Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Alfonso, Juan Carlos López
Akmatov, Manas K
MetadataShow full item record
AbstractBACKGROUND: There continues to be a great need for better biomarkers and host-directed treatment targets for community-acquired pneumonia (CAP). Alterations in phospholipid metabolism may constitute a source of small molecule biomarkers for acute infections including CAP. Evidence from animal models of pulmonary infections and sepsis suggests that inhibiting acid sphingomyelinase (which releases ceramides from sphingomyelins) may reduce end-organ damage. METHODS: We measured concentrations of 105 phospholipids, 40 acylcarnitines, and 4 ceramides, as well as acid sphingomyelinase activity, in plasma from patients with CAP (n = 29, sampled on admission and 4 subsequent time points), chronic obstructive pulmonary disease exacerbation with infection (COPD, n = 13) as a clinically important disease control, and 33 age- and sex-matched controls. RESULTS: Phospholipid concentrations were greatly decreased in CAP and normalized along clinical improvement. Greatest changes were seen in phosphatidylcholines, followed by lysophosphatidylcholines, sphingomyelins and ceramides (three of which were upregulated), and were least in acylcarnitines. Changes in COPD were less pronounced, but also differed qualitatively, e.g. by increases in selected sphingomyelins. We identified highly accurate biomarkers for CAP (AUC ≤ 0.97) and COPD (AUC ≤ 0.93) vs. Controls, and moderately accurate biomarkers for CAP vs. COPD (AUC ≤ 0.83), all of which were phospholipids. Phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins were also markedly decreased in S. aureus-infected human A549 and differentiated THP1 cells. Correlations with C-reactive protein and procalcitonin were predominantly negative but only of mild-to-moderate extent, suggesting that these markers reflect more than merely inflammation. Consistent with the increased ceramide concentrations, increased acid sphingomyelinase activity accurately distinguished CAP (fold change = 2.8, AUC = 0.94) and COPD (1.75, 0.88) from Controls and normalized with clinical resolution. CONCLUSIONS: The results underscore the high potential of plasma phospholipids as biomarkers for CAP, begin to reveal differences in lipid dysregulation between CAP and infection-associated COPD exacerbation, and suggest that the decreases in plasma concentrations are at least partially determined by changes in host target cells. Furthermore, they provide validation in clinical blood samples of acid sphingomyelinase as a potential treatment target to improve clinical outcome of CAP
CitationJ Transl Med. 2019 Nov 11;17(1):365. doi: 10.1186/s12967-019-2112-z.
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
The following license files are associated with this item:
- Creative Commons
- Diagnostic and Prognostic Value of Inflammatory Parameters Including Neopterin in the Setting of Pneumonia, COPD, and Acute Exacerbations.
- Authors: Pizzini A, Lunger F, Sahanic A, Nemati N, Fuchs D, Weiss G, Kurz K, Bellmann-Weiler R
- Issue date: 2017 Jun
- [Study of automated acid-base mapping on diagnose and treatment of community acquired pneumonia in emergency department].
- Authors: Yang XF, Wang HR, Gu JH, Jiang J, Pan SM
- Issue date: 2012 Oct
- The usefulness of serum procalcitonin, C-reactive protein, soluble triggering receptor expressed on myeloid cells 1 and Clinical Pulmonary Infection Score for evaluation of severity and prognosis of community-acquired pneumonia in elderly patients.
- Authors: Wang Y, Zhang S, Li L, Xie J
- Issue date: 2019 Jan - Feb
- Phospholipid levels in blood during community-acquired pneumonia.
- Authors: Müller DC, Kauppi A, Edin A, Gylfe Å, Sjöstedt AB, Johansson A
- Issue date: 2019
- Lipid metabolites as potential diagnostic and prognostic biomarkers for acute community acquired pneumonia.
- Authors: To KK, Lee KC, Wong SS, Sze KH, Ke YH, Lui YM, Tang BS, Li IW, Lau SK, Hung IF, Law CY, Lam CW, Yuen KY
- Issue date: 2016 Jun