Article information

Pediatr Emerg Med J. 2025;12(4):155-163

Publication date (electronic) : 2025 October 1

doi : https://doi.org/10.22470/pemj.2025.01382

Ceren Akdağ^,1, Hurşit Apa²

¹Department of Pediatrics, Kargl Ahmet Hamdi Akplnar District State Hospital, Kargl, Türkiye

²Department of Pediatric Emergency Medicine, Dr. Behcet Uz Pediatric Diseases and Surgery Training and Research Hospital, University of Health Sciences, Izmir, Türkiye

Corresponding author Ceren Akdağ Department of Pediatrics, Kargl Ahmet Hamdi Akplnar District State Hospital, Orta Neighborhood, Pazar Square No. 6, Kargl, Çorum 19900, Türkiye Tel: +90-507-208-51-84 Fax: +82-31-780-8409 E-mail: cerenszn@icloud.com

Received 2025 July 18; Revised 2025 September 13; Accepted 2025 September 16.

Trans Abstract

Introduction

Parapneumonic effusion (PPE) is a complication that occurs in approximately 2%-40% of children with community-acquired pneumonia (1,2). While simple PPE often resolves with conservative management, complicated one may necessitate thoracentesis, tube thoracostomy, intrapleural fibrinolysis, or surgical drainage (3-5). However, the differentiation between these 2 categories of PPE often relies on imaging modalities or pleural fluid analyses, which are invasive and time-consuming, or sometimes unavailable in resource-limited settings. Therefore, there is a pressing need for rapid, noninvasive, and readily available inflammatory markers that can support early decision-making.

The authors aimed to assess the utility of systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and other inflammatory markers in differentiating between simple and complicated PPE in children, and to determine the diagnostic accuracy of these markers. The findings may contribute to the development of a noninvasive diagnostic algorithm to support the classification and management of pediatric PPE.

Methods

1. Study design, setting, and patient selection

This retrospective study reviewed the medical records of pediatric patients diagnosed with PPE and hospitalized at the University of Health Sciences, Dr. BehÇet Uz Pediatric Diseases and Surgery Training and Research Hospital in Izmir, Türkiye, from January 1, 2012 through August 1, 2024. The study was approved by the institutional review board of the hospital with written informed consent obtained from the patients or their parents/legal guardians (IRB no. GOA-87). Patients aged 3 months-18 years with PPE confirmed by thoracic ultrasonography (US) and complete blood count (CBC) obtained at hospitalization were included, while those with sepsis or comorbid conditions known to cause pleural effusion were excluded.

Complicated PPE was defined by the presence of septation, loculation, or pleural thickening on thoracic US, chest computed tomography, or purulent appearance or positive bacterial culture of pleural fluid. Patients without any of these features were classified as having simple PPE. Given that a small amount of PPE does not require drainage, those with simple PPE were further stratified into 2 subgroups based on the maximal pleural fluid depth on thoracic US findings: those with < 1 cm and ≥ 1 cm of the fluid (Figure 1).

Figure 1.

Flow chart of study and inclusion-exclusion criteria.

Results

The study population consisted of 200 patients, with 110 males (55.0%) and a mean age of 80.4 ± 50.4 months. Both mean values of symptom duration and hospital length of stay were shortest in the simple < 1 cm group and longest in the complicated PPE group, with post-hoc pairwise comparisons confirming significant differences among the 3 groups (Bonferroni-corrected P < 0.001). Of the patients, 114 (57.0%) had received antibiotics prior to hospitalization. Pleural fluid was sampled from 82 patients (41.0%), with 7 positive cultures: Streptococcus pyogenes was isolated in 4, Staphylococcus aureus in 2, and Streptococcus pneumoniae in 1.

When comparing mean values of inflammatory markers, WBCs, absolute neutrophil count (ANC), absolute monocyte count (AMC), and CRP were all highest in the complicated PPE group (all Ps < 0.001) (Table 1). Conversely, mean LMR was lower in the complicated group than in the < 1 cm group (AMC, P < 0.001; LMR, P = 0.001). Mean SII and SIRI, as well as ESR, were higher in the complicated group than in the < 1 cm group (SII, P = 0.039; SIRI, P < 0.001). No differences were observed among the groups for mean absolute lymphocyte count (ALC), platelet count, NLR, and PLR. Receiver operating characteristic curves showed fair performances of ESR (AUC = 0.73) and CRP (0.72) for predicting the presence of complicated PPE. The other inflammatory markers showed poor or failed performances (e.g., WBC, AUC = 0.69) (Figure 2, Table 2).

Table 1.

Clinical and laboratory characteristics of the patients according to the presence of complicated parapneumonic effusion (N = 200)

Figure 2.

Receiver-operating characteristic curves of infection markers in predicting the presence of complicated effusion in patients with simple parapneumonic effusion. SIRI: systemic inflammation response index, AUC: area under the curve, LMR: lymphocyte-to-monocyte ratio, SII: systemic immune-inflammation index, WBC: white blood cell, ANC: absolute neutrophil count, ALC: absolute lymphocyte count, ESR: erythrocyte sedimentation rate, CRP: C-reactive protein.

Table 2.

Diagnostic performance of inflammation markers in predicting complicated parapneumonic effusion

Discussion

Complicated PPE typically requires more invasive treatment approaches and early recognition for reducing morbidity and mortality. In our study, no significant relationship was found between patient age or gender and the presence of complicated PPE, which aligns with findings from the literature (6). We found that the severity of PPE significantly influenced hospital length of stay. Additionally, delayed presentation to the hospital likely contributed to the progression of the disease into a more complicated course. Recent antibiotic therapy was also found to be associated with poor infection control. These results are consistent with prior studies (7-9).

Previous studies have reported that causative microorganisms can be isolated from the pleural fluid in approximately 25% of patients with PPE, with S. pneumoniae, S. pyogenes, and S. aureus being the most commonly identified pathogens (1,4,10,11). In our study, the low rate of positive cultures was likely due to widespread antibiotic use before hospitalization. The most frequently isolated organisms were S. aureus and S. pyogenes, and notably, all S. pyogenes cases occurred after the coronavirus disease 2019 pandemic. This aligns with findings by Bozan et al. (12) who reported an increase in PPE and empyema cases due to post-pandemic S. pyogenes infection.

In the complicated PPE group, significantly higher mean values of WBCs, ANC, AMC, CRP, and ESR were observed, consistent with findings in the literature (13-15). However, some studies have reported lower ALC in empyema cases (16). Discrepancies in the literature are expected since ALC can vary with age, gender, chronic diseases, and viral or bacterial origin of infection (17).

The significant differences in multiple markers, including WBC, ANC, AMC, ESR, CRP, LMR, SII, and SIR, between the simple < 1 cm and complicated PPE groups suggest that these parameters may aid in clinical decision-making. Conversely, only ESR differed between the simple < 1 cm and ≥ 1 cm groups, indicating that the inflammatory burden becomes more pronounced in PPE above a certain threshold. To the authors’knowledge, no prior clinical study in the literature has grouped simple PPE patients based on volume of PPE and compared inflammation markers.

In addition to acute-phase reactants commonly used in clinical practice, we aimed to assess the diagnostic performance of the novel biomarkers that have gained increasing clinical attention. Rather than monitoring a single cellular parameter, combining ratios of these parameters may yield more meaningful insights into systemic inflammation and immune response. Among these, LMR was lower in the complicated PPE group. The optimal cutoff for distinguishing between complicated and simple PPE was 2.9, with a 76.5% sensitivity and 47.0% specificity. A 2020 study found LMR to be significantly lower in empyema compared to PPE, which was attributed to heightened inflammatory response and immune activation in empyema. Diagnostic accuracy of LMR was noted to improve when evaluated alongside high values of WBCs and CRP (18).

Wu et al. (19) evaluated LMR and NLR in distinguishing pneumonia from upper respiratory tract infection in children. Their 2021 cross-sectional study retrospectively analyzed 5,211 pediatric patients, 2,548 of whom had pneumonia. LMR was significantly lower and NLR higher in pneumonia cases, with AUC values of 0.76 for LMR and 0.71 for NLR. The study concluded that both were clinically useful markers for differential diagnosis. In contrast, our study found NLR to lack sufficient diagnostic performance. A 2018 Turkish study reported a positive correlation between PLR and Pneumonia Severity Index and CRP, indicating its potential as a predictive biomarker for pneumonia (20).

SII reflects the overall inflammatory burden by combining platelet and neutrophil activity relative to the lymphocyte-mediated immune response. In our study, mean SIIs increased progressively from the simple < 1 cm group to the complicated PPE group. This marker showed a 76.5% sensitivity and 52.3% specificity, with a cutoff value of 1,292.1 × 10⁹/L for differentiating complicated from simple PPE. However, it did not show diagnostic utility within the simple groups. This suggests that SII may be more effective in identifying cases with intense inflammation and may play a guiding role in clinical management.

Similarly, SIRI, which combines neutrophil and monocyte inflammatory activity relative to lymphocyte immune response, was higher in the complicated group than in the simple < 1 cm group. SIRI values increased with disease severity, and the optimal cutoff was 3.7 × 10⁹/L with a 78.4% sensitivity and 57.0% specificity. SIRI did not show diagnostic utility in distinguishing the depth of PPE between the 2 simple groups, indicating that its relevance may also be limited to severe inflammation.

Rajvanshi et al. (21) retrospectively analyzed records of 50 children younger than 18 years diagnosed with PPE between April 2019 and September 2022. Among the patients, SII and other biomarkers were compared between the simple and complicated groups, with the latter defined as empyema, microorganisms on Gram stain, bacterial growth in pleural fluid culture, echogenic material in the pleural cavity on US, septation, loculation, or a thickened pleural peel. CRP, ANC, NLR, and SII were significantly higher in the complicated group, with SII showing the highest sensitivity (82.4%) and a cutoff of 1,557 × 10⁹/L (21).

Similarly, a study by Güneylioğ lu et al. (9) which evaluated 59 pediatric patients diagnosed with PPE or empyema in Türkiye shows that SII, LMR, ANC, and CRP were significantly different between those with PPE and those with empyema. In their study, SII showed a 75% sensitivity and 71.7% specificity, indicating its potential as a predictor for empyema. While our findings were consistent, we found no prior literature evaluating SIRI’s role in differentiating complicated from simple PPE.

A prospective cohort study conducted at Tanta University, Egypt, between September 2022 and August 2023, included 228 children aged 2 months-18 years hospitalized with community-acquired pneumonia. NLR, TLR, LMR, SII, and SIRI were calculated at hospitalization. Among the children, 42 had necrotizing pneumonia, 46 had PPE, and 140 had simple pneumonia. SII and SIRI were significantly higher in the necrotizing pneumonia group, along with a higher concentration of D-dimer. The combination of SII, SIRI, and D-dimer showed a high diagnostic accuracy for necrotizing pneumonia (22). The findings indicate that CRP and ESR demonstrated fair diagnostic performance in distinguishing complicated from simple PPE. Other markers such as WBC, SIRI, ANC, LMR, SII, ALC, NLR, and PLR exhibited overall limited performance.

The main strength of our study is its large sample size, which enhances the statistical power and reliability of the findings. However, being a single center study limits the generalizability of the results. Another limitation is the lack of analysis of all biomarkers in all patients. Additionally, the US evaluation was not performed using the same device or by the same specialist, which could have affected image standardization. The absence of reference ranges and the wide variability in biomarker values further limit their interpretability and clinical reliability.

In conclusion, our findings indicate that ESR and CRP as affordable and readily available markers may offer additional diagnostic support in the differentiation of simple versus complicated PPE. These markers may contribute to the early detection and management of patients at risk for complications. Further large scale, prospective studies are required to evaluate broader clinical utility of these biomarkers in the diagnosis and follow-up of complicated PPE.

Article information Continued