Childhood exposure to a variety of indoor air contaminants including environmental tobacco smoke (ETS) produces significant risks in asthma, airway hyperresponsiveness, and other respiratory symptoms such as cough, wheeze, and mucus production. Epidemiological studies suggest that exposure to ETS during the perinatal period may have adverse effects on lung function which can persist into adulthood. It has been estimated in the United States alone 200,000 to 1,000,000 children with asthma will have their condition worsened by exposure to ETS (USEPA, 1992). However, the mechanisms leading to this process are unknown. During the past 2.5 years, we have established a state-of-the-art inhalation system to study the effects of exposure to ETS on perinatal lung development in a nonhuman primate, the Rhesus macaque monkey. Exposure to ETS has been done using aged and diluted sidestream cigarette smoke as a surrogate for ETS. Two chambers located at the California Regional Primate Research Center Inhalation Facility have been expressly designed and configured to create conditions for passive smoke exposure to monkeys during pregnancy and early postnatal development under carefully controlled conditions. These studies have demonstrated significant alterations in lung development following exposure to ETS. These effects include changes in immune effector and inflammatory cells in the lung air spaces, alterations in pulmonary and peripheral blood cytokines and neurotrophins, alterations in the innervation and epithelial composition of the trachea, and changes in the activity and distribution of pulmonary cytochrome P450 monooxygenases and glutathione-S-transferases. All these changes are evident by 2.5 months of age in infant Rhesus monkeys. These findings confirm that ETS exposure during perinatal development significantly affects the lungs of non-human primate infants. We hypothesize that these changes represent the initial steps in the genesis of an asthmatic-like condition solely due to perinatal exposure to ETS. We also hypothesize that critical windows of exposure are present during the perinatal period which will exacerbate this effect. We propose to test these hypotheses by continuing to study this model in the Rhesus monkey to (1) determine the effects of exposure to ETS during specific periods of perinatal development in monkeys from early gestation to 6 months postnatal age using physiologic, biochemical and anatomical measures and (2) determine if cessation of exposure to ETS following 6 months postnatal age will still be associated with persistent changes in the respiratory system. Such studies should help us to better understand the potential mechanisms by which fetal and early postnatal exposure to environmental contaminants could lead to lasting, adverse consequences in children.
|Effective start/end date||5/1/02 → 2/28/08|
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