Comparative Analysis of the Host Response to Community-acquired and Hospital-acquired Pneumonia in Critically Ill Patients

作者：van Vught Lonneke A^*; Scicluna Brendon P; Wiewel Maryse A; Hoogendijk Arie J; Klouwenberg Peter M C Klein; Franitza Marek; Toliat Mohammad R; Nuernberg Peter; Cremer Olaf L; Horn Janneke; Schultz Marcus J; Bonten Marc M J; van der Poll Tom

来源：American Journal of Respiratory and Critical Care Medicine, 2016, 194(11): 1366-1374.

DOI：10.1164/rccm.201602-0368OC

• pneumonia
• sepsis
• genomics
• critically ill
• intensive care unit

Rationale: 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.
Objectives: We aimed to characterize the systemic host response in hospital-acquired pneumonia (HAP) when compared with community-acquired pneumonia (CAP).
Methods: 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).
Measurements and Main Results: 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.
Conclusions: Patients with HAP and CAP present with a largely similar host response at ICU admission.

• 出版日期2016-12-1