INDOOR AIR POLLUTION AND CHILD ARI: A RANDOMIZED TRIAL

描述(摘自调查人员摘要) 其目的是：1)在空气中进行第一个随机干预试验 污染历史，从而增加了对空气污染风险估计的信心， 目前是基于观察性研究；2)估计个人 儿童各种暴露条件下的颗粒物(PM)暴露 与改进的炉子(干预)和传统的明火相关联 (控制)因此可能有助于了解 幼儿PM的暴露-反应曲线。 经过7年的搜索和14项试点研究，一个优秀的网站已经成为 以危地马拉高原为特征，那里的PM暴露以公开为主 燃烧木头的炉子每天24小时产生的PM2.5暴露水平 1000微克/立方米或更高，即比目前的美国高出约60倍 标准。这种情况在欠发达国家很常见， 约三分之二的家庭依赖生物质燃料(木材、粪便、农作物 残留物)。试点工作已经确定了一种社会和经济上都可以接受的 干预措施，烟囱炉子能够将平均暴露量减少6- 10倍。可测量的主要健康结局，急性下呼吸道 感染(ALRI)是5岁以下儿童发病的主要原因 在全世界范围内，这是最不发达国家儿童死亡的主要原因。因此，它解释了 占全球疾病总负担的近10%，使其成为 健康状况不佳的最大类别。有必要从更多的角度审视这种关系 一些病例对照或队列研究突出了细节 年发现ALRI显著优势比的美国和最不发达国家 居住在使用木材或其他生物质燃料的家庭中的幼儿， 这表明减少对污染的暴露可能是一个强大的 预防性干预。 500名儿童，随机分配到对照组和干预组， 从出生到18个月每周进行一次访问，以检测ALRI的25%差异 发病率(幂=0.8；α=5%)。诊断将使用国际 协议和医生验证。儿童个人暴露和家庭 每个季节将对微环境进行两次监测(每年四次)， 而更强烈的是在亚样本中。因为试点研究一直表明 被动CO扩散管将成为PM的可靠指示器 木材燃料，他们将被用作主要暴露监测器 孩子们。每名儿童的PM总暴露剂量将使用 来自个人一氧化碳监测器、来自微环境PM和 部分家庭的CO测量，以及活动模式信息 对于每个孩子来说。 之前在该地点进行的试点研究表明，暴露在 干预组和控制组将从PM水平扩展到类似于 在美国城市的户外发现，以前的大多数流行病学都是在那里 聚焦，达到比数量级高出一个数量级以上的水平。主动吸烟 风险提供的证据表明，当风险敞口过大时，曲线必须变得不那么陡峭 高于环境空气污染，但尚不清楚曲线是如何形成的 在两者之间的巨大差距中，存在着这一经历的曝光 研究人口。因此，一个重要的次要目标是描述 在这个范围内，暴露与ALRI发病率之间的关系。 在美国，首要目标和次要目标都不太可能实现 今天的国家或其他发达国家，因为所需的条件已经 不再存在，即暴露不是由适合的家庭来源主导的 随机干预，也处于相对有限的范围内，因为 它们受到广泛的户外来源的严重影响。因此，除了 被指向一大群脆弱人群的严重健康问题 这项研究有助于世界范围内对PM的调查 使空气污染流行病学更接近最强者对健康的影响 阶段(布拉德福德)希尔确定因果关系的标准，“黄金” 随机干预的“标准”。

DESCRIPTION (Taken from the Investigator's Abstract) The aims are to: 1) conduct the first randomized intervention trial in air pollution history, thus increasing confidence in air pollution risk estimates, which are currently based on observational studies; 2) estimate personal particulate (PM) exposures for children across a wide range of exposures associated with an improved stove (intervention) and the traditional open fire (control) thus potentially assisting efforts to understand the shape of the exposure-response curve of PM impact in young children. After a 7-year search and 14 pilot studies, an excellent site has been characterized in highland Guatemala where PM exposures are dominated by open wood-burning cookstoves producing daily 24-hours PM 2.5 exposure levels of 1000 ug/m3 and higher, i.e., some 60 times more than current United States standards. Such conditions are common in less-developed countries (LDCs), where some two-thirds of households rely on biomass fuels (wood, dung, crop residues). Pilot work has identified a socially and economically acceptable intervention, a chimney stove that is capable of reducing mean exposures by 6- 10x. The primary health outcome to be measured, acute lower respiratory infection (ALRI), is the chief cause of morbidity in children under 5 worldwide and the chief cause of death among LDC children. It thus accounts for nearly 10% of the entire burden of global disease, making it the single largest category of ill-health. The need to examine this relationship in more detail is highlighted by some dozen case-control or cohort studies in the United States and LDCs that have found significant odds ratios for ALRI in young children living in households using wood or other biomass fuels, suggesting that reducing this exposure to pollution may be a powerful preventive intervention. 500 children, allocated randomly to control and intervention groups, will be visited weekly from birth to 18 months to detect a 25% difference in ALRI incidence (power=0.8; alpha=5%). Diagnosis will be done using international protocols and physician verification. Child personal exposures and household microenvironments will be monitored twice each season (four times per year), and more intensely in a subsample. Because pilot studies consistently show passive CO diffusion tubes to be reliable indicators of PM arising from use of wood fuel, they will be used as the primary exposure monitors for the children. Total individual PM exposure will be modeled for each child using the information from the personal CO monitors, from microenvironmental PM and CO measurements in a subsample of households, and activity pattern information for each child. Previous pilot studies at the site have shown that exposures in the intervention and control groups will extend from PM levels similar to those found outdoors in United States cities, where most previous epidemiology has focused, to levels more than an order of magnitude higher. Active smoking risks provide evidence that the curve must become less steep at exposures much higher than ambient air pollution, but it is not known how the curve is shaped in the wide gap between, within which lie the exposures experienced by this study population. An important secondary objective therefore is to describe the relationship between exposure and ALRI incidence across this range. Neither the primary nor secondary aim is likely to be achieved in the United States or other developed country today, because the needed conditions have ceased to exist, i.e., exposures are not dominated by household sources suited to randomized intervention and also lie in a relatively limited range because they are heavily influenced by widespread outdoor sources. Thus, in addition to being directed toward a serious health problem in a large vulnerable population worldwide, this research can assist the worldwide inquiry into PM health effects by moving air pollution epidemiology closer to the strongest stage of the (Bradford) Hill criteria for establishing causality, the "gold standard" of randomized intervention.