Epidemiologic studies have demonstrated that increased levels of particulate matter (PM) air pollution in the ambient air are strongly correlated with increased morbidity and mortality in exposed populations, chiefly in individuals with pre-existing cardiopulmonary disease. Particle size contributes to these adverse health associations, and PM with an aerodynamic diameter of < 1.0 um (ultra-fine PM) is thought to be the most toxic. Increased incidence and severity of symptoms associated with asthma and lower respiratory infections, such as wheezing, bronchoconstriction, and cough have been reported in children and older adults following PM excursions. Respiratory syncytial virus (RSV) causes worldwide epidemics of respiratory disease each year, and commonly afflicts infants (6 months-1 year old), immuno-compromised individuals, and older adults (60+ years old). Severe RSV is strongly associated with wheezing, childhood asthma, and repeated episodes of bronchospastic bronchitis, which can continue into adulthood. The primary aim of this proposal is to examine the effect of ultra-fine PM on host defense to RSV infection. The overall hypothesis of this proposal is that individuals with pre-existing respiratory viral infection exposed to ultra fine PM have decreased host defenses and subsequent exacerbation of viral infection, including elevated pulmonary inflammation, lung function decrements, and reduced ability to clear the virus. A mouse model of RSV infection will be used to 1) Determine the effects of ultra-fine (UF) carbon black (CB) particles on the course of RSV infection in the lung and on pulmonary inflammation and lung function; 2) Determine the effect of UF CB exposure on immune cytokine expression by RSV infected bronchial epithelial cells; 3) Determine the role of PM-induced cytokine production by RSV-infected bronchial epithelial cells in host defense to RSV. These studies will address for the first time the effects of ultra-fine PM on pulmonary host defense to a viral infection in vivo, and will provide mechanistic information regarding the pathophysiology of viral disease following PM exposure.
