We investigated associations of plasma lipoproteins with subclinical interstitial lung disease (ILD) by measuring high attenuation areas (HAA: lung voxels between −600 and −250 Hounsfield units) in 6700 adults and serum MMP-7 and SP-A in 1216 adults age 45–84 without clinical cardiovascular disease in Multi-Ethnic Study of Atherosclerosis. In cross-sectional analyses, each SD decrement in high density lipoprotein cholesterol (HDL-C) was associated with a 2.12% HAA increment (95% CI 1.44% to 2.79%), a 3.53% MMP-7 increment (95% CI 0.93% to 6.07%) and a 6.37% SP-A increment (95% CI 1.35% to 11.13%), independent of demographics, smoking and inflammatory biomarkers. These findings support a novel hypothesis that HDL-C might influence subclinical lung injury and extracellular matrix remodelling.
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Contributors AJP, DJL, RGB, SJS, KW and SMK conceived and designed the study. AJP, GR, MYT, RGB, EAH, FSA, SJS and DJL acquired the data. AJP, SMK, PLE, EP, RS, DR, CJ, RGB, KHS, JJC, DRJ, KW, SJS and DJL analysed the data. AJP drafted the initial manuscript. All authors contributed to the conception and design of the study and to the acquisition, analysis, or interpretation of data. All authors revised the manuscript for important intellectual content. All authors approved the final version of the manuscript. All authors agree to be accountable for all aspects of the work.
Funding The work is funded by the National Institutes of Health contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 and grants UL1-TR-000040, UL1-TR-001079, R01-HL-103676, RC1-HL100543, R01-HL-093081, R01-HL-077612, T32-HL-105323 and K24-HL-131937; by the Pulmonary Fibrosis Foundation; and by the Rocco Guinta Research Fund.
Competing interests DJL has received modest consulting fees from Genentech/Roche, Boehringer Ingelheim, Gilead, Pharmakea, Veracyte, Patara Pharmaceuticals, Degge Group and the France Foundation related to IPF. Columbia University has received funding for clinical trials in IPF from Boehringer Ingelheim, Gilead, Bayer and Global Blood Therapeutics. Columbia University has received funding from the Pulmonary Fibrosis Foundation for DJL's consulting services. DJL has received modest fees for serving as a deputy editor for the Annals of the American Thoracic Society and as a statistical editor for Thorax. SMK reports grants from NIH during the conduct of the study and non-financial support from the ATS. He has received personal fees from the European Respiratory Journal for serving on an editorial board. The University of Pennsylvania has received grants from Actelion, United Therapeutics, Gilead, Lung Biotech and Bayer for CME courses. EAH is a founder and shareholder in VIDA Diagnostics, a company commercialising lung image analysis software developed, in part, at the University of Iowa.
Ethics approval Institutional Review Boards at all collaborating centres.
Provenance and peer review Not commissioned; externally peer reviewed.
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