Early Life Factors In Childhood Respiratory Disease

目的：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。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。程序和技术：这是一项出生队列研究。我们将在分娩时登记6800名婴儿。将在分娩时采集脐带血和产妇血液样本。在婴儿出生后的头三个月，我们将进行一次家访，收集尘埃样本进行过敏原和内毒素检测，通过访谈获得问卷以评估饮食和风险因素，并收集婴儿的血液和尿液样本。我们会在出生一年后再进行后续访问，然后每年进行。将在出生时和每年的随访中进行人体测量。在生命的第一年，我们将在下呼吸道疾病期间获取鼻涕样本，用于病毒检测。在六岁时，我们将进行肺功能测试和皮肤测试。根据六年的随访，我们将确定目前的喘息和哮喘病例，并从剩余的队列中找出一个对照组，对存储的样本进行分析。研究成果：我设计了研究方案，并获得了外部科学审查和批准。2000年10月，我与美国和欧洲出生队列研究的研究人员以及空气污染暴露评估专家一起举办了一次研讨会。我已经将这次研讨会的反馈纳入了研究设计，并正在为试验阶段制定计划。

Aims: 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. 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. Procedures and techniques: This is a birth cohort study. We will enroll 6,800 babies at the time of delivery. Cord blood and maternal blood samples will be collected at delivery. During the first three months of life we will conduct a home visit where we will collect dust samples for allergen and endotoxin measurements, obtain questionnaires by interview to assess diet and risk factors and collect blood and urine samples from the baby. We will conduct additional follow-up visits at one year of life and then yearly thereafter. Anthropometric measurements will be made at birth and at yearly follow-ups. During the first year of life we will obtain nasal rinse samples during lower respiratory illnesses for virus detection. At age six we will conduct pulmonary function testing with challenge along with skin tests. Based on the six year old follow-up we will ascertain cases of current wheeze and asthma and a comparison group from the remaining cohort to conduct analyses of stored samples. Accomplishments: I designed the study protocol and obtained external scientific review and approval for the study. In October of 2000 I held a workshop with investigators from birth cohort studies in the US and Europe along with air pollution exposure assessment experts. I have incorporated feedback from this workshop into the study design and am making plans for the pilot phase.