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.