Viral bronchiolitis and pneumonia are major causes of morbidity and mortality in infants and children, and are often caused by respiratory syncytial virus (RSV) or parainfluenza virus type 3 (PIV3), which may be responsible for $1 billion of medical costs and 10,000 deaths annually in the United States. There is no licensed vaccine for either virus, and the only licensed drug, Ribavirin(TM), is of limited efficacy. In Phase I activities we showed that topical antibody caused clearance of virus without decreasing lesions. Triamcinolone acetonide alone cleared the lung lesions, but resulted in a 10-fold increase of virus, wile both together sterilized the lung and reversed lesions. In the Phase II work, we will test four glucocorticosteroids with enhanced mucosal and decreased systemic activity. We will then examine the potential breadth of this therapeutic approach by treating cotton rats with established RSV (enveloped, RNA) and adenovirus type 5 (non-enveloped, DNA) viral pneumonia. The mechanism of action of glucocorticosteroids in reversing the lesions of viral pneumonia will be assessed in a mouse model of adenovirus pneumonia. We anticipate initiating clinical trials immediately upon completion of the proposed Phase II workscope.
: Presently there is no effective therapy for established viral bronchiolitis and pneumonia. Topical therapy with a combination of antiviral antibody and glucocorticosteroid was shown to be effective and safe in Phase I work, and we will extend this to two additional viral pneumonias in Phase II.
