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。患哮喘和肥胖症风险最高的儿童也有 更多地暴露在污染中。新出现的证据表明，这三个因素-哮喘， 肥胖和污染--可能是因果联系的。最近的观测研究发现， 肥胖使人更容易受到颗粒物(PM)的肺部影响，包括我们自己 显示超重的巴尔的摩哮喘儿童对室内空气有更强的呼吸反应 PM与苗条的儿童。有必要用因果水平来确认这些观察结果 证据，包括超重对PM易感性影响的实验证据 并确定这一效果的合理调解人。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，以解决我们的主要问题 假设超重的儿童比苗条的儿童更容易患PM。 便携式空气净化器已成功应用于市中心儿童的临床试验，Reducts 室内PM可减少≥的50%，并减轻哮喘症状。此外，空气净化器是一种高度可行的， 廉价的干预措施，可以立即实施，以改变室内环境。至 定义看似合理的影响因素，我们将调查四个主要假设，这些假设在 1)潮气量，从而增加肺部的颗粒物剂量2)全身炎症 以及可能导致对促炎PM暴露的夸大反应的氧化应激 3)糖皮质激素抵抗，可能会削弱吸入类固醇的保护作用4)患上 阻塞性睡眠呼吸暂停(OSA)，一种最近与PM暴露有关的共病，也是 与哮喘症状恶化有关，增加超重人群对PM的易感性 与瘦孩子的对比。这项研究结果将对未来空气质量标准的修订至关重要 并有很高的潜力通过定义对污染健康敏感的新人群来影响政策 效果。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进行高度可行的干预 患有哮喘的儿童，这一群体很容易通过身高和体重测量来识别。 此外，由于我们的目标人口是低收入的少数族裔儿童，我们的调查结果将具有 对那些受肥胖和哮喘影响最大的人来说。

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.