Evaluation of Nasal Mucosal Permeability in Controls and House Dust Mite Allergic Rhinitis Patients

NCT02461797 | Completed

• 1 other identifier: biopsystudy
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Recently, a critical role in the development of allergic rhinitis (AR) has been attributed to the nasal epithelium. The airway epithelium forms a physical barrier, protecting the nasal mucosa and underlying organs from damage from contact with exogenous particles. The nasal epithelial barrier is primarily determined by the integrity of the airway epithelium, in which epithelial cells are connected to each other by complex network structures like tight junctions (TJs), ultimately sealing off the paracellular space. TJs consist of different transmembrane proteins including occludin, tricellulin, the claudin family, and junctional adhesion molecules. TJ form intercellular homodimers/heterodimers between neighboring cells. Scaffold adaptor proteins like cingulin and the zonula occludens family connect the transmembrane proteins to the actin cytoskeleton. Disturbed TJ function can facilitate the entrance of foreign pathogens and antigens into the submucosal layer, giving raise to allergic sensitization via increased access of allergens to the dendritic cells and/or inducing persistent inflammation via activation of mast cells and other inflammatory cells residing in the upper airways. Chronic disorders like allergic asthma, inflammatory bowel disease and atopic dermatitis have been linked to defective or altered TJ function. Recently, an impaired epithelial barrier function was found in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), suggesting changes in TJ arrangement in the nasal cavity. CRSwNP presents a similar inflammation of the sinonasal cavities as found in AR patients, i.e. a Th2 cytokine driven inflammation with tissue eosinophilia. Nevertheless, the role of TJs and its regulation has not been investigated in AR.

Conditions

Allergic Rhinitis

Outcome Measures

Primary Outcomes (2)

• change in Transepithelial electrical resistance (TEER)

  Nasal biopsies will be mounted in modified 3 ml Ussing chambers. Experiments will be performed in open-circuit conditions. Transepithelial electrical resistance (TEER) will be calculated from the voltage deflections induced by bipolar constant-current pulses of 16 mA every 60 s with duration of 200 ms and will be recorded every 30 min over 2 h. The average of all time points of the 2 biopsy samples/patient will be used and will be presented as Ωxcm².

  every 30 min over 2 hours

• change in mucosal permeability

  The paracellular probe, fluorescently labelled dextran 4 kDa (FD4) (2 mg/ml) will be used to determine the mucosal permeability. FD4 will be added to the mucosal compartment and serosal samples will be collected every 30 min over 2 h. The fluorescence level will be measured using a fluorescence reader. The average of time points 60, 90 and 120 min of the 2 biopsy samples/patient will be used to express mucosal permeability.

  every 30 min over 2 h

Study Arms (3)

healthy controls

OTHER

biopsy of nasal mucosa healthy controls

Other: healthy controls

AR patients with use of nasal corticoid spray

OTHER

biopsy of nasal mucosa allergic rhinitis to house dust mite with nasal corticosteroid spray

Other: AR patients with use of nasal corticoid spray

AR patients without medication

OTHER

biopsy of nasal mucosa allergic rhinitis to house dust mite without any use of medication for symptom control

Other: AR patients without medication

Interventions

healthy controls OTHER

biopsy of nasal mucosa for healthy controls

healthy controls

AR patients without medication OTHER

biopsy of nasal mucosa for allergic rhinitis patients without allergy medication

AR patients without medication

AR patients with use of nasal corticoid spray OTHER

biopsy of nasal mucosa for allergic rhinitis patients with use of nasal corticoid spray

AR patients with use of nasal corticoid spray

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with an ARIA-based diagnosis of persistent moderate/severe AR (≥ 2 nasal symptoms suggestive of allergic rhinitis and positive skin prick tests to HDM (HAL Allergy, Leiden, The Netherlands), and with VAS score for total nasal symptoms of more than 5
• Age \> 18 and \< 60 years.
• Possibility to give reliable information and written informed consent
• For AR group with nasal corticosteroid spray: Patients that use nasal corticosteroid spray for at least three weeks prior to the study, with a minimum application of two puffs per nostril once a day.

You may not qualify if:

• No common cold in the last 4 weeks
• Patients on prolonged use of decongestive nose sprays, suffering from so-called rhinitis medicamentosa
• A. For healthy controls and AR without use of nasal spray: Patients using other nasal or oral medication affecting nasal function, like nasal corticosteroids, anticholinergics, cromoglycates, leukotriene antagonists, ACE inhibitors less than 4 weeks before start of the study.
• B. For AR group with use of nasal corticosteroid spray: Patients using other nasal or oral medication affecting nasal function, like anticholinergics, cromoglycates, leukotriene antagonists, ACE inhibitors less than 4 weeks before start of the study.
• Nasal endoscopic evidence of rhinosinusitis w/wo NP or structural abnormalities such as clinically relevant septal deviation (septum reaching concha inferior or lateral nasal wall) or septal perforation
• Patients on immunotherapy (IT) for house dust mite (HDM) or with history of IT for HDM
• Patient with a psychiatric, addictive, or any disorder of which the investigators feel that this may compromise the ability to give truly informed consent for participation in this study or provide reliable information on the questionnaire
• Patients being enrolled in other clinical trials
• Pregnancy or breastfeeding
• Malignancies or severe comorbidity
• Contra-indication for local anesthesia with cocaine 5%
• Smoking
• Use of anticoagulation medication
• Absence of nasal symptoms
• Negative history of respiratory allergy

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

ORL

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Related Publications (1)

• Steelant B, Farre R, Wawrzyniak P, Belmans J, Dekimpe E, Vanheel H, Van Gerven L, Kortekaas Krohn I, Bullens DMA, Ceuppens JL, Akdis CA, Boeckxstaens G, Seys SF, Hellings PW. Impaired barrier function in patients with house dust mite-induced allergic rhinitis is accompanied by decreased occludin and zonula occludens-1 expression. J Allergy Clin Immunol. 2016 Apr;137(4):1043-1053.e5. doi: 10.1016/j.jaci.2015.10.050. Epub 2016 Feb 2.

  PMID: 26846377 DERIVED

MeSH Terms

Conditions

Rhinitis, Allergic

Interventions

Dosage Forms

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques

Study Officials

• Peter Hellings, MD PhD

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2015
• First Posted: June 3, 2015
• Study Start: August 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: June 3, 2015

Record last verified: 2015-04

Locations

BE (1)