Subacute effects of respiratory syncytial virus infection on lung function in lambs

We examined the effects of ovine respiratory syncytial virus (RSV) infection on lung mechanics, lung histology, and airway reactivity in lambs. Nine lambs were inoculated with ovine RSV and seven control lambs with normal saline or viral media. Serum neutralization titers were obtained prior to and 3 weeks post-inoculation (PI). Open lung biopsies were performed 1 and 3 weeks PI. Lung mechanics including dynamic compliance (Cdyn), resistance of the lung (RL), and functional residual capacity (FRC) were measured 2 and 6 weeks PI using a plethysmograph. Airway reactivity to aerosolized carbachol, citric acid, and histamine was determined 2 and 6 weeks PI. Most RSV and control lambs were asymptomatic after inoculation. Control lambs had significantly greater average daily weight gain by the third week after inoculation. Seven RSV lambs tested had a fourfold or greater rise in serum neutralization titers, while two control lambs had a fourfold increase. At 2 weeks PI, RSV lambs had significantly lower FRC and higher RL. At 6 weeks RL remained significantly elevated in the RSV lambs. Airway reactivity was not increased in the RSV group. This animal model is useful for studying the effects of RSV infection on lung growth and lung function over time.