Relationship Between Metabolic Profile and Clinical Phenotype in Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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Despite the high prevalence of chronic obstructive pulmonary disease (COPD), there continues to be a large gap in our understanding of disease pathogenesis and mechanisms accounting for large variability in disease phenotype. Untargeted metabolomics is an ideal approach to uncover the metabolic basis of disease, as well as discover unique drug target opportunities aimed at these nodal metabolic drivers of disease. There are very limited data from metabolomics studies from plasma/serum and exhaled breath condensate that suggest certain metabolic pathways or metabolites might predict the presence and/or severity of COPD phenotypes. Here, the investigators hope to generate comprehensive, compartment specific (blood and lung) metabolite profiles that will be correlated with various clinical phenotypes of COPD, using a complementary approach of untargeted nuclear magnetic resonance (NMR) and liquid chromatography (LC)- mass spectroscopy (MS) -based metabolomics.

Detailed Description
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Despite the high prevalence of chronic obstructive pulmonary disease (COPD), there continues to be a large gap in our understanding of disease pathogenesis and mechanisms accounting for large variability in disease phenotype. Untargeted metabolomics is an ideal approach to uncover the metabolic basis of disease, as well as discover unique drug target opportunities aimed at these nodal metabolic drivers of disease. There are very limited data from metabolomics studies from plasma/serum and exhaled breath condensate that suggest certain metabolic pathways or metabolites might predict the presence and/or severity of COPD phenotypes. The investigators hypothesize that: 1) smokers with COPD will have a metabolomics signature that is distinct from healthy non-COPD smokers; 2) this signature will be associated with clinically relevant manifestations of disease (e.g., GOLD classification, PFT). The availability of biosamples from a well-characterized population of smokers with and without COPD, combined with our established in-house metabolomics expertise, will robustly allow to test these novel hypotheses. The investigators hope to generate comprehensive, compartment specific (blood and lung) metabolite profiles that will be correlated with various clinical phenotypes of COPD, using a complementary approach of untargeted nuclear magnetic resonance (NMR) and liquid chromatography (LC)- mass spectroscopy (MS) -based metabolomics. Moreover, this strategy may identify previously unrecognized metabolic pathways that are dysregulated in COPD. Collectively, these data will be used to direct a prospective clinical study to determine the association between metabolomics signatures and clinical outcomes.

Official Title
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Compartmental Analysis of Metabolite Profiles Associated With Disease Phenotype in Smokers With and Without Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease

Participation Criteria
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Eligibility Criteria
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IInclusion Criteria: males aged 40-80; diagnosed with COPD according to the GOLD guidelines; clinically stable patients without medication changes or exacerbation in two months; smoking history of more than 10 pack years Exclusion Criteria: diagnosed with unstable cardiovascular diseases, significant renal or hepatic dysfunction or mental incompetence; diagnosed with asthma, active pulmonary tuberculosis, diffuse panbronchiolitis, cystic fibrosis, clinically significant bronchiectasis, exacerbation of COPD or pneumonia in two months; prescribed immunosuppressive medications.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COPD<br>The smokers who are diagnosed as chronic obstructive pulmonary disease according to GOLD guideline. | |
| healthy control<br>The healthy controls without chronic obstructive pulmonary disease | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolites that can predict the progress of lung function | The study is aimed to investigate the relationship between the metabolites and the progress of lung function in COPD | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolites that can predict the severity of emphysema | The association between metabolites and emphysema is also investigated | 3 months | 
| Metabolites that are associated with inflammatory mediators | The association between metabolites and inflammatory mediators is also investigated | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease, Metabolomics