Can diet- & exercise-induced weight loss improve asthma control in obese adults?

描述（由申请人提供）：项目摘要科学证据继续积累肥胖和哮喘之间的关系。最近的努力越来越多地集中在这种关系的性质上，而不是试图确定这种关系是否存在。尽管不是全部，但许多流行病学研究报告了肥胖和哮喘之间的时间正确和剂量反应关系。动物研究支持这两种疾病之间的因果关系;然而，人类的因果途径仍有待了解。在新的NIH哮喘诊断和管理指南中，首次明确承认肥胖是一种重要的合并症，并且基于有限的研究，认为肥胖治疗对哮喘控制具有潜在益处。虽然目前的证据表明减肥对哮喘的影响是令人鼓舞的，但还远远没有定论。这项随机对照试验（RCT）的总体目标是调查循证生活方式减肥干预对肥胖成年人哮喘控制的有效性。干预措施将包括饮食和身体活动的改变以及行为改变。这种方法已经证明在预防和控制公认的肥胖相关的合并症如糖尿病和高血压方面有效。我们将从北方加州Kaiser Permanente（KPNC）的4个医疗中心的约20，000名潜在合格哮喘患者中随机抽取324名18-70岁的控制欠佳、持续性哮喘且体重指数为30.0 - 39.9 kg/m2的患者，KPNC是一家大型团体模式健康维护组织。所有受试者将在随机化前完成与现场KPNC哮喘护理经理的办公室访视和电话咨询，所有受试者将在随机化后继续接受其医生的KPNC标准护理。被随机分配到实验组的人将接受全面的生活方式减肥干预。主要结局为12个月时Juniper哮喘控制问卷的总体评分。具体目标是：1）确定干预是否改善了与哮喘相关的当前损害的测量（哮喘症状、肺功能、活动受限、急救药物使用和哮喘相关生活质量）; 2）确定干预是否改善了与哮喘相关的未来风险的测量（哮喘急性发作和哮喘药物的不良反应）; 3）检查干预效应的潜在机制，重点是体重，体力活动和饮食组成变化的相对贡献，在控制哮喘药物效力和依从性之后;和4）探索潜在的效应调节因子，例如性别、种族/民族、教育和其他基线特征。该项目将有助于推进目前对肥胖与哮喘关系性质的理解。如果减肥干预被证明可以改善哮喘的结果，它将增加其他可用于管理肥胖成人哮喘的医疗和环境策略，这反过来可能会降低与哮喘和肥胖相关的发病率和死亡率。公共卫生相关性：尽管其潜在机制尚不清楚，但越来越多的科学证据表明，肥胖的儿童和成人患哮喘的风险较高，或者对于那些已经患有哮喘的人来说，症状更严重。新的国家哮喘管理指南建议临床医生考虑建议超重或肥胖的哮喘患者减肥，这是基于非常有限的研究表明，减肥除了其他已知的健康益处外，还可以改善哮喘控制。目前的研究旨在严格调查减肥，通过饮食调整，身体活动和行为改变的建议策略，是否对肥胖成年人哮喘的管理具有显着的临床益处。如果成功，该项目将有助于推进目前治疗肥胖成人哮喘的临床指南，从而降低与哮喘和肥胖相关的发病率和死亡率。

DESCRIPTION (provided by applicant): Project Summary Scientific evidence continues to accumulate on the relation between obesity and asthma. More recent efforts are increasingly focused on the nature of the relation, as opposed to trying to determine whether such a relation exists. Many, although not all, epidemiological studies report a temporally correct and dose-response relationship between obesity and asthma. Animal studies support a causal link between the two disorders; however, the causal pathway remains to be understood in humans. In the new NIH asthma diagnosis and management guidelines, obesity is explicitly recognized, for the first time, as an important co-morbidity, and treatment of obesity is deemed to have potential benefits on asthma control based on limited studies. Although current evidence of the effects of weight loss on asthma outcomes is encouraging, it is far from being conclusive. The overall goal of the proposed randomized controlled trial (RCT) is to investigate the efficacy of an evidence-based lifestyle weight loss intervention on asthma control among obese adults. The intervention will involve a combination of dietary and physical activity changes and behavioral modification. This approach has demonstrated efficacy in preventing and controlling well-recognized obesity-related co- morbidities such as diabetes and hypertension. We will randomize 324 patients ages 18-70 years who have suboptimally controlled, persistent asthma and a body mass index of 30.0 to 39.9 kg/m2 from ~20,000 potentially eligible asthma patients at four medical centers of Kaiser Permanente in Northern California (KPNC), a large, group-model health maintenance organization. All participants will complete an office visit and a phone consultation, pre-randomization, with an on-site KPNC asthma care manager, and all will continue to receive KPNC standard of care from their physician post-randomization. Those randomly assigned to the experimental group will receive the comprehensive lifestyle weight loss intervention. The primary outcome will be the overall score at 12 months on the Juniper Asthma Control Questionnaire. The specific aims are to: 1) Determine whether the intervention improves measures of current impairment associated with asthma (asthma symptoms, spirometric lung function, activity limitations, rescue medication use, and asthma-related quality of life); 2) Determine whether the intervention improves measures of future risk associated with asthma (asthma exacerbations and adverse effects of asthma medication); 3) Examine potential mechanisms of intervention effects, focusing on the relative contributions of changes in weight, physical activity, and diet composition, after controlling for asthma medication potency and adherence; and 4) Explore potential effect modifiers, e.g. sex, race/ethnicity, education, and other baseline characteristics. This project will help advance current understanding of the nature of obesity-asthma relationship. If the weight loss intervention is proven to improve asthma outcomes, it will add to the other medical and environmental strategies available to manage asthma in obese adults, which may, in turn, lead to reduced morbidity and mortality associated with asthma and obesity. PUBLIC HEALTH RELEVANCE: Although the underlying mechanisms remain unclear, growing scientific evidence suggests that children and adults who are obese are at elevated risk of developing asthma or, for those who already have the disease, having worse symptoms. The new national asthma management guidelines recommend that clinicians consider advising asthma patients who are overweight or obese to lose weight, based on very limited studies showing that weight loss may improve asthma control, in addition to its other known health benefits. The current study aims to rigorously investigate whether weight loss, through recommended strategies for dietary modification, physical activity, and behavioral change, has significant clinical benefits for the management of asthma in obese adults. If successful, this project will help advance the current clinical guidelines for treating obese adults with asthma, which, in turn, may lead to reduced morbidity and mortality associated with asthma and obesity.