Polycyclic aromatic hydrocarbons, environmental tobacco smoke, and respiratory symptoms in an inner-city birth cohort.
ABSTRACT Several studies have found associations between diesel exposure, respiratory symptoms, and/or impaired pulmonary function. We hypothesized that prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAH), important components of diesel exhaust and other combustion sources, may be associated with respiratory symptoms in young children. We also hypothesized that exposure to environmental tobacco smoke (ETS) may worsen symptoms beyond that observed to be associated with PAH alone.Design/participants: To test our hypotheses, we recruited 303 pregnant women from northern Manhattan believed to be at high risk for exposure to both PAH and ETS, collected 48-h personal PAH exposure measurements, and monitored their children prospectively.
By 12 months of age, more cough and wheeze were reported in children exposed to prenatal PAH in concert with ETS postnatally (PAH x ETS interaction odds ratios [ORs], 1.41 [p < 0.01] and 1.29 [p < 0.05], respectively). By 24 months, difficulty breathing and probable asthma were reported more frequently among children exposed to prenatal PAH and ETS postnatally (PAH x ETS ORs, 1.54 and 1.64, respectively [p < 0.05]).
Our results suggest that early exposure to airborne PAH and ETS can lead to increased respiratory symptoms and probable asthma by age 12 to 24 months. Interventions to lower the risk of respiratory disease in young children living in the inner city may need to address the importance of multiple environmental exposures.
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ABSTRACT: Although epidemiologic data strongly suggest a role for inhaled environmental pollutants in modulating the susceptibility to respiratory infection in humans, the underlying cellular and molecular mechanisms have not been well studied in experimental systems. The current study assessed the impact of inhaled diesel engine emissions (DEE) on the host response in vivo to a common pediatric respiratory pathogen, respiratory syncytial virus (RSV). Using a relatively resistant mouse model of RSV infection, prior exposure to either 30 microg/m3 particulate matter (PM) or 1,000 microg/m3 PM of inhaled DEE (6 h/d for seven consecutive days) increased lung inflammation to RSV infection as compared with air-exposed RSV-infected C57Bl/6 mice. Inflammatory cells in bronchoalveolar lavage fluid were increased in a dose-dependent manner with regard to the level of DEE exposure, concomitant with increased levels of inflammatory mediators. Lung histology analysis indicated pronounced peribronchial and peribronchiolar inflammation concordant with the level of DEE exposure during infection. Mucous cell metaplasia was markedly increased in the airway epithelium of DEE-exposed mice following RSV infection. Interestingly, both airway and alveolar host defense and immunomodulatory proteins were attenuated during RSV infection by prior DEE exposure. DEE-induced changes in inflammatory and lung epithelial responses to infection were associated with increased RSV gene expression in the lungs following DEE exposure. These findings are consistent with the concept that DEE exposure modulates the lung host defense to respiratory viral infections and may alter the susceptibility to respiratory infections leading to increased lung disease.American Journal of Respiratory Cell and Molecular Biology 05/2003; 28(4):451-63. · 5.13 Impact Factor
Article: Diesel exhaust particulate induces airway hyperresponsiveness in a murine model: essential role of GM-CSF.[show abstract] [hide abstract]
ABSTRACT: Inhaled pollutants were recently shown to be responsible for an increased incidence of airway allergic diseases, including asthma. A common feature of all forms of asthma is airway hyperresponsiveness. Our purpose was to elucidate the effects of diesel exhaust particulate (DEP), one of the most prevalent inhaled pollutants, on airway responsiveness. A/J and C57Bl/6 mice were used; the former are genetically predisposed to be hyperresponsive to acetylcholine, whereas the latter are not. DEP was administered intranasally for 2 weeks, after which pulmonary function was analyzed by whole-body plethysmography. Intranasal administration of DEP increased airway responsiveness to acetylcholine in both A/J and C57Bl/6 mice and induced displacement of ciliated epithelial cells by mucus-secreting Clara cells. The effect was mediated by M(3) muscarinic receptors. Acetylcholine-evoked bronchial constriction was reversed by administration of terbutaline, a beta(2)-adrenergic antagonist, which is also characteristic of human asthma. Intranasal administration of antibody raised against GM-CSF abolished DEP-evoked increases in airway responsiveness and Clara cell hyperplasia. The antibody raised against IL-4 also inhibited DEP-evoked increases in airway responsiveness. However, it was to a lesser extent compared with antibody against GM-CSF. In addition, DEP stimulated GM-CSF messenger RNA expression in the lung. DEP induces airway hyperresponsiveness by stimulating GM-CSF synthesis.Journal of Allergy and Clinical Immunology 12/1999; 104(5):1024-30. · 11.00 Impact Factor
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ABSTRACT: Cigarette smoke contains two very different populations of free radicals, one in the tar and one in the gas phase. The tar phase contains several relatively stable free radicals; we have identified the principal radical as a quinone/hydroquinone (Q/QH2) complex held in the tarry matrix. We suggest that this Q/QH2 polymer is an active redox system that is capable of reducing molecular oxygen to produce superoxide, eventually leading to hydrogen peroxide and hydroxyl radicals. In addition, we have shown that the principal radical in tar reacts with DNA in vitro, possibly by covalent binding. The gas phase of cigarette smoke contains small oxygen- and carbon-centered radicals that are much more reactive than are the tar-phase radicals. These gas-phase radicals do not arise in the flame, but rather are produced in a steady state by the oxidation of NO to NO2, which then reacts with reactive species in smoke such as isoprene. We suggest that these radicals and the metastable products derived from these radical reactions may be responsible for the inactivation of alpha 1-proteinase inhibitor by fresh smoke. Cigarette smoke oxidizes thiols to disulfides; we suggest the active oxidants are NO and NO2. The effects of smoke on lipid peroxidation are complex, and this is discussed. We also discuss the toxicological implications for the radicals in smoke in terms of a number of radical-mediated disease processes, including emphysema and cancer.Environmental Health Perspectives 01/1986; 64:111-26. · 7.04 Impact Factor