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Observational Study
. 2015 Jan;70(1):41-7.
doi: 10.1136/thoraxjnl-2014-205766. Epub 2014 Oct 8.

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

Thomas P Hellyer  1 , Andrew Conway Morris  2 , Daniel F McAuley  3 , Timothy S Walsh  4 , Niall H Anderson  5 , Suveer Singh  6 , Paul Dark  7 , Alistair I Roy  8 , Simon V Baudouin  9 , Stephen E Wright  10 , Gavin D Perkins  11 , Kallirroi Kefala  12 , Melinda Jeffels  13 , Ronan McMullan  14 , Cecilia M O'Kane  15 , Craig Spencer  16 , Shondipon Laha  16 , Nicole Robin  17 , Savita Gossain  18 , Kate Gould  19 , Marie-Hélène Ruchaud-Sparagano  1 , Jonathan Scott  1 , Emma M Browne  1 , James G MacFarlane  1 , Sarah Wiscombe  1 , John D Widdrington  1 , Ian Dimmick  20 , Ian F Laurenson  21 , Frans Nauwelaers  22 , A John Simpson  1
Affiliations
Observational Study

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

Thomas P Hellyer et al. Thorax. 2015 Jan.

Abstract

Background: Excessive 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.

Objectives: We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP.

Methods: A 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 >10(4) 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.

Results: Paired 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%).

Conclusions: Low 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.

Keywords: Pneumonia.

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Figures

Figure 1
Figure 1
Frequency distribution of AFD in the 7 days following bronchoalveolar lavage. AFD, antibiotic-free days, represented as an integer value.
Figure 2
Figure 2
Receiver operator characteristic (ROC) curve of interleukin (IL)-1β and IL-8 combination. ROC curve of linear predictor of IL-1β and IL-8 logistic regression. Area under the ROC curve=0.81 (95% CI 0.74 to 0.88).
Figure 3
Figure 3
STARD diagram for IL-1β/IL-8 combination. BAL, bronchoalveolar lavage; IL, interleukin; VAP, ventilator-acquired pneumonia; STARD, Standards for Reporting of Diagnostic Accuracy.
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Comment in

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