The Research of Metabolomics on COPD (COPD)

The Correlation Research Between the Omega-3 and Omega-6 Inflammatory Metabolites and Stable COPD.

Targeted metabolomics research was conducted on patients with chronic obstructive pulmonary disease (COPD). The correlation analyst between inflammation-related metabolites and lung function was analyzed by explored the metabolic pathways of inflammation-related omega-6 and omega-3 and combining them with lung function.

Study Overview

• Status: Completed
• Conditions: COPD; Metabolomics; Omega 3; Omega 6
• Intervention / Treatment: Diagnostic test: Routine blood test; Diagnostic test: Lung function test was performed on the subjects with Jaeger lung function instrument of Germany.; Diagnostic test: Agilent 1290 Infinity LC system (UHPLC, Santa Clara CA) was used for Targeted metabolite detection.

Detailed Description

Based on the global initiative for chronic obstructive pulmonary disease, the 80 confirmed stable COPD patients with mild-to-moderate were involved, 80 COPD patients with severe and very severe, and age, sex, all matching 40 cases without lung disease. The participants information was collected. Whole blood and pulmonary function were examined at three time points: admission, six months and one year, at the same time, targeted metabolomic analysis method are applied to detect serum metabolites, According to the access to assess the different severity of COPD in the stable period and the level of metabolites in different admission periods. After that, correlation analysis was conducted with pulmonary function indicators and other clinical indicators to observe the research value of inflammation-related metabolites in the development of COPD.

• Study Type: Observational
• Enrollment (Actual): 200

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Based on the global initiative for chronic obstructive pulmonary disease, the 80 confirmed stable COPD patients with mild-to-moderate were involved, 80 COPD patients with severe and very severe, and age, sex, all matching 40 cases without lung disease. The participants information was collected. Whole blood and pulmonary function were examined at three time points: admission, six months and one year, at the same time, targeted metabolomic analysis method are applied to detect serum metabolites, According to the access to assess the different severity of COPD in the stable period and the level of metabolites in different admission periods.

Description

Inclusion Criteria:

• COPD diagnosis
• The age ranges from 40 to 80
• No other pulmonary diseases
• No immune-related diseases

Exclusion Criteria:

• Not consistent with COPD diagnosis
• Age is out of range
• Interstitial lung disease, asthma and other lung diseases
• Immune system diseases
• Lost to follow-up

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy control; age - and sex-matched healthy individuals without lung disease	Diagnostic test: Routine blood test; Blood routine test results include CRP, PCT, white blood cell count, red blood cell count, neutrophil percentage, eosinophil, basophil, et al.
Patients with mild and moderate COPD; Grading according to the GOLD guide standards	Diagnostic test: Routine blood test; Blood routine test results include CRP, PCT, white blood cell count, red blood cell count, neutrophil percentage, eosinophil, basophil, et al.; Diagnostic test: Lung function test was performed on the subjects with Jaeger lung function instrument of Germany.; This Jaeger lung function instrument of Germany is used to test the pulmonary ventilation function of COPD patients. Since the condition requires drug control and treatment, the drug cannot be stopped.; Diagnostic test: Agilent 1290 Infinity LC system (UHPLC, Santa Clara CA) was used for Targeted metabolite detection.; We used the Agilent 1290 Infinity LC system mass spectrometer to analyze and detect metabolite peaks of patients according to retention time and mass/charge ratio after preliminary experiments and derivatization.
Patients with severe and very severe COPD; Grading according to the GOLD guide standards	Diagnostic test: Routine blood test; Blood routine test results include CRP, PCT, white blood cell count, red blood cell count, neutrophil percentage, eosinophil, basophil, et al.; Diagnostic test: Lung function test was performed on the subjects with Jaeger lung function instrument of Germany.; This Jaeger lung function instrument of Germany is used to test the pulmonary ventilation function of COPD patients. Since the condition requires drug control and treatment, the drug cannot be stopped.; Diagnostic test: Agilent 1290 Infinity LC system (UHPLC, Santa Clara CA) was used for Targeted metabolite detection.; We used the Agilent 1290 Infinity LC system mass spectrometer to analyze and detect metabolite peaks of patients according to retention time and mass/charge ratio after preliminary experiments and derivatization.
The severe and very severe COPD group baseline; Severe and very severe COPD patients were in the baseline time group	Diagnostic test: Routine blood test; Blood routine test results include CRP, PCT, white blood cell count, red blood cell count, neutrophil percentage, eosinophil, basophil, et al.; Diagnostic test: Lung function test was performed on the subjects with Jaeger lung function instrument of Germany.; This Jaeger lung function instrument of Germany is used to test the pulmonary ventilation function of COPD patients. Since the condition requires drug control and treatment, the drug cannot be stopped.; Diagnostic test: Agilent 1290 Infinity LC system (UHPLC, Santa Clara CA) was used for Targeted metabolite detection.; We used the Agilent 1290 Infinity LC system mass spectrometer to analyze and detect metabolite peaks of patients according to retention time and mass/charge ratio after preliminary experiments and derivatization.
The severe and very severe COPD group six months; Patients with severe and very severe COPD were six months from baseline.	Diagnostic test: Routine blood test; Blood routine test results include CRP, PCT, white blood cell count, red blood cell count, neutrophil percentage, eosinophil, basophil, et al.; Diagnostic test: Lung function test was performed on the subjects with Jaeger lung function instrument of Germany.; This Jaeger lung function instrument of Germany is used to test the pulmonary ventilation function of COPD patients. Since the condition requires drug control and treatment, the drug cannot be stopped.; Diagnostic test: Agilent 1290 Infinity LC system (UHPLC, Santa Clara CA) was used for Targeted metabolite detection.; We used the Agilent 1290 Infinity LC system mass spectrometer to analyze and detect metabolite peaks of patients according to retention time and mass/charge ratio after preliminary experiments and derivatization.
The severe and very severe COPD group one year; Patients with severe and very severe COPD were one year from baseline.	Diagnostic test: Routine blood test; Blood routine test results include CRP, PCT, white blood cell count, red blood cell count, neutrophil percentage, eosinophil, basophil, et al.; Diagnostic test: Lung function test was performed on the subjects with Jaeger lung function instrument of Germany.; This Jaeger lung function instrument of Germany is used to test the pulmonary ventilation function of COPD patients. Since the condition requires drug control and treatment, the drug cannot be stopped.; Diagnostic test: Agilent 1290 Infinity LC system (UHPLC, Santa Clara CA) was used for Targeted metabolite detection.; We used the Agilent 1290 Infinity LC system mass spectrometer to analyze and detect metabolite peaks of patients according to retention time and mass/charge ratio after preliminary experiments and derivatization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced expiratory volume in 1 second (FEV1)	The FEV1 percentage of predicted value is an important indicator in the diagnosis and treatment of COPD, and plays an important role in the severity rating.; level (mild) : FEV1 / FVC < 70%, FEV1% pred > 80%. Ⅱ level (moderate) : FEV1 / FVC < 70%, 50% ≦ FEV1% pred< 80%. Ⅲ level (severe) : FEV1 / FVC < 70%, 30% ≦ FEV1% pred < 50%. IV level (very severe) : FEV1/FVC<70%, FEV1% pred < 30%, or FEV1% pred <50% with chronic respiratory failure.	October 1, 2016 to October 1, 2018
Forced vital capacity (FVC)	FVC is an important index to determine the resistance of respiratory tract. FEV1 and FEV1/FVC% in patients with obstructive airway obstruction, such as patients with chronic obstructive pulmonary disease, were reduced due to airway obstruction and prolonged expiratory.	October 1, 2016 to October 1, 2018
FEV1/FVC ratio	This index is an important basis for the diagnosis of COPD and is crucial in the early stage of the disease to the later stage of the evaluation.	October 1, 2016 to October 1, 2018
The metabolites of Omega-6 inflammatory indicator	Agilent 1290 Infinity LC system (UHPLC, Santa Clara CA) was used for the targeted determination of metabolites in the serum of subjects. Omega6 metabolites are closely related to inflammation and have been shown to be involved in a variety of diseases such as COPD, rheumatism, cardiovascular disease, et al.	October 1, 2016 to October 1, 2018
The metabolites of Omega-3 inflammatory indicator	As an important anti-inflammatory factor, omega-3 is widely used in chronic inflammatory diseases, which can fight against the pro-inflammatory metabolites of omega-6.	October 1, 2016 to October 1, 2018

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-reaction protein	CRP is an acute phase protein synthesized by liver cells in response to inflammatory stimuli such as microbial invasion or tissue injury. Can reflect the inflammation level in COPD patients.	October 1, 2016 to October 1, 2018
Leukocyte Count	White blood cells are very important blood cells in human blood. White blood cells bear many important tasks in the human body. They have the function of swallowing foreign bodies and producing antibodies.	October 1, 2016 to October 1, 2018

Collaborators and Investigators

• Sponsor: Guangzhou Institute of Respiratory Disease
• Collaborators: The Fifth Affiliated Hospital of Zunyi Medical College

Publications and helpful links

General Publications

• Maltais F, Decramer M, Casaburi R, Barreiro E, Burelle Y, Debigare R, Dekhuijzen PN, Franssen F, Gayan-Ramirez G, Gea J, Gosker HR, Gosselink R, Hayot M, Hussain SN, Janssens W, Polkey MI, Roca J, Saey D, Schols AM, Spruit MA, Steiner M, Taivassalo T, Troosters T, Vogiatzis I, Wagner PD; ATS/ERS Ad Hoc Committee on Limb Muscle Dysfunction in COPD. An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2014 May 1;189(9):e15-62. doi: 10.1164/rccm.201402-0373ST.
• Das UN. Ageing: Is there a role for arachidonic acid and other bioactive lipids? A review. J Adv Res. 2018 Feb 15;11:67-79. doi: 10.1016/j.jare.2018.02.004. eCollection 2018 May.
• Serkova NJ, Standiford TJ, Stringer KA. The emerging field of quantitative blood metabolomics for biomarker discovery in critical illnesses. Am J Respir Crit Care Med. 2011 Sep 15;184(6):647-55. doi: 10.1164/rccm.201103-0474CI. Epub 2011 Jun 16.
• Fulton AS, Hill AM, Williams MT, Howe PR, Frith PA, Wood LG, Garg ML, Coates AM. Feasibility of omega-3 fatty acid supplementation as an adjunct therapy for people with chronic obstructive pulmonary disease: study protocol for a randomized controlled trial. Trials. 2013 Apr 24;14:107. doi: 10.1186/1745-6215-14-107.
• Tantucci C, Modina D. Lung function decline in COPD. Int J Chron Obstruct Pulmon Dis. 2012;7:95-9. doi: 10.2147/COPD.S27480. Epub 2012 Feb 9.
• D'Archivio M, Scazzocchio B, Giammarioli S, Fiani ML, Vari R, Santangelo C, Veneziani A, Iacovelli A, Giovannini C, Gessani S, Masella R. omega3-PUFAs exert anti-inflammatory activity in visceral adipocytes from colorectal cancer patients. PLoS One. 2013 Oct 7;8(10):e77432. doi: 10.1371/journal.pone.0077432. eCollection 2013.
• Lemoine S CM, Brigham EP, Woo H, Hanson CK, McCormack MC, Koch A, Putcha N, Hansel NN. Omega-3 fatty acid intake and prevalent respiratory symptoms among U.S. adults with COPD. BMC Pulm Med. 2019 May 21;19(1):97. doi: 10.1186/s12890-019-0852-4.
• Kilk K, Aug A, Ottas A, Soomets U, Altraja S, Altraja A. Phenotyping of Chronic Obstructive Pulmonary Disease Based on the Integration of Metabolomes and Clinical Characteristics. Int J Mol Sci. 2018 Feb 27;19(3):666. doi: 10.3390/ijms19030666.
• Wang Y, Xu J, Meng Y, Adcock IM, Yao X. Role of inflammatory cells in airway remodeling in COPD. Int J Chron Obstruct Pulmon Dis. 2018 Oct 12;13:3341-3348. doi: 10.2147/COPD.S176122. eCollection 2018.
• Pizzini A, Lunger L, Sonnweber T, Weiss G, Tancevski I. The Role of Omega-3 Fatty Acids in the Setting of Coronary Artery Disease and COPD: A Review. Nutrients. 2018 Dec 2;10(12):1864. doi: 10.3390/nu10121864.
• Mesaros C, Blair IA. Targeted chiral analysis of bioactive arachidonic Acid metabolites using liquid-chromatography-mass spectrometry. Metabolites. 2012 Apr 20;2(2):337-65. doi: 10.3390/metabo2020337.
• Schrimpe-Rutledge AC, Codreanu SG, Sherrod SD, McLean JA. Untargeted Metabolomics Strategies-Challenges and Emerging Directions. J Am Soc Mass Spectrom. 2016 Dec;27(12):1897-1905. doi: 10.1007/s13361-016-1469-y. Epub 2016 Sep 13.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2016
• Primary Completion (ACTUAL): October 1, 2018
• Study Completion (ACTUAL): July 5, 2019

Study Registration Dates

• First Submitted: July 29, 2019
• First Submitted That Met QC Criteria: July 31, 2019
• First Posted (ACTUAL): August 2, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 2, 2019
• Last Update Submitted That Met QC Criteria: July 31, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: COPD; Metabolomics; Omega 3; lung function tests; Omega 6
• Other Study ID Numbers: MG-201909

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In this study, smoking time data were also included. Next, we plan to grade smoking time or sick time(Time from baseline or from the time of first diagnosis) to evaluate the change trend of inflammation-related metabolites.
• IPD Sharing Time Frame: We will use the part of data for smoking-related research projects until 2020-06-01.
• IPD Sharing Access Criteria: Patients aged 40 to 80 diagnosed with stable COPD according to diagnostic criteria were selected, regardless of gender. No lung tumor, no interstitial lung disease, no immune-related lung disease. The patient himself or his family signed the informed consent for the experiment.
• IPD Sharing Supporting Information Type: SAP

Drug and device information, study documents

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