Drivers of Eosinophilic COPD Exacerbations (DICE)

University Medical Center Groningen (UMCG)

Status: Enrolling

Conditions: COPD Exacerbation; Eosinophilia

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT04961060

NL75151.042.20

Details and patient eligibility

About

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

Full 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

Enrollment: 100 estimated patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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

Trial design

100 participants in 4 patient groups

Eosinophilic exacerbation

Description:

COPD exacerbation associated with eosinophilia.

Viral exacerbation

Description:

COPD exacerbation associated with viral infection.

Bacterial exacerbation

Description:

COPD exacerbation associated bacterial infection.

Pauci-inflammatory exacerbation

Description:

Pauci-inflammatory COPD exacerbation