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

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

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.

Study Overview

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

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.

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

• Study Contact: Name: Magnus Skold, MD, PhD; Phone Number: +46 8 517 748 43; Email: magnus.skold@ki.se
• Study Contact Backup: Name: Asa M Wheelock, PhD; Phone Number: +46 8 517 70664; Email: asa.wheelock@ki.se

Study Locations

• Sweden
  • Gothenburg, Sweden
    • Recruiting
    • Göteborg University / Sahlgrenska University Hospital
    • Contact: Anders Andersson, MD
    • Contact: Sara Tengvall, MD, PhD
  • Linköping, Sweden
    • Recruiting
    • Linköping Unversity /Linköping University Hospital
    • Contact: Lennart Persson, MD
  • Lund, Sweden
    • Recruiting
    • Lund University / Lund University Hospital
    • Contact: Leif Bjermer, MD
    • Contact: Ellen Tufvesson, PhD
  • Umeå, Sweden
    • Recruiting
    • Umeå University / Umeå University Hospital
    • Contact: Anders Blomberg, MD
  • Uppsala, Sweden
    • Recruiting
    • Uppsala University / Uppsala University Hospital
    • Contact: Christer Janson, MD
    • Contact: Helena Igelström, MD
  • Sverige
    • Stockholm, Sverige, Sweden, 17176
      • Recruiting
      • Karolinska Institutet/Karolinska University Hospital Solna
      • Contact: Magnus Skold, MD, PhD; Email: magnus.skold@ki.se
      • Contact: Asa M Wheelock, PhD; Email: asa.wheelock@ki.se
      • Principal Investigator: C. Magnus Skold, MD, PhD
      • Principal Investigator: Asa M Wheelock, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
Never-smoker COPD participants; COPD patients with mild-to-moderate COPD (GOLD I-II) that have never smoked. Definition of never-smoker: Lifetime consumption of <100 cigarettes. No cigarettes the past 2 years.
Ex-smoker COPD participants; COPD patients with mild-to-moderate COPD (GOLD I-II) that stopped smoking. Definition of smoking: > 10 pack years. Definition of ex-smoker: > 2 years since smoke cessation.
Current-smoker COPD participants; COPD patients with mild-to-moderate COPD (GOLD I-II) that are currently smoking. Definition of smoking: > 10 pack years. Definition of current-smoker: > 10/cigarettes/dat the past 6 months.
Current-smoker healthy controls; Current-smokers that are otherwise healthy, with normal lung function. Definition of smoking: > 10 pack years. Definition of current-smoker: > 10/cigarettes/dat the past 6 months.
Never-smoker healthy controls; Healthy participants that have never smoked. Definition of never-smoker: Lifetime consumption of <100 cigarettes. No cigarettes the past 2 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced expiratory volume in 1 second (FEV1)	Calculated as percent predicted based on the European Coal and Steel Community reference values	Measured at baseline
Emphysema, as shown on chest CT scan	Based on lung densities < (-950) Hounsfield units (HU)	Measured at baseline
Airway wall thickness on chest CT scan	Based on lung densities in the range of (-750) - (-900) HU	Measured at baseline
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Karolinska University Hospital; Lund University; Uppsala University; Göteborg University; Umeå University; Linkoeping University; Sahlgrenska University Hospital, Sweden; Region Stockholm; University Hospital, Linkoeping; Lund University Hospital; University Hospital, Umeå; Swedish Heart Lung Foundation; Uppsala University Hospital
• Investigators: Principal Investigator: Magnus Skold, MD, PhD, Karolinska Institutet /Karolinska University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2028

Study Registration Dates

• First Submitted: January 31, 2017
• First Submitted That Met QC Criteria: February 7, 2017
• First Posted (Estimate): February 9, 2017

Study Record Updates

• Last Update Posted (Actual): November 28, 2022
• Last Update Submitted That Met QC Criteria: November 24, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Bronchial Diseases; Respiratory Insufficiency; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Emphysema; Airway Obstruction; Bronchitis; Bronchitis, Chronic
• Other Study ID Numbers: 2016/841-31/2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No