Correlates of cockroach nasal challenge responsiveness among sensitized urban children with asthma

Background: The nasal allergen challenge (NAC) is a tool for evaluating upper airway allergic responses. In the CRITICAL study, NAC with cockroach allergen was used to confirm clinical reactivity in sensitized individuals from urban environments before enrollment onto a subcutaneous immunotherapy trial. Objective: Immunologic and transcriptomic predictors of NAC responsiveness were identified. Methods: NAC was performed in 103 participants. Clinical responses were assessed by the Total Nasal Symptom Score (TNSS) and sneeze score (TSNEEZ), which scale positively with symptom severity. Baseline immunologic markers—including skin prick test wheal size, cockroach-specific IgE, IgG, and IgG₄, and T-cell responses were evaluated. Nasal lavage samples were analyzed for gene expression modules. Clinical trial registration: ClinicalTrials.gov NCT03541187. Results: Larger skin prick test wheal sizes were significantly associated with positive NAC outcomes (2.2 mm larger than negative NAC) and lower reactive doses (hazard ratio = 1.10). Cockroach (i6 extract)-specific IgE levels were inversely correlated with TNSS, while levels of IgE, IgG, and IgG₄ specific to the extract used for therapy showed no association. Higher IL-10 T-cell responses were observed in those without reaction, while Bla g 5 and Bla g 9 dominance correlated negatively with TNSS and positively with TSNEEZ, respectively. Transcriptomic analysis revealed that higher expression of eosinophil- and neutrophil-associated modules and lower expression of type 1 interferon, macrophage, and epithelial barrier modules were linked to positive NAC responses. Conclusion: NAC responsiveness to cockroach extract is influenced by skin test reactivity, T- and B-cell regulation, and nasal gene expression. These findings highlight the role of both adaptive and innate immunity in allergic airway responses and suggest potential biomarkers for clinical reactivity.