Moving Towards Precision Medicine in United Airways Disease: Unraveling Inflammatory Patterns in Asthmatic Patients With or Without Nasal Polyps

NCT05009758 | Recruiting

• 1 other identifier: PREMIUM2021
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Asthma and chronic rhinosinusitis (CRS) are inflammatory diseases of the respiratory tract, asthma from the lower part, and CRS, from the upper part. In theory, these parts are correlated as if they are one single organ, namely "united airways", which means that if one is affected by any condition, the other might be impacted as well. However, this relationship has not yet been described down to the cellular and molecular levels. By investigating patients that have (1) asthma and CRS with nasal polyp, (2) asthma and CRS without nasal polyp, and (3) just CRS with nasal polyp, we aim to determine the correlation of the upper and lower part of the respiratory tract. At first, the characterization of disease will be determined by established clinical criteria, such as lung function, blood analysis for the presence of eosinophils (a type of white cells), and nasal polyp score. To continue, in-depth analysis of nose, oropharynx, and lung samples will help gain information about the inflammatory profile and local microbiome of the three different groups of patients through molecular and cellular assays. The results of this study will help to describe the hypothesis of the united airways which will provide better guidance for medical treatment of asthma and CRS with or without polyp, thus improving the life quality of patients.

Conditions

Asthma; Chronic Rhinosinusitis With Nasal Polyps; Chronic Rhinosinusitis (Diagnosis); Nasal Polyps

Keywords

Asthma; Chronic Rhinosinusitis (CRS); CRS with Nasal Polyps; CRS without Nasal Polyps; Inflammatory profile; Type 2 inflammation

Outcome Measures

Primary Outcomes (1)

• Inflammatory profile in different sections of the airways

  Concentration of selected inflammatory mediators in T2-high asthmatic patients with and without polyps and in patients with CRSwNP in absence of asthma

  2 years

Secondary Outcomes (2)

• Endotype and immunological profile of CRSwNP

  2 years

• Microbiome composition in nose, oropharynx and bronchi in T2-high asthmatic patients with and without CRSwNP, N-ERD compared to patients with CRSwNP in absence of asthma

  2 years

Study Arms (3)

T2-high asthma with nasal polyps

ACTIVE COMPARATOR

* FeNO \> 25 ppB * Had either two times \>= 250 eosinophils /µl measured in the blood OR one measurement of blood eosinophils \>= 250 cells/µl (one of the two measurements at the screening visit) and/or one measurement of sputum eosinophils \> 2% within the last 12 months * Presence of CRSwNP as confirmed by endoscopy or CT according to the European Position Paper on Rhinosinusitis and CRSwNP Guidelines) * Patients with a history of treatment with monoclonal antibodies for asthma or polyps will only be included if at least a washout period of 5 half-lives or at least 3 months have passed

Procedure: Blood sampling; Procedure: Nasosorption; Procedure: Oral sampling; Procedure: Bronchoscopy; Procedure: Nasal biopsy; Procedure: Nasal sampling; Procedure: Nasal mucosa mRNA sampling; Diagnostic Test: Pregnancy test; Other: Medical history of patients, demographic data, concomitant medication, questionnaire; Diagnostic Test: UPSIT smell test; Procedure: Spirometry; Procedure: FeNO; Procedure: Lung X-Ray

T2-high asthma without nasal polyps

ACTIVE COMPARATOR

* FeNO \> 25 ppB * Had either two times \>= 250 eosinophils /µl measured in the blood OR one measurement of blood eosinophils \>= 250 cells/µl (one of the two measurements at the screening visit) and/or one measurement of sputum eosinophils \> 2% within the last 12 months * Absence of NP as confirmed by endoscopy or CT according to the European Position Paper on Rhinosinusitis and CRSwNP Guidelines) * Patients with a history of treatment with monoclonal antibodies for asthma or polyps will only be included if at least a washout period of 5 half-lives or at least 3 months have passed

Procedure: Blood sampling; Procedure: Nasosorption; Procedure: Oral sampling; Procedure: Bronchoscopy; Procedure: Nasal sampling; Procedure: Nasal mucosa mRNA sampling; Diagnostic Test: Pregnancy test; Other: Medical history of patients, demographic data, concomitant medication, questionnaire; Diagnostic Test: UPSIT smell test; Procedure: Spirometry; Procedure: FeNO; Procedure: Lung X-Ray

CRSwNP in absence of asthma

ACTIVE COMPARATOR

* Presence of CRSwNP as confirmed by endoscopy or CT according to the European Position Paper on Rhinosinusitis and Nasal Polyps Guidelines26 * Evidence of Type 2 inflammation: blood eosinophils \>= 250 cells/µl measured in the blood OR total IgE \>100 kU/L26 at the screening visit * Absence of asthma and N-ERD * Patients with a history of treatment with monoclonal antibodies for asthma or polyps will only be included if at least a washout period of 5 half-lives or at least 3 months have passed

Procedure: Blood sampling; Procedure: Nasosorption; Procedure: Oral sampling; Procedure: Bronchoscopy; Procedure: Nasal biopsy; Procedure: Nasal sampling; Procedure: Nasal mucosa mRNA sampling; Diagnostic Test: Pregnancy test; Other: Medical history of patients, demographic data, concomitant medication, questionnaire; Diagnostic Test: UPSIT smell test; Procedure: Spirometry; Procedure: FeNO; Procedure: Lung X-Ray

Interventions

Blood sampling PROCEDURE

Blood collection for PBMC isolation, measurement of cytokines in serum, and mass cytometry

CRSwNP in absence of asthma; T2-high asthma with nasal polyps; T2-high asthma without nasal polyps

Nasosorption PROCEDURE

Nasosorptions will be applied for the collection of nasal secretions (Nasosorption FX-I, Hunt Developments (UK) Limited, Midhurst, West Sussex, United Kingdom). Under visualization, the device will be inserted into the nasal cavity and be placed along the lateral wall against the inferior turbinate. The index finger of the patient will be used to press onto the external aspects of the alar and lateral nasal cartilages to hold the device in place. After 1 minute, the devices will be removed.

CRSwNP in absence of asthma; T2-high asthma with nasal polyps; T2-high asthma without nasal polyps

Oral sampling PROCEDURE

For oral sampling, saliva collection devices (SuperSAL or PureSAL, Oasis Diagnostic Corporation, USA) will be applied followed by elution. Then swabs optimized for the collection of specimens will be applied (CLASSIQSwabs, Copan Diagnostics Inc. Murietta, CA, USA) to the dorsum of the tongue.

CRSwNP in absence of asthma; T2-high asthma with nasal polyps; T2-high asthma without nasal polyps

Bronchoscopy PROCEDURE

The bronchoscopy will be performed in the outpatient clinic of the Department of Pulmonology. Bronchial alveolar lavage (BAL): the bronchoscope is wedged in the segmental or subsegmental bronchus of the middle lobe. Up to 300 ml sterile normal saline is injected stepwise via handheld syringe and then gradually withdrawn back into the syringe. BAL fluid (BALF) will be prepared and further analyzed in the lab. Transbronchial biopsy (TBLB): performed by forceps in the lung periphery under fluoroscopy guidance. Up to 4 biopsies are taken in two different lobes of one lung with a distance of 1-2 cm to the pleura. TBLB is only performed in patients who have got not contraindications.

CRSwNP in absence of asthma; T2-high asthma with nasal polyps; T2-high asthma without nasal polyps

Nasal biopsy PROCEDURE

Nasal biopsies will be taken during routine endoscopy performed to score CRSwNP. Patients will receive local anesthesia and decongestants prior to obtaining the biopsy. Samples will either be embedded in OCT or processed for cellular analysis

CRSwNP in absence of asthma; T2-high asthma with nasal polyps

Nasal sampling PROCEDURE

Swabs optimized for the collection of specimens will be applied (CLASSIQSwabs, Copan Diagnostics Inc. Murietta, CA, USA) to the anterior naris and middle meatus of each nostril

CRSwNP in absence of asthma; T2-high asthma with nasal polyps; T2-high asthma without nasal polyps

Nasal mucosa mRNA sampling PROCEDURE

Mucosal mRNA sampling will be performed using a 10cm nasal curette (either Rhino-Probe, Arlington Scientific, USA or Cellskim, Hunt Developments, UK). Under direct visualization, the curette will be brought to lie against the mid-inferior portion of the inferior turbinate. The curette will be pressed against the mucosal surface moved outwards 2-3 times. This motion will be repeated 2-3 times to ensure good sample collection. This curette and technique have been shown to cause no significant discomfort to patients and thus it has the advantage of no requirement for local anesthetics.

CRSwNP in absence of asthma; T2-high asthma with nasal polyps; T2-high asthma without nasal polyps

Pregnancy test DIAGNOSTIC_TEST

In female patients, pregnancy will be excluded with a standard urine pregnancy test at the beginning of the main visit.

CRSwNP in absence of asthma; T2-high asthma with nasal polyps; T2-high asthma without nasal polyps

Medical history of patients, demographic data, concomitant medication, questionnaire OTHER

Patients will be asked for their medical history including demographic data and concomitant medication. Details will be noted in the source data file. Furthermore, patients will receive a questionnaire including tools to assess QOL impairment by CRS and asthma

CRSwNP in absence of asthma; T2-high asthma with nasal polyps; T2-high asthma without nasal polyps

UPSIT smell test DIAGNOSTIC_TEST

University of Pennsylvania Smell Identification Test (UPSIT) smell test will be performed by the patients during the study. It consists of 40 questions in 4 different booklets. The patient needs to scratch a sniff strip with the microencapsulated odorant using a pencil and mark his choice on four-choice multiple-choice questions. The test is then scored by the study team out of the 40 items.

CRSwNP in absence of asthma; T2-high asthma with nasal polyps; T2-high asthma without nasal polyps

Spirometry PROCEDURE

Lung function will be measured by spirometry in the lung function unit of the Department of Pulmonology. Spirometry will be performed according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines by authorized and properly certified personal.

CRSwNP in absence of asthma; T2-high asthma with nasal polyps; T2-high asthma without nasal polyps

FeNO PROCEDURE

Airway inflammation will be evaluated using a standardized single-breath FeNO test in accordance with the lung function unit of the Department of Pulmonology. A single exhalation technique recommended by the manufacturer will be followed. The FeNO measurements will not be performed within 2 weeks of a respiratory infection. The FeNO test will be performed prior to spirometry. Subjects should not eat or drink 1 hour prior to having the FeNO test. Subjects should not use their rescue SABA medication (e.g., albuterol/salbutamol) within 6 hours of the measurement. Inhaled bronchodilators (including ICS/LABA) should be withheld for the effect duration specific to the bronchodilator. If not, the assessment should be postponed till after the required time has passed since the meal or drink or bronchodilator inhalation. The NIOX VERO® Airway Inflammation Monitor will be used to measured FeNO in the lung function unit of the Department of Pulmonology.

CRSwNP in absence of asthma; T2-high asthma with nasal polyps; T2-high asthma without nasal polyps

Lung X-Ray PROCEDURE

After the bronchoscopy, a lung x-ray will be performed and patients will stay overnight in the ward of the Department of Pulmonology.

CRSwNP in absence of asthma; T2-high asthma with nasal polyps; T2-high asthma without nasal polyps

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients who
• years of age
• have a recorded clinical diagnosis of asthma (ICD-10 Code: J45)
• undergo moderate-serve asthma treatment according to GINA/DAL treatment step 4 or step 5 without oral corticosteroid or monoclonal antibody therapy
• Asthma treatment for a minimum of 12 weeks prior to screening visit
• Group 1 and 2 - T2-high asthma with or without polyps:
• FeNO \> 25 ppB
• had either two times \>= 250 eosinophils /µl measured in the blood OR one measurement of blood eosinophils \>= 250 cells/µl (one of the two measurements at the screening visit) and/or one measurement of sputum eosinophils \> 2% within the last 12 months
• Group with polyps: Presence of CRSwNP as confirmed by endoscopy or CT according to the European Position Paper on Rhinosinusitis and CRSwNP Guidelines)
• Group 3 - CRSwNP in absence of asthma:
• Presence of CRSwNP as confirmed by endoscopy or CT according to the European Position Paper on Rhinosinusitis and Nasal Polyps Guidelines
• Evidence of Type 2 inflammation: eosinophils \>= 250 cells/µl measured in the blood OR total IgE \>100 kU/L at the screening visit
• Absence of asthma and N-ERD
• Patients with a history of treatment with monoclonal antibodies for asthma or polyps will only be included if at least a wash out period of 5 half-lives or at least 3 months have passed

You may not qualify if:

• Pregnancy (as determined by ß-HCG test)
• Patients with severe anatomic variations or deviations that do not allow access to all areas in the nasal cavity
• Patients undergoing chronic oral corticosteroid therapy
• Patients with any other confounding underlying lung disorder including but not limited to:
• Bronchiectasis, chronic obstructive pulmonary disorder (COPD), pulmonary fibrosis, emphysema, primary ciliary dyskinesia
• Cystic fibrosis, any known parasitic infections, and lung cancer
• Patients with pulmonary conditions with symptoms of asthma and blood eosinophilia including but not limited to: Eosinophilic granulomatosis with polyangiitis (EGPA), allergic bronchopulmonary aspergillus, and hypereosinophilic syndrome
• A mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
• Patients with clinically meaningful comorbidity as determined by the evaluating committee
• Patients with a history of exacerbation of chronic rhinosinusitis or asthma 4 weeks prior to any visit
• Intake of a burst of systemic corticosteroids 4 weeks prior to any visit.
• Immunosuppressive treatment (e.g. cyclosporine)
• Drug and alcohol abuses
• Current smoker
• Former smoker if stopped smoking \<6 months and/or has \>10 pack-years

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Allgemeines Krankenhaus (AKH) Wien

Vienna, 1090, Austria

RECRUITING

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  BACKGROUND

MeSH Terms

Conditions

Asthma; Disease; Nasal Polyps

Interventions

Blood Specimen Collection; Bronchoscopy; Pregnancy Tests; Demography; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nose Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Diagnostic Techniques, Respiratory System; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Pulmonary Surgical Procedures; Thoracic Surgical Procedures; Diagnostic Techniques, Obstetrical and Gynecological; Population Characteristics; Epidemiologic Measurements; Public Health; Environment and Public Health; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation

Study Officials

• Julia Eckl-Dorna, PhD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

• Sven Schneider, MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

• Marco Idzko, MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julia Eckl-Dorna, PhD

CONTACT

+4314040034380; julia.eckl-dorna@meduniwien.ac.at

Sven Schneider, MD

CONTACT

+4314040034380; sven.schneider@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ap. Prof. Priv.-Doz. Dr

Model Details: Subjects attending the outpatient clinic of the Department of Othorrinolaringology or Pulmonology of the Medical University of Vienna for symptoms of asthma or CRS with nasal polyposis will be recruited during their routine visit. After informing patients about the scopes of the study, they will be invited for a screening visit. During this visit, patients will be informed about the nature of the study and asked whether they are willing to participate. After signing the informed consent, they will undergo a screening visit to determine their eligibility for the study and group allotment. The following parameters will be recorded at the screening visit: medical history including concomitant medication, nasal examination (endoscopy), lung function and FeNO measurement, blood draw (eosinophil levels and for exploratory parameters). Thereafter, eligible patients will attend a single study visit for the collection of all clinical parameters and samples.

Study Record Dates

• First Submitted: August 5, 2021
• First Posted: August 17, 2021
• Study Start: September 1, 2021
• Primary Completion: September 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 7, 2025

Record last verified: 2025-05

Locations

AU (1)