Early Life Factors In Childhood Respiratory Disease

目的：最近的数据表明，生命早期在儿童哮喘免疫反应特征的发展中至关重要。此外，暴露的时间似乎是决定其生物效应的关键。为了研究这些因素，需要尽可能早地对一组儿童进行研究。我们计划对6,800名新生儿进行一项出生队列研究，以探讨儿童哮喘发生的早期生活因素。这项研究将在墨西哥城进行，这是因为在美国城市中，面对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，哮喘发病率相对较低。这种模式表明保护因素可能起作用。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）的可能保护作用。这些因素在墨西哥城可能特别重要，因为墨西哥城的臭氧含量最高，是北美最强的氧化剂。我们还将研究早期暴露于某些传染性病原体的潜在保护作用。为此，我们将评估室内灰尘中的内毒素暴露、肠道和呼吸道感染以及肠道微生物菌群模式。为了与美国城市的研究进行比较，我们将研究与常见抗原的相关性，包括屋尘螨和蟑螂。将从儿童及其父母那里收集遗传材料，以研究关键暴露与对这些制剂作出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6,800名婴儿。将在分娩时采集脐带血和母体血液样本。在出生后的前三个月，我们将进行家访，收集灰尘样本进行过敏原和内毒素测量，通过访谈获得问卷调查以评估饮食和风险因素，并收集婴儿的血液和尿液样本。我们将在出生后一年进行额外的随访访视，此后每年进行一次。将在出生时和每年随访时进行人体测量。在生命的第一年，我们将在下呼吸道疾病期间获得鼻冲洗液样本用于病毒检测。在6岁时，我们将进行肺功能测试，并进行沿着皮肤测试。基于6年随访，我们将确定当前喘息和哮喘的病例，并从剩余队列中确定一个对照组，以对储存的样本进行分析。成就：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，我与来自美国和欧洲出生队列研究的调查人员沿着空气污染暴露评估专家举行了一次研讨会。我已将本次研讨会的反馈纳入研究设计，并正在制定试点阶段的计划。

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.