The ALOHA trial: Addressing Quality of Life, Clinical Outcomes, and Mechanisms in Uncontrolled Asthma Following the DASH Dietary Pattern

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PROJECT SUMMARY Asthma is a chronic inflammatory disease of the airways. Asthma prevalence has increased markedly in the United States, with 19 million adults reporting current asthma and 62% of them with uncontrolled asthma. Poor diet quality is an important risk factor implicated in this alarming trend as a typical western diet features processed, energy-dense, nutrient-deficient foods, promoting a proinflammatory host environment. Diet quality in asthma is an emerging area of research; few interventional trials have investigated healthy dietary patterns in adults with asthma, none was adequately powered to determine efficacy, and underlying mechanisms are poorly understood. OBJECTIVE: To fill this gap, the current 2-phase, milestone-driven ALOHA trial will rigorously evaluate the efficacy and mechanisms of a behavioral intervention promoting the Dietary Approaches to Stop Hypertension (DASH). This behavioral intervention showed promising results in a pilot trial among adults with uncontrolled asthma. METHODS: The R61 phase (1 year) will focus on finalizing trial planning and preparation and begin early enrollment; in the R33 phase (4 years) we will conduct a 2-arm randomized clinical trial over 12 months. Adults with uncontrolled asthma (n=320) on standard controller therapy will be equally randomized and assessed at baseline (0), 3, 6 and 12 months. The control and intervention groups will be matched on the number, frequency, and format of sessions over 12 months while the length of each session is proportional to the content delivered. Control participants will receive education on lung health, asthma, and other general health topics using American Lung Association and UpToDate materials. The intervention group will receive the same health education and materials in addition to DASH behavioral counseling. Central hypothesis: Compared with the education-only control, the DASH behavioral intervention will lead to significantly more participants with a clinically significant improvement (responders) in asthma-specific quality of life (primary outcome) and significantly greater improvements in related asthma and non-asthma outcomes, which will be mechanistically linked to improved diet quality. SPECIFIC AIMS: First, to determine intervention efficacy on the primary outcome of clinically significant improvement in asthma-specific quality of life at 12 months and secondary outcomes (asthma control, lung function, generic qualify of life, blood pressure, mental health, sleep health). Second, to examine the intervention effects on metabolomic (circulating short-chain fatty acids: propionate, butyrate, acetate), immune response (interferon-gamma, IL-5, IL-17A, IL-10, IL-1β, IL-6, IL-8, TNFα), and physiologic (bronchodilator responsiveness) biomarkers of asthma. Third, to examine the intervention effects on self- reported and objective indices of diet quality (DASH score, dietary inflammatory index, serum carotenoids). We also will conduct exploratory analyses of causal mediation linking diet quality, biomarkers, and asthma outcomes as well as effect modification by sex and other biological variables (age of asthma onset, atopy). IMPACT: This trial has high potential to advance the clinical and mechanistic understandings of diet quality in asthma.