EGPA - Eosinophilic Granulomatosis With Polyangiitis
Conditions
Brief summary
Rationale: Eosinophilic Granulomatosis with Polyangiitis (eGPA), eosinophilic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) are airway diseases where eosinophils and interleukine-5 are involved in the pathogenesis. eGPA differs from the other diseases with respect to involvement of other organs. The investigators hypothesize that nasal microbiome dysbiosis with a central augmenting role for S. Aureus plays an important role in disease expression. The investigators expect that anti-interleukin-5 treatment with mepolizumab restores the changes of the nasal microbiome and immune responses to a healthy control phenotype. To study this, the nasal microbiome, the local and systemic immune response and the effect of mepolizumab treatment will be assessed.
Detailed description
See Brief summary.
Interventions
DIAGNOSTIC_TESTlaboratory experiments before and after mepolizumab treatment
Patients that start with mepolizumab treatment on the basis of the clinical disease course will be measured prior and after start of mepolizumab to evaluate the effects this medication has on various immunological parameters and microbiome
Sponsors
GlaxoSmithKline
University Medical Center Groningen
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 18 years of age * able to give informed consent * In CRSwNP group: availability of bilateral nasal polyps as diagnosed by endoscopy or CT scan * In Severe asthma group: clinical diagnosis of asthma with forced expiratory volume at one second(FEV1) \<80% AND either FEV1 reversibility \>12% initial or documented positive metacholine challenge (PC20 \< 8 mg/ml) * In eGPA group: Fulfilling the 2022 ACR/EULAR criteria for eGPA (Wechsler et al., 2017) * In GPA group: fulfilling the American College of Rheumatology (ACR)/EULAR GPA criteria (Robson et al., 2022) * In healthy controls: absence of asthma symptoms, no bronchial hyperresponsiveness
Exclusion criteria
* unable to give informed consent * Active smoking \< (less than) 6 months from baseline visit * Concomitant use of dupilumab within 6 months of baseline visit * pregnant or breastfeeding woman * in CRSwNP group: current use of asthma medication, eGPA * in healthy controls: chronic use of local anti-inflammatory agents * in healthy controls: use of immunosuppressive medication * in healthy controls: use of antibiotics within the last month (before start study/screening/)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The effect mepolizumab treatment has on the nasal microbiome profiles | three months | Paired change in microbiome diversity index for patients treated with mepolizumab. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory evaluation of between group differences | Through study completion, an average of two years | Microbiome and immunological gene expression values will be measured and differential expression analysis will be performed |
| Mepolizumab effect on outcome 2 | Through study completion, an average of two years | The effect mepolizumab treatment has on the immunological gene expression will be measured by differential gene expression analysis. |
| s there a correlation between the disease activity, the quality of life and the microbiome and immune parameters? | Through study completion, an average of two years | Spearman ranks correlation |
Countries
Netherlands
Contacts
Primary ContactAbraham Rutgers, MD-PhD
Outcome results
None listed