This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The URECA study will be a longitudinal prospective evaluation over a three-year time period, beginning at birth. The primary objective of the study is to establish in inner city children the immunologic causes for the development of recurrent wheezing by 36 months of age. The secondary objective is to identify patterns of immunologic development associated with the development of atopy in inner city children. Other secondary objectives are to identify environmental exposures associated with inner city life that modify immune development, and ultimately, the development of atopy and recurrent wheezing as defined above. Although the initial study will involve a three-year follow-up of study participants, the sample size (125 participants at this site) will be large enough so that, if the initial phases of the study are successful, the children could be followed to the age of six years to assess the development of bona fide childhood asthma. Families with a positive parental history of allergic diseases or asthma will be enrolled prior to birth. Maternal stress and other environmental exposures will be assessed prenatally. Beginning at birth and continuing for the first three years of life, the children will be evaluated longitudinally for blood cell cytokine responses, and for postnatal environmental influences (infections, allergen and microbial exposure, stress, indoor pollutants) that could affect the development of cytokine responses, and for clinical manifestations of allergy and asthma (recurrent wheeze). Periodic clinic visits will occur to perform physical examinations in order to track the development and persistence of significant lower respiratory tract symptoms. Scheduled visits will correspond with the home visit (age three months) for environmental assessment and dust collection, and yearly clinic visits beginning at age one year. Finally, DNA will be obtained from study participants and their mothers to evaluate genetic correlates to the observed patterns of immune development as they relate to wheezing diseases and asthma. Hypotheses: + IFN-g responses at birth will be inversely related to the risk of recurrent wheeze at 3 years of age. + Recurrent wheeze will be associated with an abnormal pattern in the development of IL-13 responses: IL-13 responses will be low at birth, and then elevated by three years of age.
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