Evaluation of Plasma Sphingosine-1-Phosphate as A Diagnostic and Prognostic Biomarkers of Community-Acquired Pneumonia

July 9, 2019 updated by: Taipei Medical University WanFang Hospital

Acute Effects of Particulate Matter on Pulmonary Diseases: Discovery Its Chemo-signatures

Pneumonia is a major infectious cause of death worldwide and imposes a considerable burden on healthcare resources. Obstructive lung diseases (COPD and Asthma) are increasingly important causes of morbidity and mortality worldwide. The patients with community-acquired pneumonia (CAP), and acute exacerbations of obstructive lung diseases commonly present with similar signs and symptoms. For antibiotic use, the rapid and accurate differentiation of clinically relevant of bacterial lower respiratory tract infections from other mimics is essential. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid has both extracellular and intracellular effects in mammalian cells. S1P is involved in many physiological processes including immune responses and endothelial barrier integrity. In term of endothelial barrier integrity, S1P plays a crucial role in protecting lungs from the pulmonary leak and lung injury. Because of the involvement in lung injury, S1P would be the potential biomarker of pneumonia. Based on the above evidence, S1P plays an essential role in the pathobiology of pneumonia was hypothesized.

Study Overview

Status

Unknown

Conditions

Detailed Description

The study was a branch of our PM2.5 observational study (Acute Effects of Particulate Matter on Pulmonary Diseases) and mainly focus on lipid biomarker for the target diseases. Lower respiratory tract infections are the most frequent infectious cause of death worldwide[1] and impose a considerable burden on healthcare resources. Despite the advancement in treatment and diagnostic technique, the overall 30-day mortality rate of community-acquired pneumonia (CAP) is as high as 12.1% for patients who aged 65 years and older admitted to hospital[2]. Obstructive lung diseases (COPD and Asthma) are increasingly important causes of morbidity and mortality worldwide. The patients with CAP, and acute exacerbations of obstructive lung diseases commonly present with similar signs and symptoms.

The use of conventional diagnostic markers, such as complete blood count (CBC) with differential and C-reactive protein is the current mainstream method for differentiating clinically relevant to bacterial lower respiratory tract infections from other mimics. However, for patients with a clinical suspicion of infection, those conventional methods have suboptimal sensitivity and specificity[3,4] The limitations often cause the ambiguity of the initiation of antibiotic treatment. As a result, unnecessary use of antibiotics adversely affects patient outcomes. Also, inappropriate antibiotic therapy increases antibiotic resistance in patients, which poses a public health problem. Current strategies to reduce antibiotic usage have included the development of biomarker-directed treatment algorithms. However, a recent study suggested that procalcitonin-guided therapy has not been effective in reducing antibiotic use[5]. Therefore, developing new biomarkers may be the answer to the problems.

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid has both extracellular and intracellular effects in mammalian cells[6-9]. S1P is synthesized by two sphingosine kinases (SphK1 and SphK 2) and degraded by S1P lyase (S1PL)[6] S1P is a ligand for five G protein-coupled receptors, S1P receptors1-5[6,7], and also acts as an intracellular second messenger[10,11]. S1P is involved in many physiological processes including immune responses and endothelial barrier integrity[12-15]. In term of endothelial barrier integrity, S1P plays a crucial role in protecting lungs from the pulmonary leak and lung injury. [16-19] Previous research suggests that S1P signaling through S1PR1 is crucial for endothelial barrier function. [20] The S1P induces actin polymerization and then results in the spreading of endothelial cells which fills intercellular gaps. Also, the S1P-signaling can stabilize the endothelial cell-cell junctions such as adherens junction and tight junction. [21-23] Both actin-dependent outward spreading of endothelial cells and cell junction stabilization enhance the endothelial barrier function. Because of the involvement in lung injury and endothelial barrier function, S1P would be the potential biomarker of pneumonia.

For the study, a case-control design was utilized for collecting clinical samples. the investigators plan to enroll 150 individuals for each targeted disease (CAP, Asthma, Asthma with CAP, COPD, and COPD with CAP) and control. Peripheral blood will be collected from the patients presenting at the emergency department (ED) of Wan Fang Hospital for an acute event of the candidate diseases. Each recruited individual will fill out a specific questionnaire, which will include lifestyle, occupation, habits, and general dietary information. The initial peripheral blood sample will be obtained in the emergency department, and if the patients were admitted, the individual's blood sample would be collected one day before a planned discharge again. The following parameters will be recorded for each participant: sex, age, body weight, body temperature, vital signs at the ED, and clinical characteristics of the disease. The laboratory testing will include baseline analyses (hematocrit, white blood count with differential, serum sodium, and chloride), ALT, AST, CRP, BUN, and creatinine. The plasma S1P will also be tested and will be measured by ELISA. The questionnaire will provide the individual's basic information of living area, occupational environment, personal habits and family history for further analysis.

Study Type

Observational

Enrollment (Anticipated)

600

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Taiwan
    • Wenshan District
      • Taipei, Wenshan District, Taiwan
        • Recruiting
        • The Emergency Department of Wan Fang Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The individuals who have the target diseases (CAP, Asthma, Asthma with CAP COPD, and COPD with CAP) and healthy controls will be recruited at the emergency department (ED) of Wan Fang Hospital (Taipei, Taiwan). The hospital is affiliated with Taipei Medical University and is located in the metropolitan area of Taipei City, Taiwan, at Wenshan District, and has had more than 65,000 emergency visits annually.

Description

Inclusion Criteria:

  • Clinical diagnosis of chronic obstructive pulmonary disease (COPD; ICD-9 codes 490-492, 494, 496)
  • Clinical diagnosis of Asthma (ICD-9 code 493),
  • Clinical diagnosis of pneumonia (ICD-9 codes 480-488).

Exclusion Criteria:

  • Underage incapacity
  • Pregnant women,
  • Psychiatric history
  • Unfamiliar with Chinese

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Control
Healthy individuals
Asthma
Asthma acute exacerbations
Asthma with CAP
Asthma acute exacerbations with community-acquired pneumonia
COPD
Acute exacerbations of chronic obstructive pulmonary disease
COPD with CAP
Acute exacerbations of chronic obstructive pulmonary disease with community-acquired pneumonia
CAP
Community-acquired pneumonia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: 3 months
3 months mortality
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ICU
Time Frame: During the hospital admission
ICU admission
During the hospital admission
ETT
Time Frame: During the hospital admission
On Tracheal tube
During the hospital admission
BiPAP
Time Frame: During the hospital admission
Using Bilevel Positive Airway Pressure
During the hospital admission
Length of Stay
Time Frame: During the hospital admission
length of hospital stay
During the hospital admission

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Taipei Medical University WanFang Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 19, 2016

Primary Completion (Anticipated)

March 19, 2021

Study Completion (Anticipated)

March 19, 2021

Study Registration Dates

First Submitted

March 14, 2018

First Submitted That Met QC Criteria

March 14, 2018

First Posted (Actual)

March 22, 2018

Study Record Updates

Last Update Posted (Actual)

July 10, 2019

Last Update Submitted That Met QC Criteria

July 9, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • N201602089

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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