Chronic lower respiratory disease (CLRD) is the 3rd leading cause of death in the United States (US). The most prevalent components of CLRD are chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis and asthma. The primary cause of CLRD mortality and morbidity is exacerbations, yet risk factors for exacerbations are inadequately understood, especially among the elderly, never-smokers and minorities. High density lipoprotein cholesterol (HDL-c) and HDL sub-fractions may contribute to CLRD pathogenesis due to their roles in sphingolipid regulation and transport, which have been implicated in both asthma and emphysema. Preliminary results from one cohort suggest that higher levels of HDL-c and large HDL sub-fractions are associated with higher rates of CLRD events and more rapid decline in lung function. We propose to perform analyses across five NHLBI population-based cohorts of predominantly older adults to test if higher baseline HDL-c levels and large HDL sub-fractions will be associated with increased rates of CLRD events and a more rapid longitudinal decline in lung function independent of standard socio- demographic and clinical risk factors whereas small HDL sub-fractions will demonstrate the inverse associations. We will further examine if these associations are similar across strata defined by race/ethnicity, smoking status and age group;consistent across components of CLRD;and comparable for genetically- estimated HDL-c based on genotype at LIPG rs61755018. Confirmation of these hypotheses would impact future lipid management for patients at risk for CLRD events and suggest targets for drug development on the HDL-sphinoglipid pathway to prevent CLRD events.

Public Health Relevance

CLRD is the 3rd leading cause of death in the US and mortality is rising. Risk factors for CLRD exacerbations and hospitalizations are inadequately understood, particularly among the elderly, never-smokers, and minorities. This study would provide information from a large, highly characterized general population sample for a novel, biologically-plausible risk factor for CLRD events: high density lipoprotein cholesterol and its sub-fractions. The results will have the potential to change lipid management strategies and suggest targets for drug development on the HDL-sphingolipid pathway to prevent CLRD exacerbations.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-PSE-P (56))
Program Officer
Postow, Lisa
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Columbia University (N.Y.)
Internal Medicine/Medicine
Schools of Medicine
New York
United States
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Oelsner, Elizabeth C; Balte, Pallavi P; Cassano, Patricia A et al. (2018) Harmonization of Respiratory Data From 9 US Population-Based Cohorts: The NHLBI Pooled Cohorts Study. Am J Epidemiol 187:2265-2278
Oelsner, Elizabeth C; Loehr, Laura R; Henderson, Ashley G et al. (2016) Classifying Chronic Lower Respiratory Disease Events in Epidemiologic Cohort Studies. Ann Am Thorac Soc 13:1057-66
Oelsner, Elizabeth C; Carr, J Jeffrey; Enright, Paul L et al. (2016) Per cent emphysema is associated with respiratory and lung cancer mortality in the general population: a cohort study. Thorax 71:624-32
Burkart, Kristin M; Manichaikul, Ani; Wilk, Jemma B et al. (2014) APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema. Eur Respir J 43:1003-17