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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 167

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Clinically stable patients with COPD and controls without COPD are enrolled.

Description

IInclusion Criteria:

1. males aged 40-80;
2. diagnosed with COPD according to the GOLD guidelines;
3. clinically stable patients without medication changes or exacerbation in two months;
4. smoking history of more than 10 pack years

Exclusion Criteria:

1. diagnosed with unstable cardiovascular diseases, significant renal or hepatic dysfunction or mental incompetence;
2. diagnosed with asthma, active pulmonary tuberculosis, diffuse panbronchiolitis, cystic fibrosis, clinically significant bronchiectasis, exacerbation of COPD or pneumonia in two months;
3. prescribed immunosuppressive medications.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
COPD; The smokers who are diagnosed as chronic obstructive pulmonary disease according to GOLD guideline.
healthy control; The healthy controls without chronic obstructive pulmonary disease

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking University Third Hospital

Publications and helpful links

General Publications

• Diao W, Labaki WW, Han MK, Yeomans L, Sun Y, Smiley Z, Kim JH, McHugh C, Xiang P, Shen N, Sun X, Guo C, Lu M, Standiford TJ, He B, Stringer KA. Disruption of histidine and energy homeostasis in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2019 Sep 3;14:2015-2025. doi: 10.2147/COPD.S210598. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2015
• Primary Completion (Actual): July 20, 2017
• Study Completion (Actual): July 20, 2017

Study Registration Dates

• First Submitted: October 10, 2017
• First Submitted That Met QC Criteria: October 10, 2017
• First Posted (Actual): October 16, 2017

Study Record Updates

• Last Update Posted (Actual): October 17, 2017
• Last Update Submitted That Met QC Criteria: October 15, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Metabolomics; Chronic Obstructive Pulmonary Disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: Metabolomcs-HB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No