Allergic sensitization increases airway reactivity in guinea pigs with respiratory syncytial virus bronchiolitis

Abstract

Background: Respiratory syncytial virus (RSV) causes acute bronchiolitis in children and has been implicated in the pathogenesis of recurrent wheezing and asthma. However, few children exposed to RSV experience acute bronchiolitis or its sequelae, suggesting a subgroup of susceptible children. An allergic diathesis may predispose children to subsequent airway disease. Objective: This study was carried out to determine whether a preexisting allergic state, induced by repeated inhalational exposures to ovalbumin, potentiates nonspecific airway responsiveness to acetylcholine and increases airway inflammation during acute RSV bronchiolitis in guinea pigs. Methods: Forty guinea pigs were randomized into four groups: nonsensitized, noninfected (ovalbumin–, RSV–); sensitized, noninfected (ovalbumin+, RSV–); nonsensitized, infected (ovalbumin–, RSV+); sensitized, infected (ovalbumin+, RSV+). Depending on grouping, animals were exposed to either repeated aerosols of ovalbumin or saline solution and were subsequently inoculated with either human RSV or uninfected culture medium. Six days after inoculation, animals underwent acetylcholine challenge, and lung specimens were prepared for histologic scoring of airway inflammation. Results: Maximal increases in pulmonary resistance (centimeters of water per milliliter per second) to acetylcholine were greater for RSV alone (12.4 ± 3.9) and ovalbumin alone (13.7 ± 3.9) compared with controls (4.3 ± 1.1), but significantly greater increases occurred in ovalbumin+, RSV+ animals (34.0 ± 11.0). These ovalbumin+, RSV+ animals demonstrated the combined histologic changes noted with RSV alone and ovalbumin alone including airway epithelial necrosis, mononuclear and granulocyte infiltrates, airway wall edema, hyperplasia of bronchus-associated lymphoid tissue, and goblet cell metaplasia. Conclusion: Prior allergic sensitization potentiates the physiologic and structural changes induced by acute RSV bronchiolitis. These results suggest that an allergic diathesis may increase the severity of RSV infections in children. (J Allergy Clin Immunol;100:492-8.)