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

Community-acquired Pneumonia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04686331
• Other study ID #: SHS-ED-12d-2020
• Status: Completed
• Start date: March 1, 2021
• Est. completion date: June 1, 2022

Study information

• Verified date: September 2022
• Source: University of Southern Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 411
• Est. completion date: June 1, 2022
• Est. primary completion date: February 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Community-acquired Pneumonia
• Lung Injury
• Pneumonia

Intervention

Diagnostic Test:
• Biomarkers for pneumonia
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

Locations

Country	Name	City	State
Denmark	Hospital of Southern Jutland	Aabenraa

Sponsors (1)

Lead Sponsor	Collaborator
University of Southern Denmark

Country where clinical trial is conducted

Denmark, 

References & Publications (3)

Furuhashi K, Suda T, Nakamura Y, Inui N, Hashimoto D, Miwa S, Hayakawa H, Kusagaya H, Nakano Y, Nakamura H, Chida K. Increased expression of YKL-40, a chitinase-like protein, in serum and lung of patients with idiopathic pulmonary fibrosis. Respir Med. 2010 Aug;104(8):1204-10. doi: 10.1016/j.rmed.2010.02.026. Epub 2010 Mar 27. — View Citation

Ishikawa N, Hattori N, Yokoyama A, Kohno N. Utility of KL-6/MUC1 in the clinical management of interstitial lung diseases. Respir Investig. 2012 Mar;50(1):3-13. doi: 10.1016/j.resinv.2012.02.001. Epub 2012 Mar 8. Review. — View Citation

Sorensen GL. Surfactant Protein D in Respiratory and Non-Respiratory Diseases. Front Med (Lausanne). 2018 Feb 8;5:18. doi: 10.3389/fmed.2018.00018. eCollection 2018. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Bacteriuria	Binary outcome defined by microbiologist on urine culture analysis	urine collected within 4 hours of arrival to emergency department
Other	Diagnostic capabilities of Ultra low-dose computer thermography for pneumonia	True positive, true negative, false positive and false negative for ultra low-dose computer thermography for pneumonia.	Within 24 hours from hospital admission
Other	Diagnostic capabilities of lung ultrasound for pneumonia	True positive, true negative, false positive and false negative for lunge ultrasound for pneumonia.	Within 24 hours from hospital admission
Other	Diagnostic capabilities of chest x-ray for pneumonia	True positive, true negative, false positive and false negative for chest x-ray for pneumonia	Within 24 hours from hospital admission
Other	Level of infection markers	Concentration of serum procalcitonin, CRP and suPAR	blood collected with 4 hours of arrival to emergency department
Other	CURB-65 severity score	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
Other	Pneumonia severity index (PSI)	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
Other	Microbial agents	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
Primary	Verified and non-verified community acquired pneumonia (CAP)	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	Intensive care unit treatment	transfer to ICU during current admission (binary outcome)	within 60 days from admission to the emergency department
Secondary	Length of stay	days spent in hospital during current admission	within 60 days from current admission to the emergency department
Secondary	the number of participants who died within 30 days	binary - 30-days mortality	within 30 days from arrival day
Secondary	The number of participants who died within 90 days	binary - 90-days mortality	within 90 days from arrival day
Secondary	Readmission	binary	within 30 days from day of discharge
Secondary	In-hospital mortality	binary	within 60 days from admission to the emergency department