Startseite Association of serum sphingomyelin profile with clinical outcomes in patients with lower respiratory tract infections: results of an observational, prospective 6-year follow-up study
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Association of serum sphingomyelin profile with clinical outcomes in patients with lower respiratory tract infections: results of an observational, prospective 6-year follow-up study

  • Thomas Baumgartner EMAIL logo , Giedre Zurauskaite , Christian Steuer , Luca Bernasconi , Andreas Huber , Beat Mueller und Philipp Schuetz
Veröffentlicht/Copyright: 29. September 2018
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 57 Heft 5

Abstract

Background

Sphingolipids – the structural cell membrane components – and their metabolites are involved in signal transduction and participate in the regulation of immunity. We investigated the prognostic implications of sphingolipid metabolic profiling on mortality in a large cohort of patients with lower respiratory tract infections (LRTIs).

Methods

We measured 15 different sphingomyelin (SM) types in patients with LRTIs from a previous Swiss multicenter trial that examined the impact of procalcitonin-guided antibiotic therapy on total antibiotic use and rates and duration of hospitalization. Primary and secondary end points were adverse outcomes – defined as death or intensive care unit admission within 30 days – and 6-year mortality.

Results

Of 360 patients, 8.9% experienced an adverse outcome within 30 days and 46% died within 6 years. Levels of all SM types were significantly lower in pneumonia patients vs. those with chronic obstructive pulmonary disease (COPD) exacerbation (p<0.0001 for all comparisons). Sphingomyelin subspecies SM (OH) C22:1 and SM (OH) C22:2 were associated with lower risk for short-term adverse outcomes (sex-, gender- and comorbidity-adjusted odds ratios [OR]: 0.036; 95% confidence interval [CI], 0.002–0.600; p=0.021 and 0.037; 95% CI, 0.001–0.848; p=0.039, respectively). We found no significant associations with 6-year mortality for any SM.

Conclusions

Circulating sphingolipid levels are lower in inflammatory conditions such as pneumonia and correlate with adverse short-term outcomes. Further characterization of the physiological, pathophysiological and metabolic roles of sphingolipids under inflammatory conditions may facilitate understanding of their roles in infectious disease.

Keywords: lower respiratory infections; mortality; outcomes; sphingolipids

Acknowledgments

We would like to thank all patients, their relatives and local general practitioners for their participation in this study. We would also like to acknowledge the contributions of the staff of the emergency department, medical clinic and central laboratory of the University Hospital Basel and the cantonal hospitals of Aarau, Lucerne, Liestal and Muensterlingen, and the ‘Buergerspital’ Solothurn for their assistance and technical support. We also thank members of the ProHOSP Study Group for their valuable support. Assistance with the preparation of this manuscript was provided by Prasad Kulkarni, PhD, CMPP of Asclepius Medical Communications LLC, Ridgewood, NJ, USA and was funded by PS.

  1. Author contributions: TB, GZ and PS designed the study, performed the statistical analyses and drafted the manuscript. CS, LB and AH performed laboratory measurements using the p180 kit. All authors contributed to the acquisition and interpretation of the data, critical review and revision of the manuscript for important content, and final approval of the manuscript for submission. PS had full access to all study data and takes responsibility for the integrity of the work and the accuracy of the data analysis. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This study was supported by the Swiss National Science Foundation (SNSF Professorship, PP00P3_150531) and the Forschungsrat of the Kantonsspital Aarau (1410.000.058 and 1410.000.044) awarded to PS.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. World Health Organization. The top 10 causes of death. Available at: http://www.who.int/mediacentre/factsheets/fs310/en/. Accessed: 11 April 2018. 2017.Suche in Google Scholar

2. Pralhada Rao R, Vaidyanathan N, Rengasamy M, Mammen Oommen A, Somaiya N, Jagannath MR. Sphingolipid metabolic pathway: an overview of major roles played in human diseases. J Lipids 2013;2013:178910.10.1155/2013/178910Suche in Google Scholar PubMed PubMed Central

3. Rolando M, Escoll P, Nora T, Botti J, Boitez V, Bedia C, et al. Legionella pneumophila S1P-lyase targets host sphingolipid metabolism and restrains autophagy. Proc Natl Acad Sci USA 2016;113:1901–6.10.1073/pnas.1522067113Suche in Google Scholar PubMed PubMed Central

4. Platt FM. Sphingolipid lysosomal storage disorders. Nature 2014;510:68–75.10.1038/nature13476Suche in Google Scholar PubMed

5. Halmer R, Walter S, Fassbender K. Sphingolipids: important players in multiple sclerosis. Cell Physiol Biochem 2014;34:111–8.10.1159/000362988Suche in Google Scholar PubMed

6. Jiang XC, Paultre F, Pearson TA, Reed RG, Francis CK, Lin M, et al. Plasma sphingomyelin level as a risk factor for coronary artery disease. Arterioscler Thromb Vasc Biol 2000;20:2614–8.10.1161/01.ATV.20.12.2614Suche in Google Scholar

7. Egom EE, Mamas MA, Chacko S, Stringer SE, Charlton-Menys V, El-Omar M, et al. Serum sphingolipids level as a novel potential marker for early detection of human myocardial ischaemic injury. Front Physiol 2013;4:130.10.3389/fphys.2013.00130Suche in Google Scholar PubMed PubMed Central

8. Ueda N. Sphingolipids in genetic and acquired forms of chronic kidney diseases. Curr Med Chem 2017;24:1238–75.10.2174/0929867324666170112114525Suche in Google Scholar PubMed

9. Abou Daher A, El Jalkh T, Eid AA, Fornoni A, Marples B, Zeidan YH. Translational aspects of sphingolipid metabolism in renal disorders. Int J Mol Sci 2017;18:2528.10.3390/ijms18122528Suche in Google Scholar PubMed PubMed Central

10. Do SI, Kim HS, Kim K, Lee H, Do IG, Kim DH, et al. Predictive value of sphingosine kinase 1 expression in papillary thyroid carcinoma. Anticancer Res 2017;37:5399–405.Suche in Google Scholar

11. Lee YH, Tan CW, Venkatratnam A, Tan CS, Cui L, Loh SF, et al. Dysregulated sphingolipid metabolism in endometriosis. J Clin Endocrinol Metab 2014;99:E1913–21.10.1210/jc.2014-1340Suche in Google Scholar PubMed PubMed Central

12. Kitatani K, Taniguchi M, Okazaki T. Role of sphingolipids and metabolizing enzymes in hematological malignancies. Mol Cells 2015;38:482–95.10.14348/molcells.2015.0118Suche in Google Scholar PubMed PubMed Central

13. Degagne E, Saba JD. S1pping fire: sphingosine-1-phosphate signaling as an emerging target in inflammatory bowel disease and colitis-associated cancer. Clin Exp Gastroenterol 2014;7:205–14.10.2147/CEG.S43453Suche in Google Scholar PubMed PubMed Central

14. Ghidoni R, Caretti A, Signorelli P. Role of sphingolipids in the pathobiology of lung inflammation. Mediators Inflamm 2015;2015:487508.10.1155/2015/487508Suche in Google Scholar PubMed PubMed Central

15. Bowler RP, Jacobson S, Cruickshank C, Hughes GJ, Siska C, Ory DS, et al. Plasma sphingolipids associated with chronic obstructive pulmonary disease phenotypes. Am J Respir Crit Care Med 2015;191:275–84.10.1164/rccm.201410-1771OCSuche in Google Scholar PubMed PubMed Central

16. To KK, Lee KC, Wong SS, Sze KH, Ke YH, Lui YM, et al. Lipid metabolites as potential diagnostic and prognostic biomarkers for acute community acquired pneumonia. Diagn Microbiol Infect Dis 2016;85:249–54.10.1016/j.diagmicrobio.2016.03.012Suche in Google Scholar PubMed PubMed Central

17. Schuetz P, Christ-Crain M, Wolbers M, Schild U, Thomann R, Falconnier C, et al. Procalcitonin guided antibiotic therapy and hospitalization in patients with lower respiratory tract infections: a prospective, multicenter, randomized controlled trial. BMC Health Serv Res 2007;7:102.10.1186/1472-6963-7-102Suche in Google Scholar PubMed PubMed Central

18. Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. J Am Med Assoc 2009;302:1059–66.10.1001/jama.2009.1297Suche in Google Scholar PubMed

19. Alan M, Grolimund E, Kutz A, Christ-Crain M, Thomann R, Falconnier C, et al. Clinical risk scores and blood biomarkers as predictors of long-term outcome in patients with community-acquired pneumonia: a 6-year prospective follow-up study. J Intern Med 2015;278:174–84.10.1111/joim.12341Suche in Google Scholar PubMed

20. Nickler M, Ottiger M, Steuer C, Huber A, Anderson JB, Muller B, et al. Systematic review regarding metabolic profiling for improved pathophysiological understanding of disease and outcome prediction in respiratory infections. Respir Res 2015;16:125.10.1186/s12931-015-0283-6Suche in Google Scholar PubMed PubMed Central

21. Nickler M, Schaffner D, Christ-Crain M, Ottiger M, Thomann R, Hoess C, et al. Prospective evaluation of biomarkers for prediction of quality of life in community-acquired pneumonia. Clin Chem Lab Med 2016;54:1831–46.10.1515/cclm-2016-0001Suche in Google Scholar PubMed

22. Nickler M, Ottiger M, Steuer C, Kutz A, Christ-Crain M, Zimmerli W, et al. Time-dependent association of glucocorticoids with adverse outcome in community-acquired pneumonia: a 6-year prospective cohort study. Crit Care 2017;21:72.10.1186/s13054-017-1656-7Suche in Google Scholar PubMed PubMed Central

23. Ottiger M, Nickler M, Steuer C, Odermatt J, Huber A, Christ-Crain M, et al. Trimethylamine-N-oxide (TMAO) predicts fatal outcomes in community-acquired pneumonia patients without evident coronary artery disease. Eur J Intern Med 2016;36:67–73.10.1016/j.ejim.2016.08.017Suche in Google Scholar PubMed

24. Weinberger KM. Metabolomics in diagnosing metabolic diseases. Ther Umsch 2008;65:487–91.10.1024/0040-5930.65.9.487Suche in Google Scholar PubMed

25. Yet I, Menni C, Shin SY, Mangino M, Soranzo N, Adamski J, et al. Genetic influences on metabolite levels: a comparison across metabolomic platforms. PLoS One 2016;11:e0153672.10.1371/journal.pone.0153672Suche in Google Scholar PubMed PubMed Central

26. Illig T, Gieger C, Zhai G, Romisch-Margl W, Wang-Sattler R, Prehn C, et al. A genome-wide perspective of genetic variation in human metabolism. Nat Genet 2010;42:137–41.10.1038/ng.507Suche in Google Scholar PubMed PubMed Central

27. Muller A, Heseler K, Schmidt SK, Spekker K, Mackenzie CR, Daubener W. The missing link between indoleamine 2,3-dioxygenase mediated antibacterial and immunoregulatory effects. J Cell Mol Med 2009;13:1125–35.10.1111/j.1582-4934.2008.00542.xSuche in Google Scholar PubMed PubMed Central

28. Berger M, Gray JA, Roth BL. The expanded biology of serotonin. Annu Rev Med 2009;60:355–66.10.1146/annurev.med.60.042307.110802Suche in Google Scholar PubMed PubMed Central

29. Majno G, Palade GE, Schoefl GI. Studies on inflammation. II. The site of action of histamine and serotonin along the vascular tree: a topographic study. J Biophys Biochem Cytol 1961;11:607–26.10.1083/jcb.11.3.607Suche in Google Scholar PubMed PubMed Central

30. Muller AJ, Malachowski WP, Prendergast GC. Indoleamine 2,3-dioxygenase in cancer: targeting pathological immune tolerance with small-molecule inhibitors. Expert Opin Ther Targets 2005;9:831–49.10.1517/14728222.9.4.831Suche in Google Scholar PubMed

31. Yang Y, Uhlig S. The role of sphingolipids in respiratory disease. Ther Adv Respir Dis 2011;5:325–44.10.1177/1753465811406772Suche in Google Scholar PubMed

32. Lee J, Yeganeh B, Ermini L, Post M. Sphingolipids as cell fate regulators in lung development and disease. Apoptosis 2015;20:740–57.10.1007/s10495-015-1112-6Suche in Google Scholar PubMed PubMed Central

33. Telenga ED, Hoffmann RF, Ruben tK, Hoonhorst SJ, Willemse BW, van Oosterhout AJ, et al. Untargeted lipidomic analysis in chronic obstructive pulmonary disease. Uncovering sphingolipids. Am J Respir Crit Care Med 2014;190:155–64.10.1164/rccm.201312-2210OCSuche in Google Scholar PubMed

34. Barnawi J, Tran H, Jersmann H, Pitson S, Roscioli E, Hodge G, et al. Potential link between the sphingosine-1-phosphate (S1P) system and defective alveolar macrophage phagocytic function in chronic obstructive pulmonary disease (COPD). PLoS One 2015;10:e0122771.10.1371/journal.pone.0122771Suche in Google Scholar PubMed PubMed Central

35. Li JF, Qu F, Zheng SJ, Ren F, Wu HL, Liu M, et al. Plasma sphingolipids: potential biomarkers for severe hepatic fibrosis in chronic hepatitis C. Mol Med Rep 2015;12:323–30.10.3892/mmr.2015.3361Suche in Google Scholar PubMed

36. Ohkawa R, Kurano M, Nakamura K, Okubo S, Yokota H, Ikeda H, et al. Sphingolipids, possible biomarkers for atherosclerotic disorders. Rinsho Byori 2013;61:795–802.Suche in Google Scholar

37. Russo SB, Ross JS, Cowart LA. Sphingolipids in obesity, type 2 diabetes, and metabolic disease. Handb Exp Pharmacol 2013:373–401. doi: 10.1007/978-3-7091-1511-4_19.10.1007/978-3-7091-1511-4_19Suche in Google Scholar PubMed PubMed Central

38. Joo EJ, Weyers A, Li G, Gasimli L, Li L, Choi WJ, et al. Carbohydrate-containing molecules as potential biomarkers in colon cancer. OMICS 2014;18:231–41.10.1089/omi.2013.0128Suche in Google Scholar PubMed PubMed Central

39. Cordts F, Pitson S, Tabeling C, Gibbins I, Moffat DF, Jersmann H, et al. Expression profile of the sphingosine kinase signalling system in the lung of patients with chronic obstructive pulmonary disease. Life Sci 2011;89:806–11.10.1016/j.lfs.2011.08.018Suche in Google Scholar PubMed

40. Chen L, Luo LF, Lu J, Li L, Liu YF, Wang J, et al. FTY720 induces apoptosis of M2 subtype acute myeloid leukemia cells by targeting sphingolipid metabolism and increasing endogenous ceramide levels. PLoS One 2014;9:e103033.10.1371/journal.pone.0103033Suche in Google Scholar PubMed PubMed Central

41. Gatt S, Dagan A. Cancer and sphingolipid storage disease therapy using novel synthetic analogs of sphingolipids. Chem Phys Lipids 2012;165:462–74.10.1016/j.chemphyslip.2012.02.006Suche in Google Scholar PubMed

Received: 2018-05-13
Accepted: 2018-08-21
Published Online: 2018-09-29
Published in Print: 2019-04-24

©2019 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2018-0509
Schlagwörter für diesen Artikel
lower respiratory infections; mortality; outcomes; sphingolipids

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Cardiac biomarkers – 2019
  4. Reviews
  5. Current understanding and future directions in the application of TIMP-2 and IGFBP7 in AKI clinical practice
  6. Serum cytokines, adipokines and ferritin for non-invasive assessment of liver fibrosis in chronic liver disease: a systematic review
  7. Opinion Papers
  8. Detection capability of quantitative faecal immunochemical tests for haemoglobin (FIT) and reporting of low faecal haemoglobin concentrations
  9. Should phosphatidylethanol be currently analysed using whole blood, dried blood spots or both?
  10. IFCC Papers
  11. High sensitivity, contemporary and point-of-care cardiac troponin assays: educational aids developed by the IFCC Committee on Clinical Application of Cardiac Bio-Markers
  12. Cardiac troponin and natriuretic peptide analytical interferences from hemolysis and biotin: educational aids from the IFCC Committee on Cardiac Biomarkers (IFCC C-CB)
  13. Genetics and Molecular Diagnostics
  14. Droplet digital PCR for the simultaneous analysis of minimal residual disease and hematopoietic chimerism after allogeneic cell transplantation
  15. General Clinical Chemistry and Laboratory Medicine
  16. Commutable whole blood reference materials for hemoglobin A1c validated on multiple clinical analyzers
  17. When results matter: reliable creatinine concentrations in hyperbilirubinemia patients
  18. Mass spectrometry based analytical quality assessment of serum and plasma specimens with patterns of endo- and exogenous peptides
  19. Association of serum sphingomyelin profile with clinical outcomes in patients with lower respiratory tract infections: results of an observational, prospective 6-year follow-up study
  20. Effect of an activated charcoal product (DOAC Stop™) intended for extracting DOACs on various other APTT-prolonging anticoagulants
  21. Hematology and Coagulation
  22. Commutability assessment of reference materials for the enumeration of lymphocyte subsets
  23. Circulating platelet-neutrophil aggregates as risk factor for deep venous thrombosis
  24. Reference Values and Biological Variations
  25. A comparison of complete blood count reference intervals in healthy elderly vs. younger Korean adults: a large population study
  26. Indirect determination of hematology reference intervals in adult patients on Beckman Coulter UniCell DxH 800 and Abbott CELL-DYN Sapphire devices
  27. Cancer Diagnostics
  28. Large platelet size is associated with poor outcome in patients with metastatic pancreatic cancer
  29. Cardiovascular Diseases
  30. Sample matrix and high-sensitivity cardiac troponin I assays
  31. Preoperative proteinuria and clinical outcomes in type B aortic dissection after thoracic endovascular aortic repair
  32. Infectious Diseases
  33. The rational specimen for the quantitative detection of Epstein-Barr virus DNA load
  34. Letters to the Editor
  35. Letter to the Editor on article Dimech W, Karakaltsas M, Vincini G. Comparison of four methods of establishing control limits for monitoring quality controls in infectious disease serology testing. Clin Chem Lab Med 2018;56:1970–8
  36. Counterpoint to the Letter to the Editor by Badrick and Parvin in regard to Comparison of four methods of establishing control limits for monitoring quality controls in infectious disease serology testing
  37. Is creatine kinase an ideal biomarker in rhabdomyolysis? Reply to Lippi et al.: Diagnostic biomarkers of muscle injury and exertional rhabdomyolysis (https://doi.org/10.1515/cclm-2018-0656)
  38. Blood neuron cell-derived microparticles as potential biomarkers in Alzheimer’s disease
  39. A fast, nondestructive, low-cost method for the determination of hematocrit of dried blood spots using image analysis
  40. Association of fibroblast growth factor 21 plasma levels with neonatal sepsis: preliminary results
  41. Impact of continuous renal replacement therapy (CRRT) and other extracorporeal support techniques on procalcitonin guided antibiotic therapy in critically ill patients with septic shock
  42. Determining the cutoff value of the APTT mixing test for factor VIII inhibitor
  43. Determining the cut-off value of the APTT mixing test for factor VIII inhibitor: reply
  44. Euthyroid Graves’ disease with spurious hyperthyroidism: a diagnostic challenge
  45. A pilot plasma-ctDNA ring trial for the Cobas® EGFR Mutation Test in clinical diagnostic laboratories
  46. MS-based proteomics: a metrological sound and robust alternative for apolipoprotein E phenotyping in a multiplexed test
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