Asthma is a common disease and a significant public health problem, affecting one in every 10 individuals, nearly 30 million people in the US alone. About 5-10% of asthmatics have severe disease that is difficult to control with standard therapies. Severe asthmatics are considered to be relatively resistant to corticosteroids, a mainstay of therapy in asthma. Furthermore, chronic corticosteroid therapy often results in side effects that adversely affect outcomes. Thus, more effective treatment options, which are safe, cost-effective and easy to administer, are needed for severe asthmatics. A better understanding of the different factors that contribute to disease severity and pathogenesis will be necessary to identify new, personalized treatment and management approaches for severe asthmatics. Our goal is to gain a better understanding of the pathogenic mechanisms that differentiate severe asthma from mild to moderate asthma. In so doing, we hope to discover novel pathways that can be targeted to achieve our primary aim of developing new therapies for severe asthmatics. Progress achieved under this protocol is summarized as follows: 1. Serum levels of apolipoprotein A-I and large High Density Lipoprotein particles have been shown to be positively correlated with FEV1 in patients with atopic asthma. This demonstrates that circulating HDL particles are associated with less severe airflow obstruction in allergic asthma. A manuscript describing these finding has been published in the American Journal of Respiratory and Critical Care Medicine. 2. Serum levels of high-density lipoproteins have been shown to be negatively correlated with biomarkers of type 2 inflammation (e.g., blood eosinophil counts and serum periostin levels) in atopic asthmatics. In atopic asthmatics, blood eosinophils negatively correlated with serum HDL-cholesterol and total HDL particles measured by NMR spectroscopy (HDLNMR). Serum periostin levels negatively correlated with total HDLNMR. In contrast, blood eosinophil counts positively correlated with serum triglyceride levels. This study demonstrates for the first time that HDL particles were negatively correlated, whereas serum triglycerides were positively correlated, with blood eosinophils in atopic asthmatics. This finding supports the concept that serum levels of HDL and triglycerides may be linked to systemic type 2 inflammation in atopic asthma. Patients continue to be actively followed and samples continue to be collected under this protocol.

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Budget End
Support Year
7
Fiscal Year
2019
Total Cost
Indirect Cost
Name
National Heart, Lung, and Blood Institute
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Barochia, Amisha V; Gordon, Elizabeth M; Kaler, Maryann et al. (2017) High density lipoproteins and type 2 inflammatory biomarkers are negatively correlated in atopic asthmatics. J Lipid Res 58:1713-1721
Yao, Xianglan; Gordon, Elizabeth M; Barochia, Amisha V et al. (2016) The A's Have It: Developing Apolipoprotein A-I Mimetic Peptides Into a Novel Treatment for Asthma. Chest 150:283-8
Gordon, Elizabeth M; Figueroa, Debbie M; Barochia, Amisha V et al. (2016) High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the Prevention and Treatment of Lung Disease. Front Pharmacol 7:323
Yao, Xianglan; Gordon, Elizabeth M; Figueroa, Debbie M et al. (2016) Emerging Roles of Apolipoprotein E and Apolipoprotein A-I in the Pathogenesis and Treatment of Lung Disease. Am J Respir Cell Mol Biol 55:159-69
Barochia, Amisha V; Kaler, Maryann; Cuento, Rosemarie A et al. (2015) Serum apolipoprotein A-I and large high-density lipoprotein particles are positively correlated with FEV1 in atopic asthma. Am J Respir Crit Care Med 191:990-1000
Barochia, Amisha V; Levine, Stewart J (2015) Reply: A Potential Link between Serum Low-Density Lipoproteins and Asthma. Am J Respir Crit Care Med 192:262-3