Increased airway reactivity in human RSV bronchiolitis in the guinea pig is not due to increased wall thickness

Bronchiolitis due to the respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in the first year of life. It has been suggested that RSV infection may cause subsequent asthma, but a mechanism for this relationship has not been demonstrated. Studies examining the presence of airway reactivity in infants with RSV bronchiolitis are limited by our inability to administer provocative agents such as histamine to such ill infants. This makes a small animal model of this condition a useful tool in which to investigate the pathophysiology of RSV bronchiolitis. We, therefore, evaluated airway responsiveness in vivo and airway morphometric changes in 20 guinea pigs infected by instilling 4,000 plaque-forming units of human RSV virus onto the nasal mucosa under halothane anaesthesia, while 20 control animals received an equivalent volume of sterile cell culture medium. Six days following instillation, 10 infected animals and 10 controls underwent measurements of pulmonary resistance (RL) following increasing doses of inhaled acetylcholine (Ach). These guinea pigs were then sacrificed and the lung and heart removed en bloc for morphometric studies. There were no differences in baseline RL between infected and control groups. At Ach concentrations of 15 and 50 mg/mL, RSV-infected animals had higher RL values than controls (P < 0.05). Fourteen days following RSV instillation no differences in Ach responses were detected in the 10 infected and 10 control animals studied. To determine whether the increase in airway reactivity 6 days after RSV instillation was associated with changes in airway wall morphometry, 125 airways (69 infected, 56 control) were studied. Analysis of wall area, wall area internal to the smooth muscle, or smooth muscle area standardized by the internal perimeter of the airway showed no significant differences between the infected and control airways. These results demonstrated that airway hyperresponsiveness correlated with previously reported histologic changes of acute bronchiolitis 6 days after guinea pigs were infected with human RSV, but neither hyperresponsiveness nor histological changes persisted following resolution of the primary infection. The increased airway reactivity and the previously observed histological changes seen at day 6 following infection was not due to increased airway wall thickness.