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

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ClinicalTrials.gov Identifier: NCT03473119
Recruitment Status : Recruiting
First Posted : March 22, 2018
Last Update Posted : July 6, 2018
Sponsor:
Information provided by (Responsible Party):
Taipei Medical University WanFang Hospital

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
Pneumonia Chronic Obstructive Pulmonary Disease Asthma

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.


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Study Type : Observational
Estimated 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 : March 19, 2016
Estimated Primary Completion Date : March 19, 2021
Estimated Study Completion Date : March 19, 2021

Resource links provided by the National Library of Medicine


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



Primary Outcome Measures :
  1. Mortality [ Time Frame: 3 months ]
    3 months mortality


Secondary Outcome Measures :
  1. ICU [ Time Frame: During the hospital admission ]
    ICU admission

  2. ETT [ Time Frame: During the hospital admission ]
    On Tracheal tube

  3. BiPAP [ Time Frame: During the hospital admission ]
    Using Bilevel Positive Airway Pressure

  4. Length of Stay [ Time Frame: During the hospital admission ]
    length of hospital stay


Biospecimen Retention:   Samples Without DNA
plasma and Urine


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03473119


Contacts
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Contact: Shih-Chang Hsu, MD 29307930 ext 1279 1980bradhsu@gmail.com
Contact: Chin-Wang Hsu, MD Wan11119@gmail.com

Locations
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Taiwan
The Emergency Department of Wan Fang Hospital Recruiting
Taipei, Wenshan District, Taiwan
Contact: Shih-Chang Hsu, MD    29307930 ext 1279    1980bradhsu@gmail.com   
Sponsors and Collaborators
Taipei Medical University WanFang Hospital

Publications:

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Responsible Party: Taipei Medical University WanFang Hospital
ClinicalTrials.gov Identifier: NCT03473119     History of Changes
Other Study ID Numbers: N201602089
First Posted: March 22, 2018    Key Record Dates
Last Update Posted: July 6, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Pneumonia
Respiratory Tract Diseases
Respiratory Tract Infections