373 - Mitochondrial Dysfunction in Children Presenting to the Emergency Department with Febrile Illness Versus Sepsis

Poster Number: 373
Publication Number: 373.312

Laura F. Sartori, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Elena Tsemberis, Children's Hospital of Philadelphia, Washington, DC, United States; Tyne Hernandez, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Katherine Luchette, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Donglan Zhang, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Sumera Farooqi, Childrens Hospital of Philadelphia, Clementon, NJ, United States; Jenny L. Bush, CHOP Children's Hospital of Philadelphia, Medford, NJ, United States; Fran Balamuth, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Scott L. Weiss, Children's Hospital of Philadelphia, Philadelphia, PA, United States

Background: Mitochondrial dysfunction has been linked to immune dysregulation and organ failure in sepsis but whether early mitochondrial alterations play a causal role in progression to sepsis is unknown. Understanding mitochondrial profiles by illness severity will help address this knowledge gap.

Objective: We hypothesized that children with uncomplicated febrile illness would exhibit peripheral blood mononuclear cell (PBMC) mitochondrial respiration intermediate between sepsis and non-infected controls.

Design/Methods: We performed a prospective observational study of 27 patients < 18 years in the ED with uncomplicated febrile illness and 152 in the PICU for sepsis/septic shock at a single institution. A control group of 28 patients without fever or infection was enrolled from the ED/PICU. Basal and ATP-linked mitochondrial oxygen consumption (pmol/s/million cells) were measured in PBMCs using high-resolution respirometry. Spare respiratory capacity (SRC), an index of bioenergetic reserve for cells under stress that is low in sepsis, was calculated as uncoupled minus basal respiration. Data are reported as proportions, median (IQR), or mean ±SD, and compared using Fisher’s exact, Wilcoxon rank sum, or unpaired t-tests.

Results: The febrile illness group was younger (median 2.4 yrs, 1.3-12.1) than sepsis (8.1, 3.4-13.4; p=0.02) and controls (10.3, 5.7-14.4; p=0.01), though respiration was not correlated with age (all Spearman’s rho < 0.1, p >0.1). Sex was not different across groups. Black race was more frequent in febrile illness (41%) than sepsis (25%, p=0.10) and controls (14%, p=0.04) but respiration did not vary by race. Basal respiration was higher in febrile illness (mean 5.7 ±3.7) than in sepsis (3.5 ±2.1, p= < 0.01) or controls (4.1 ±1.4, p=0.04). ATP-linked respiration was higher in febrile illness (3.8 ±2.6) than sepsis (2.5 ±1.6, p=0.02) but not significantly different from controls (2.8 ±1.3, p=0.07). SRC in febrile illness (6.8 ±2.4) was not different than in sepsis (5.7 ±4.7, p=0.08) but was lower than in controls (8.7 ±3.7, p=0.03).Conclusion(s): Children with febrile illness exhibited higher basal and ATP-linked PBMC mitochondrial respiration than sepsis or controls, but low SRC, as in sepsis. Risk for sepsis based on early PBMC mitochondrial respiration in febrile illness warrants further study.