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