Obesity and Asthma: Nutrigenetic Response to Omega-3 Fatty Acids (NOOA)

This project will assess the effectiveness of omega-3 fatty acid supplementation in controlling asthma symptoms among obese asthmatics, and will assess if a person's genes influence response to treatment (personalized medicine). This project may improve our ability to treat asthma and our understanding of the link between obesity and asthma.

Obesity increases the risk for asthma diagnosis in children and adults. With obesity on the rise, a better understanding of this association may become critically important to public health. We will determine the impact of fish oil-derived Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) on asthma control among obese asthmatics. These omega-3 fatty acids have been shown to: reduce inflammation important to asthma and improve asthma outcomes in an inconsistent manner across previous smaller studies - results that are consistent with a pharmacogenetic influence. There exists evidence that omega-3 fatty acid response displays a pharmacogenetic response related to ALOX5 genotype. Preliminary data suggests that obese individuals are at greater risk for possessing this same ALOX5 variant and thus obese asthmatics may be more responsive to fish oil. We will determine (in a sub-aim) if there exists an ALOX5 genotype-related response effect with fish oil. This will be the largest clinical trial of omega-3 fatty acid for the treatment of asthma, and the first applying pharmacogenetic/nutrigenetic analysis.

The ACQ ranges from 0 to 6 (higher values indicate worse asthma control). A score greater than 1.25 in children is considered poor asthma control, and a change of 0.4 or greater is considered clinical meaningful.

Ratio of total omega-3 to total omega-6 polyunsaturated fatty acids from granulocytes in peripheral blood

Ratio of total omega-3 to total omega-6 polyunsaturated fatty acids from monocytes in peripheral blood

The asthma control test assesses patient reported symptoms from the prior month and has a range from 5 to 25 with a higher score suggesting better asthma control.

Leukotriene E4 obtained from urine was measured using liquid chromatography tandem mass spectrometry.

Exacerbations of asthma were defined by the need for urgent medical care (emergency room or urgent care clinic) or systemic corticosteroids to avoid severe worsening of asthma determined by study physician or local provider

Inclusion Criteria: age 12-25 BMI > 25 (age 18-25) or BMI%>85th (age 12-17) (BMI Liberalized) Physician diagnosis of persistent asthma Lung function responsiveness by bronchodilator reversibility or bronchoprovocation testing Exclusion Criteria: pregnancy currently taking LTRA for asthma control other serious chronic medical condition bleeding diathesis

Lang JE, Mougey EB, Hossain MJ, Livingston F, Balagopal PB, Langdon S, Lima JJ. Fish Oil Supplementation in Overweight/Obese Patients with Uncontrolled Asthma. A Randomized Trial. Ann Am Thorac Soc. 2019 May;16(5):554-562. doi: 10.1513/AnnalsATS.201807-446OC.