Accuracy of Lung Injury Biomarkers in the Initial Investigation of Patients With Suspected Pneumonia

September 13, 2022 updated by: University of Southern Denmark

Diagnostic and Prognostic Accuracy of Surfactant Protein D, Krebs Von Den Lungen, and Chitinase-3-like Protein 1 (YKL-40 ) in the Initial Investigation of Patients With Suspected Pneumonia

The aim of this study is to investigate the diagnostic and prognostic value of surfactant protein D, Krebs von den Lungen (KL-6), and Chitinase-3-like protein 1 (YKL-40) in the initial investigation of patients hospitalized with suspected pneumonia. This to improve the diagnosis of pneumonia, contribute to a more rapid and accurate antibiotic treatment, and assess disease severity to predict short-term and long-term mortality in community-acquired pneumonia patients.

Study Overview

Status

Completed

Detailed Description

Community-acquired pneumonia (CAP) is one of the most common infection diseases in the emergency department (ED). Diagnosis of pneumonia is challenging as symptoms are often weak and nonspecific and the current methods for focal and etiological diagnosis have low sensitivity and specificity and often deliver results after the antibiotic treatment decision has been made.

The abundant and restricted expression of surfactant protein D (SP-D) within the lung makes this protein a specific marker for lung disease. Krebs von den Lungen-6 (KL-6) is expressed in the lung and is a diagnostic and prognostic marker of interstitial lung disease. The inflammatory glycoprotein Chitinase-3-like protein 1 commonly known as YKL-40 is associated with severity of interstitial lung disease. The value of these lung injury markers for diagnosing pneumonia needs further investigation.

The investigators hypothesize that surfactant protein D, Krebs von den Lungen (KL-6), and Chitinase-3-like protein 1 (YKL-40) have an impact on diagnosing, prognosis, and treatment of patients with verified CAP.

The objectives of the study are:

  • To investigate the diagnostic accuracy of surfactant protein D, Krebs von den Lungen (KL-6), and Chitinase-3-like protein 1 (YKL-40) in the diagnosis of CAP
  • To identify the prognostic value surfactant protein D, Krebs von den Lungen (KL-6), and Chitinase-3-like protein 1 (YKL-40) in relation to adverse events in patients with verified CAP

Study Type

Observational

Enrollment (Actual)

411

Contacts and Locations

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

Study Locations

      • Aabenraa, Denmark
        • Hospital of Southern Jutland

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

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Acutely admitted patients with suspected Acute pyelonephritis (APN) from three emergency departments (EDs) in the Region of Southern Denmark (Hospital Sønderjylland, Hospital Lillebælt, Odense University Hospital)

Description

Inclusion Criteria:

  • Suspicion of APN assessed by the receiving physician at the ED

Exclusion Criteria:

  • If the attending physician considers that participation will delay a life-saving treatment or patient needs direct transfer to the intensive care unit.
  • Admission within the last 14 days
  • Verified COVID-19 disease within 14 days before admission
  • Pregnant women
  • Severe immunodeficiencies: Primary immunodeficiencies and secondary immunodeficiencies (HIV positive CD4 <200, Patients receiving immunosuppressive treatment (ATC L04A), Corticosteroid treatment (>20 mg/day prednisone or equivalent for >14 days within the last 30 days), Chemotherapy within 30 days)

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Suspected CAP
All patients admitted to the emergency department with suspected community-acquired pneumonia (CAP) assessed by the receiving physician

Blood samples will be collected by a medical laboratory technologist and transferred to the local laboratory for analysis of surfactant protein D, Krebs von den Lungen (KL-6), and YKL-40. Laboratory staff will be blinded to participant diagnosis and outcome. None of the biomarkers will be available to the treating physician.

  • Diagnostic test of surfactant protein D - will be quantified using enzyme-linked immunosorbent assay (ELISA)-based analysis
  • Diagnostic test of KL-6: will be quantified using enzyme-linked immunosorbent assay (ELISA)-based analysis
  • Diagnostic test of YKL-40 - will be quantified using enzyme-linked immunosorbent assay (ELISA)-based analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Verified and non-verified community acquired pneumonia (CAP)
Time Frame: 2 months after patient discharge
The decision of whether patients admitted with suspicion of CAP actually has a final diagnosis of CAP is based on a combination of all findings during admission. The verification of diagnosis requires human handling, interpretation and judgment. Therefore, in this study, an expert panel will define the reference standard for the diagnosis CAP. The expert panel consists of two independent consultants from the emergency department with significant experience in emergency medicine and acute infections. They will individually determine whether or not the patient admitted suspected with CAP actually had this diagnosis. The final diagnosis will be based on all available relevant information from the patient medical record including HR-CT of lungs. A standardized template will be used. Disagreement will be discussed until a consensus is reached.
2 months after patient discharge

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Readmission
Time Frame: within 30 days from day of discharge
binary
within 30 days from day of discharge
Intensive care unit treatment
Time Frame: within 60 days from admission to the emergency department
transfer to ICU during current admission (binary outcome)
within 60 days from admission to the emergency department
Length of stay
Time Frame: within 60 days from current admission to the emergency department
days spent in hospital during current admission
within 60 days from current admission to the emergency department
the number of participants who died within 30 days
Time Frame: within 30 days from arrival day
binary - 30-days mortality
within 30 days from arrival day
The number of participants who died within 90 days
Time Frame: within 90 days from arrival day
binary - 90-days mortality
within 90 days from arrival day
In-hospital mortality
Time Frame: within 60 days from admission to the emergency department
binary
within 60 days from admission to the emergency department

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bacteriuria
Time Frame: urine collected within 4 hours of arrival to emergency department
Binary outcome defined by microbiologist on urine culture analysis
urine collected within 4 hours of arrival to emergency department
Diagnostic capabilities of Ultra low-dose computer thermography for pneumonia
Time Frame: Within 24 hours from hospital admission
True positive, true negative, false positive and false negative for ultra low-dose computer thermography for pneumonia.
Within 24 hours from hospital admission
Diagnostic capabilities of lung ultrasound for pneumonia
Time Frame: Within 24 hours from hospital admission
True positive, true negative, false positive and false negative for lunge ultrasound for pneumonia.
Within 24 hours from hospital admission
Diagnostic capabilities of chest x-ray for pneumonia
Time Frame: Within 24 hours from hospital admission
True positive, true negative, false positive and false negative for chest x-ray for pneumonia
Within 24 hours from hospital admission
Level of infection markers
Time Frame: blood collected with 4 hours of arrival to emergency department
Concentration of serum procalcitonin, CRP and suPAR
blood collected with 4 hours of arrival to emergency department
CURB-65 severity score
Time Frame: within 4 hours from admission
Confusion of new onset, Blood Urea nitrogen greater than 7 mmol/L (19 mg/dL), respiratory rate of 30 breaths per minute or greater, blood pressure less than 90 mmHg systolic or diastolic blood pressure 60 mmHg or less and age 65 or older. The score stratify patients to groups 1 (mild pneumonia), 2 (moderate pneumonia) and 3-5 (severe pneumonia).
within 4 hours from admission
Pneumonia severity index (PSI)
Time Frame: within 4 hours from admission
Risk classes to predict the severity of pneumonia. Scores are given based on demographics, comorbidity, clinical measurements and physical Exam Findings (<70 = Risk Class II, 71-90 = Risk Class III, 91-130 = Risk Class IV, >130 = Risk Class V)
within 4 hours from admission
Microbial agents
Time Frame: results within 7 days from sputum sample collection
Microbial agents (bacteria and viruses) identified in standard culture, PCR and multiplex PCR. Sputum or tracheal secretion samples are collected within 1 hour from patient admission.
results within 7 days from sputum sample collection

Collaborators and Investigators

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

Investigators

  • Study Chair: Christian Backer Mogensen, University Hospital of Southern Denmark

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.

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 1, 2021

Primary Completion (Actual)

February 28, 2022

Study Completion (Actual)

June 1, 2022

Study Registration Dates

First Submitted

December 22, 2020

First Submitted That Met QC Criteria

December 22, 2020

First Posted (Actual)

December 28, 2020

Study Record Updates

Last Update Posted (Actual)

September 14, 2022

Last Update Submitted That Met QC Criteria

September 13, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

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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