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Circulating Histones and Severity of Illness in Children with Sepsis: A Prospective Observational Study

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Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Objectives

To measure circulating histone H3 levels in children with severe sepsis and explore its relationship with severity of illness and organ failures.

Methods

Children aged 3 mo to 12 y with severe sepsis admitted to pediatric intensive care unit (PICU) were prospectively studied. Healthy controls were enrolled from the outpatient department for comparison. Levels of H3 histones were measured on day 1 and day 3.

Results

Thirty-seven patients and 14 controls with median (IQR) age 5 (0.67, 8) and 5 (3, 7) y, respectively were enrolled. Common diagnoses included severe pneumonia (n = 9), staphylococcal sepsis (n = 6), and seasonal tropical infections (n = 4). Two-third (n = 26, 70%) had septic shock. One third (35%) had an unfavorable outcome; 11 died and 2 discontinued care. Median (IQR) H3 levels were not statistically different among patients with sepsis and controls [0.84 (0.62, 1.13) vs. 0.72 (0.52, 0.87) ng/mL; p = 0.10]. There was no significant change in H3 between day 1 and day 3 [0.84 (0.62, 1.13) vs 0.74 (0.5, 0.98) ng/mL; p = 0.22]. Children with thrombocytopenia (n = 27) showed a trend towards higher H3 compared to those without thrombocytopenia (n = 10) [0.9 vs. 0.67 ng/mL; p = 0.06]. However, H3 levels were not elevated in patients with cardiovascular dysfunction, those needing renal-replacement therapy, or unfavorable outcomes.

Conclusion

The present data provides early evidence that in children hospitalized with severe sepsis, histone H3 is not elevated as compared to healthy controls. H3 levels during initial days of sepsis requiring PICU admission were not different with regards to severity of illness, organ dysfunction, and clinical outcome. There was a trend towards elevated H3 in children with thrombocytopenia, which needs further evaluation.

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Funding

This work was supported by PGIMER institute thesis grant (INR 50000/-) for procurement of Histone H3 ELISA Kit.

Author information

Authors and Affiliations

  1. Pediatric Intensive Care Unit, Advanced Pediatrics Center, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Vishal Sidana, Karthi Nallasamy & Muralidharan Jayashree

  2. Pediatric Intensive Care, NMC Royal Hospital, Abu Dhabi, UAE

    Javed Ismail

  3. Pediatric Hematology, Advanced Pediatric Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Prateek Bhatia

Authors
  1. Vishal Sidana
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  2. Javed Ismail
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  3. Karthi Nallasamy
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  4. Prateek Bhatia
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  5. Muralidharan Jayashree
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Contributions

PB and KN conceived the idea and all authors contributed to the design of the study; PB carried out histone H3 measurements; VS collected the data; JI helped in statistical analysis; VS wrote the first draft. KN, PB, JI, and MJ critically reviewed the draft and contributed to revision; All authors read and approved the final manuscript. MJ will act as the guarantor for this paper.

Corresponding author

Correspondence to Karthi Nallasamy.

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Ethics Approval

PGIMER Institute ethics committee approved this study (IEC/2018/00351, dated 26/03/2018). Informed consent was taken from parents/legal guardians.

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Sidana, V., Ismail, J., Nallasamy, K. et al. Circulating Histones and Severity of Illness in Children with Sepsis: A Prospective Observational Study. Indian J Pediatr 89, 989–995 (2022). https://doi.org/10.1007/s12098-022-04084-5

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  • DOI: https://doi.org/10.1007/s12098-022-04084-5

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