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

项目总结 哮喘是一种慢性呼吸道炎症性疾病。哮喘患病率在中国显著增加。 在美国，有1900万成年人报告了目前的哮喘，其中62%的人哮喘得不到控制。穷 饮食质量是这一令人震惊的趋势中隐含的一个重要风险因素，作为典型的西方饮食特征 加工、高能量、缺乏营养的食物，促进促炎宿主环境。中国人的饮食质量 哮喘是一个新兴的研究领域；很少有干预试验研究健康的饮食模式。 成人哮喘患者，没有足够的动力来确定疗效，潜在的机制也很差 明白了。目标：为了填补这一空白，目前的两阶段、里程碑驱动的ALOHA试验将严格 评价促进饮食戒烟的行为干预的有效性和机制 高血压(DASH)。这一行为干预在成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)将侧重于最终确定试验计划和准备 并开始早期招募；在R33阶段(4年)，我们将在12个月内进行一项双臂随机临床试验 月份。接受标准控制疗法的成人哮喘患者(n=320)将同样随机和 在基线(0)、3个月、6个月和12个月进行评估。对照组和干预组将在 12个月的会议次数、频率和形式，而每次会议的时间长短与 提供的内容。对照组参与者将接受有关肺部健康、哮喘和其他一般健康的教育。 使用美国肺脏协会和UpToDate材料的主题。干预组将收到相同的 除了DASH行为咨询外，还有健康教育和材料。中心假说：与 在仅受教育控制的情况下，DASH行为干预将导致更多的参与者具有 临床显著改善(应答者)哮喘特有的生活质量(主要结果)和 显著改善相关哮喘和非哮喘结果，这将是机械性的 与改善饮食质量有关。具体目标：首先，确定干预对主要结果的效果 12个月后哮喘患者的生活质量和二次结局的临床显著改善 (哮喘控制、肺功能、一般生活质量、血压、心理健康、睡眠健康)。第二，到 检查对代谢物(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-17A、IL-10、IL-1β、IL-6、IL-8、肿瘤坏死因子α)和生理 (支气管扩张剂反应性)哮喘的生物标志物。第三，考察干预对自我的影响。 已报道的和客观的饮食质量指标(DASH评分、饮食炎症指数、血清胡萝卜素)。我们 还将对饮食质量、生物标记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变量(哮喘发病年龄、特应性)的影响修正。影响：这 这项试验具有很高的潜力，可以促进对哮喘患者饮食质量的临床和机制理解。

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.