Local and systemic effects of cat allergen nasal provocation

BackgroundCat allergen is widely distributed in homes and schools; allergic sensitization is common. ObjectiveTo develop a model of cat allergen nasal challenge to establish dose-response and time-course characteristics and investigate local and systemic biomarkers of allergic inflammation. MethodsNineteen cat-allergic individuals underwent titrated nasal challenge, range 0.243 to 14.6g/mL Fel d1, and matched diluent-only provocation. Clinical response to 8h was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Nasal fluid was collected using polyurethane sponges and analysed by ImmunoCAP and multiplex assays. Whole blood flow cytometry for basophil surface CD63, CD107a, and CD203c was carried out at baseline and 6h post-challenge. ResultsA dose-response to allergen was seen in symptom scores and PNIF, maximal at 10000 BU/mL (4.87g/mL Fel d1), P<0.0001 vs. diluent. Nasal fluid tryptase was elevated at 5min after challenge (P<0.05 vs. diluent); eotaxin, IL-4, -5, -9, and -13 were increased at 8h (P<0.05 to P<0.0001 vs. diluent); TSLP was undetectable; IL-10, IL-17A, and IL-33 were unchanged compared to diluent challenge. Nasal fluid IL-5 and IL-13 correlated inversely with PNIF after challenge (IL-5, r=-0.79, P<0.0001; IL-13, r=-0.60, P=0.006). Surface expression of CD63 and CD107a was greater at 6h than at baseline, both in the presence (both P<0.05) and absence (CD63, P<0.01; CD107a, P<0.05) of in vitro allergen stimulation; no changes were seen on diluent challenge day. ConclusionsCat allergen nasal challenge produces local and systemic Th2-driven inflammatory responses and has potential as a surrogate outcome measure in clinical trials.