The major objective of this competitive renewal is to establish the principal mechanisms and risk factors that modify incidence and persistence of asthma from birth into early adult life.
Specific aims are to: 1) identify factors that alter persistence and remission of asthma symptoms among young adults who developed asthma in childhood; 2) assess the role of persistent eosinophilia during childhood as a mechanism which determines progression and incidence of asthma in early adult life, and prevalence of persistent BHR; 3) measure noninvasive markers of airway inflammation in early adult life, and identify correlates of these markers, both with childhood and current asthma symptoms, BHR and immune system indicators of allergy; 4) predict early (by age 20 ) decline in lung function with reference to childhood lower respiratory tract illnesses, asthma-like symptoms, and the initiation of smoking; and 5) investigate the role of gender in incidence of and risk factors for asthma during adolescence and young adult life. More detailed knowledge of the natural history, risk factors, and mechanisms of asthma are essential for the development of effective strategies for the primary and secondary prevention of this and complex and costly disease. This project is designed to continue into early adult life our prospective investigation of risk factors for the development and persistence of asthma, and to study longitudinally assessed mechanisms associated specifically with asthma, in a multiethnic population. The children enrolled at birth in the Tucson Children's Respiratory Study are approaching a critical age during which lung growth slows, ceases, or begins to decline, and when environmental influences may be changing. Collection of questionnaire data regarding respiratory symptoms will occur in all 974 subjects still being followed at three ages: 18, 20 and 22 years. In addition, at age 20 there will be a comprehensive evaluation of respiratory health on subjects (n=400-450) who have relatively complete longitudinal data. At that time, subjects will be tested for baseline lung function, airway reactivity (using methacholine challenge, peak flow variability and bronehodilator response), markers of airway inflammation (exhaled nitric oxide) and allergy skin test response. Blood will also be drawn for measurements of total serum and allergen specific IgE, cytokine studies, and a CBC with differential. A subgroup will provide a sample of induced sputum for assessment of percent eosinophils, cytokine studies, and total and allergen specific IgE. Linking this extensive data set to the genetic analyses conducted in related projects will provide a powerful means of addressing fundamental questions about the relative roles of environmental exposures and familial factors in the development of asthma from birth through young adult life.
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