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

Chronic Obstructive Pulmonary Disease Clinical Trial

— BRONCOSCAPIS  

Official title:

BROnchoalveolar Investigations of Never-smokers With CHronic Obstructive Lung Disease From the Swedish CardioPulmonary bioImage Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03049202
• Other study ID #: 2016/841-31/2
• Status: Recruiting
• Start date: February 1, 2017
• Est. completion date: December 31, 2028

Study information

• Verified date: November 2022
• Source: Karolinska Institutet
• Contact: Magnus Skold, MD, PhD
• Phone: +46 8 517 748 43
• Email: magnus.skold[@]ki.se
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 68 Years

Eligibility

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.

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

Related Conditions & MeSH terms

• Airway Obstruction
• Bronchitis
• Bronchitis, Chronic
• Chronic Bronchitis
• Chronic Obstructive Pulmonary Disease
• Emphysema
• Gender
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive
• Smoking, Tobacco

Locations

Country	Name	City	State
Sweden	Göteborg University / Sahlgrenska University Hospital	Gothenburg
Sweden	Linköping Unversity /Linköping University Hospital	Linköping
Sweden	Lund University / Lund University Hospital	Lund
Sweden	Karolinska Institutet/Karolinska University Hospital Solna	Stockholm	Sverige
Sweden	Umeå University / Umeå University Hospital	Umeå
Sweden	Uppsala University / Uppsala University Hospital	Uppsala

Sponsors (14)

Lead Sponsor	Collaborator
Karolinska Institutet	Göteborg University, Karolinska University Hospital, Linkoeping University, Lund University, Lund University Hospital, Region Stockholm, Sahlgrenska University Hospital, Sweden, Swedish Heart Lung Foundation, Umeå University, University Hospital, Linkoeping, University Hospital, Umeå, Uppsala University, Uppsala University Hospital

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forced expiratory volume in 1 second (FEV1)	Calculated as percent predicted based on the European Coal and Steel Community reference values	Measured at baseline
Primary	Emphysema, as shown on chest CT scan	Based on lung densities < (-950) Hounsfield units (HU)	Measured at baseline
Primary	Airway wall thickness on chest CT scan	Based on lung densities in the range of (-750) - (-900) HU	Measured at baseline
Primary	COPD status (COPD participants versus control group participants) based on GOLD criteria	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	Measured at baseline
Primary	COPD status (COPD participants versus control group participants) based on GLI criteria	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)	Measured at baseline
Secondary	Molecular phenotypes of never-smoker COPD group(s) as compared to control groups	mRNA, miRNA, proteomes, lipidomes and metabolomes will be quantified from airway exudates (BAL fluid), BAL cells, and airway epithelium (bronchial brushings)	Measured at baseline