Mediators in Nasal Hyperreactivity in Allergic Rhinitis and Chronic Rhinosinusitis

Identification of Mediators Associated With Presence of Nasal Hyperreactivity in Allergic Rhinitis and Chronic Rhinosinusitis

Rhinitis, or inflammation of the nasal mucosa, can present with nasal obstruction, nasal discharge, itch or sneezing. If the sinusal mucosa is involved as well, it is called rhinosinusitis and facial pain or loss of smell is possible. Several causes are known, such as an underlying allergy ("allergic rhinitis", AR). If at least 2 symptoms are present for at least 12 weeks, it is called "chronic rhinosinusitis" (CRS).

Up to 2/3 of the AR and CRS patients have symptoms upon exposure to triggers such as sudden temperature changes, smoke, fragrances… a phenomenon called "nasal hyperreactivity" (NHR). It is currently not clear why some patients suffer NHR while others do not.

In this study, the investigators want to identify the mediators associated with NHR in patients with allergic rhinitis, chronic rhinosinusitis and healthy control subjects.To do so, participants will be provoked with cold, dry air in order to objectively diagnose NHR. Before and after provocation, the peak nasal inspiratory flow will be measured and samples will be collected (nasal secretions, biopsies).

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Rhinosinusitis With Nasal Polyps; Hyperactivity; Allergic Rhinitis Due to House Dust Mite
• Intervention / Treatment: Diagnostic test: Cold, dry air

Detailed Description

Patients with perennial allergic rhinitis, chronic rhinosinusitis with nasal polyps and healthy control subjects will be recruited. At baseline, nasal secretions and mucosal biopsies will be collected. After 3 weeks, participants will be provoked with cold, dry air, and samples will be harvested again. A decrease in the peak nasal inspiratory flow of >20% will be used as a cutoff to define nasal hyperreactivity.

Nasal secretions will be analysed for various mediators using a multiplex assay. The biopsies will be used for RT-q-PCR and immunohistochemistry of various transient receptor potential (TRP) channels.

• Study Type: Interventional
• Enrollment (Anticipated): 144
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • KULeuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-65 years
• positive skin prick test for house dust mite (for allergic rhinitis group), presence of nasal polyps (for chronic rhinosinusitis with nasal polyps group)
• VAS-score >5 for rhino(sinus)itis symptoms

Exclusion Criteria:

• positive skin prick test (for chronic rhinosinusitis with nasal polyps group and healthy control group), presence of nasal polyps (for allergic rhinitis group and healthy control group)
• Acute rhinitis in the past 2 weeks
• (History of) immunotherapy for house dust mite
• Relevant anatomic abnormalities
• Participation in another clinical trial at the moment of this study.
• Use of anticoagulants (apart from acetylsalicylic acid)
• Use of tricyclic antidepressants
• History of intranasal drug usage in the past 12 months
• Pregnancy or breastfeeding
• Malignancy or severe comorbidity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Provocation with cold air; Participants will be exposed to cold dry air for 15 minutes	Diagnostic test: Cold, dry air; Participants will be exposed to cold (<-10°C, <10% relative humidity), dry air for 15 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective nasal hyperreactivity	The peak nasal inspiratory flow will be measured before and after provocation with cold, dry air. A decrease of >20% will be used as a cutoff to objectively diagnose nasal hyperreactivity.	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of histamine in nasal secretions	In nasal secretions, the investigators will measure the levels of histamine by using a multiplex assay. They will do so at baseline and after cold dry air provocation test.	3 weeks
Levels of tryptase in nasal secretions	In nasal secretions, the investigators will measure the levels of tryptase by using a multiplex assay. They will do so at baseline and after cold dry air provocation test.	3 weeks
Levels of substance P in nasal secretions	In nasal secretions, the investigators will measure the levels of substance P by using a multiplex assay. They will do so at baseline and after cold dry air provocation test.	3 weeks
Levels of neurokinin A in nasal secretions	In nasal secretions, the investigators will measure the levels of neurokinin A by using a multiplex assay. They will do so at baseline and after cold dry air provocation test.	3 weeks
Levels of neurokinin B in nasal secretions	In nasal secretions, the investigators will measure the levels of neurokinin B by using a multiplex assay. They will do so at baseline and after cold dry air provocation test.	3 weeks
Levels of calcitonin gene-related peptide in nasal secretions	In nasal secretions, the investigators will measure the levels of calcitonin gene-related peptide by using a multiplex assay. They will do so at baseline and after cold dry air provocation test.	3 weeks
Levels of interleukin (IL) 4 in nasal secretions	In nasal secretions, the investigators will measure the levels of IL-4 by using a multiplex assay. They will do so at baseline and after cold dry air provocation test.	3 weeks
Levels of IL-5 in nasal secretions	In nasal secretions, the investigators will measure the levels of IL-5 by using a multiplex assay. They will do so at baseline and after cold dry air provocation test.	3 weeks
Levels of IL-13 in nasal secretions	In nasal secretions, the investigators will measure the levels of IL-13 by using a multiplex assay. They will do so at baseline and after cold dry air provocation test.	3 weeks
Presence of TRP Vanilloid 1 in nasal mucosa.	The investigators will determine the presence of TRP vanilloid 1 on nasal mucosal biopsies at baseline and after provocation with cold, dry air by using RT-q-PCR and immunohistochemistry.	3 weeks
Presence of TRP Ankyrin 1 in nasal mucosa.	The investigators will determine the presence of TRP Ankyrin 1 on nasal mucosal biopsies at baseline and after provocation with cold, dry air by using RT-q-PCR and immunohistochemistry.	3 weeks
Presence of TRP Melastatin 8 in nasal mucosa.	The investigators will determine the presence of TRP Melastatin 8 on nasal mucosal biopsies at baseline and after provocation with cold, dry air by using RT-q-PCR and immunohistochemistry.	3 weeks

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: February 21, 2020
• First Submitted That Met QC Criteria: February 25, 2020
• First Posted (Actual): February 27, 2020

Study Record Updates

• Last Update Posted (Actual): May 25, 2022
• Last Update Submitted That Met QC Criteria: May 24, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Respiratory Hypersensitivity; Hypersensitivity; Paranasal Sinus Diseases; Nose Diseases; Polyps; Sinusitis; Rhinitis; Rhinitis, Allergic; Nasal Polyps
• Other Study ID Numbers: S63139

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No