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 subfractions 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 subfractions 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 subfractions 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 subfractions 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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL121457-01
Application #
8624969
Study Section
Special Emphasis Panel (ZRG1-PSE-P (56))
Program Officer
Postow, Lisa
Project Start
2013-09-15
Project End
2015-07-31
Budget Start
2013-09-15
Budget End
2014-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$114,240
Indirect Cost
$42,840
Name
Columbia University (N.Y.)
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032