The goal of Project 2 is to address several questions concerning the health effects of exposure to arsenic and manganese in water (WAs and WMn, respectively) among adolescents. First, does the As-induced respiratory disease observed in adults also manifest itself in adolescents, and what are possible physiologic mechanisms? Second, to what extent do associations between WAs and both lung function brain function reflect the effects of exposure in utero and in infancy, periods of dramatic development for these systems? Third, are WAs and WMn associated with specific cognitive functions in addition to intelligence? We will draw on an existing sample of 780 adolescents (15-17 years old) whose mothers are participants in the HEALS Study. Based on mothers' well As, measured five times from 2000 until the present, we are able to define four groups of adolescents with varying levels and patterns of exposure to As. Defined on the basis of WAs levels, four groups include adolescents with exposures that are: Group 1) consistently low (mean WAs = 3 ppb); Group 2) consistently moderate (mean WAs = 26 ppb); Group 3) consistently high (mean WAs = 146 ppb); and Group 4) high from conception through roughly age one (mean WAs = 201 ppb) but much lower thereafter (mean WAs =13 ppb). Within each group, there is wide variation in WMn concentrations. Three specific aims target As exposure and pulmonary function (FEV1 and FVC) as well as biomarkers of lung dysfunction in exhaled breath condensate. Three additional aims expand our earlier work on As, Mn and neuropsychologic outcomes by considering components of Executive Function (planning, sustained attention, working memory) that have been mapped to brain regions thought to be affected by exposure to these elements. Components of Executive Function will be measured with the Cambridge Neuropsychological Test Automated Battery (CANTAB), a computerized and well validated set of tests; intelligence will also be assessed. We will examine adolescents, an understudied age group, because certain components of Executive Function and lung development do not mature until this age; studies with younger children would miss these health effects.