Drivers of Eosinophilic COPD Exacerbations

Recruiting

• Conditions: COPD Exacerbation; Eosinophilia

• Registration Number: NCT04961060
• Lead Sponsor: University Medical Center Groningen

Brief Summary

Main objective: investigate gene expression differences in nasal epithelium and sputum between eosinophilic COPD exacerbations and other subtypes.

Detailed Description

Main objective: investigate gene expression differences in nasal epithelium and sputum between eosinophilic COPD exacerbations and other subtypes to better understand why some patients are more at risk for eosinophilic COPD exacerbations. Secondary objectives:

1. Investigate differences in microbiome composition and immunophenotyping profiles in peripheral blood per subtype.

2. Assess for clinical differences between all COPD exacerbation subtypes.

3. Assess if and how baseline meta-transcriptomics either in nasal epithelium or sputum and blood immunophenotyping can be utilized to predict COPD exacerbation subtype.

4. Determine if the microbiome in sputum and nasal epithelial material are comparable.

5. Determine if different subtypes of COPD exacerbations respond differently to standard treatment with oral prednisolone (40 mg daily) with or without antibiotics.

6. To evaluate if metabolic responses during recovery are different in patients with increased systemic inflammation compared to patients without systemic inflammation at exacerbation

Study Timeline

• Study First Submitted: 2021-04-28
• Status Verified: 2021-07
• Study Start: 2021-07
• Study First Submitted QC: 2021-07-02
• Last Update Submitted: 2021-07-02
• Study First Posted: 2021-07-14
• Last Update Posted: 2021-07-14
• Primary Completion: 2024-09
• Study Completion: 2025-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. COPD patient admitted to the hospital for an acute exacerbation of COPD
2. Physician diagnosed COPD according to the GOLD 2020 guidelines, including symptoms consistent with COPD, post-bronchodilator FEV1 < 80% predicted and FEV1/FVC < 70%.
3. Age > 40 years.
4. Smoker or ex-smoker, ≥ 10 pack years of smoking.

Exclusion Criteria

1. Current asthma, or prior physician diagnosis of asthma without a symptom- free interval of at least 10 years before the age of 40.

2. Chronic use of prednisolone.

3. Use of systemic corticosteroids ≥4 days prior to hospital admission.

4. Necessity (upon hospitalization) for non-invasive ventilation or ICU admission.

5. Pneumonia at presentation documented by chest roentgenography.

6. Any other clinically relevant lung disease deemed to interfere with the concept of the study design.

7. Allergy to systemic corticosteroids or to antibiotics.

8. Females of childbearing potential without an efficient contraception unless they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH >40 mIU/mL or the use of one or more of the following acceptable methods of contraception:

   1. Surgical sterilization (e.g. bilateral tubal ligation, hysterectomy).
   2. Hormonal contraception (implantable, patch, oral, injectable).
   3. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/cream/suppository.
   4. Continuous abstinence

9. Pregnancy or lactation.

10. Known immunodeficiency.

11. Life expectancy less than 60 days

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in gene expression profiles in nasal epithelium by using RNA sequencing	At admission and after 6-8 weeks after discharge.	Change in gene expression profilesin nasal epithelium between the four groups using RNA sequencing. The differences between the expression levels of transcripts (counts) will be analyzed.
Change in gene expression profiles in sputum by RNA sequencing	At admission and after 6-8 weeks after discharge.	Change in gene expression profiles in sputum between the four groups using RNA sequencing. The differences between the expression levels of transcripts (counts) will be analyzed.

Secondary Outcome Measures

Name	Time	Method
Phenotype blood cell population by flow cytometry.	At admission, at day 5 of admission and 6-8 weeks after discharge.	Differences in blood cell population between the four groups as measured by flow cytometry.
Microbiome composition in sputum by using RNA sequencing.	At admission, at day 5 of admission and 6-8 weeks after discharge.	Differences in microbiome composition in sputum between the four groups by using RNA sequencing.
Phenotypic analysis of the T cell compartment by staining of whole blood or isolated peripheral blood mononuclear cells using antibodies	At admission, at day 5 of admission and 6-8 weeks after discharge.	Differences in the T cell compartment between the four groups by staining of whole blood or isolated peripheral blood mononuclear cells using antibodies.
Clinical differences between groups by peak flow measurements.	Every day of hospital admission.	Differences in number of participants per group with a low peak expiratory flow rate as measured by a handheld peak flow meter.
Comparison of microbiome composition in sputum and nasal epithelial material by RNA sequencing.	At admission and 6-8 weeks after discharge.	Measure microbiome composition in sputum and nasal epithelium by RNA sequencing. Compare them by the bacterial taxa which are significantly different between groups
Clinical differences between groups by the COPD Assessment Test (CAT).	Every day of hospital admission.	Differences in number of participants per group with a high impact of COPD related symptoms as assessed by the CAT.

Trial Locations

Locations (2)

Univesity Medical Center Groningen; 🇳🇱 Groningen, Netherlands

University Maastricht; 🇳🇱 Maastricht, Limburg, Netherlands