BROnchoalveolar Investigations of Never-smokers With Chronic Obstruction From the Swedish CardioPulmonary bioImage Study

Recruiting

• Conditions: Gender; Chronic Obstructive Pulmonary Disease; Emphysema; Airway Obstruction; Chronic Bronchitis; Smoking, Tobacco

• Registration Number: NCT03049202
• Lead Sponsor: Karolinska Institutet

Brief Summary

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.

Detailed Description

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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2017-01-31
• Study Start: 2017-02-01
• Study First Submitted QC: 2017-02-07
• Study First Posted: 2017-02-09
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-24
• Last Update Posted: 2022-11-28
• Primary Completion: 2023-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

• 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.

Read More

Exclusion Criteria

• 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

Read More

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Forced expiratory volume in 1 second (FEV1)	Measured at baseline	Calculated as percent predicted based on the European Coal and Steel Community reference values
Emphysema, as shown on chest CT scan	Measured at baseline	Based on lung densities \< (-950) Hounsfield units (HU)
Airway wall thickness on chest CT scan	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	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	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)

Secondary Outcome Measures

Name	Time	Method
Molecular phenotypes of never-smoker COPD group(s) as compared to control groups	Measured at baseline	mRNA, miRNA, proteomes, lipidomes and metabolomes will be quantified from airway exudates (BAL fluid), BAL cells, and airway epithelium (bronchial brushings)

Trial Locations

Locations (6)

Karolinska Institutet/Karolinska University Hospital Solna; 🇸🇪 Stockholm, Sverige, Sweden

Göteborg University / Sahlgrenska University Hospital; 🇸🇪 Gothenburg, Sweden

Linköping Unversity /Linköping University Hospital; 🇸🇪 Linköping, Sweden

Uppsala University / Uppsala University Hospital; 🇸🇪 Uppsala, Sweden

Lund University / Lund University Hospital; 🇸🇪 Lund, Sweden

Umeå University / Umeå University Hospital; 🇸🇪 Umeå, Sweden