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

Sponsor
Taipei Medical University WanFang Hospital (Other)
Overall Status
Unknown status
CT.gov ID
NCT03473119
Collaborator
(none)
600
Enrollment
1
Location
60
Anticipated Duration (Months)
10
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase

    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 Design

    Study Type:
    Observational
    Anticipated Enrollment :
    600 participants
    Observational Model:
    Case-Control
    Time Perspective:
    Prospective
    Official Title:
    Acute Effects of Particulate Matter on Pulmonary Diseases: Discovery Its Chemo-signatures
    Actual Study Start Date :
    Mar 19, 2016
    Anticipated Primary Completion Date :
    Mar 19, 2021
    Anticipated Study Completion Date :
    Mar 19, 2021

    Arms and Interventions

    Arm Intervention/Treatment
    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

    Outcome Measures

    Primary Outcome Measures

    1. Mortality [3 months]

      3 months mortality

    Secondary Outcome Measures

    1. ICU [During the hospital admission]

      ICU admission

    2. ETT [During the hospital admission]

      On Tracheal tube

    3. BiPAP [During the hospital admission]

      Using Bilevel Positive Airway Pressure

    4. Length of Stay [During the hospital admission]

      length of hospital stay

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The Emergency Department of Wan Fang Hospital Taipei Wenshan District Taiwan

    Sponsors and Collaborators

    • Taipei Medical University WanFang Hospital

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Taipei Medical University WanFang Hospital
    ClinicalTrials.gov Identifier:
    NCT03473119
    Other Study ID Numbers:
    • N201602089
    First Posted:
    Mar 22, 2018
    Last Update Posted:
    Jul 10, 2019
    Last Verified:
    Apr 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Taipei Medical University WanFang Hospital
    Sphingosine-1-phosphate
    Additional relevant MeSH terms:
    Pneumonia
    Lung Diseases
    Lung Diseases, Obstructive
    Pulmonary Disease, Chronic Obstructive

    Study Results

    No Results Posted as of Jul 10, 2019