Toll-like receptor –2 and 4 as a diagnostic method for ventilator-associated pneumonia

Abstract

Background & objective: Ventilator-associated pneumonia (VAP) is a nosocomial infection associated with high mortality, especially in the critical care settings. VAP extends the duration and cost of hospitalization and increases the antibiotic usage. Toll-like Receptor (TLR) detects and responds to bacteria, enabling innate immune response. We explored the performance of TLR–2 and TLR–4 assessment as an additional diagnostic tool for VAP.

Methodology: A prospective cohort study was conducted, from November 2019 to April 2020 in three teaching hospitals in Surakarta, Central Java, Indonesia, in intubated and mechanically ventilated patients, aged between 19 and 65 y. Blood samples for TLR–2 and TLR–4 were obtained from the venous blood. Blood sampling was done on the 24th and 48th hour after intubation. TLR–2 and TLR–4 expression was evaluated using RT–PCR (Real-Time Polymerase Chain Reaction). We used IBM SPSS Statistics 25 for data analysis. The Mann–Whitney test was carried out to determine the expression difference of TLR–2 and TLR–4 between VAP and non–VAP patients. The results were considered significant when the P < 0.05.

Results: TLR–2 and TLR–4 were expressed higher at the 24th hour after mechanical ventilation, especially in non–VAP patients. TLR–2 and TLR–4 assessment had low sensitivity, specificity, and performance for diagnosing VAP.

Conclusion: Patients with VAP have lower expressions of TLR-2 and TLR-4 compared to non-VAP patients. TLR–2 and TLR–4 assay may not be beneficial as an additional diagnostic method for VAP.

Abbreviations: VAP - Ventilator-associated pneumonia; TLR - Toll-like Receptor; ICU - Intensive Care Unit; CPIS - The Clinical Pulmonary Infection Score; RT-PCR – Real Time - Polymerase Chain Reaction; ROC - Receiver operating characteristic; AUC - Area under curve; TIR - Toll-interleukin-1 receptor; ITTMs - immunoreceptor tyrosine-based inhibitory motifs; IRAK - IL–1 receptor-associated kinase; GM-CSF – Granulocyte Macrophage-Colony Stimulating Factor; PAMP - pathogen-associated molecular pattern; DAMPs - damage-associated molecular patterns

Key words: Ventilator-associated pneumonia; VAP; TLR–2; TLR–4

Citation: Dewi FH, Purwanto B, Wasita B, Purwoko. Toll-like receptor –2 and 4 as a diagnostic method for ventilator-associated pneumonia. Anaesth. pain intensive care 2022;26(2):148-153; DOI: 10.35975/apic.v26i2.1811

Received: Oct 29, 2021, Reviewed: February 19, 2022, Accepted: February 26, 2022