URBAN ENVIRONMENT AND CHILDHOOD ASTHMA

点击翻译按钮获取中文摘要

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. Urban Environment and Childhood Asthma(URECA) Overview Description: The URECA study is a longitudinal birth cohort study, which is following inner-city children at high risk for developing asthma for 3 years. If the initial phases of the study are successful and funding can be secured, the children will be followed to the age of 6 to assess the development of bon fide childhood asthma. Background and Rationale: Asthma is more prevalent, and may be more severe, in the inner city, even after taking differences in ethnicity and socioeconomic status into account. This strongly suggests that environmental factors unique to the inner city may promote the development of asthma in early childhood. Although there are other studies of allergen exposure in the inner city environment, information relating early life exposures to viral infections and stress in the inner city to the development of asthma are lacking. Furthermore, despite studies which link asthma to abnormal development of the immune system and patterns of cytokine secretion, there has been no prospective evaluation of the effects of the environmental exposures unique to the inner city on immune development and the incidence of asthma. The URECA study will attempt to answer the following questions: 1) Does dysregulation of innate immune responses, which may already be present at birth, increase the risk of allergen sensitization (adaptive immune responses) and asthma, and if so, which cytokines are key in this process? 2) How do lower respiratory infections in infancy affect the subsequent risk of recurrent wheezing and asthma in inner city children? 3) Is the immune system of inner city children already abnormal at birth, due to a unique prenatal environment? 4) Of the many unique features associated with the inner city environment, which are the principal factors that adversely affect immune development, and thereby increase the risk of asthma? 5) Does the inner city environment(e.g. increased stress and pollution) increase the frequency or severity of lower respiratory infections (LRI), and if so, what are the relevant mechanisms (immune modulation versus lung-specific effects), and 6) Do environmental factors interact at a critical time point to establish a particular wheezing phenotype with future infections and/or exposures? Study Design and Population: The URECA study has enrolled children who are at high risk for developing allergic diseases and asthma, on the basis of a parental history of asthma, allergic rhinitis or atopic dermatitis, and residence in the inner city. Families with a positive parental history of allergic diseases or asthma are enrolled prior to birth. Maternal stress and other environmental exposures are assessed prenatally. Children are being evaluated each year 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 clinical manifestations of allergy and asthma (recurrent wheeze). DNA is also being obtained from study participants and their mothers to evaluate genetic risk for developing wheezing diseases and asthma. Yearly clinic visits include physical examinations to track the development and persistence of significant lower respiratory tract symptoms. Nasopharyngeal mucus specimens are being analyzed for the presence of viral pathogens. Measurement of allergen-specific IgE and IgG will be performed at 12, 24, and 36 months. Home visits for environmental assessment and dust collection are being performed. Frequent telephone contact is maintained with the families to assess the development of respiratory infections, wheeze, the appearance of atopic diseases, changes in environmental exposures and to encourage participation in the scheduling and completion of study visits. An ancillary group of children with no family history of asthma or allergies has been added to the URECA study to provide information on cytokine responses in a lower-risk population with similar environmental exposures. Knowing how family history alters immune development, lifestyle and early life environmental exposures will be an important advantage to the URECA study. All URECA participants are also invited to participate in an ancillary URECA weight study. The objective of the URECA weight study is to examine the relationship between the body weight/composition, childhood weight gain, asthma morbidity and biomarkers of inflammation. Primary and Secondary Outcome Measures The primary outcome measure of the URECA study is recurrent wheeze. For the purposes of the study, recurrent wheeze is defined as at least two episodes of wheezing in the first three years of life with one of these episodes of wheezing occurring during the third year. A number of secondary outcome variables will also be assessed as follows: 1) Stringent index for the prediction of childhood asthma from the Tucson Children's Respiratory Study 2) Atopy, defined as either a total IgE60KU/L at age three years, atopic dermatitis(doctor diagnosed or staff observed) or one or more positive skin tests to aeroallergens at age three years. 3) Use of an anti-inflammatory medication for asthma (Corticosteroids, Cromolyn, Montelukast) for at least two weeks after age two years. 4) Pulmonary Function 5) Asthma diagnosed by a health provider