BROnchoalveolar Investigations of Never-smokers With CHronic Obstructive Lung Disease From the Swedish CardioPulmonary bioImage Study
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 1,000
- 试验地点
- 6
- 主要终点
- Forced expiratory volume in 1 second (FEV1)
研究概览
简要总结
Obstructive lung disease is an increasing global health problem of pandemic proportions, with COPD alone affecting >10% of the population. Smoking is the main and most well studies risk factor for developing COPD. However, chronic airway obstruction also in never-smoking populations has recently been recognized as an increasing health problem.
In the clinical segment (PI: Prof. C. Magnus Skold), 1000 subjects from the Swedish national SCAPIS study will be clinically well characterized in one of the six Swedish University Hospital Respiratory clinics (clinical site PIs: Anders Andersson, Leif Bjermer, Anders Blomberg, Christer Janson, Lennart Persson, Magnus Skold). This first screening includes all never-smokers with COPD identified in the SCAPIS study. A subset of 300 subjects from the groups of Healthy never-smokers, current-smokers with normal lung function, current-smokers with COPD, ex-smokers with COPD, and never-smokers with COPD will be selected for the Bronchoscopy segment, were sampling will be performed from a number of anatomical locations, including bronchial biopsies, airway epithelial brushings, and bronchoalveolar lavage. Serum, plasma, and urine samples will also be collected.
In the systems medicine segment (PI: Assoc. prof Asa M. Wheelock), alterations at the epigenetic, mRNA, microRNA, proteome, metabolome and microbiome level will be performed from multiple lung compartments (airway epithelium, alveolar macrophages, exosomes, and bronchoalveolar exudates). By means of biostatistics and bioinformatics approaches, specific mediators and molecular pathways critical in the pathological mechanisms of obstructive lung disease related to never-smoker disease phenotypes will be identified.
In the immunohistochemistry segment (PI: Prof. Jonas Erjefalt), a number of molecules of relevance for disease pathology will be investigated in bronchial biopsies collected from the 300 subjects in the Bronchoscopy segment.
详细描述
Chronic Obstructive Pulmonary Disease (COPD) is an umbrella diagnosis defined by obstructive lung function impairments, and is likely to be caused by a multitude of etiologies including environmental exposures, genetic predispositions and developmental factors. Due to the heterogeneity of the disease, molecular and mechanistic sub-phenotyping of COPD represents an essential step to facilitate the development of relevant diagnostic and treatment options for this constantly growing patient group. In the BRONCHO-SCAPIS study, molecular sub-phenotypes of smoking-induced COPD are investigated. A particular focus relates to recent epidemiological indications of an increasing proportion of never-smokers developing the disease. The study encompasses profiling of mRNA, miRNA, proteomes, metabolomes and lipid mediators of from multiple lung compartments (airway epithelium, alveolar macrophages, exosomes, and bronchoalveolar exudates) using a range of 'omics platforms, in combination with extensive clinical phenotyping of early stage COPD patients, never-smokers, and smokers with normal lung function from both genders. The primary objective of the study is to identify molecular sub-phenotypes of never-smokers with COPD, specifically by correlating clinical phenotypes multi-molecular 'omics profiling from multiple lung compartments of early stage COPD patients compared to healthy and at-risk control populations. Secondary goals involve identification of subsets of prognostic/diagnostic biomarkers for classification of the defined subgroups, as well as relevant pharmaceutical targets.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 50 Years 至 68 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Spirometry of postbronchodilator forced expiratory volume in 1 second (FEV1) >50% of predicted level for all groups.
- •Spirometry of postbronchodilator FEV1 >80% of predicted level and FEV1/FVC ratio >0.70 for Healthy control groups
- •Spirometry of postbronchodilator FEV1/FVC ratio <0.70 for COPD groups.
排除标准
- •Smoking (for never-smoker groups)
- •Other lung diseases
- •Received antibiotics in the 3 months prior to study entry
- •Treatment with oral or inhaled glucocorticoids within past 3 months prior to study entry
结局指标
主要结局
Forced expiratory volume in 1 second (FEV1)
时间窗: Measured at baseline
Calculated as percent predicted based on the European Coal and Steel Community reference values
Emphysema, as shown on chest CT scan
时间窗: Measured at baseline
Based on lung densities \< (-950) Hounsfield units (HU)
Airway wall thickness on chest CT scan
时间窗: Measured at baseline
Based on lung densities in the range of (-750) - (-900) HU
COPD status (COPD participants versus control group participants) based on GOLD criteria
时间窗: Measured at baseline
Calculated using, post-bronchodilator values defined as meeting the criteria based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) of a fixed FEV1/forced vital capacity (FVC) ratio \< 0.7
COPD status (COPD participants versus control group participants) based on GLI criteria
时间窗: Measured at baseline
Calculated using, post-bronchodilator values defined as meeting the Global Lung Initiative (GLI) ratio of FEV1/FVC below of lowest limit of normal z-score \< (-1.64)
次要结局
- Molecular phenotypes of never-smoker COPD group(s) as compared to control groups(Measured at baseline)
研究者
Asa Wheelock
Associate professor
Karolinska Institutet