A Pilot Study Investigating Clinical Responses and Biological Pathways of Azelastine/Fluticasone in Nonallergic Vasomotor Rhinitis before and after Cold Dry Air Provocation

Int Arch Allergy Immunol. 2017;173(3):153-164. doi: 10.1159/000478698. Epub 2017 Aug 9.


Background: Nonallergic vasomotor rhinitis (NAVMR) has been considered a diagnosis by exclusion due to unknown mechanisms or lack of diagnostic biomarkers.

Methods: To determine clinical responses and biological pathways in NAVMR subjects challenged to cold dry air (CDA) in an environmental exposure chamber (EEC) pre- and posttreatment with azelastine/fluticasone (AzeFlu), 30 NAVMR subjects, prescreened for CDA-induced symptoms (approx. 14°C, <15% relative humidity, ×1 h) were randomized to treatment with AzeFlu (n = 20) or placebo (n = 10) for 2 weeks. Total nasal symptoms scores, minimum cross-sectional area, cough, and conjunctival redness were recorded at visit 1 (pretreatment) and visit 2 (posttreatment) before, during, and after CDA challenge. At both visits, nasal lavage fluid (NLF) and nasal scrapings (NS) were collected pre- and post-CDA challenge. Substance P, neurokinin-A, and calcitonin gene-related peptide concentrations in NLF were analyzed pre- and postchallenge at each visit. Their relationship with CDA-induced symptoms was determined by statistical analysis. MicroRNA sequencing from NS determined differentially expressed miRNA between the treatment groups post-CDA challenge at each visit.

Results: The minimum cross-sectional area (p < 0.05), cough count (p < 0.05), and substance P (p < 0.01) improved posttreatment with AzeFlu versus placebo. Gene targets for differentially expressed miRNAs at visit 1 were enriched for biological pathways regulating epithelial ciliogenesis and cell integrity that were modified in the AzeFlu-treated group versus placebo posttreatment.

Conclusions: This study demonstrated the feasibility of an EEC model to investigate CDA-induced clinical responses and pathobiology in NAVMR subjects pre- and posttreatment with AzeFlu. NAVMR disease mechanisms for other nonallergic triggers can be investigated similarly.

Keywords: Antihistamines; Azelastine; Cold stimulation; Environmental exposure chamber; Fluticasone; MicroRNA; Nasal lavage; Nasal mucosa; Nonallergic vasomotor rhinitis; Substance P.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Air
  • Anti-Inflammatory Agents / therapeutic use*
  • Bronchial Provocation Tests*
  • Cold Temperature
  • Cough / drug therapy*
  • Cough / metabolism
  • Female
  • Fluticasone / therapeutic use*
  • Humans
  • Male
  • MicroRNAs / metabolism
  • Middle Aged
  • Nasal Mucosa / metabolism
  • Phthalazines / therapeutic use*
  • Pilot Projects
  • Rhinitis, Vasomotor / drug therapy*
  • Rhinitis, Vasomotor / metabolism


  • Anti-Inflammatory Agents
  • MicroRNAs
  • Phthalazines
  • Fluticasone
  • azelastine