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

NCT03049202 | Active Not Recruiting DMC

• 1 other identifier: 2016/841-31/2
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 6

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.

Conditions

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

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (1)

• Molecular phenotypes of never-smoker COPD group(s) as compared to control groups

  Measured at baseline

Study Arms (5)

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.

Eligibility Criteria

• Age: 50 Years - 68 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Karolinska Institutet: lead
• Swedish Heart Lung Foundation: collaborator
• Lund University: collaborator
• Göteborg University: collaborator
• Linkoeping University: collaborator
• Uppsala University: collaborator
• Umeå University: collaborator
• Karolinska University Hospital: collaborator
• Lund University Hospital: collaborator
• Sahlgrenska University Hospital: collaborator
• University Hospital, Linkoeping: collaborator
• Uppsala University Hospital: collaborator
• University Hospital, Umeå: collaborator
• Region Stockholm: collaborator

Study Sites (6)

Karolinska Institutet/Karolinska University Hospital Solna

Stockholm, Sverige, 17176, Sweden

Location

Göteborg University / Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Linköping Unversity /Linköping University Hospital

Linköping, Sweden

Location

Lund University / Lund University Hospital

Lund, Sweden

Location

Umeå University / Umeå University Hospital

Umeå, Sweden

Location

Uppsala University / Uppsala University Hospital

Uppsala, Sweden

Location

Biospecimen

Retention: SAMPLES WITH DNA

Mouth wash, bronchoalveolar lavage (BAL) cells, BAL fluid, bronchial wash (BW) cells, BW fluid, bronchial biopsies, airway epithelial brushings, serum, plasma, blood cells, and urine are collected and stored.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Emphysema; Bronchitis, Chronic; Airway Obstruction; Tobacco Smoking; Coitus

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases; Respiratory Insufficiency; Respiration Disorders; Smoking; Behavior; Tobacco Use; Sexual Behavior

Study Officials

• Magnus Skold, MD, PhD

  Karolinska Institutet /Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: January 31, 2017
• First Posted: February 9, 2017
• Study Start: February 1, 2017
• Primary Completion: June 30, 2024
• Study Completion (Estimated): December 31, 2030
• Last Updated: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (6)