Fish Oil to Prevent Asthma Exacerbations in Patients With ALOX5 Polymorphisms

Overview

This is a clinical study that is designed to study the effects of the supplemental intake of enriched omega-3 polyunsaturated fatty acids (fish oil) in patients with moderate to severe asthma. Some asthmatics produce a large amount of inflammatory leukotriene proteins-proteins that contribute to wheezing and inflammation in the airway. Inhibiting the detrimental effects of leukotrienes is a key goal of controller therapy in severe asthmatics. Some asthmatic patients appear to have specific mutations of the arachidonate 5-lipoxygenase (ALOX5) gene, one gene that regulates the production of the inflammatory leukotrienes. Omega-3 fatty acids can interfere with the arachidonic acid pathway and decrease the production of leukotrienes, and this may benefit moderate and severe asthma patients. Our hypothesis is that omega-3 fatty acid supplements, added on to a patient's asthma medication regimen, can decrease the number of minor asthma exacerbations compared to patients who do not receive the supplement. Furthermore, we believe that asthma patients with specific ALOX5 gene mutations will benefit most. We will enroll 30 asthma subjects to take part in this trial. They will undergo genotyping of the ALOX5 gene and be treated with omega3-fatty acids (fish oil) and placebo over a nine month period. We expect that this strategy will allow us to discover which moderate and severe asthma patients will benefit most from supplements of omega-3 fatty acids. Treatment of chronic diseases, such as asthma, is a key mission of the Center of Health and Nutrition Research.

This study is a single-center, investigator-initiated, randomized, double-blind, placebo-controlled, cross-over trial. A total of 30 subjects will be recruited from the U.C. Davis Asthma Network (UCAN) clinics. Some of the research will be conducted at the USDA-WHNRC (Western Health Nutrition Research Center) here at U.C. Davis. This clinical trial is designed to study the effects of supplemental intake of eicosapentanoic acid (EPA)-enriched omega-3 polyunsaturated fatty acids (n3-PUFA, fish oil) in a subset of moderate to severe asthmatics, who have a high susceptibility to increased leukotriene production due to a polymorphism in the promoter region of the arachidonate 5-lipoxygenase (ALOX5) gene. EPA competes with AA and can decrease leukotriene production; thus our central hypothesis is that EPA-enriched n3-PUFA supplements will decrease the production of inflammatory leukotrienes and decrease the number of acute exacerbations of asthma in patients with moderate to severe asthma and that these benefits will be greater in subjects with the "high susceptibility" ALOX5 promoter variants. Our specific aims are to: 1) Determine the prevalence of the "high-susceptibility" ALOX5 pathway gene polymorphisms in a diverse cohort of moderate to severe adult asthmatics, 2) Perform a 32 week (12 wk treatment A - 8 wk washout - 12 wk treatment B), blinded, cross-over design clinical trial, during which we treat 15 "high susceptibility" and 15 "low susceptibility" ALOX5 gene polymorphism asthmatics with n-3 PUFA supplements and placebo, and 3) Determine the baseline level and treatment effect of n-3 PUFA supplements on leukotriene metabolite and inflammatory cytokine production in subjects with the 'high' and 'low' susceptibility genotypes. Patients will be recruited primarily from the UC Davis Asthma Network (UCAN).