Applicability and Reproducibility of Biomarkers for the Evaluation of Anti. Inflammatory Therapy in Allergic Rhinitis

Background: We aimed to study the reproducibility of several biomarkers of allergic rhinitis to investigate their potential as outcome measures in clinical intervention trials. Furthermore, we investigated the kinetics of the biomarkers studied in nasal lavage and brush material following a placebo-controlled nasal allergen challenge. Methods: We performed a skin prick test and measured serum specific immunoglobulin (Ig) E levels and inflammatory biomarkers in nasal lavage and brush material in 20 patients with allergic rhinitis on 2 separate days (washout, 14-21 days). The patients were then randomly assigned to undergo an intranasal challenge with a relevant allergen (n = 10) or diluent (n =10) in order to assess the kinetics of several biomarkers of allergic airway inflammation in nasal lavage and brush samples. Results: Baseline serum IgE levels and skin wheal sizes were highly reproducible measurements, with a coefficient of variation (CV) of 13.4% and 18.2%, respectively. This was not the case with the majority of inflammatory biomarkers, whose CV varied considerably (range, 6.1%-224.1%). The nasal allergen challenge induced an increase in composite symptom scores in all patients. Compared to placebo, tryptase (P=.004), eosinophilic cationic protein (ECP) (P=.03) and (alpha 2-macroglobulin (P=.002) were increased in nasal lavage at 20 minutes post allergen. Nasal lavage ECP levels and nasal brush eosinophils were still significantly increased at 7 hours (P=.03 and P=.04), but all statistical significance had been lost at 24 hours post challenge. Conclusion: Serum specific IgE assays and skin prick tests exhibited good reproducibility in patients with clinically stable allergic rhinitis. M were also able to investigate the kinetics of allergen-incluced upper airway inflammatory markers in nasal lavage and brush material. Hence, nasal allergen challenge, when used in combination with nasal lavage and brush sampling, is a suitable research tool for early drug development