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