Diagnostic importance of pulmonary interleukin-1β and interleukin-8 in ventilator-associated pneumonia

Andrew Conway Morris^1,*, Kallirroi Kefala¹, Thomas S Wilkinson¹, Olga Lucia Moncayo-Nieto¹, Kevin Dhaliwal¹, Lesley Farrell¹, Timothy S Walsh², Simon J Mackenzie², David G Swann², Peter JD Andrews³, Niall Anderson¹, John RW Govan¹, Ian F Laurenson², Hamish Reid⁴, Donald J Davidson¹, Christopher Haslett¹, Jean-Michel Sallenave¹, A John Simpson¹

¹ University of Edinburgh, United Kingdom;
² Royal Infirmary of Edinburgh, United Kingdom;
³ Western General Hospital, Edinburgh, United Kingdom;
⁴ Penicuick Health Centre, United Kingdom

Correspondence to: Andrew Conway Morris, Centre for Inflammation Research, University of Edinburgh, Room C2.17, Centre for Inflammation Research, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, United Kingdom; mozza{at}doctors.org.uk

Accepted 11 September 2009

Ventilator-associated pneumonia (VAP) is the most commonly fatal nosocomial infection. Clinical diagnosis of VAP remains notoriously inaccurate. We tested the hypothesis that significantly augmented inflammatory markers distinguish VAP from conditions closely mimicking VAP.

Methods: A prospective, observational cohort study in two university hospital intensive care units recruiting 73 patients with clinically suspected VAP, and a semi-urban primary care practice recruiting a reference group of 21 age- and sex-matched volunteers.

Growth of pathogens at >104 colony forming units/ml bronchoalveolar lavage fluid (BALF) distinguished VAP from ‘non-VAP’. Inflammatory mediators were quantified in BALF and serum. Mediators showing significant differences between patients with and without VAP were analysed for diagnostic utility by receiver operator characteristic (ROC) curves.

Results: Seventy-two patients had recoverable lavage - 24% had VAP. BALF interleukin (IL)-1β, IL-8, granulocyte-colony stimulating factor and macrophage inflammatory protein 1 were significantly higher in the VAP group (all P<0·005). Using a cut off of 10 pg/ml, BALF IL-1β generated negative likelihood ratios for VAP of 0·09. In patients with BALF IL-1β <10 pg/ml the post-test probability of VAP was 2·8%. Using a cut off value for IL-8 of 2 ng/ml, positive likelihood ratio was 5.03. There was no difference in cytokine levels between patients with sterile BALF and those with growth of <104 CFU/ml.

Conclusions: BALF IL-1β and IL-8 are amongst the strongest markers yet identified for accurately demarcating VAP within the larger population of patients with suspected VAP. These findings have potential implications for reduction in unnecessary antibiotic use but require further validation in larger populations.

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