epithelial injury via tractional forces and intermittent hypoxia.

OBJECTIVE:

To determine whether OSA is associated with subclinical interstitial lung disease (ILD) and with biomarkers of alveolar epithelial injury and remodeling.

METHODS:

We performed cross-sectional analyses of 1,690 community-dwelling adults who underwent 15-channel in-home polysomnography and thoracic computed tomography (CT) imaging in the Multi-Ethnic Study of Atherosclerosis. We measured the obstructive apnea-hypopnea index (oAHI) from polysomnography and high attenuation areas (HAA) and interstitial lung abnormalities (ILA) from CT. 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.

RESULTS:

The mean age was 68 years, and the mean forced vital capacity was 97% predicted. The median oAHI was 8.4 events/hr, and 32% had an oAHI >15. After adjusting for demographics, smoking, and center, an oAHI >15 was associated with a 4.0% HAA increment (95% CI 1.4-6.8%, p=0.003) and a 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 <25 kg/m2, an oAHI>15 was associated with a 6.1% HAA increment (95% CI 0.5-12%, p=0.03) and a 2.3-fold increased odds of ILA (95% CI 1.3-4.1, p=0.005). Among those with a BMI >30 kg/m2, an oAHI >15 was associated with a 1.8 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/m2. Greater oAHI was associated higher serum SP-A and MMP-7 levels, particularly among those with a body mass index <25 kg/m2.

CONCLUSIONS:

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.

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