Interferon-γ release assay for the diagnosis of latent tuberculosis in children younger than 5 years of age.

BACKGROUND: There are limited data available on interferon-γ release assay (IGRA) performance in children up to 5 years of age, with documented exposure to active tuberculosis (TB). The aim of this study was to evaluate (1) the influence of infectivity of adult source cases on test results, (2) the impact of age, and (3) the level of agreement, between IGRA and tuberculin skin test (TST) results. METHODS: A total of 142 Bacille Calmette-Guerin-vaccinated children up to 5 years of age were investigated because of a history of exposure to active TB. QuantiFERON-TB Gold In-Tube IGRA (QFT) and TST assays were performed. RESULTS: Test results were significantly influenced by positive finding of cavitary lesions (QFT, odds ratio [OR] = 6.15; TST, OR = 7.48) and positive acid-fast bacilli (QFT, OR = 4.01; TST, OR = 4.47) in active TB contacts. QFT resulted in 1 indeterminate response (0.7%), attributable to low mitogen. There was no evidence for age having any effect on QFT performance. The 2 tests showed a moderate overall concordance (89%; κ = 0.591) at a TST cutoff value of ≥ 10 mm. CONCLUSIONS: Association of positive QFT and TST results with risk factors for infection in child contacts (presence of cavitary lesions and acid-fast bacilli smear positivity in index cases) suggests that both the tests have good diagnostic accuracy. However, there was significant discord between results of the 2 tests that could not be definitively resolved. Thus, in a high-risk population of children up to 5 years of age, both tests (QFT and TST) should be performed and the child should be considered infected if either or both tests are positive.

Correlation between asthma severity and serum IgE in asthmatic children sensitized to Dermatophagoides pteronyssinus.

BACKGROUND: We undertook this study to test the possible correlation between serum concentration of total and specific IgE antibodies and asthma severity in asthmatic children sensitized to the house dust mite Dermatophagoides pteronyssinus. METHODS: The study included 157 asthmatic children aged 5-15 years (8 +/- 3 years). Clinical diagnosis was based on personal and family history, physical examination, pulmonary function testing and skin tests. Asthma severity was determined according to GINA guidelines. In vitro tests included serum concentration of total and specific IgE. RESULTS: All asthmatic children had elevated serum concentration of total IgE. The children with elevated serum concentration of total IgE also showed an increased serum concentration of specific IgE. Asthma of higher higher severity was present in patients with total IgE concentration >288.0 kIU/L (AUC = 0.736) and specific IgE to Dermatophagoides pteronyssinus >44.1 kIUA/L (AUC = 0.843). Intermittent asthma was present in 76.9% of children with specific IgE concentration <44.1 kIUA/L. The positive predictive value suggested with 79.2% probability that a child with a concentration of specific IgE to Dermatophagoides pteronyssinus >44.1 kIUA/L would have a more severe form of asthma. CONCLUSIONS: Asthmatic children with higher asthma severity have a higher serum concentration of both total IgE (>288.0 kIU/L) and specific IgE to Dermatophagoides pteronyssinus (>44.1 kIUA/L), respectively.

Cut-off values for total serum immunoglobulin E between non-atopic and atopic children in north-west Croatia.

BACKGROUND: The aim of this study was to determine cut-off values for total serum immunoglobulin E (IgE) between non-atopic and atopic children with respiratory symptoms. Children of 0-16 years of age were evaluated for respiratory symptoms of >4-week duration. METHODS: Children were divided into two groups: non-atopic children (n=3355) who were non-IgE-sensitized with undetectable allergen-specific IgE (<0.35 kIU(A)/L), and atopic children (n=4620) who were sensitized to > or =1 allergens (specific IgE > or =0.35 kIU(A)/L). Upper and lower centiles were determined and cut-off values calculated using receiver operating characteristic (ROC) analysis. RESULTS: Serum total IgE increased with age in both groups, although at a variable level and rate, and reached a plateau at 9 and 10 years in non-atopic and atopic children, respectively. Atopic children had on average 14-fold higher serum total IgE compared to non-atopic children. In both groups, the median was lower than the corresponding mean and the distribution skewness was always positive (group I, 0.87; group II, 0.91). In almost all age groups, the 95th percentile for non-atopic children corresponded to the calculated cut-off values, whereas the 10th percentile for atopic children corresponded to the respective cut-off values only until the age of 8 years, after which greater differences between the cut-off values and the 10th percentile were recorded. Cut-off values for total serum IgE in children up to 16 years were determined with diagnostic sensitivity, specificity and area under the ROC curve of 96%, 91% and 0.950, respectively. CONCLUSIONS: The 95th percentile for total IgE in non-atopic children and the 10th percentile in atopic children could be taken as cut-off values in children up to 8 years of age, after which significant percentile discrepancies between non-atopic and atopic children were recorded. Since atopic subjects show a more irregular centile distribution, cut-off values are best determined by ROC analysis.

Chest radiography findings in primary pulmonary tuberculosis in children.

Plain chest radiography plays a major role in the diagnosis and follow-up of pulmonary tuberculosis in childhood. The aim of our study was to investigate the distribution of characteristic chest radiographic findings at diagnosis in children with pulmonary tuberculosis. The age of the patients and the type and localization of radiographic changes at admission were retrospectively analyzed. We reviewed chest radiographs in 204 children admitted from January 1, 1991 until June 30, 1994 for newly diagnosed pulmonary tuberculosis. Mean age +/- SD was 6.4 +/- 4.2 years (range 0-14). The most common lesion was lymphadenopathy (found in 172 children, 84.3%). It was significantly more common in the youngest age group (0-4 years) and was more significantly present in the right hilo-mediastinal region. Parenchymal changes were found in 125 children (61.3%). They were also significantly more common in the young age group and in the right lung. Other less common lesions included pleuritis, atelectasis, destructive-cavitary lesions and miliary dissemination. In conclusion, the leading radiographic finding in pulmonary tuberculosis in childhood remains hilar lymphadenopathy, but parenchymal changes are clearly strongly present, and should be sought and appreciated in the diagnostic work-up for pulmonary tuberculosis in childhood.

Thrombopoietin and interleukin-6 in children with pneumonia-associated thrombocytosis.

BACKGROUND: The aim of this study was to investigate why some, but not all, children develop thrombocytosis during the course of pneumonia. METHODS: The retrospective study included 40 healthy children and 75 children with pneumonia: 17 patients with platelet count within the reference values, i.e., platelet count 450 x 10(9)/L. Erythrocyte sedimentation rate, leukocyte and platelet counts, and concentrations of hemoglobin, C-reactive protein, interleukin-6 and thrombopoietin were determined in the blood of patients and control groups of children. RESULTS: Patients with thrombocytosis were slightly younger (3.0 +/- 1.8 years and median 2.5 years, respectively) than patients with normal platelet count (3.8 +/- 2.4 years and median 4 years, respectively). Additionally, according to clinical and radiological findings, pneumonia in children with thrombocytosis had a more severe and protracted course. Serum thrombopoietin concentrations were found to be 91.2 +/- 41.7 ng/L (range: 14.3-166.7 ng/L) in patients with normal platelet count (313 +/- 70 x 10(9)/L, range: 206-428 x 10(9)/L). In patients with thrombocytosis (581 +/- 131 x 10(9)/L, range: 450-830 x 10(9)/L) serum thrombopoietin ranged from 63.6 to 1115.9 ng/L (526.6 +/- 268.4 ng/L). In these patients both concentration of hemoglobin (114 +/- 12 g/L) and iron (4.3 +/- 1.3 micromol/L) significantly decreased as compared with the control group. CONCLUSIONS: Study results suggested the possible development of reactive thrombocytosis in children with pneumonia. As platelets are involved in inflammatory reaction, reactive thrombocytosis might be part of the mechanism of defense. Reactive thrombocytosis may develop as a sequel of either anemia or inflammatory reaction (or both).

Structural analysis and fatty acid-binding properties of two Croatian variants of human serum albumin.

BACKGROUND: The aim of the present work was to characterize the molecular defects of a slow-migrating (albumin Zagreb) and a fast-migrating (albumin Krapina) genetic variant of human serum albumin detected in heterozygous persons living in Croatia and to elucidate the fatty acid-binding properties of the two alloalbumins. METHODS: Purification and structural identification of the variants were performed by conventional protein chemistry methods, whereas types and amounts of albumin-bound, endogenous fatty acids were determined by gas chromatography. RESULTS: Protein sequencing established that albumin Zagreb is a proalbumin variant (-1Arg-->Gln), and that albumin Krapina is due to a mutation within the mature polypeptide chain (573Lys-->Glu). The gas chromatographic results showed that the fatty acid-binding properties of the proalbumin variant are normal, while the amino acid substitution in position 573 resulted in a general decrease of fatty acid binding. CONCLUSIONS: The structural defects of the first alloalbumins, detected by routine clinical electrophoresis among the Croatian population, were characterized. Albumin Zagreb is caused by a hot-spot mutation occurring in a CpG sequence in the albumin gene. It is commonly assumed that bisalbuminaemia has no direct clinical relevance. However, the present study suggests that naturally occurring mutations can affect the ligand-binding properties of human serum albumin.

[Bronchial impairment of main bronchus by aspiration of ferrous sulphate tablet]. / Ostecenje glavnog bronha uzrokovano aspiracijom tablete zeljeznog sulfata.

The late occurrence of broncial impairment in two children who had aspirated ferrous sulphate tablet ih presented. Local release of cytotoxic oxidant radicals led up to tissue necrosis and consequently to bronchial stenosis and obliteration. Bronchoscopy in the first child confirmed total obliteration of the left main bronchus eleven months after aspiration of iron tablet, and pulmectomy had to be done. In the second child five months after aspiration of iron tablet bronchoscopy confirmed severe stenosis of the right main bronchus and atelectasis of the right lung lobe. Reventilation of right lung has been achieved one month after administration of antibiotics, metilprednisolon and physical therapy. The patient underwent laser therapy (few times) and baloon dilatation in the University Clinic in Graz, but it did not hold passability of the right bronchus. Reventilation of the right middle and lower lobe (but not upper lobe) has been achieved by insertion of endobronchial stent in the main right bronchus. Formation of granulomatous tissue at stent borders necessitated further laser therapy and baloon dilatation. Treatment of this child must be continued.

[Diaphragmatic eventration]. / Eventracija osita.

Eventration of the diaphragm is an abnormal elevation of an intact diaphragm. There are two distinct etiologic types of eventration, congenital and acquired. Congenital eventration is characterized by muscular aplasia, and acquired eventration is caused by injury to the phrenic nerve. The one-year-old girl had recurrent respiratory inflammations and permanent cough since she was two months old. Examinations, such as chest radiogram, chest and abdominal ultrasound, liver doppler, computed tomography of thorax and abdomen, did not distinguish eventration from possible tumorous formation in the right lower lung. The eventration of the diaphragm and atelectasis of the right lower lobe was confirmed during the surgery. Diaphragmatic plication was done, and atelectactic lobe as well as hypoplastic part of the diaphragm were removed. The eventration was confirmed pathohystologically.