MedPath

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

Not Applicable
Recruiting
Conditions
Nasal Polyps
Chronic Rhinosinusitis With Nasal Polyps
Asthma
Chronic Rhinosinusitis (Diagnosis)
Interventions
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
Registration Number
NCT05009758
Lead Sponsor
Medical University of Vienna
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.

Detailed Description

1. Background Both, asthma and chronic rhinosinusitis (CRS) are inflammatory conditions of the airways. The prevalence of asthma - with its cardinal symptoms wheezing, breathlessness, chest tightness, and coughing - has risen over the past decades not only in industrial but also in developing countries. For instance, about 8% of the United States' population and 8.2% of Europeans are diagnosed with asthma. Chronic rhinosinusitis with (CRSwNP) and without nasal polyps (CRSsNP) is a condition affecting up to 16% and 11% of the US and European population, respectively3. Both diseases, asthma and CRS, can severely impair quality of life as well as productivity and therefore embody an immense socioeconomic burden.

 Despite the distinction of the respiratory tract in the upper and lower airways, both parts are anatomically and immunologically related. This led to the concept of "United airway diseases" assuming that upper and lower airways form a single organ. Consequently, inflammation in the upper affects the lower respiratory tract and vice versa. This concept initially described in the context of allergic respiratory disease can also be extended to the link between sinonasal and lower airway diseases. Accordingly, the association between asthma and CRS prevalence has been unambiguously shown in epidemiological studies: around 20% of CRSsNP patients and around 48% of CRSwNP patients suffer from asthma. Conversely, nasal polyposis is detected in 19 to 25% of asthmatics. In cases of severe asthma, even up to 54% of patients were reported to have a history of nasal polyposis. However, the pathophysiological mechanism underlying the association of asthma and CRS has been poorly investigated so far.

 Based on the predominant inflammatory profile, asthma can be separated into T2-high and T2-low endotypes. Thereby, around 60% of severe asthma patients show a T2-high profile. The picture is becoming even more complex regarding classifications of CRS. Phenotypically we distinguish between CRSsNP and CRSwNP. However, up to 10 different endotypes of CRS can be defined based on various different inflammatory markers in nasal polyps or nasal secretions. Approaches to characterize endotypes describing conditions involving both asthma and CRS have barely been made so far.

 On a cellular and protein level, it seems that higher concentrations of Staphylococcus enterotoxin-specific IgE, total IgE and eosinophil cationic protein in nasal polyp tissue are indicators for a higher risk of asthma. Furthermore, it was observed that patients with CRS and eosinophilic asthma (as determined by FeNO levels only) show high numbers of eosinophils in their nasal polyps. This nasal polyp eosinophilia was associated with a more severe asthma phenotype as well as larger polyps and a significantly higher nasal polyp recurrence rate compared to non-eosinophilic patients. However, up to this point, no study investigated whether inflammatory profiles in polyps and asthmatic lungs correspond and how inflammatory profiles of patients suffering from asthma with or without polyps may differ.

 Novel antibody-based therapies targeting mediators of type 2 immune response are constantly emerging as new treatment options for patients with severe chronic airway diseases. Therapeutic antibodies targeting IgE or IL-4/IL-13, IL-5, or IL-5 receptor-mediated pathways are currently licensed for the treatment of asthma but have also successfully been used to treat CRSwNP to some extent. In this respect, anti-IgE (omalizumab) and anti-IL4α receptor (dupilumab) specific monoclonal antibodies have recently been licensed for the treatment of nasal polyps and CRSwNP respectively. Antibodies targeting molecules further upstream in the inflammatory cascade such as TSLP or IL-33 are currently under development. Anti-TSLP antibodies showed first promising results in clinical trials including patients suffering from uncontrolled asthma. Despite targeting molecular pathways involved in the pathogenesis of both diseases, some monoclonal antibodies such as reslizumab are effective in treating asthma but fail to significantly ameliorate nasal polyposis. Interestingly, a post-hoc responder analysis showed that the group of patients with high baseline IL-5 levels in nasal secretions improved upon reslizumab treatment, while the other patient groups did not. These findings illustrate the urgent need to better understand the pathomechanism and potential links underlying both diseases in order to choose the right therapy for the right patient.

2. Study rationale In this study, we aim to unravel the pathophysiological mechanisms underlying T2-high asthma with or without nasal polyposis. Therefore, we plan to thoroughly examine T2-high asthmatic patients with and without nasal polyposis at the cellular and molecular level and compare them to patients suffering from eosinophilic polyps in the absence of asthma. Deep analysis of nose, oropharynx, and lung samples will yield information on inflammatory patterns at protein and mRNA level, cellular tissue architecture in the different disease subtypes as well as microbiome composition. This pilot study will help to unravel underlying pathomechanisms in these united airway diseases and, therefore, provide a rationale for new therapy approaches including biologicals.

3. Study objectives

In this study we plan to:

* evaluate the inflammatory profile in different sections of the airways;

* evaluate the endotype and immunological profile of CRSwNP (when applicable);

* determine the 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

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
30
Inclusion Criteria

All patients who

  • 18-99 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

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Exclusion Criteria

  • 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

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
T2-high asthma with nasal polypsOral sampling* 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
T2-high asthma with nasal polypsBlood sampling* 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
T2-high asthma with nasal polypsNasosorption* 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
T2-high asthma with nasal polypsNasal sampling* 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
T2-high asthma with nasal polypsPregnancy test* 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
T2-high asthma with nasal polypsBronchoscopy* 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
T2-high asthma with nasal polypsNasal biopsy* 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
T2-high asthma without nasal polypsBlood sampling* 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
T2-high asthma without nasal polypsNasosorption* 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
T2-high asthma with nasal polypsNasal mucosa mRNA sampling* 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
T2-high asthma with nasal polypsLung X-Ray* 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
T2-high asthma without nasal polypsBronchoscopy* 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
CRSwNP in absence of asthmaBronchoscopy* 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
T2-high asthma without nasal polypsNasal sampling* 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
CRSwNP in absence of asthmaNasal mucosa mRNA sampling* 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
CRSwNP in absence of asthmaMedical history of patients, demographic data, concomitant medication, questionnaire* 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
T2-high asthma with nasal polypsSpirometry* 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
T2-high asthma with nasal polypsFeNO* 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
T2-high asthma without nasal polypsNasal mucosa mRNA sampling* 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
T2-high asthma without nasal polypsPregnancy test* 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
T2-high asthma with nasal polypsMedical history of patients, demographic data, concomitant medication, questionnaire* 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
T2-high asthma with nasal polypsUPSIT smell test* 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
T2-high asthma without nasal polypsOral sampling* 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
T2-high asthma without nasal polypsFeNO* 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
CRSwNP in absence of asthmaOral sampling* 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
CRSwNP in absence of asthmaNasal sampling* 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
T2-high asthma without nasal polypsMedical history of patients, demographic data, concomitant medication, questionnaire* 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
CRSwNP in absence of asthmaBlood sampling* 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
T2-high asthma without nasal polypsUPSIT smell test* 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
T2-high asthma without nasal polypsSpirometry* 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
CRSwNP in absence of asthmaNasosorption* 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
CRSwNP in absence of asthmaPregnancy test* 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
CRSwNP in absence of asthmaFeNO* 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
T2-high asthma without nasal polypsLung X-Ray* 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
CRSwNP in absence of asthmaNasal biopsy* 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
CRSwNP in absence of asthmaSpirometry* 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
CRSwNP in absence of asthmaUPSIT smell test* 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
CRSwNP in absence of asthmaLung X-Ray* 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
Primary Outcome Measures
NameTimeMethod
Inflammatory profile in different sections of the airways2 years

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

Secondary Outcome Measures
NameTimeMethod
Endotype and immunological profile of CRSwNP2 years

Number of patients with specific endotypes of polyps and concentration of selected inflammatory mediators of various anatomic locations in the airways both in tissue and secretion samples in patients suffering from T2-high asthma with or without CRSwNP and in patients with CRSwNP in absence of asthma.

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 asthma2 years

Number of different bacterial strains in different anatomical locations in asthmatic patients with and without polyps and CRSwNP patients in absence of asthma and to evaluate differences.

Trial Locations

Locations (1)

Allgemeines Krankenhaus (AKH) Wien

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Wien, Austria

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