Medical and Biological Sciences XXVI/2 - Collegium Medicum ...

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12 Elżbieta Grześk et. al. z CRP, PCT i OB, dla CRPxPCT wynosiły odpowiednio 0,2862, 0,5564 i 0,9047, dla CRPxOB odpowiednio 0,2311, 0,4487 i 0,7418, dla PCTxOB odpowiednio – 0,3157, 0,5492 i 0.8398. W n i o s k i . Otrzymane wyniki sugerują, że oznaczenie CRP, OB oraz PCT stanowią porównywalną wartość diagnostyczną do pojedynczych testów stosowanych w różnicowaniu infekcji wirusowych i bakteryjnych, tak więc mogą być pomocne podczas podejmowania decyzji o rozpoczęciu antybiotykoterapii u pacjentów z zapaleniem oskrzelików. Key words: erythrocyte sedimentation rate, C-reactive protein, procalcytonin, bronchiolitis Słowa kluczowe: OB, białko ostrej fazy (CRP), prokalcytonina, zapalenie oskrzelików INTRODUCTION Bronchiolitis in children is a serious self-limited disease of respiratory tract infections. The presence of swelling and destruction of bronchial epithelial cells without the spasm of bronchial smooth muscle cells is a common histological sign of bronchiolitis [1, 2]. The main clinical symptoms of bronchiolitis are wheezing, cough and dyspnea. The leading causes of bronchiolitis are viral infections, among them the respiratory syncytial virus infection is the most frequent (60-80% of cases) [3,4]. There are two strategies in the treatment of bronchiolitis: etiological and symptomatic. During the viral infection the symptomatic treatment is the most important but in the presence of bacterial infection or co-infection, etiological treatment with the use of antibiotics should be started as soon as possible. On the other hand, the unnecessary use of antibiotics may cause many different complications. In this condition, the possibility of the most accurate and early distinguishing between viral and bacterial infection is extremely important. The use of single marker strategy may not be adequate, thus the use of multi marker strategy should be considered. The best widely available markers used in differentiation between viral and bacterial infection etiology are C- reactive protein and procalcitonin [5]. C-reactive protein (CRP) has proven to be a reliable marker for infectious diseases thus measurements of CRP concentration are routinely used in the clinical practice for diagnosis and monitoring of infectious diseases such as bronchitis, pneumonia, sepsis etc. [6, 7]. CRP is an acute phase protein produced by hepatocytes as a response to the inflammatory conditions. The transcription of CRP gene is upregulated by interleukin-6, interleukin-8 and tumor necrosis factor, thus CRP concentration reflects the severity of inflammation [7]. During inflammation the concentration of CRP increases significantly. Normally CRP is present in the blood in the concentration below 5 mg/L. It is generally accepted that serum CRP levels below 10 mg/L suggest minor viral infections, whereas level of CRP between 10 and 20 mg/L suggests serious viral infection. Serum CRP levels above 20-30 mg/L are observed during bacterial infections in children; in adults this level is usually beyond 50 mg/L [5, 6, 8]. The concentration of procalcitonin (PCT) increases significantly in bacterial infections. High plasma concentrations of PCT typically occur in children with severe bacterial infections especially sepsis, meningitis and infections of lower respiratory tract. In viral infections PCT concentration remains normal, thus PCT is one of the best inflammatory markers in differentiation between viral and bacterial infections [9]. According to the Westergren method, erythrocytes sedimentation rate (ESR), is commonly used for years as an index of inflammation process [10]. However, in children CRP appears to be more useful than WBC or ESR [11]. There has been limited investigation into the role of CRP measurement in distinguishing bacterial from viral lower respiratory tract infection [12]. In our study we analyzed the efficacy of use the CRP, PCT and ESR tests in comparison to routinely evaluated examinations in children with clinical symptoms of viral bronchiolitis and bacterial coinfection. PATIENTS AND METHODS The study included 149 children hospitalized because of bronchiolitis. The main criterion of inclusion was the clinical presentation of bronchiolitis thus typical clinical presentation including presence of seasonal viral illness characterized by fever, nasal discharge and dry, wheezy cough and in physical examination inspiratory cracles and/or high pitched expiratory wheeze should be present [12]. Of these children aged 1-24 months (102 boys – median age 8.2 months and 47 girls – median age 10.5 months) that presented clinical signs of lower respiratory tract infection, pathogens were identified in 16 children.
Value of erythrocyte sedimentation rate, C-reactive protein and procalcitonin concentration versus multimarker strategy... 13 To get the homogeneous group of patients, the children with the presence of bronchial asthma, cystic fibrosis, pulmonary bronchodysplasts, congenital heart diseases, abnormalities of chest and lungs, children treated with bronchodilatators and anti-inflammatory drugs, children with gastroesophageal reflux were excluded from the study. The agreement of parent(s) for participation in the study was obligatory. According to the results of physical examination in pediatric emergency department and during first two days of hospitalization at the pediatric department, children were included into one of two subgroups: children with clinical presentation of viral infection (group A) and children with respiratory tract bacterial co-infection (group B). In the study group of children the concentrations of CRP, PCT and ESR were analyzed. Additionally, in the suspicion of bacterial infection, in some cases, according to the results of physician examination chest X ray (CXR) was performed. To classify a child into the group A the chest X-ray (if performed) had to be without inflammatory changes but the presence of peripheral oedema or atelectasis should be present. The CXR examination was performed in 130 children in total. WBC count of 12 M/L or more in the presence of clinical symptoms suggested possibility of bacterial coinfection [5,9,10]. Characteristics of the whole group of children with bronchiolitis and subgroups A and B are presented in Table I. Table I. Age and sex of children hospitalized because of bronchiolitis Number of children Sex Age [months] Age ♂ [months] Age ♀ [months] Total Group A Group B 149 (100%) ♂ 102 (68.5%) ♀ 47 (31.5%) 7 (1-24) 6,5 (1-24) 10 (1-24) 91 (61.1%) 58 (38.9%) p=0,0003 ♂ 62 (68.1%) ♀ 29 (31,9%) p=0,0001 ♂ 40 (69,0%) ♀ 18 (31%) 8 (1-24) 5 (1-24) p=0.001 7 (1-24) 5 (1-24) p=0.0043 11 (1-24) 6 (1-24) p=0.0559 ♂ - boys, ♀ - girls Presented data are median and (minimal – maximal values). Statistical significance was calculated for data in group A and B. Etiology was identified with the Directigen RSV test kit (RSV detection set) (Becton-Dickinson) and Euroimmun Pneumo – FIDE M (RTP1) (Lencomm), detecting viruses such as RS virus, adenovirus, influenza and parainfluenza viruses and bacterial pathogens such as Bordetella, Mycoplasma, Legionella and Chlamydia. [5,11,13,14]. We found respiratory syncytial virus in 3 cases, in 1 case - adenovirus infection, in 8 cases - mycoplasma pneumoniae infection and in 4 - Bordetella pertusis infection. In the study group of children the concentrations of inflammatory biomarkers such as CRP, PCT and ESR were analyzed. CRP was assayed in the serum using high-sensitivity assay (BN II Dade Behring). The assay detection limit is 0.15 mg/L and CV is 5% for concentration of 0.35 and 0.5 mg/L. PCT was assayed using chemiluminescent immunoassay (Liaison-Byk), ESR was measured with Sedisystem (Becton- Dickinson). Border line values suggesting the presence of bacterial infection were: for ESR – 15mm/h, CRP 15 mg/L and PCT 1.0 ng/ml [5,6,7,9,10]. Study was approved by the Ethics Committee of the Collegium Medicum of Nicolaus Copernicus University. STATISTICAL METHODS Calculations were performed using Statistica PL 6.0 and Analyse-it for Microsoft Excel (version 2.12) [15]. Quantitative data from patients of groups A and B, after confirmation of normal distribution, were compared using Student’s T test, whereas qualitative parameters were compared with χ 2 test with Yaets correction when necessary. Receiver operating curves (ROC) analysis was used to define the value of CRP, PCT and ESR better in the distinguishing viral from viral coexisting with bacterial infection. The area under the curve calculated for CRP PCT and ESR alone and in different combination was compared using two-tailed Student’s t test. RESULTS Mean ESR in the study group was 14.1 ± 20.4 mm/1h. Mean CRP concentration was 4.94 ± 4.92 mg/L and PCT concentration was 0.48 ± 1.50 ng/ml. Mean ESR was 7.5 ± 5.4 mm/1h in the group A and significantly higher in the group B 25.5 ± 27.5 mm/1h (p
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