Early Life Factors In Childhood Respiratory Disease

我们计划对6800名新生儿进行出生队列研究，以探索儿童哮喘发展中的早期生活因素。这项研究将在墨西哥城进行，这是因为墨西哥城的哮喘发病率相对较低，因为美国城市高暴露于与哮喘风险增加相关的因素，如蟑螂和尘螨过敏原、贫困和城市空气污染。这种模式暗示了保护性因素的可能作用。在这项研究中，我们将重点关注早期饮食中摄入抗氧化剂和长链脂肪酸(omega-3和omega-6)可能的保护作用。这些因素在墨西哥城可能尤其重要，墨西哥城是北美臭氧水平最高的城市，臭氧是一种强氧化剂。我们还将研究早期接触某些感染性物质的潜在保护作用。为此，我们将评估室内灰尘、腹泻和呼吸道感染中的内毒素暴露情况，以及肠道微生物群的模式。为了与美国城市的研究相比较，我们将检查常见抗原的相关性，包括屋尘螨和蟑螂。将从儿童及其父母那里收集遗传物质，以检查关键暴露与参与这些病原体反应的基因之间的相互作用。 最近的数据表明，早期生命阶段在儿童哮喘特有的免疫反应的发展过程中至关重要。此外，暴露的时间似乎对确定它们的生物效应至关重要。为了研究这些因素，需要尽可能早地对一群儿童进行研究。 在过去的一年里，我们获得了NIEHS和墨西哥合作机构的人体受试者批准。我们还获得了研究风险保护办公室的临床豁免。我们已经拟定了所有研究工具的草稿，为2002年的试点研究做准备。

We plan to conduct a birth cohort study of 6,800 births to explore early life factors in the development of childhood asthma. The study will be conducted in Mexico City which is of interest because of the relatively low rates of asthma in the face of high exposures to factors associated with increased risk of asthma in US cities, such as cockroach and dustmite allergens, poverty, and urban air pollution. This pattern suggests the possible operation of protective factors. In this study, we will focus on the possible protective effect of early dietary intake of antioxidants and long chain fatty acids (omega-3 and omega-6). These factors may be especially important in Mexico City which has the highest levels of ozone, a strong oxidant, in North America. We will also examine the potential protective effect of early exposure to certain infectious agents. To this end, we will assess exposure to endotoxin in house dust, diarrheal and respiratory infections and pattern of intestinal microflora. For comparability with studies in US cities, we will examine the association with common antigens, including house dust mite and cockroach. Genetic material will be collected from children and their parents to examine interactions between key exposures and genes involved in response to these agents. Recent data suggests that the early life period is crucial in the development of the immune response characteristic of childhood asthma. Further, the timing of exposures appears to be critical in determining their biologic effects. In order to study these factors, a cohort of children needs to be studied as early in life as possible. In the past year, we obtained human subjects approval from NIEHS and the collaborating institution in Mexico. We have also received clinical exemption from the Office for Protection for Research Risks. We have developed drafts of all study instruments in preparation for pilot studies in 2002.