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

 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