Metabolic signatures of pneumonia in critical care : a paradigm shift in diagnosis and therapeutic monitoring

Pneumonia and ventilator associated pneumonia (VAP) are a frequent cause for admission to Intensive Care and complication of ventilation respectively. VAP occurs in 10-40% of patients requiring mechanical ventilation and is associated with increased mortality, morbidity and healthcare costs. Diagnosis can be difficult due to poor predictive value of clinical features and low specificity of radiological changes. Bronchoscopic techniques are often invasive, may not be suitable for all patients and are not without complications. New tests are required to improve the diagnosis of these conditions allowing early, appropriate antibiotic treatment. In this study several techniques were used to explore the value of profiling of a range of biofluids obtained from ventilated patients as an aid to diagnosis of pneumonia. Patients were recruited from Intensive Care with either a diagnosis of pneumonia or brain injury. Those with brain injuries were tracked to identify patients who developed VAP. Serum, urine and exhaled breath condensate (EBC) were collected from all patients. Metabonomics, an approach that identifies changes in metabolic profiles associated with disease, was applied using proton nuclear magnetic resonance spectroscopy to both blood and urine and with mass spectrometry (MS) to exhaled breath condensate. Following from the metabonomic work a panel of inflammatory mediators, including cytokines and eicosanoids were measured in serum using MS and flow cytometry to explore the inflammatory changes in these patients. Overall metabolic and inflammatory profiling of serum showed potential as an adjunct to clinical diagnosis especially when combined with clinical data. Analysis of urine and EBC proved more challenging due the number of drug metabolites and low concentration of metabolites they respectively contained. In summary this study has added to the field by demonstrating the potential for profiling techniques of serum from critically ill patients to assist in the diagnosis of both pneumonia and VAP.