Asthma has shown dramatic increase worldwide. The disorder is diagnosed in 7-15 percent of U.S. children and is more prevalent in boys throughout childhood;however, during puberty a gender reversal occurs. We do not know if asthma persists in girls and remits in boys or there is new onset asthma in girls. In addition, we do not understand factors driving these changes in asthma occurrence, but they seem to be related to gender- specific developments during puberty. We propose to test the following hypotheses: (1) Gender reversal of asthma is due to new onset in girls and higher rates of clinical remission in boys. (2) Risk factors include early onset of puberty, obesity, pollutants, and early life factors such as parental smoking and lack of breastfeeding. (3) Identification of prognostic factors will allow for targeted interventions to prevent persistence and recurrence of asthma in adulthood. In 1989, we recruited a population birth cohort (1,456 children) on the Isle of Wight, an island one mile off the south coast of England with a population of 130,000. This cohort has been extensively phenotyped for asthma and other allergic diseases at 1, 2, 4 and 10 years of age. High follow up proportions (80-95 percent) have been achieved at each age. A wealth of information is available from prior examinations of the cohort. Participants are now adolescents. Therefore, this cohort is uniquely suited to address the above hypotheses. We propose to study these children at the age of 18 years and anticipate that 1,200 will participate. We will assess symptoms, lung function, airway inflammation, and atopic markers using questionnaire, physical examination, spirometry, bronchial provocation, exhaled nitric oxide, sputum induction, skin prick test, and total IgE. Using regression models with clinical markers as outcomes, we will determine the impact of pubertal factors, obesity-related factors (body mass index, serum leptin levels, genotypes for leptin and leptin receptor), and environmental risk factors (including, breastfeeding, tobacco smoke exposure, markers of pollution and agriculture exposure). Using all available information, we will determine a predictive model to identify children who are at high risk of persistent or recurrent asthma in adult life. These results will facilitate prevention of asthma persistence and recurrence. Our work brings together a multidisciplinary research team with a proven record of collaboration and expertise in respiratory medicine, allergy and immunology, epidemiology, genetics, and biostatistics.
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