Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia

Abstract

BackgroundExcessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare.ObjectivesWe sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP.MethodsA prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at >104 colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1β), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination.ResultsPaired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (p<0.001). The area under the receiver operator characteristic curve for IL-1β was 0.81; IL-8, 0.74; MMP-8, 0.76; MMP-9, 0.79 and HNE, 0.78. A combination of IL-1β and IL-8, at the optimal cut-point, excluded VAP with a sensitivity of 100%, a specificity of 44.3% and a post-test probability of 0% (95% CI 0% to 9.2%).ConclusionsLow BALF IL-1β in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship.

A 2015 Update on Ventilator-Associated Pneumonia: New Insights on Its Prevention, Diagnosis, and Treatment

“…Both IL-1β and IL-8 are significantly elevated in BALF from patients with confirmed VAP [41]. Hellyer et al carried out a prospective, multicentre study which showed that there is a high negative predictive value when IL-1β and IL-8 are used together [41].…”

Biomarkers to exclude the diagnosis of ventilator-associated pneumonia

“…The most important limitation in the current study by Hellyer et al 8 relates to the need to do fiberoptic bronchoscopy and lavage. The use of lavage was rational in this study because the investigators were able to direct the bronchoscope to the areas of the lung that showed maximal or substantial pulmonary consolidation.…”

“…In this issue of Thorax , Hellyer et al 8 have reported the results of an interesting and well done clinical study to test for the potential value of measuring biomarkers in BAL that may be useful in excluding pneumonia in patients with suspected VAP. The study was multicentre and prospective and was carried out in 12 intensive care units.…”

What was old is new again: using the host response to diagnose infectious disease

“…One study showed that a combination of IL-4, IL-5, IL-6, IL-10 and GM-CSF showed promise in distinguishing viral and bacterial etiologies in acute respiratory infection [58]. Low levels of IL-1B and IL-8 in bronchoalveolar lavage fluid have been found to rule out VAP with a high degree of certainty, although the invasive sampling limits clinical utility [59]. A combination of IL-6 and CRP has been used to stratify infectious and noninfectious causes of febrile neutropenia [62].…”