Diagnostic Accuracy of Infection Biomarkers in the Initial Investigation of Patients With Suspected Pneumonia

Study Overview
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Brief Summary
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The aim of this study is to investigate the diagnostic and prognostic value of C-reactive protein (CRP), serum procalcitonin (PCT) and soluble urokinase plasminogen activator receptor (suPAR) in the initial investigation of patients acute hospitalized with suspected community-acquired-pneumonia (CAP)

Detailed Description
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Target pneumonia treatment should be initiated within a few hours, which is why early and accurate diagnosis is extremely important. Uncertain or delayed diagnosis will often lead to an overconsumption of broad-spectrum antibiotics, which contributes to increased development of resistant bacteria and thus threaten the treatment options of the future. Pneumonia diagnosis is primarily made today on the basis of clinical symptoms and findings in the form of cough, vomiting, chest pain, fever, shortness of breath, supplemented with X-ray of the lungs, relevant blood tests and analysis of expectoration. However, X-ray is an imprecise diagnostic tool. The diagnosis of CAP is challenged by nonspecific symptoms, uncertain diagnostic methods and waiting time for test results up to several days. Therefore, numerous studies have investigated biomarkers that can possibly support the diagnosis of CAP. C-reactive protein (CRP) and serum procalcitonin (PCT) are biomarkers that may distinguish CAP from other causes of acute respiratory infections. The CRP biomarker has been endorsed as a guide for antibiotic treatment by the National Institute for Health and Care Excellence (NICE) and PCT was suggested by the American Infectious Diseases Society of America. Soluble urokinase plasminogen activator receptor (suPAR) has emerged as a potentially novel biomarker for inflammatory diseases including pneumonia. Several studies have highlighted suPAR as a significant prognostic mortality marker and strongly related to disease severity and worse outcome in a variety of conditions. It is also a promising biological marker in the diagnosis of CAP. The diagnostic value of the optimal biomarkers for the diagnosis of CAP remains controversial. The investigators hypothesize that serum CRP, PTC and suPAR have an impact on diagnosing, prognosis, and treatment of patients with a verified community-acquired-pneumonia. The objectives of the study are: To identify the diagnostic accuracy of CRP, PCT and suPAR in community-acquired pneumonia To identify the prognostic value of CRP, PCT and suPAR in relation to adverse events

Official Title
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What is the Diagnostic and Prognostic Accuracy of C-reactive Protein, Serum Procalcitonin and Soluble Urokinase Plasminogen Activator Receptor in the Initial Investigation of Patients With Suspected Community-acquired Pneumonia

Conditions
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Pneumonia, Bacterial

Intervention / Treatment
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* Diagnostic Test: PCT
* Diagnostic Test: suPAR
* Diagnostic Test: Standard care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients ≥ 18 years old Patients suspected with pneumonia by the attending physician. The physician will base his/her suspicion on e.g. clinical symptoms such as cough, increased sputum production, chest tightness, dyspnea and fever > 38⁰C, and indication for chest x-ray 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients suspected of community-acquired pneumonia<br>All patients admitted to the emergency department with suspected community- acquired pneumonia by the attending physician | Diagnostic Test: PCT<br>* Serum PCT concentration is quantified with an automated sandwich immunoassay ECLIA (Elecsys®, BRAHMS PCT-analyses) on Cobas e801. Calibration (BRAHMS PCT LIA assay) is performed once per reagent lot and no later than 24 h after Cobas e pack has been registered in the instrument. Quality control is performed after each calibration.<br>Diagnostic Test: suPAR<br>* Serum suPAR was measured using suPARnostic© Turbilatex assay reagents (validated on Cobas© c111) protocol for Cobas© c702 and c502 applying the Multi-Pack cassettes (Roche Diagnostics, Mannheim, Germany). Calibration is performed at least once a month or in connection to a new batch of TurbiLatex reagents, after calibration a quality control is performed.<br>Diagnostic Test: Standard care<br>* Standard care is the measurement of CRP (C-reactive protein) will be measured with C - reactive protein (CRP4) immunoturbidimetric assay (Tina-quant®, Roche) on Roche/Hitachi cobas© systems c701/702. Calibration is performed (Tina-quant® C - reactive protein IV) once per reagent lot and after 6 months using the same reagent lot. Quality control is required after calibration and according manufacturing instructions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic of community acquired pneumonia | The percentage of patients diagnosed with community-acquired pneumonia determined by an expert panel. This outcome measure is a binary variable - verified pneumonia or no pneumonia. The expert panel consists of two independent consultants from the emergency department with experience in infection and emergency medicine, who individually will determine whether the patient admitted with suspected community-acquired pneumonia, had the diagnosis. The diagnosis will be based on all available relevant information from the patient medical record within 48 hours from admission including computed tomography. A standardized template will be used. Disagreement will be discussed until a consensus is reached. . | expert assessment within 3 months after patient discharge from the hospital | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensive care unit (ICU) treatment | Transfer to the intensive care unit will be recorded during the current hospitalization as a binary variable (transferred/not-transferred) | within 60 days from admission to the emergency department | 
| Length of hospital stay (LOS | Defined as the time (in days) spent in hospital during the current admission. Measured in days from admission to hospital discharge. Discharge date minus admission date. | within 60 days from current admission to the emergency department | 
| 30-days mortality | Mortality within 30 days from admission to the Emergency Department | 30 days from the admission to the emergency department | 
| 90-days mortality | Mortality within 90 days from admission to the Emergency Department | 90 days from the admission to the emergency department | 
| Readmission | If a subject is admitted over a 30 day period after the current hospitalization discharge measured as a binary outcome Re-admissions/not re-admissions | within 30 days from the discharge to the hospital | 
| In-hospital mortality | Patient mortality during the current hospitalization. Binary outcome - Died/ Not died | within 60 days from admission to the emergency department | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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C-reactive protein,, serum procalcitonin,, soluble urokinase plasminogen activator receptor