An alarming increase in the prevalence of childhood asthma has been observed in the past several decadesand is likely the result of an interaction among poorly understood immune, environmental, and geneticfactors. Exercise is a common cause of asthma exacerbation in children, and it is now known that whenchildren exercise, even healthy children engaged in real-life activities, a robust stress/inflammatory responseensues leading to activation of immune cells and cytokines, many of which are known to be involved in thepathogenesis of asthma. A seemingly paradoxical response to exercise occurs characterized bysimultaneous and vigorous pro- and anti-inflammatory activation. Whether or not the naturally occurringleukocyte stress/inflammatory response to exercise is imbalanced in pediatric asthma and contributes toexercise-induced bronchoconstriction (EIB) has not been investigated in children. The goal of this Project isto test a series of hypotheses focused on novel mechanisms that link exercise with asthma pathogenesis inchildren. Specifically, the aims are:To systematically measure in children and adolescents with mild persistent asthma the effects of briefbouts of exercise on leukocyte production of key cytokines and growth factors that determine TH1, TH2,and T-regulatory balance.To measure the relationship between the leukocyte response to exercise and the magnitude of EIB inchildren and adolescents with asthma.To determine in children and adolescents with asthma how the acute leukocyte responses to exercise arealtered by fitness, habitual physical activity, body composition, and gender and maturational status.The research relies on state-of-the-art techniques to assess gene regulation in leukocytes including:microarray, RT-PCR, flow cytometry for surface and intracellular expression of key cytokines, and growthfactors. A series of in-vitro cell culture experiments have been designed to determine whether leukocytesin children with asthma differ in their responses to exercise than in healthy controls; or, alternatively, whetherthe mechanism is found in factors within the circulation (e.g., mediators such as growth hormone, insulin-likegrowth factor-l and its binding proteins, interleukin-6, and heat shock proteins- mediators that are altered byexercise and are known to influence stress and immune responses. Exercise will consist of cycle ergometrywith gas exchange measured breath by breath. Habitual physical activity will be measured withaccelerometry, and body composition with DEXA. Lung function will be measured by spirometry before andafter exercise.Lay Summary. Asthma is the major chronic disease of childhood, and exercise and play are, unfortunately,key triggers of asthma attacks. This research is designed to better understand how immune cells respond toexercise in asthma. This knowledge will help develop strategies to limit asthma attacks permitting affectedchildren to prevent chronic lung disease and fully accrue the many health benefits of exercise during growth.
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