Phthalate Exposure and Inner City Pediatric Asthma

描述（由申请人提供）：拟议的研究将确定儿童早期暴露于邻苯二甲酸盐是否与5至7岁儿童当前哮喘和原过敏性免疫球蛋白（Ig） E产生的发展有关，以及当前暴露于邻苯二甲酸盐是否与5至7岁儿童气道炎症增强和肺功能减弱有关。这项研究将证实或驳斥最近的流行病学发现，即邻苯二甲酸盐暴露与儿童哮喘、特应性反应和肺功能下降之间存在关联。先前的研究受到不完全暴露和结果测量的限制。然而，为拟议研究进行的试点结果也支持邻苯二甲酸盐暴露是哮喘发展的危险因素的假设。这项拟议的研究将在纽约市少数民族社区的400名儿童中进行。这些社区的儿童哮喘发病率是世界上最高的。邻苯二甲酸盐暴露也很普遍。该研究将在哥伦比亚儿童环境健康中心（CCCEH）正在进行的纵向出生队列研究中进行。CCCEH正在评估产前和产后暴露对哮喘发展和其他健康结果的贡献。孩子们从怀孕到七岁都被跟踪。拟议的研究具有成本效益，因为许多所需的暴露和结果测量已经在CCCEH队列中收集。这些包括呼吸道和过敏症状的详细病史，哮喘治疗和急诊室就诊；6岁时肺功能检查；从怀孕到五岁收集的室内灰尘样本中的过敏原水平；以及过敏致敏性的测量（在2岁、3岁和5岁时测量总IgE和特异性IgE）。邻苯二甲酸盐将在从母亲怀孕期间和从3岁和5岁儿童收集的尿液样本中以及在新收集的室内空气和5至7岁儿童的尿液样本中进行测量。此外，在5至7岁时，将测量呼出的一氧化氮，作为气道炎症的指标，并确定总IgE和过敏原特异性IgE水平。确诊5 - 7岁儿童哮喘的病例将由纽约长老会医院的摩根斯坦利儿童医院指定的委员会认证的儿科肺病专家进行。需要测试的假设是：(1)通过在怀孕期间和3岁和5岁时收集的尿液样本中的代谢物水平来测量儿童早期接触邻苯二甲酸盐，可以预测5至7岁时当前的哮喘和7岁时IgE抗体的产生；(2)在校正了早期邻苯二甲酸盐暴露后，通过室内空气样本中母体化合物的水平和5至7岁儿童尿液样本中代谢物的水平来测量的当前暴露与5至7岁儿童的肺功能呈负相关，与气道炎症呈正相关。

DESCRIPTION (provided by applicant): The proposed study will determine whether early childhood exposures to phthalates are associated with the development of current asthma and proallergic immunoglobulin (Ig) E production at ages five to seven and whether current exposures to phthalates are associated with augmented airway inflammation and diminished lung function at ages five to seven. The research will confirm or refute recent epidemiologic findings of associations between phthalate exposures and childhood asthma, atopy and reduced lung function. This prior research is limited by incomplete exposure and outcome measures. However, results from a pilot undertaken for the proposed study also support the hypothesis that phthalate exposures are risk factors in the development of asthma. The proposed study will be conducted among a cohort of 400 children who reside in minority communities in New York City. These communities experience some of the highest childhood asthma rates in the world. Phthalate exposures are also widespread. The research will be performed within the ongoing longitudinal birth cohort study being conducted by the Columbia Center for Children's Environmental Health (CCCEH). The CCCEH is evaluating the contribution of prenatal and postnatal exposures in the development of asthma and other health outcomes. Children are followed from pregnancy through age seven years. The proposed research is cost effective in that many of the required exposure and outcome measurements are already being gathered within the CCCEH cohort. These include detailed history of respiratory and allergic symptoms, asthma treatment and emergency room visits; lung function testing at age six; allergen levels in house dust samples collected from pregnancy through age five; and measurement of allergic sensitization (total and specific IgE measured at ages two, three, and five years). The phthalates will be measured in stored urine samples collected from the mother during pregnancy and from children at ages three and five years and in newly collected indoor air and urine samples at ages five to seven. Also at age five to seven years, exhaled nitric oxide will be measured as an indicator of airway inflammation and total and allergen-specific IgE levels will be determined. The case ascertainment of current asthma at ages five to seven will be made by a designated board- certified pediatric pulmonologist at the Morgan Stanley Children's Hospital of New York Presbyterian Hospital. Hypotheses to be tested are: (1) that early childhood exposures to the phthalates, as measured by metabolite levels in urine samples collected during pregnancy and at ages three and five years, predict current asthma at ages five to seven and production of IgE antibodies at age seven; and (2) after correcting for early phthalate exposure, current exposure as measured by levels of the parent compounds in indoor air samples and metabolites in urine samples collected at ages five to seven years, will be associated inversely with lung function and positively with airway inflammation at ages five to seven years.