Characterisation of the Nasal Microbiome in Patients With N-ERD (MicroNERD)

Characterisation of the Nasal Microbiome in Patients Suffering From Non-steroidal Anti-inflammatory Drugs-exacerbated Respiratory Disease (N-ERD) - a Pilot Study

Chronic rhinosinusitis (CRS) with (w) and without (s) nasal polyps (NP) in its different shapes is currently affecting up to 16% of the total population of the United States and around 11% of the population in Europe. It may also be associated with a hypersensitivity to non-steroidal anti-inflammatory (NSAID) drugs in a syndrome called NSAID-exacerbated respiratory disease (N-ERD) characterized by highly recurrent polyps and concomitant asthma. The pathophysiological mechanisms especially with regards to the potential role of the microbiome in driving N-ERD are so far not fully understood. Here, the investigators plan to analyse the nasal microbiome in these patients and to compare it to nasal samples from CRSwNP and CRSsNP patients as well as healthy controls (in total 80 subjects). This will provide insights into potential differences in the microbiome as compared to other CRS patients and the impact of the microbiome in driving this disease.

Study Overview

• Status: Completed
• Conditions: Chronic Rhinitis; Aspirin Exacerbated Respiratory Disease
• Intervention / Treatment: Other: Microbiome swabs

Detailed Description

Chronic rhinosinusitis (CRS) with (w) and without (s) nasal polyps (NP) in its different shapes is currently affecting up to 16% of the total population of the United States and around 11% of the population in Europe . However CRS may also be associated with hypersensitivity to aspirin and other non-selective cyclooxygenase inhibitors. This syndrome of combined CRSwNP, asthma and intolerance to inhibitors of the cyclooxygenase-1 enzyme was termed Samter's triad, aspirin-exacerbated respiratory disease (AERD) and recently NSAID-exacerbated respiratory disease (N-ERD). N-ERD is thought to affect around 16% of patients suffering from CRSwNP , around 7% of adult asthmatic patients and 0.3-2.5% of the general population. One characteristic feature of this disease is the presence of nasal polyps that frequently relapse after surgery rendering this disease difficult to manage. Despite its relatively high prevalence, the pathophysiologic mechanisms are yet not fully understood. In this respect, an overproduction of and overresponsiveness to cysteinyl leukotrienes accompanied by and underproduction of and underresponsiveness to prostaglandins was observed in N-ERD patients.This indicates a dysregulation of pro and anti-inflammatory pathways.

Our mucosal body surfaces are colonized by a large variety of microbes organized within complex community structures. Novel sequencing techniques (e.g. 16SrRNA sequencing) have facilitated in-depth analysis of the nasal microbiome in health and disease. Recent studies show amongst other an enrichment in Haemophilus and Streptococcus in the nose of CRS patients, whereas nasal microbiome of healthy patients is rich in Propionibacterium acnes . So far, differences in microbiome were observed in healthy versus CRS patients, but the impact of the microbial environment in N-ERD has not been assessed yet and is thus aim of the study.

The investigators will collect nasal microbiome and nasal secretions from patients suffering from N-ERD and will compare them to the microbiome of CRSwNP, CRSsNP and healthy controls (n=20 per group). Additionally, cytokines in nasal secretions, protein expression at mRNA levels in nasal mucosa, and serum of these patients and clinical parameters (e.g. total nasal polyp score, quality of life questionnaire, olfactory performance) will be determined.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or Female
• Age: 18-90
• Willingness to participate in the study
• No use of nasal or systemic corticosteroids or immunosuppressants 2 weeks prior to their visit

• Patient groups:

  • Control group: absence of any signs of acute or chronic rhinosinusitis
  • CRS:

CRSsNP CRSwNP N-ERD: N-ERD as previously confirmed by clinical history or provocation testing

The presence of CRS will be confirmed by endoscopy (part of routine assessment at the ORL department, no study procedure) according to AAO-HNSF guidelines as follows :

• Twelve weeks or longer of two or more of the following signs and symptoms:

• mucopurulent drainage (anterior, posterior, or both)
• nasal obstruction (congestion)
• facial pain-pressure-fullness, or
• decreased sense of smell

AND inflammation is documented by one or more of the following findings:

• purulent (not clear) mucus or edema in the middle meatus or anterior ethmoid region
• polyps in nasal cavity or the middle meatus, and/or
• radiographic imaging showing inflammation of the paranasal sinuses

Exclusion Criteria:

• Children
• Pregnant women (pregnancy test will be performed in women with child bearing potential)
• A mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study
• Use of nasal or systemic corticosteroids or immunosuppressants 2 weeks prior to their visit
• Patients with cystic fibrosis or immunosuppression.
• Severe anatomic variations or deviations that do not allow access to all areas in the nasal cavity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AERD; Patients suffering from AERD	Other: Microbiome swabs; Swabs for analysis of microbiome
Sham Comparator: Healthy; Healthy Controls	Other: Microbiome swabs; Swabs for analysis of microbiome
Active Comparator: CRSwNP; Patients suffering from CRS with nasal polyps	Other: Microbiome swabs; Swabs for analysis of microbiome
Active Comparator: CRSsNP; Patients suffering from CRS without nasal polyps	Other: Microbiome swabs; Swabs for analysis of microbiome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nasal microbiome	Differences in microbial community composition between patients with N-ERD, CRSsNP, CRSwNP and healthy controls will be determined by 16S rRNA gene amplicon sequencing	1 year

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2020
• Primary Completion (Actual): July 25, 2021
• Study Completion (Actual): July 25, 2021

Study Registration Dates

• First Submitted: January 24, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (Actual): May 5, 2020

Study Record Updates

• Last Update Posted (Actual): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: aerd, microbiome
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Otorhinolaryngologic Diseases; Nose Diseases; Rhinitis; Respiration Disorders; Respiratory Tract Diseases
• Other Study ID Numbers: MicroNERD

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