Clinical & Systems Medicine Investigations of Smoking-related Chronic Obstructive Pulmonary Disease

Active, not recruiting

• Conditions: Chronic Airways Obstruction; Emphysema; Smoking; Chronic Obstructive Pulmonary Disease; Chronic Bronchitis

• Registration Number: NCT02627872
• Lead Sponsor: Karolinska Institutet

Brief Summary

Chronic Obstructive Pulmonary Disease (COPD) is an increasing global health problem, which primarily increases among the female population. The purpose of this study is to perform in-depth clinical and molecular characterizations of early stage COPD patients, as well as healthy never-smoker and at-risk smoking control populations to identify molecularly related subgroups patients, including gender-related sub-phenotypes of COPD.

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 Karolinska COSMIC study, the investigators are investigating molecular sub-phenotypes of smoking-induced COPD. A particular focus relates to recent epidemiological indications of gender differences in both incidence and severity of disease, with post-menopausal women being at greatest risk. 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 patients 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
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2007-03
• Study First Submitted: 2015-12-09
• Study First Submitted QC: 2015-12-10
• Study First Posted: 2015-12-11
• Primary Completion: 2021-12
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-24
• Last Update Posted: 2022-11-30
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• For smokers, at least 10 pack-years of cigarette smoking
• For smokers, at least 10 cigarettes/day the past 6 months before study entry Spirometry that meets stage I-II of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages (postbronchodilator forced expiratory volume in 1 second (FEV1) of 50%-100% of predicted level and FEV1/forced vital capacity [FEV1/FVC] less than 0.7) or normal (postbronchodilator FEV1 greater than 80% of predicted level and forced expiratory volume in 1 second/forced vital capacity [FEV1/FVC] greater than 0.7)

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Exclusion Criteria

• Other lung diseases
• Atopy (defined as positive specific IgE test)
• Asthma
• Received antibiotics for a COPD exacerbation in the 3 months prior to study entry
• Treatment with oral or inhaled glucocorticoids within past 3 months prior to study entry
• Significant ischaemic heart disease or arrhythmia

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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 and up to 10 year follow-up
Molecular gender differences	Measured at baseline	Molecular levels investigated: mRNA, miRNA, proteome, metabolome, lipidome
Airway wall thickness on chest CT scan	Measured at baseline and up to 10 year follow-up
COPD status (COPD participants versus control group participants)	Measured at baseline and up to 10 year follow-up
Emphysema, as shown on chest CT scan	Measured at baseline and up to 10 year follow-up

Trial Locations

Locations (1)

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