Histopathological alterations in airways associated with physiological changes in airway allergy phenotypes

Introduction Ovalbumin sensitization in guinea pigs induces diverse allergic responses. The asthma model exhibits airway obstruction, hyperresponsiveness, fibrosis, and reduced airway caliber, associated with elevated β1 integrin subunit expression. In contrast, the non-responder (NR) phenotype shows no obstruction or hyperresponsiveness under chronic antigen exposure. It is likely that NR guinea pigs lack increased β1 integrin subunit expression due to the absence of a typical asthma response. This study aimed to compare the histopathological and pathophysiological characteristics between the asthma model and NR phenotype in ovalbumin-sensitized guinea pigs to understand the differences in airway β1 integrin subunit expression. Methods Guinea pigs were sensitized and challenged with ovalbumin nine times at 10-day intervals. The animals were then categorized into either the asthma model or the NR group. After the ninth antigen challenge, baseline obstruction, antigen-induced airway hyperresponsiveness, and immunohistopathological changes were evaluated. Results Airway hyperresponsiveness to histamine was only observed in the asthma model. Both asthma and NR groups had increased basal obstruction and accumulation of the integrin β1 subunit in the subepithelial region compared to controls, with a greater increase in NR. Integrin β1 subunit expression in airway smooth muscle was higher in the asthma model than in NR. The subepithelial area was enlarged in both asthma and NR groups compared to controls. Basal caliber reduction was correlated with fibrosis and integrin β1 subunit in the subepithelial region. Discussion Fibrosis and deposition of the β1 integrin subunit in the subepithelial region are associated with baseline obstruction but not with the magnitude of airway obstruction or hyperresponsiveness. In the asthma model, the airway smooth muscle phenotype, characterized by high β1 integrin subunit, could influence contraction and hyperreactivity.