Hyperoxia-induced airway remodeling in immature rats: Correlation with airway responsiveness

We recently found that exposure of 21-day-old rats to hyperoxia (>95% O₂ for 8 days) significantly increased in vivo airway cholinergic responsiveness and that O₂ exposure also increased airway epithelial and smooth muscle layer thicknesses in a separate cohort of animals. There was substantial variation in the magnitude of both the functional and structural responses to hyperoxia. The present study was designed to test whether the magnitude of O₂-induced airway remodeling could account for individual differences in airway responsiveness after O₂ exposure, as well as for the difference in responsiveness between air- and O₂-exposed animals. We assessed in vivo airway responsiveness to aerosolized acetylcholine (ACh) and airway architecture in 14 O₂- and 5 air-exposed, immature rats. Total respiratory system resistance was determined using a plethysmographic method. The mean thicknesses and fractional areas of the airway epithelial and smooth muscle layers were determined by contour tracing using a digitizing pad and microcomputer. Both the small (circumference < 1,000 μm) and central (circumference 1,000 to 4,000 μm) airways were studied. For O₂-exposed rats, individual values of EC₂₀₀ ACh correlated negatively with small airway smooth muscle layer thickness (r = -0.59, p < 0.05; ANOVA), small airway smooth muscle layer fractional area (r = -0.75, p < 0.01), small airway epithelial thickness (r = -0.54, p < 0.05), small airway epithelial fractional area (r = -0.69, p < 0.01), and central airway smooth muscle layer thickness (r = -0.53, p < 0.05). When both air- and O₂-exposed animals were considered, EC₂₀₀ ACh correlated negatively with all eight parameters of airway layer thickness and fractional area. These correlations are consistent with the notion that, in immature rats, airway wall layer thickness in part determines airway responsiveness.