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.
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.
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.
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.
Employment or leadership: None declared.
Honorarium: None declared.
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.
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