Ignite Creation Date:
2024-05-06 @ 11:15 AM
Last Modification Date:
2024-10-26 @ 12:42 PM
Study NCT ID:
NCT03473119
Status:
UNKNOWN
Last Update Posted:
2019-07-10
First Post:
2018-03-14
Brief Title:
Evaluation of Plasma Sphingosine-1-Phosphate as A Diagnostic and Prognostic Biomarkers of Community-Acquired Pneumonia
Sponsor:
Taipei Medical University WanFang Hospital
Organization:
Taipei Medical University WanFang Hospital
Study Overview
Official Title:
Acute Effects of Particulate Matter on Pulmonary Diseases Discovery Its Chemo-signatures
Status:
UNKNOWN
Status Verified Date:
2019-04
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
Detailed Description:
The study was a branch of our PM25 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 worldwide1 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 121 for patients who aged 65 years and older admitted to hospital2 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 specificity34 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 use5 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 cells6-9 S1P is synthesized by two sphingosine kinases SphK1 and SphK 2 and degraded by S1P lyase S1PL6 S1P is a ligand for five G protein-coupled receptors S1P receptors1-567 and also acts as an intracellular second messenger1011 S1P is involved in many physiological processes including immune responses and endothelial barrier integrity12-15 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 individuals 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 individuals basic information of living area occupational environment personal habits and family history for further analysis
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 specificity34 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 use5 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 cells6-9 S1P is synthesized by two sphingosine kinases SphK1 and SphK 2 and degraded by S1P lyase S1PL6 S1P is a ligand for five G protein-coupled receptors S1P receptors1-567 and also acts as an intracellular second messenger1011 S1P is involved in many physiological processes including immune responses and endothelial barrier integrity12-15 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 individuals 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 individuals basic information of living area occupational environment personal habits and family history for further analysis
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None