Dose-Response Ratio (RDR) Outperforms -lgPC100 in Predicting Airway Hyperresponsiveness: Correlations with Lung Function and Mucus Pathology in Murine Asthma Models

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Background: Assessing airway hyperresponsiveness(AHR) in asthma models often relies on -lgPC100(Acetylcholine chloride(Ach) concentration doubling baseline airway resistance(RL)), which has limitations. Objective: This study aimed to evaluate the predictive performance of RDR(peak RL increase/cumulative Ach dose) and -lgPC100 for asthma and their associations with lung function, inflammatory cytokine, and mucus pathology. Methods: 31 mice were divided into control and asthma groups, with the latter further classified into mild and severe inflammation subgroups based on pathology scores(PS). Cytokines(IL-1β/TNF-α/IFN-γ/IL-2/IL-6/IL-4/IL-5/IL-10/KC/IL-12p70) were measured, and airway pathology was evaluated via HE/PAS staining. ROC analysis compared the predictive performance of RDR and -lgPC100 for asthma, Spearman’s correlation examined their links to lung function, cytokines, and PS. Results: Asthma mice showed lower -lgPC100 (p=0.04) and higher RDR (p<0.01) vs. controls. In mild inflammation group, both -lgPC100(p=0.05) and RDR(p=0.03) differed from controls, while in severe inflammation group, only RDR was elevated(p=0.04), though less than in mild group. ROC analysis indicated that RDR(AUC=0.74, 0.55–0.88) outperformed -lgPC100(AUC=0.57, 0.38–0.74). RDR was negatively correlated with -lgPC100(r=-0.53, p<0.01) and FEV25/FVC(r=-0.37, p=0.04) and positively correlated with small airway PAS staining scores(r=0.37, p=0.04). Neither parameter showed correlations with cytokines. Conclusion: RDR was closely associated with impaired lung function and small airway mucus pathology. RDR is an effective indicator for assessing AHR.

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