Clinical trial NCT03049202: BROnchoalveolar Investigations of Never-smokers With Chronic Obstruction From the Swedish CardioPulmonary bioImage Study
Official title: BROnchoalveolar Investigations of Never-smokers With CHronic Obstructive Lung Disease From the Swedish CardioPulmonary bioImage Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Chronic Obstructive Pulmonary Disease
Emphysema
Chronic Bronchitis
Airway Obstruction
Smoking, Tobacco
Gender
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Swedish Heart Lung Foundation
name: Lund University
name: Göteborg University
name: Linkoeping University
name: Uppsala University
name: Umeå University
name: Karolinska University Hospital
name: Lund University Hospital
name: Sahlgrenska University Hospital
name: University Hospital, Linkoeping
name: Uppsala University Hospital
name: University Hospital, Umeå
name: Region Stockholm
First posted: 2017-02-09
Enrollment: 1000
Sex: ALL
Minimum age (years): 50
Maximum age (years): 68
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The 1000 participants are recruited from the Swedish SCAPIS study, a cross sectional study screening 30,000 subjects across the six University Hospitals in Sweden, based on lung function criteria and questionnaire criteria collected during SCAPIS.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Forced expiratory volume in 1 second (FEV1)
timeFrame: Measured at baseline
measure: Emphysema, as shown on chest CT scan
timeFrame: Measured at baseline
measure: Airway wall thickness on chest CT scan
timeFrame: Measured at baseline
measure: COPD status (COPD participants versus control group participants) based on GOLD criteria
timeFrame: Measured at baseline
measure: COPD status (COPD participants versus control group participants) based on GLI criteria
timeFrame: Measured at baseline
Secondary outcomes:
measure: Molecular phenotypes of never-smoker COPD group(s) as compared to control groups
timeFrame: Measured at baseline
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska Institutet/Karolinska University Hospital Solna
state: Sverige
city: Gothenburg
country: Sweden
facility: Göteborg University / Sahlgrenska University Hospital
city: Linköping
country: Sweden
facility: Linköping Unversity /Linköping University Hospital
city: Lund
country: Sweden
facility: Lund University / Lund University Hospital
city: Umeå
country: Sweden
facility: Umeå University / Umeå University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University / Uppsala University Hospital
Study officials:
affiliation: Karolinska Institutet /Karolinska University Hospital
name: Magnus Skold, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: