The blood transcriptional response in patients developing intensive care unit-acquired pneumonia

We aimed to determine differences in the blood leukocyte transcriptome trajectories between patients who develop ICU-acquired pneumonia (cases) and those who do not (controls). We performed a nested case-control study in trauma and surgery patients undergoing mechanical ventilation at ICU admission with an expected stay of at least 48 hours, enrolled in 30 hospitals in 11 European countries. We collected blood for RNA sequencing at baseline, day 7 and (in cases) pneumonia diagnosis. We performed gene set enrichment analysis and compared gene expression trajectories using linear mixed models with an interaction term between sampling time and patient group.We enrolled 113 cases and 115 controls, with similar baseline characteristics. At baseline (median 2 days after ICU admission) cases showed upregulation of gene pathways relating to innate immunity and downregulation of adaptive immune pathways, which was sustained at the day of pneumonia diagnosis (versus day 7 in controls). Direct comparison of gene expression trajectories in time between cases and controls established a stronger upregulation of pathways relating to innate immunity, adaptive immunity and hemostasis, and a stronger downregulation of metabolism pathways in cases, which was largely confirmed in an independent trauma cohort. Cases had higher quantitative sepsis response signature scores, reflective of more immune dysregulation.