95 Host response in patients with ICU-acquired pneumonia Conclusions Immune stimulatory therapy has been suggested as a novel approach to treat sepsisinduced immune suppression in order to reduce the occurrence of secondary infections and late mortality [5, 8]. We here report that critically ill patients developing ICUacquired pneumonia show changes in plasma protein biomarkers that are indicative of a more broadly disturbed host response entailing several proinflammatory reactions prior to development of pneumonia as compared to critically ill patients who did not develop ICU-acquired pneumonia. Together, these data suggest that critically ill patients who develop pneumonia while on the ICU show heterogeneous baseline immune alterations and that the broad application of immune stimulatory therapy may be harmful in some patients. Additional observational studies should focus on identifying biological factors that may inform the personalized application of immunomodulatory (stimulation versus suppression) therapies in critically ill patients at risk of ICU-acquired infections. Declarations Ethics approval: This study was performed in line with the principles of the 1964 Declaration of Helsinki. The study protocol was approved by the institutional review boards or ethical committees in each country and/or site. Consent to participate: All participants or their legally authorized representative provided written, informed consent for additional data and sample collection. Availability of data and materials: The data and code that support the findings of this study are available from the corresponding author, TvE, upon reasonable request. Competing interests: On behalf of all authors, the corresponding author states that there are no competing interests. Funding: This paper was supported by Innovative Medicines Initiative Joint Undertakings 115523, 115620 and 115737 to M.J.B. The funding source had no role in the design of the study and collection, analysis, and interpretation of data. Author’s contributions: FP, MB, LT, SMK, JK and TvdP contributed to the conception and design of the work. FP and LT contributed to the acquisition of the samples and clinical data. TvE and TR acquired the biomarker data. TvE, TR, HPS contributed to the analysis of the data. All authors contributed to interpretation of data for the work. TvE, TR, HPS and TvdP drafted the manuscript; all authors revised it critically for important intellectual content. All authors gave final approval of this version, agree to be accountable for all aspects of the work, and declare that they have no competing interests. 5
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