Ignite Creation Date:
2024-05-06 @ 10:26 AM
Last Modification Date:
2024-10-26 @ 12:30 PM
Study NCT ID:
NCT03256604
Status:
COMPLETED
Last Update Posted:
2017-08-22
First Post:
2017-08-16
Brief Title:
A Sputum Screening Test to Rule-out Pneumonia at an Early Stage
Sponsor:
University Hospital Linkoeping
Organization:
University Hospital Linkoeping
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2017-08
Last Known Status:
None
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:
self-test
Brief Summary:
In patients with clinical symptoms of respiratory infection rapid identification of cases requiring antibiotic therapy is crucial to avoid development of multiple resistant bacteria Identification of local acute-phase reactants can help assess the hosts response to bacterial infection at the injury site Here the investigators developed an affordable stable feasible and accurate diagnostic tool based on a locally produced protein with specific binding affinity to polysaccharides The investigators further evaluated the ability of the novel test strip to rule out pneumonia
Detailed Description:
A lower respiratory tract infection is a serious situation that can abruptly become complicated by sepsis respiratory failure lung tissue necrosis and multiple organ dysfunction Hence empiric antibiotic treatment is commonly initiated as soon as infection is suspected and cultures andor other diagnostic tests are procured representing a major reason for antibiotic prescription Widespread antibiotic overuse and misuse have led to the emergence of multiple resistant bacterial strains posing a major health threat There exists a critical need for practical solutions to prevent antibiotic overuse especially in communities where antibiotics are available without prescription
Pathophysiologic studies show that infection does not result from bacterial or viral overgrowth alone but rather from the microorganisms penetration beyond the host immune system Therefore infection assessment requires investigation of both microorganism presence and the defense mechanisms activated within the patients body Bacteria overgrowth leads to lung tissue inflammation recruitment of white blood cells to the infected area and chemokine and cytokine production and release which can cause the alveoli to become filled with fluid leading the patient to develop a cough with phlegm or pus fever chills and dyspnea
Microbiological diagnosis of lower respiratory tract infections requires assessment of the invading microorganism by examination of sputum using microscopy quantitative culture and PCR However such microbiological investigations have limited value in pneumonia management Polymicrobial flora make it difficult to interpret cultures from patients with chronic bronchitis It is also difficult to evaluate cultures from nosocomial pneumonia since the pathogenic bacteria are often identical to those appearing in the throat flora Immunosuppressed patients frequently produce sputum containing low number of white blood cells The patients clinical signs such as respiratory and circulatory status are the most reliable markers for determining treatment efficacy
In practice most physicians choose to examine additional markers at early stages to closely monitor the effects of therapy particularly in high-risk patients who have been admitted to intensive care units Commonly used systemic markers include body temperature C-reactive protein CRP procalcitonin PCT and interleukin 6 IL-6 Hepatocyte growth factor HGF concentration reportedly increases during organ damage such as that caused by infectious diseases Studies show increased HGF concentrations in serum and exhaled-breath condensate from patients with pneumonia with HGF presence being significantly correlated with survival Moreover HGF levels markedly decrease within 48 hours of initiating appropriate antibiotic therapy Surface plasmon resonance SPR results indicate that HGF produced during acute infection shows high affinity for the extracellular matrix component heparan sulfate proteoglycan HSPG These findings suggest that HGF assessment in sputum could be a tool for detecting bacterial infection at the site of injury
Proteins can be detected based on their specific interaction with a corresponding antibody However this measurement system relies on specialized resources limiting its usefulness in non-equipped centers or as a self-test Metachromasia is a characteristic color change exhibited by certain aniline dyes upon binding to chromotropic substances This phenomenon has been widely used in histology Methylene blue O-Toluidine is an excellent metachromatic dye that changes from blue to pink upon binding to high-molecular-weight polysaccharides such as sulfated glycan The pink dye will then quickly turn back to blue following addition of a proportional amount of a protein with high affinity to sulfated glycan inverted metachromacia
Here the investigators used this approach to develop a new strip test-referred to herein as the index text-to assess the presence of dextran-sulfate-binding proteins in sputum The investigators then assessed the accuracy of this strip test for detecting bacterial infection in sputum by analyzing leftover sputum samples that were sent for examination to the Department of Microbiology University hospital in Linköping
Pathophysiologic studies show that infection does not result from bacterial or viral overgrowth alone but rather from the microorganisms penetration beyond the host immune system Therefore infection assessment requires investigation of both microorganism presence and the defense mechanisms activated within the patients body Bacteria overgrowth leads to lung tissue inflammation recruitment of white blood cells to the infected area and chemokine and cytokine production and release which can cause the alveoli to become filled with fluid leading the patient to develop a cough with phlegm or pus fever chills and dyspnea
Microbiological diagnosis of lower respiratory tract infections requires assessment of the invading microorganism by examination of sputum using microscopy quantitative culture and PCR However such microbiological investigations have limited value in pneumonia management Polymicrobial flora make it difficult to interpret cultures from patients with chronic bronchitis It is also difficult to evaluate cultures from nosocomial pneumonia since the pathogenic bacteria are often identical to those appearing in the throat flora Immunosuppressed patients frequently produce sputum containing low number of white blood cells The patients clinical signs such as respiratory and circulatory status are the most reliable markers for determining treatment efficacy
In practice most physicians choose to examine additional markers at early stages to closely monitor the effects of therapy particularly in high-risk patients who have been admitted to intensive care units Commonly used systemic markers include body temperature C-reactive protein CRP procalcitonin PCT and interleukin 6 IL-6 Hepatocyte growth factor HGF concentration reportedly increases during organ damage such as that caused by infectious diseases Studies show increased HGF concentrations in serum and exhaled-breath condensate from patients with pneumonia with HGF presence being significantly correlated with survival Moreover HGF levels markedly decrease within 48 hours of initiating appropriate antibiotic therapy Surface plasmon resonance SPR results indicate that HGF produced during acute infection shows high affinity for the extracellular matrix component heparan sulfate proteoglycan HSPG These findings suggest that HGF assessment in sputum could be a tool for detecting bacterial infection at the site of injury
Proteins can be detected based on their specific interaction with a corresponding antibody However this measurement system relies on specialized resources limiting its usefulness in non-equipped centers or as a self-test Metachromasia is a characteristic color change exhibited by certain aniline dyes upon binding to chromotropic substances This phenomenon has been widely used in histology Methylene blue O-Toluidine is an excellent metachromatic dye that changes from blue to pink upon binding to high-molecular-weight polysaccharides such as sulfated glycan The pink dye will then quickly turn back to blue following addition of a proportional amount of a protein with high affinity to sulfated glycan inverted metachromacia
Here the investigators used this approach to develop a new strip test-referred to herein as the index text-to assess the presence of dextran-sulfate-binding proteins in sputum The investigators then assessed the accuracy of this strip test for detecting bacterial infection in sputum by analyzing leftover sputum samples that were sent for examination to the Department of Microbiology University hospital in Linköping
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