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

描述(由申请者提供)：项目摘要关于肥胖和哮喘之间的关系的科学证据不断积累。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。虽然不是全部，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联系；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，肥胖症首次被明确承认为一种重要的并存疾病，根据有限的研究，肥胖症的治疗被认为对哮喘控制具有潜在的好处。尽管目前关于减肥对哮喘结果的影响的证据令人鼓舞，但远不是决定性的。这项拟议的随机对照试验(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效果。干预将包括改变饮食和体力活动以及改变行为。这种方法在预防和控制公认的与肥胖相关的共病，如糖尿病和高血压方面表现出了有效性。我们将从北加州Kaiser Permanente(KPNC)四个医疗中心的约20,000名潜在符合条件的哮喘患者中随机选择324名年龄在18-70岁之间、体重指数在30.0至39.9公斤/平方米之间的哮喘患者，KPNC是一家大型团体模式健康维护组织。所有参与者将在现场KPNC哮喘护理经理的陪同下完成办公室访问和电话会诊，并在随机化后继续接受KPNC医生的标准护理。随机分配到试验组的人将接受全面的生活方式减肥干预。主要结果将是12个月时Juniper哮喘控制问卷的总分。其具体目的是：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、活动限制、救援药物的使用以及哮喘相关的生活质量)；2)确定干预是否改善了与哮喘相关的未来风险测量(哮喘加重和哮喘药物的不良反应)；3)研究干预效果的潜在机制，重点是在控制哮喘药物的效力和依从性之后，关注体重、体力活动和饮食结构变化的相对贡献；以及4)探索潜在的影响因素，例如性别、种族/民族、教育和其他基线特征。该项目将有助于促进当前对肥胖和哮喘关系的本质的理解。如果减肥干预被证明可以改善哮喘结果，它将增加其他可用于管理肥胖成年人哮喘的医疗和环境策略，这反过来可能导致与哮喘和肥胖症相关的发病率和死亡率降低。与公共卫生相关：尽管根本机制尚不清楚，但越来越多的科学证据表明，肥胖的儿童和成年人患哮喘的风险更高，或者对于那些已经患有这种疾病的人来说，他们的症状更严重。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，除了其他已知的健康好处外，减肥可能会改善哮喘的控制。目前的研究旨在严格调查通过推荐的饮食调整、体力活动和行为改变的策略来减肥是否对肥胖成年人的哮喘管理具有显著的临床益处。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，这反过来可能会降低与哮喘和肥胖症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.