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

项目摘要 哮喘是一种慢性气道炎症性疾病。哮喘的患病率在1990年 在美国，有1900万成年人报告目前患有哮喘，其中62%患有不受控制的哮喘。贫困 饮食质量是一个重要的危险因素牵连在这一惊人的趋势作为一个典型的西方饮食特点 加工过的、能量密集的、营养不足的食物，促进了促炎的宿主环境。饮食质量 哮喘是一个新兴的研究领域;很少有干预性试验调查了健康的饮食模式， 成人哮喘，没有足够的把握度来确定疗效，潜在的机制也很差。 明白目的：为了填补这一空白，目前的2期，里程碑驱动的ALOHA试验将严格 评估行为干预的有效性和机制，促进饮食方法停止 高血压（DASH）。这种行为干预在成年人中的试点试验中显示出有希望的结果， 无法控制的哮喘方法：R61阶段（1年）将重点完成试验计划和准备 并开始早期入组;在R33期（4年），我们将进行一项12年以上的2组随机临床试验 个月接受标准对照治疗的哮喘不受控制的成人（n=320）将被同等随机化， 在基线（0）、3、6和12个月时进行评估。对照组和干预组将在 在12个月内举行会议的次数、频率和形式，而每次会议的时间长短与会议的规模成比例。 内容交付。对照组参与者将接受肺部健康、哮喘和其他一般健康方面的教育 主题使用美国肺脏协会和UpToDate材料。干预组将获得相同的 健康教育和材料，以及DASH行为咨询。中心假设：与 仅教育控制，DASH行为干预将导致更多的参与者， 哮喘特异性生活质量（主要结局）的临床显著改善（应答者）， 相关哮喘和非哮喘结局的显著更大改善，这将在机制上 与改善饮食质量有关。具体目标：首先，确定干预对主要结局的有效性 12个月时哮喘特异性生活质量的临床显著改善和次要结局 （哮喘控制、肺功能、一般生活质量、血压、心理健康、睡眠健康）。二是 检查对代谢组学（循环短链脂肪酸：丙酸，丁酸， 醋酸盐）、免疫反应（干扰素-γ、IL-5、IL-17 A、IL-10、IL-1β、IL-6、IL-8、TNFα）和生理反应 （支气管扩张剂反应性）哮喘的生物标志物。第三，检验自我的干预效果。 报告的和客观的饮食质量指数（DASH评分，饮食炎症指数，血清类胡萝卜素）。我们 我还将对饮食质量、生物标志物和哮喘结果之间的因果关系进行探索性分析 以及性别和其他生物学变量（哮喘发作年龄、特应性）的影响。影响：这个 这项试验有很大的潜力，以促进临床和机制的理解，饮食质量的哮喘。

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.