Components of airway hyperresponsiveness and their associations with inflammation and remodeling in mice

BackgroundPathologic changes, including inflammation and remodeling, occur in the asthmatic airway. However, their relative contribution to the components of airway hyperresponsiveness (AHR) remains unclear.ObjectiveAttempting to delineate AHR into discrete immune-mediated and structural remodeling components, we performed a detailed time course of the development, progression, and persistence of maximal respiratory system resistance, airway reactivity, and airway sensitivity.MethodsMice exposed to increasing durations of persistent allergen were assessed for airway function, morphometry, and inflammation.ResultsAllergen exposure resulted in increases for all indices of AHR that persisted for at least 4 weeks after chronic allergen exposure (P < .01 for all values). Early increases in AHR were associated with increases in immune-mediated events, including airway eosinophils (P < .01), whereas sustained AHR was associated with structural remodeling events. Increased maximal respiratory system resistance, evident by 6 weeks postallergen and persisting for at least 4 weeks after 8 weeks of chronic exposure, was associated with an increase in collagen deposition (P < .01). Increased airway reactivity and sensitivity, each evident by 1 week after allergen and persisting for at least 4 weeks after 8 weeks of chronic exposure, were associated with an increase in airway smooth muscle area (P < .01).ConclusionOur novel observation of distinct temporal relationships in the development, progression, and persistence of the individual indices of AHR supports our hypothesis that multiple underlying factors contribute to airway dysfunction.Clinical implicationsThese findings illustrate the importance of clearly addressing specific components of airway dysfunction to provide greater insight into specific pathophysiologic mechanisms in airway disease.