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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&lt;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.

clinical chemistry and laboratory medicine (cclm)

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