AIRWEIGHS: Investigating obesity as a susceptibility factor for air pollution in childhood asthma

项目摘要 哮喘和肥胖是过去几十年来同时出现的公共卫生危机， 影响了美国数百万儿童，并不成比例地影响了低收入少数群体， 城市地区的儿童。哮喘和肥胖风险最高的儿童也有 更大的暴露于污染。新的证据表明这三个因素-哮喘， 肥胖和污染可能有因果关系。最近的观察研究发现， 肥胖使人对颗粒物（PM）的肺部效应易感，包括我们自己的 显示患有哮喘的超重巴尔的摩儿童对室内有更大的呼吸反应 PM与瘦孩子。有必要证实这些观察结果与钙水平 证据，包括超重对PM易感性影响的实验证据 并鉴定这种效应的可能介质。为了提供实验证据，项目1 将进行一项空气净化器干预的随机临床试验，以解决我们的总体问题。 假设超重儿童比瘦儿童更容易患PM。 便携式空气净化器已成功用于市中心儿童的临床试验， 室内PM降低≥ 50%，并减轻哮喘症状。此外，空气净化器是一个高度可行的， 可以立即实施以改变室内环境的廉价干预。到 定义合理的中介效应，我们将调查四个主要假设，增加 1)潮气量，从而增加肺部的颗粒剂量2）全身性炎症 和氧化应激，可能导致对促炎PM暴露的过度反应 3)糖皮质激素抵抗，这可能会削弱吸入类固醇的保护作用4） 阻塞性睡眠呼吸暂停（OSA），一种最近与PM暴露有关的并发症， 与哮喘症状恶化相关，增加超重人群对PM的易感性 与瘦的孩子相比。研究结果将对未来修订空气质量标准至关重要 通过定义一个新的对污染健康敏感的人群， 方面的影响.此外，我们的发现将立即影响哮喘临床实践指南， 提供证据支持对最高风险亚群的高度可行的干预措施， 哮喘儿童，一个很容易通过身高和体重测量识别的人群。 此外，由于我们的目标人群是低收入的少数民族儿童，我们的研究结果将 这对那些受肥胖和哮喘影响最严重的人来说是有意义的。

Project Summary Asthma and obesity are public health crises that have concurrently arisen over the past decades, affecting millions of children in the US and disproportionately affecting low-income minority children in urban areas. The same children at highest risk for asthma and obesity also have greater exposure to pollution. Emerging evidence suggests that these three factors –asthma, obesity, and pollution– may be causally linked. Recent observational studies have found that obesity confers susceptibility to pulmonary effects of particulate matter (PM), including our own showing overweight Baltimore children with asthma have greater respiratory response to indoor PM versus lean children. There is a need to confirm these observational findings with causal-level evidence, including experimental evidence of the effect of being overweight on PM susceptibility and identification of plausible mediators of this effect. To provide experimental evidence, project 1 will conduct a randomized, clinical trial of an air purifier intervention to address our overarching hypothesize that overweight children are more susceptible to PM compared to lean children. Portable air purifiers have been used successfully in clinical trials of inner-city children, reduce indoor PM by ≥50%, and reduce asthma symptoms. Moreover, air purifiers are a highly feasible, inexpensive intervention that can be implemented immediately to modify indoor environments. To define plausible mediators of effect, we will investigate four leading hypotheses that increases in 1) tidal volume and thereby increases in particulate dose to the lungs 2) systemic inflammation and oxidative stress that may result in exaggerated responses to pro-inflammatory PM exposure 3) glucocorticoid resistance which may dampen the protective effect of inhaled steroids 4) risk of obstructive sleep apnea (OSA), a comorbidity recently linked to PM exposure that is also associated with worsening of asthma symptoms, enhance susceptibility to PM among overweight versus lean children. The study findings will be critical to future revisions of air quality standards and have high potential to impact policy by defining a new sensitive population to pollution health effects. Further, our findings will immediately impact asthma clinical practice guidelines by providing evidence to support a highly feasible intervention for the highest risk subpopulation of children with asthma, a population easily identifiable by height and weight measurements. Moreover, as our target population is low-income, minority children, our findings will have implications for those most affected by both obesity and asthma.