Introduction
Pneumonia is a serious infection associated with considerable mortality and morbidity in children younger than 5 years [1]. Acute phase reactants are widely used for the differentiation of bacterial and viral pneumonia, the most important of which are the white blood cell (WBC) count, absolute neutrophil count, neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate, and C-reactive protein (CRP). Various studies have reported the beneficial effects of using NLR in diagnosing diseases such as acute appendicitis and acute pancreatitis [2, 3]. Different studies have shown that the mean platelet volume (MPV) is significantly higher in hospitalized patients with pneumonia than in outpatients. The MPV is valuable for predicting disease mortality and severity among patients with community-acquired pneumonia at the time of admission to the emergency departments [4]. 
Despite advanced methods in diagnosing and treating pneumonia, pleural empyema still occurs as one of the severe complications of pneumonia in children [5]. Due to the importance and risks of empyema in children, its early diagnosis and treatment is necessary. If the value of the inflammatory markers be assesses, it can help in the timely diagnosis and proper treatment of pneumonia and its complication (pleural empyema) in children. This study aims to compare the MPV and NLR values in children suffering from bacterial pneumonia with and without pleural empyema.
Methods
This case-control study was conducted on the data of 128 children aged 3 months to 14 years with bacterial pneumonia and pleural empyema and 128 children with bacterial pneumonia but without pleural empyema who were admitted to the 17 Shahrivar Hospital in Rasht, Iran. Patients are identified based on their final diagnosis mentioned in the medical records (uncomplicated pneumonia or pneumonia with pleural empyema). A form surveying demographic information, the season of hospitalization, clinical manifestations, and laboratory and imaging findings were used for data collection. The collected data were analyzed in SPSS version 18 software. The statistically significant level was set at 0.05. First, the normality of the data was checked using the Kolmogorov-Smirnov test; in the case of a normal distribution, the t-test was used; otherwise, the Mann-Whitney U test was used to compare the two groups. In order to determine the predictive power of MPV and NLR in the diagnosis of empyema, the area under the ROC curve (AUC) was calculated. DeLong et al.’s method was used to calculate the standard error, and Binomial exact test was used to calculate the confidence interval for AUC. It should be noted that these calculations were made in MedCalc software v. 20.026. 
Results
Of 256 children, 108 (42.2%) were girls and 148 (57.8%) were boys. Their mean age was 59.89±39.62 months; 90 (35.2%) aged <3 years, 83 (32.4%) aged 3-6 years, and 83 (32.4%) aged ≥7 years. The most frequent season of hospitalization was spring (33.6%). The most common initial complaints were fever (n=249, 97.3%) and cough (n=232, 90.6%). 
Table 1 shows the results of the main laboratory findings in two groups.


Children with empyema had significantly higher NLR, platelet count, and MPV than children without empyema  (P=0.04, 0.005, and 0.021, respectively). The WBC count had a significant positive correlation with MPV in patients with bacterial pneumonia without empyema; the MPV increased with the increase in the WBC count (r=0.196, P=0.027). The lymphocyte count was negatively correlated with MPV in patients with bacterial pneumonia with empyema (r=-0.282, P=0.001). The NLR (r=0.227, P=0.01) and platelet count in in patients with bacterial pneumonia with empyema (r=0.245, P=0.005) had a positive correlation with MPV. To determine the predictive power of MPV and NLR in the diagnosis of empyema, the AUC was calculated. The results showed that both indices were effective. The maximum AUC with a cut-off point of 8.2 for MPV was 0.58 (P=0.020), and the maximum AUC with a cut-off point of 2.7 for NLR was 0.57 (P=0.039).
Discussion
Our study showed that children suffering from bacterial pneumonia with empyema had higher platelet count and MPV than children with uncomplicated pneumonia. Golcuk et al. in 2015 showed that MPV was valuable in predicting the severity of pneumonia and its mortality during admission to the emergency departments [6]. The results of a retrospective study by Gorelik et al. in 2017 on the relationship between the MPV and the prognosis of patients with community-acquired pneumonia admitted to the hospital are also consistent with the findings of our study. They showed that patients with increased MPV suffered more complications and required more mechanical ventilation [7]. Erdogan et al. in 2015 showed that in hospitalized children with a critical condition, the increased MPV level had a direct relationship with the increased mortality [8]. Bekdas et al. also showed that combining NLR, MPV, and CRP indices could help differentiate bacterial and viral pneumonia and predict their complications [1]. Our study also showed that children with bacterial pneumonia and empyema had a significantly higher NLR and a lower lymphocyte count than children with uncomplicated pneumonia.
In conclusion, the NLR (with a cut-off point of 2.7) and MPV (with a cut-off point of 8.2) are useful for the early diagnosis of empyema in children with bacterial pneumonia.

Ethical Considerations
Compliance with ethical guidelines
This study has been approved by the Ethics Committee of Guilan University of Medical Sciences (Code: IR.GUMS.REC.1396.430).

Funding
This article is taken from Fina Sanati pediatric specialist thesis, at the medical school of Gilan University of Medical Sciences.

Authors' contributions
Conceptualization, editing and finalization: Homan Hashemian; Drafting: Fina Santi; Visualization, supervision, project management, funding, methodology, validation, analysis, research and resource review: all authors.

Conflicts of interest
The authors declared no conflict of interest.

Acknowledgements
The authors would like to thank the staff of the 17 Shahrivar Hospital in Rasht who cooperated in conducting this research.

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