Relationship Between Plasma Metabolome and the Efficacy of Systemic Glucocorticoid in AECOPD

Relationship Between Plasma Metabolome and the Efficacy of Systemic Glucocorticoid in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) significantly increases the mortality of the patients with COPD. Guidelines have recommended systemic glucocorticoid as regular treatment. Recently, evidences have shown that systemic glucocorticoid cannot not be benefit to all of the patients with AECOPD. Thus the problem that how the clinicians can screen the patients who can benefit from systemic glucocorticoid needs to be solved urgently.

Study Overview

• Status: Recruiting
• Conditions: COPD; COPD Exacerbation Acute
• Intervention / Treatment: Diagnostic test: Serum metabolic markers

Detailed Description

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) significantly increases the mortality of the patients with COPD. Guidelines have recommended systemic glucocorticoid as regular treatment. Recently, evidences have shown that systemic glucocorticoid cannot not be benefit to all of the patients with AECOPD. Thus the problem that how the clinicians can screen the patients who can benefit from systemic glucocorticoid needs to be solved urgently. A previous study found that plasma metabolome changed significantly after dexamethasone treatment in health participants. Furthermore, inter-person variability was high and remained uninfluenced by treatment, suggesting the potential of metabolomics for predicting the efficacy and side effects of systemic glucocorticoid. Our previous study found that serum metabolites profile in COPD patients differed from that in controls. Therefore, the investigators hypothesized that metabolome changes in patients with AECOPD may be associated with the efficacy of systemic glucocorticoid. In this study, the investigators will utilize ultraperformance liquid chromatography / mass spectrometry (LC-MS) and gas chromatography / mass spectrometry (GC-MS) methods for analysis of the metabolites in AECOPD patients and compare the metabolites profiles between patients with systemic glucocorticoid treatment success and treatment failure. The investigators aim to detect the metabolic biomarkers and metabolic pathways which are related to efficacy of systemic glucocorticoid and contribute to the precise treatment of COPD.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100191
    • Recruiting
    • Peking University Third Hospital
    • Contact: Qiu-Yu Li, MD; Phone Number: 15901118991; Email: liqiuyu19871011@foxmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A prospective study was conducted to recruit consecutive patients from January 1, 2020 to January 1, 2021 who were hospitalized in the Department of Respiratory and Critical Care Medicine in Peking University Third Hospital and met the diagnostic criteria of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Global Initiative for Chronic Obstructive Lung Diseas 2016 (GOLD 2016).

Description

Inclusion Criteria:

• Patients who meet the diagnostic criteria for acute exacerbation of chronic obstructive pulmonary disease in GOLD 2016 and require hospitalization.

Exclusion Criteria:

• Bronchial asthma, bronchiectasis and other airflow obstructive diseases;
• Combined with community-acquired pneumonia, hospital-acquired pneumonia or aspiration pneumonia;
• Combined with severe liver and kidney insufficiency;
• Malignant tumor;
• Immune deficiency due to chemotherapy or HIV infection;
• Received systemic hormone therapy due to acute exacerbation of chronic obstructive pulmonary disease within 1 month before this admission;
• Severe trauma or stress, etc.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Treatment Failure Group; The diagnostic criteria of AECOPD is defined in global initiative for chronic obstructive lung disease (GOLD 2016). According to the efficacy of systemic hormone therapy during hospitalization, they were divided into treatment success group and treatment failure group. Definition of systemic glucocorticoid treatment failure during hospitalization is (Reference: Crisafulli E, Torres A, Huerta A, et al. COPD, 2016, 13(1): 82-92): The following occurs from the 2nd to the 7th day after admission Situation: ①Need to receive mechanical ventilation treatment or need to be admitted to the ICU due to illness; ②72 hours after the initial anti-infective treatment, clinical signs of infection persist and need to change antibiotic treatment; ③Death from any cause.	Diagnostic test: Serum metabolic markers; Ultraperformance liquid chromatography / mass spectrometry (LC-MS) and gas chromatography / mass spectrometry (GC-MS) methods for analysis of the metabolites in AECOPD patients and compare the metabolites profiles between patients with systemic glucocorticoid treatment success and treatment failure.; Other Names: Metbolomics
Treatment Success Group; The diagnostic criteria of AECOPD is defined in global initiative for chronic obstructive lung disease (GOLD 2016). According to the efficacy of systemic hormone therapy during hospitalization, they were divided into treatment success group and treatment failure group. The treatment success group was defined as not meeting any of the following conditions for failure of systemic hormone therapy during hospitalization (reference: Crisafulli E, Torres A, Huerta A, et al. COPD, 2016, 13(1): 82-92): ①Need to receive mechanical ventilation treatment or need to be admitted to the ICU due to illness; ②72 hours after the initial anti-infective treatment, clinical signs of infection persist and need to change antibiotic treatment; ③Death from any cause.	Diagnostic test: Serum metabolic markers; Ultraperformance liquid chromatography / mass spectrometry (LC-MS) and gas chromatography / mass spectrometry (GC-MS) methods for analysis of the metabolites in AECOPD patients and compare the metabolites profiles between patients with systemic glucocorticoid treatment success and treatment failure.; Other Names: Metbolomics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic markers related to systemic glucocorticoid therapy	Through metabolomics research methods such as liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry, study the metabolic marker group profile of patients with acute exacerbation of COPD before receiving systemic glucocorticoid therapy, and look for possible systemic metabolic markers related to the short-term and long-term effects of glucocorticoids.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay	The time interval from admission to discharge of the patient this time	1 year
Time from discharge to the next exacerbation	The time interval from the patient's discharge from the hospital to the next acute exacerbation of chronic obstructive pulmonary disease	1 year
Side effects of glucocorticoid therapy	Any side effects related to glucocorticoid therapy, including osteoporosis, hyperglycemia, infection, etc.	1 year
Mortality within 1 year	The mortality rate of the patients within 1 year after enrollment, including overall mortality and COPD-related mortality	1 year
Acute exacerbation frequency	The number of acute exacerbations of chronic obstructive pulmonary disease in the one year follow-up after enrollment	1 year
mMRC score	Evaluate the severity of dyspnea through a modified version of the British Medical Research Council Respiratory Questionnaire (mMRC)	1 year
CAT score	Evaluate the severity of dyspnea through the COPD assessment Test questionnaire (CAT)	1 year
Changes in pulmonary function	Ventilation function and changes indicated by the patient's pulmonary function test	1 year

Collaborators and Investigators

• Sponsor: Peking University Third Hospital

Publications and helpful links

General Publications

• Li QY, An ZY, Pan ZH, Qi RY. Rationale and design of REGULATE: an observational study protocol for relationship between plasma metabolome and the efficacy of systemic glucocorticoid in acute exacerbation of chronic obstructive pulmonary disease. BMC Pulm Med. 2021 Jul 28;21(1):250. doi: 10.1186/s12890-021-01614-3.

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2021
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: January 10, 2021
• First Submitted That Met QC Criteria: January 12, 2021
• First Posted (Actual): January 15, 2021

Study Record Updates

• Last Update Posted (Actual): January 15, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: PUTH-COPD001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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