Children's Health Study II Childhood Determinants of Lung Susceptibility to Air Pollution

Principal Investigator: Frank Gilliland  Co-Investigators: Ed Avol, John Peters, Rob McConnell, Jim Gauderman, Duncan Thomas, Louis Dubeau, Bryan Langholz  Description: This study builds on an ongoing prospective cohort study of children in 12 California communities to assess the hypotheses that 1) dietary intake of fruits, vegetables and antioxidants; and 2) polymorphisms in genes involved in lung defenses (GSTM1, GSTT1, GSTP1, MPO, TNFa) affect children's susceptibility for slow lung function growth and increased occurrence of respiratory illnesses from chronic exposure to ozone (O3), nitrogen dioxide (NO2), and respirable particles (PM10 and PM2.5 ). These hypotheses are based on a mechanistic model that chronic respiratory effects from oxidant air pollutants (O3, NO2) and particulates (PM10 and PM2.5) are caused by chronically increased oxidative stress and repeated pathologic inflammatory responses. The effects of O3, NO2, PM10 and PM2.5 are mediated by interacting self-enhancing processes of oxidative, radical, and enzymatic attack on the lung and a pathologic inflammatory response that produce ongoing tissue damage, decreased ventilatory capacity, and altered immune function. Determinants of susceptibility modulate lung defenses to these insults. We have received funding from NIEHS and EPA to recruit 2500 active participants and 500 former participants from the ongoing study, to collect a dietary assessment using a validated food frequency questionnaire, to validate medical histories, and to collect biologic samples for genotyping. We have also received funding from the NHLBI to recruit an additional 3000 participants into the study, and to expand the focus to studies of asthma and air pollution.