Nasal hyperreactivity in allergic rhinitis and chronic rhinosinusitis with polyps: a role for neuronal pathways

BACKGROUND: Nasal hyperreactivity (NHR) is prevalent in all chronic upper airway inflammatory phenotypes, including allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP). Although NHR in patients with non-allergic rhinitis is mediated by neuronal pathways, AR and CRSwNP are mainly characterized by type 2 inflammation. METHODS: Eighteen healthy controls and 45 patients with symptomatic AR/CRSwNP underwent a cold, dry air (CDA) provocation test for objective diagnosis of NHR. Before and after, questionnaires were filled out and nasal secretions and biopsies were collected. Markers for neurogenic inflammation (substance P, calcitonin gene-related peptide, neurokinin A), epithelial activation (IL-33), and histamine were measured in secretions by ELISA; and expression of neuronal markers PGP9.5, TRPV1, and TRPM8 was studied in biopsies by RT-q-PCR. Effects of histamine on TRPV1/A1 were studied with Ca2+-imaging using murine trigeminal neurons. RESULTS: CDA-provocation reduced peak nasal inspiratory flow (PNIF) of patients with subjective NHR but not of non-NHR controls/ patients (p