Recent studies have revealed that the human and nonrodent mammalian airway mucosa contains an oxidative host defense system. This three-component system consists of the hydrogen peroxide (H 2 O 2 )-producing enzymes dual oxidase (Duox)1 and Duox2, thiocyanate (SCN 2 ), and secreted lactoperoxidase (LPO
Clinical RelevanceThis study demonstrates that enhancement of dual oxidase/ lactoperoxidase oxidative responses by potassium iodide administration reduces respiratory syncytial virus disease severity in a lamb model that has much similarity to disease condition in human infants. The work is readily translational.Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection in infants and young children and is a leading cause of infantile bronchiolitis worldwide (1, 2). In industrialized countries, human RSV (hRSV) accounts for up to 70% of hospitalized bronchiolitis cases (1-3). Although the antiviral drugs palivizumab and ribavirin have virucidal activity against RSV in vivo, there are no fully satisfactory therapeutic regimens or vaccines (4-6). It is estimated that 3% of RSV cases in the United States and 10% of cases worldwide result in hospitalization; the reported number of new cases of lower respiratory infection due to RSV in children under 5 years of age in 2005 was 33.8 million (7,8). Thus, there is a need for new therapies for RSV infection.The host defense activity of the airway epithelium is critical for the continuous inactivation and removal of inhaled microbes from the respiratory tract. Although the role of mucociliary clearance and epithelial host defense proteins and peptidesin lung immunity is well established, the recognition that airway epithelial cells express an oxidative