Key result
Sepsis secondary to hospital-acquired pneumonia was associated with significant impairment in lipid metabolism, including reduced median total cholesterol (105-110.5 mg/dL vs 198 mg/dL) compared to healthy volunteers.
Why the study?
Host responses may differ in septic patients secondary to community-acquired pneumonia versus hospital-acquired pneumonia, prompting evaluation of plasma proteome changes specifically in sepsis secondary to hospital-acquired pneumonia.
Observational (n=50)
Yes
p-value: p=≤0.05
Sepsis secondary to hospital-acquired pneumonia is associated with significant impairment in lipid metabolism, characterized by reduced levels of cholesterol moieties and apolipoproteins.
Hypothesis-generating for lipid pathways in septic pneumonia; observational data leave open any therapeutic role.
BACKGROUND: Sepsis is a dysregulated host response to infection and a major cause of death worldwide. Respiratory tract infections account for most sepsis cases and depending on the place of acquisition, i.e., community or hospital acquired infection, differ in etiology, antimicrobial resistance and outcomes. Accordingly, the host response may be different in septic patients secondary to community-acquired pneumonia and hospital acquired pneumonia (HAP). Proteomic analysis is a useful approach to evaluate broad alterations in biological pathways that take place during sepsis. Here we evaluated plasma proteome changes in sepsis secondary to HAP. METHODS: Plasma samples were obtained from patients (n = 27) at admission and after 7 days of follow-up, and were analyzed according to the patients' outcomes. The patients' proteome profiles were compared with healthy volunteers (n = 23). Pooled plasma samples were labeled with isobaric tag for relative and absolute quantitationand analyzed by LC-MS/MS. We used bioinformatics tools to find altered functions and pathways. Results were validated using biochemical estimations and ELISA tests. RESULTS: We identified 159 altered proteins in septic patients; most of them were common when comparing patients' outcomes, both at admission and after 7 days. The top altered biological processes were acute inflammatory response, response to wounding, blood coagulation and homeostasis. Lipid metabolism emerged as the main altered function in patients, with HDL as a central node in the network analysis, interacting with downregulated proteins, such as APOA4, APOB, APOC1, APOL1, SAA4 and PON1. Validation tests showed reduced plasma levels of total cholesterol, HDL-C, LDL-C, non-HDL cholesterol, apolipoproteins ApoA1 and ApoB100, and Paraoxonase 1 in HAP patients. CONCLUSION: Proteomic analysis pointed to impairment of lipid metabolism as a major change in septic patients secondary to HAP, which was further validated by the reduced levels of cholesterol moieties and apolipoproteins in plasma. Our results stress the involvement of lipids in the pathogenesis of sepsis, which is in accordance with previous reports supporting the role of lipid moieties in pathogen toxin clearance and in modulating inflammatory responses.
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Sharma et al. (2019) conducted an observational in Sepsis secondary to hospital-acquired pneumonia (n=50). Sepsis secondary to hospital-acquired pneumonia vs. Healthy volunteers was evaluated on Plasma proteome alterations and lipid metabolism markers (e.g., total cholesterol, HDL-C) (p=≤0.05). Sepsis secondary to hospital-acquired pneumonia was associated with significant impairment in lipid metabolism, including reduced median total cholesterol (105-110.5 mg/dL vs 198 mg/dL) compared to healthy volunteers.
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