Supplementary Material for: A Pilot Study Investigating Clinical Responses and Biological Pathways of Azelastine/Fluticasone in Nonallergic Vasomotor Rhinitis before and after Cold Dry Air Provocation Singh U. Bernstein J.A. Lorentz H. Sadoway T. Nelson V. Patel P. Salapatek A.M. 10.6084/m9.figshare.5285671.v1 https://karger.figshare.com/articles/figure/Supplementary_Material_for_A_Pilot_Study_Investigating_Clinical_Responses_and_Biological_Pathways_of_Azelastine_Fluticasone_in_Nonallergic_Vasomotor_Rhinitis_before_and_after_Cold_Dry_Air_Provocation/5285671 <p><b><i>Background:</i></b> Nonallergic vasomotor rhinitis (NAVMR) has been considered a diagnosis by exclusion due to unknown mechanisms or lack of diagnostic biomarkers. <b><i>Methods:</i></b> 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 (<i>n</i> = 20) or placebo (<i>n</i> = 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. <b><i>Results:</i></b> The minimum cross-sectional area (<i>p</i> < 0.05), cough count (<i>p</i> < 0.05), and substance P (<i>p</i> < 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. <b><i>Conclusions:</i></b> 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.</p> 2017-08-08 14:20:03 Antihistamines Nonallergic vasomotor rhinitis Environmental exposure chamber Azelastine Fluticasone MicroRNA Cold stimulation Nasal lavage Nasal mucosa Substance P