Comparative Analysis of the Host Response to Community-acquired and Hospital-acquired Pneumonia in Critically Ill Patients.
Preclinical studies suggest that hospitalized patients are susceptible to infections caused by nosocomial respiratory pathogens at least in part because of immune suppression caused by the condition for which they were admitted.



We aimed to characterize the systemic host response in hospital-acquired pneumonia (HAP) when compared with community-acquired pneumonia (CAP).



We performed a prospective study in two intensive care units (ICUs) in 453 patients with HAP (n = 222) or CAP (n = 231). Immune responses were determined on ICU admission by measuring 19 plasma biomarkers reflecting organ systems implicated in infection pathogenesis (in 192 patients with HAP and 183 patients with CAP) and by applying genome-wide blood gene expression profiling (in 111 patients with HAP and 110 patients with CAP).



Patients with HAP and CAP presented with similar disease severities and mortality rates did not differ up to 1 year after admission. Plasma proteome analysis revealed largely similar responses, including systemic inflammatory and cytokine responses, and activation of coagulation and the vascular endothelium. The blood leukocyte genomic response was greater than 75% common in patients with HAP and CAP, comprising proinflammatory, antiinflammatory, T-cell signaling, and metabolic pathway gene sets. Patients with HAP showed overexpression of genes involved in cell-cell junction remodeling, adhesion, and diapedesis, which corresponded with lower plasma levels of matrix metalloproteinase-8 and soluble E-selectin. In addition, patients with HAP demonstrated underexpression of a type-I interferon signaling gene signature.



Patients with HAP and CAP present with a largely similar host response at ICU admission.
1 Center for Experimental and Molecular Medicine.|2 Center for Infection and Immunity.
Lonneke A
LA
van Vught
1 Center for Experimental and Molecular Medicine.|2 Center for Infection and Immunity.
Brendon P
BP
Scicluna
1 Center for Experimental and Molecular Medicine.|2 Center for Infection and Immunity.
Maryse A
MA
Wiewel
1 Center for Experimental and Molecular Medicine.|2 Center for Infection and Immunity.
Arie J
AJ
Hoogendijk
3 Department of Intensive Care Medicine.|4 Department of Medical Microbiology, and.|5 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; and.
Peter M C
PM
Klein Klouwenberg
6 Cologne Center for Genomics.|7 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, and.
Marek
M
Franitza
6 Cologne Center for Genomics.
Mohammad R
MR
Toliat
6 Cologne Center for Genomics.|7 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, and.|8 Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
Peter
P
Nürnberg
3 Department of Intensive Care Medicine.
Olaf L
OL
Cremer
9 Department of Intensive Care, and.
Janneke
J
Horn
9 Department of Intensive Care, and.
Marcus J
MJ
Schultz
4 Department of Medical Microbiology, and.
Marc M J
MM
Bonten
1 Center for Experimental and Molecular Medicine.|2 Center for Infection and Immunity.|10 Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Tom
T
van der Poll
D017714:Community-Acquired Infections / Q000276:immunology*; D016638:Critical Illness; D003428:Cross Infection / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000276:immunology*; D011446:Prospective Studies; D012720:Severity of Illness Index
critically ill; genomics; intensive care unit; pneumonia; sepsis