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A1428 - Omega-3 Fatty Acid Supplementation in Obese Adolescents and Young Adults with Poor Asthma Control
Author Block: J. Lang1, E. B. Mougey2, M. Hossain3, J. J. Lima4; 1Pediatrics/Duke Clinical Research Institute, Duke University, Durham, NC, United States, 2Ctr for Pharmacogenetics and Translational Research, Nemours Children's Clinic, Jacksonville, FL, United States, 3Nemours AI Dupont Hospital for Children, Wilmington, DE, United States, 4Nemours Childrens Clin, Jacksonville, FL, United States.
Introduction. Obesity is associated with difficult-to-control asthma. Omega-3 fatty acid (n3PUFA) supplementation has been reported to reduce leukotriene production and ameliorate exercise-induced asthma, and has been proposed as a candidate control treatment for persistent asthma. The ALOX5 promoter SP1 tandem repeat polymorphism (rs59439148) affects leukotriene production and treatment responses to n3PUFA. No studies have assessed the effect of n3PUFA supplementation and ALOX5 genotype on asthma control in obese patients with poorly controlled asthma. Methods. This multi-center randomized controlled trial (NCT01027143) of n3PUFA (4g per day) (Nordic Naturals, Inc., Watsonville, CA USA) vs. soy oil control (3:1 allotment) for 24 weeks was conducted among overweight/obese 12-25 year olds with uncontrolled asthma. The primary outcome was change in Asthma Control Questionnaire (ACQ) at 6 months; secondary outcomes included n-3/n-6 PUFA ratio in blood granulocytes (gas-liquid chromatography), urinary leukotrienes (uLTE) (LC-MS/MS analysis), spirometry, asthma-related events and adverse events. rs59439148 was genotyped from whole blood samples by TaqMan assay. Five repeats of the SP1 tandem were considered the wildtype allele. 1 or 2 copies of a non-5 SP1 tandem repeat were considered heterozygous mutant (5/X) and homozygous mutant (X/X), respectively. Simple and multivariable generalized linear models and negative binomial regression were used to test the effect of treatment on change in ACQ and asthma-related events. The statistical package SAS 9.4 (SAS Institute Inc, Cary NC, USA). Results. A total of 98 were randomized (77 to PUFA, 21 to control), with > 86% of participants completed all study visits. Baseline mean (SD) BMI% and ACQ was 96.8 (3.5) and ACQ 1.6 (0.9), respectively. Asthma and demographic characteristics were similar among treatment groups. Mutant ALOX5 genotypes associated with higher mean uLTE (5/5: 61.1, 5/X: 77.1, X/X: 108.2 pg/mg Cr , p=0.005 trend). At 6 months, n3PUFA treatment increased n-3/n-6 PUFA ratios compared to controls, (0.13 vs. -0.004mcg/mcg, p=.003) but did not affect uLTE (p=.236), ACQ (p=.577), FEV1 percent predicted (p=.880) or exacerbations (RR 0.92, 0.30-2.89). Though, n3PUFA-treatment did reduce asthma-related urgent health care contacts (RR 0.34, 0.13, 0.86, p=.023). Conclusion. n3PUFA supplementation increased leukocyte n3/n6 PUFA ratios without affecting systemic leukotrienes and nearly all asthma-related outcomes.