Fever duration enhanced biomarker sensitivity in diagnosing radiographically confirmed community-acquired pneumonia in children

Abstract

Aim: Our aim was to examine how fever duration affected the ability of biomarkers to diagnose community-acquired pneumonia (CAP).

Methods: This was a retrospective cohort study of children aged 2-18 years who attended the emergency department at Schneider Children's Medical Centre of Israel with CAP from June 2015 to May 2020. The children underwent biomarker measurements and chest radiographs and optimal biomarker thresholds were identified. Biomarker predictions of x-ray positive CAP were analysed, using receiver operating characteristic curves and area under the curve calculations.

Results: We screened 3346 children, 509 met the inclusion criteria and 363 of those had x-ray positive CAP. White blood counts of >15 000/mm³ and absolute neutrophil counts of >11 200/mm³ showed significant discriminatory power on day 2 of a fever. A neutrophil to lymphocyte ratio (NLR) of >4.5 displayed significant discriminatory power from days 2-5 and peaked on day 4. C-reactive protein of 6.23 mg/dL was discriminatory on day 4.

Conclusion: Fever duration affected how effectively biomarkers diagnosed x-ray positive CAP and all were unreliable on day 1. The NLR showed the most consistent reliability and may be suitable for clinical decision-making. Fever duration should be considered to optimise diagnostic accuracy.

Keywords: C‐reactive protein; biomarkers; community‐acquired pneumonia; emergency department; neutrophil–lymphocyte ratio.

FIGURE 1

Flowchart showing the selection process for the final cohort. Children were excluded if they presented to the ED with chronic diseases, chest x‐rays, and complete blood counts were not available and the days of fever were not recorded. The cohort was divided into children with radiographic evidence of community‐acquired pneumonia (x‐ray positive) and those without (x‐ray negative). CAP, community‐acquired pneumonia; CBC, complete blood count; CXR, chest x‐ray; DOF, days of fever.

FIGURE 2

Biomarkers at emergency department attendance, in relation to time elapsed since fever onset for radiographically confirmed (x‐ray‐positive, blue line) versus cases with no radiographic confirmation (x‐ray‐negative, red line) community‐acquired pneumonia. Statistically significant AUCs between the two groups at each time point are marked with asterisks. Values displayed are means and 95% confidence intervals. The yellow line represents cut‐off values for the various biomarkers respectively. Abnormal WBC was defined as above 15 000/mm³, ANC above 11 200/mm³, NLR above 4.5, and CRP above 6.23 mg/dL. ANC, absolute neutrophil count; AUC, area under the curve; CRP, C‐reactive protein; NLR, neutrophil to lymphocyte ratio; WBC, white blood count.