84 Chapter 5 Abstract Background: Immune suppression has been implicated in the occurrence of pneumonia in critically ill patients. We tested the hypothesis that Intensive Care Unit (ICU)-acquired pneumonia is associated with broad host immune aberrations in the trajectory to pneumonia, encompassing inflammatory, endothelial and coagulation responses. We compared plasma protein biomarkers reflecting the systemic host response in critically ill patients who acquire a new pneumonia (cases) with those who do not (controls). Methods: We performed a nested case-control study in patients undergoing mechanical ventilation at ICU admission with an expected stay of at least 48 hours enrolled in 30 hospitals in 11 European countries. Nineteen host response biomarkers reflective of key pathophysiological domains were measured in plasma obtained on study inclusion and day 7, and – in cases – on the day of pneumonia diagnosis. Results: Of 1997 patients, 316 developed pneumonia (15.8%) and 1681 did not (84.2%). Plasma protein biomarker analyses, performed in cases and a randomly selected subgroup of controls (1:2 ratio to cases, n=632), demonstrated considerable variation across time points and patient groups. Yet, cases showed biomarker concentrations suggestive of enhanced inflammation and a more disturbed endothelial barrier function, both at study enrolment (median 2 days after ICU admission) and in the path to pneumonia diagnosis (median 5 days after ICU admission). Baseline host response biomarker aberrations were most profound in patients who developed pneumonia either shortly (<5 days, n=105) or late (>10 days, n=68) after ICU admission. Conclusions: Critically ill patients who develop an ICU-acquired pneumonia, compared with those who do not, display alterations in plasma protein biomarker concentrations indicative of stronger proinflammatory, procoagulant and (injurious) endothelial cell responses. Graphical abstract 1997 patients 30 hospitals 11 European countries Patients at risk for ICU-acquired pneumonia ICU-ACQUIRED PNEUMONIA NO ICU-ACQUIRED PNEUMONIA on day of study inclusion on day of pneumonia (cases) and on day 7 in the ICU (controls) 316 patients (15.8%) - cases 1681 patients (84.2%) - controls MAIN FINDING Patients who develop an ICU-acquired pneumonia demonstrate alterations in plasma biomarker levels indicative of enhanced inflammation and more disturbed endothelial barrier function Comparison of plasma levels of 19 biomarkers reflective of key pathophysiological domains between cases and a subgroup of controls (1:2 ratio to cases)
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