Drivers of Eosinophilic COPD Exacerbations
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Change in gene expression profiles in nasal epithelium by using RNA sequencing
研究概览
简要总结
Main objective: investigate gene expression differences in nasal epithelium and sputum between eosinophilic COPD exacerbations and other subtypes.
详细描述
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:
- Investigate differences in microbiome composition and immunophenotyping profiles in peripheral blood per subtype.
- Assess for clinical differences between all COPD exacerbation subtypes.
- Assess if and how baseline meta-transcriptomics either in nasal epithelium or sputum and blood immunophenotyping can be utilized to predict COPD exacerbation subtype.
- Determine if the microbiome in sputum and nasal epithelial material are comparable.
- Determine if different subtypes of COPD exacerbations respond differently to standard treatment with oral prednisolone (40 mg daily) with or without antibiotics.
- To evaluate if metabolic responses during recovery are different in patients with increased systemic inflammation compared to patients without systemic inflammation at exacerbation
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •COPD patient admitted to the hospital for an acute exacerbation of COPD
- •Physician diagnosed COPD according to the GOLD 2020 guidelines, including symptoms consistent with COPD, post-bronchodilator FEV1 < 80% predicted and FEV1/FVC < 70%.
- •Age > 40 years.
- •Smoker or ex-smoker, ≥ 10 pack years of smoking.
排除标准
- •Current asthma, or prior physician diagnosis of asthma without a symptom- free interval of at least 10 years before the age of
- •Chronic use of prednisolone.
- •Use of systemic corticosteroids ≥4 days prior to hospital admission.
- •Necessity (upon hospitalization) for non-invasive ventilation or ICU admission.
- •Pneumonia at presentation documented by chest roentgenography.
- •Any other clinically relevant lung disease deemed to interfere with the concept of the study design.
- •Allergy to systemic corticosteroids or to antibiotics.
- •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:
- •Surgical sterilization (e.g. bilateral tubal ligation, hysterectomy).
- •Hormonal contraception (implantable, patch, oral, injectable).
- •Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/cream/suppository.
- •Continuous abstinence
- •Pregnancy or lactation.
- •Known immunodeficiency.
- •Life expectancy less than 60 days
结局指标
主要结局
Change in gene expression profiles in nasal epithelium by using RNA sequencing
时间窗: 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
时间窗: 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.
次要结局
- Microbiome composition in sputum by using RNA sequencing.(At admission, at day 5 of admission and 6-8 weeks after discharge.)
- Phenotype blood cell population by flow cytometry.(At admission, at day 5 of admission and 6-8 weeks after discharge.)
- 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.)
- Clinical differences between groups by peak flow measurements.(Every day of hospital admission.)
- Comparison of microbiome composition in sputum and nasal epithelial material by RNA sequencing.(At admission and 6-8 weeks after discharge.)
- Clinical differences between groups by the COPD Assessment Test (CAT).(Every day of hospital admission.)
研究者
Maarten van den Berge
Principal Investigator
University Medical Center Groningen