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Allergic sensitization increases airway reactivity in guinea pigs with respiratory syncytial virus bronchiolitis
P J Robinson1, R G Hegele, R R Schellenberg
1University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, Canada.
Insights
Allergic sensitization exacerbates respiratory syncytial virus (RSV) bronchiolitis in guinea pigs, increasing airway inflammation and responsiveness. This suggests allergies may worsen RSV severity in children.
Area of Science:
- Immunology
- Pediatric Respiratory Medicine
- Virology
Background:
- Respiratory syncytial virus (RSV) is a common cause of acute bronchiolitis in infants and is linked to recurrent wheezing and asthma.
- A subset of children exposed to RSV develops severe illness, indicating potential susceptibility factors.
- Allergic diathesis is hypothesized to predispose children to subsequent airway diseases.
Purpose of the Study:
- To investigate if a pre-existing allergic state potentiates airway hyperresponsiveness and inflammation during acute RSV bronchiolitis.
- To determine the impact of allergic sensitization on the physiological and structural changes induced by RSV infection in a guinea pig model.
Main Methods:
- Forty guinea pigs were divided into four groups: non-sensitized/non-infected, sensitized/non-infected, non-sensitized/infected, and sensitized/infected.
- Sensitization involved repeated ovalbumin aerosol exposure; infection was induced by human RSV inoculation.
- Airway responsiveness to acetylcholine was measured, and lung tissues were histologically analyzed for inflammation.
Main Results:
- Animals with prior allergic sensitization and RSV infection exhibited significantly greater increases in pulmonary resistance to acetylcholine compared to RSV or ovalbumin alone.
- Histological examination of these animals revealed combined pathologies, including airway epithelial necrosis, inflammatory cell infiltration, edema, lymphoid tissue hyperplasia, and goblet cell metaplasia.
Conclusions:
- Pre-existing allergic sensitization amplifies the physiological and structural damage caused by acute RSV bronchiolitis.
- The findings suggest that an allergic predisposition may heighten the severity of RSV infections in pediatric populations.
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.
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