Association of bacterial load in drinking water and allergic diseases in childhood.

BACKGROUND: Treatment of drinking water may decrease microbial exposure. OBJECTIVE: To investigate whether bacterial load in drinking water is associated with altered risk of allergic diseases. METHODS: We recruited 1,110 schoolchildren aged 6-16 years between 2011 and 2013 in Pozega-Slavonia County in Croatia, where we capitalized on a natural experiment whereby individuals receive drinking water through public mains supply or individual wells. We obtained data on microbial content of drinking water for all participants; 585 children were randomly selected for more detailed assessments, including skin prick testing. Since water supply was highly correlated with rural residence, we compared clinical outcomes across four groups (Rural/Individual, Rural/Public, Urban/Individual and Urban/Public). For each child, we derived quantitative index of microbial exposure (bacterial load in the drinking water measured during the child's first year of life). RESULTS: Cumulative bacterial load in drinking water was higher (median [IQR]: 6390 [4190-9550] vs 0 [0-0]; P < .0001), and lifetime prevalence of allergic diseases was significantly lower among children with individual supply (5.5% vs 2.3%, P = .01; 14.4% vs 6.7%, P < .001; 25.2% vs 15.1%, P < .001; asthma, atopic dermatitis [AD] and rhinitis, respectively). Compared with the reference group (Urban/Public), there was a significant reduction in the risk of ever asthma, AD and rhinitis amongst rural children with individual supply: OR [95% CI]: 0.14 [0.03,0.67], P = .013; 0.20 [0.09,0.43], P < .001; 0.17 [0.10,0.32], P < .001. Protection was also observed in the Rural/Public group, but the effect was consistently highest among Rural/Individual children. In the quantitative analysis, the risk of allergic diseases decreased significantly with increasing bacterial load in drinking water in the first year of life (0.79 [0.70,0.88], P < .001; 0.90 [0.83,0.99], P = .025; 0.80 [0.74,0.86], P < .001; current wheeze, AD and rhinitis). CONCLUSIONS AND CLINICAL RELEVANCE: High commensal bacterial content in drinking water may protect against allergic diseases.

Respiratory and allergic disorders in children with severe and partial immunoglobulin A immunodeficiency.

BACKGROUND: Immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency. Although most people with selective IgAD (sIgAD) are asymptomatic, many patients often suffer from recurrent respiratory infections and different allergic disorders. Our aim was to investigate connection between subtypes of sIgAD and incidence of respiratory and allergic disorders, as well as connection with lung function changes in children. METHODS: Children with IgAD where divided into two groups; severe IgAD in patients was defined as serum IgA level <7 mg/dL, while partial IgA deficiency diagnosis was made when serum IgA levels was higher than 7 mg/dL but at least two standard deviations (SD) below mean normal concentrations for their age. All patients were evaluated by their clinical and laboratory investigation parameters and compared to control group of children. RESULTS: Group of children with IgAD, severe as well as partial, showed higher prevalence of allergic diseases and total number of infections, compared to controls. There was a statistically significant difference in lung function for peak expiratory flow (PEF), the maximal expiratory flow at 50% of the forced vital capacity (MEF50) and fraction of exhaled nitric oxide (FENO) between group of patients with severe as well as partial IgAD and control group, where children with IgAD showed reduced lung function. CONCLUSIONS: Children with sIgAD are at increased risk for higher number of respiratory infections and developing allergic diseases, resulting in significantly lower pulmonary function which is related with the severity of sIgAD.

Immunophenotyping of a Stromal Vascular Fraction from Microfragmented Lipoaspirate Used in Osteoarthritis Cartilage Treatment and Its Lipoaspirate Counterpart.

Osteoarthritis (OA) is a degenerative joint disease accompanied by pain and loss of function. Adipose tissue harbors mesenchymal stem/stromal cells (MSC), or medicinal signaling cells as suggested by Caplan (Caplan, 2017), used in autologous transplantation in many clinical settings. The aim of the study was to characterize a stromal vascular fraction from microfragmented lipoaspirate (SVF-MLA) applied for cartilage treatment in OA and compare it to that of autologous lipoaspirate (SVF-LA). Samples were first stained using a DuraClone SC prototype tube for the surface detection of CD31, CD34, CD45, CD73, CD90, CD105, CD146 and LIVE/DEAD Yellow Fixable Stain for dead cell detection, followed by DRAQ7 cell nuclear dye staining, and analyzed by flow cytometry. In SVF-LA and SVF-MLA samples, the following population phenotypes were identified within the CD45- fraction: CD31+CD34+CD73±CD90±CD105±CD146± endothelial progenitors (EP), CD31+CD34-CD73±CD90±CD105-CD146± mature endothelial cells, CD31-CD34-CD73±CD90+CD105-CD146+ pericytes, CD31-CD34+CD73±CD90+CD105-CD146+ transitional pericytes, and CD31-CD34+CD73highCD90+CD105-CD146- supra-adventitial-adipose stromal cells (SA-ASC). The immunophenotyping profile of SVF-MLA was dominated by a reduction of leukocytes and SA-ASC, and an increase in EP, evidencing a marked enrichment of this cell population in the course of adipose tissue microfragmentation. The role of EP in pericyte-primed MSC-mediated tissue healing, as well as the observed hormonal implication, is yet to be investigated.

Overnight Video-Polysomnographic Studies in Children with Intractable Epileptic Encephalopathies.

BACKGROUND The aim of this study was to assess sleep architecture and respiration during sleep in children with intractable epileptic encephalopathies using overnight video-polysomnography (V-PSG). MATERIAL AND METHODS Between 2015 to 2017 overnight V-PSG recordings were made for 31 children (22 boys and 9 girls) with intractable epileptic encephalopathy with a mean age of 6.78±3.61 years and a mean body mass index (BMI) of 15.83±3.16 kg/m3. Thirty-one healthy children were matched for sex, age, and BMI as the control group. The phases of sleep studied included rapid eye movement (REM) sleep, and non-REM (NREM) phases NREM 1, NREM 2, and NREM 3. Respiratory function during sleep was evaluated. RESULTS Children with epileptic encephalopathies receiving antiepileptic treatment had significantly decreased total sleep time (TST) (p=0.038), significantly increased percentage of NREM1 (p=0.033), and a significantly lower percentage of total REM (p<0.0001), compared with the control group. All children 31/31 (100%) with epileptic encephalopathies had interictal epileptiform discharges, and 4/31 (12.9%) had ictal events. The number of respiratory events did not differ significantly between the two groups (p=0.118), but children in the epileptic encephalopathy group had a significantly shorter average duration (p=0.008) and longest duration (p=0.048) of respiratory events. Average (p=0.006) and least (p=0.0004) oxygen saturation (SatO2) were significantly lower in children with epileptic encephalopathies compared with the control group. CONCLUSIONS Children with epileptic encephalopathies had altered sleep architecture and marked oxygen desaturation, which supports the need for referral of children with epileptic encephalopathy for overnight sleep evaluation.

Allergen-Specific IgE Measurement: Intermethod Comparison of Two Assay Systems in Diagnosing Clinical Allergy.

BACKGROUND: Our aim was to examine the performance of IMMULITE 2000 assay for specific IgE (sIgE) by comparing it with ImmunoCAP technology in light of a clinical background. METHODS: Measurements of sIgE were done in a selected patient group (N = 569; varied sample size for each allergen) and in a random sample group (N = 100; 8 allergens). sIgE results were correlated with skin-prick test results (selected patients) and medical history (nonselected patients). RESULTS: We have detected fair to excellent correlation and agreement between the results of both assays, despite their methodological differences, both in selected and nonselected patient group (ρc = 0.431-0.976; ρc = 0.390-0.972, respectively). Associations of sIgE levels with skin-prick test (SPT) levels and medical history have shown significant correlation for both assays for majority of tested allergens, where applicable (D. pteronyssinus, cat dander, egg white, milk, peanut, orchard grass, Alternaria tenuis, and common ragweed in selected patients; birch, cat dander, common ragweed, D. pteronyssinus, and orchard grass in nonselected; P < 0.05 for all). CONCLUSIONS: Laboratory testing for sIgE can be successfully accomplished by IMMULITE 2000 immunoanalyzer at a diagnostic accuracy relative to SPT, comparable to the results acquired by CAP technology but not fully comparable on the level of an individual patient.

Successful Treatment of Autoimmune Pulmonary Alveolar Proteinosis in a Pediatric Patient.

BACKGROUND Pulmonary alveolar proteinosis (PAP) is a rare condition characterized by the intra-alveolar accumulation of surfactant-derived material, which impairs gas exchange and results in respiratory insufficiency. Two major subtypes of PAP are autoimmune and non-autoimmune PAP. The diagnosis relies on clinical presentation, ground glass opacities on CT scan, bronchoscopy with PAS stain of BAL fluid (BALF), lung biopsy with PAS-positive material in the alveoli, and the presence of anti GM-CSF antibodies in serum or BALF for an autoimmune subtype. The therapeutic approach to pediatric cases varies according to age and the general clinical state of the child; however, whole lung lavage (WLL) and inhaled or subcutaneous GM-CSF are generally first-line therapy. CASE REPORT We report a unique case of an autoimmune type of PAP in a 12-year-old boy, who underwent successful bilateral lung transplantation after inefficacious treatment with GM-CSF, and who developed post-transplant lymphoproliferative disease (PTLD) and was successfully treated with a chemotherapeutic protocol. CONCLUSIONS Although lung transplantation is a rarely used therapeutic approach for patients with an autoimmune subtype of PAP, in cases of inefficacious treatment with other modalities, lung transplantation should be considered.

Rational Therapy of Urinary Tract Infections in Children in Croatia

Resistance to chemotherapeutics used in the treatment of urinary tract infection is increasing throughout the world. Taking into account clinical experiences, as well as current bacterial resistance in Croatia and neighboring countries, the selection of antibiotic should be the optimal one. Treatment of urinary tract infection in children is particularly demanding due to their age and inclination to severe systemic reaction and renal scarring. If parenteral antibiotics are administered initially, it should be switched to oral medication as soon as possible. Financial aspects of antimicrobial therapy are also very important with the main goal to seek the optimal cost/benefit ratio. Financial orientation must appreciate the basic primum non nocere as a conditio sine qua non postulate as well.

Ataxia-Telangiectasia Presenting as Cerebral Palsy and Recurrent Wheezing: A Case Report.

BACKGROUND: Ataxia-telangiectasia (A-T) is an autosomal recessive disease that consists of progressive cerebellar ataxia, variable immunodeficiency, sinopulmonary infections, oculocutaneous telangiectasia, radiosensitivity, early aging, and increased incidence of cancer. CASE REPORT: We report the case of an 8-year-old boy affected by A-T. At 12 months of age, he had a waddling gait, with his upper body leaning forward. Dystonic/dyskinetic cerebral palsy was diagnosed at the age of 3 years. At age 6 he was diagnosed with asthma based on recurrent wheezing episodes. A-T was confirmed at the age 8 years on the basis of clinical signs and laboratory findings (increased alpha fetoprotein--AFP, immunodeficiency, undetectable ataxia-telangiectasia mutated (ATM) protein on immunoblotting, and identification A-T mutation, 5932G>T). CONCLUSIONS: The clinical and immunological presentation of ataxia-telangiectasia (A-T) is very heterogeneous and diagnostically challenging, especially at an early age, leading to frequent misdiagnosis.

[The prevalence of symptoms of allergic diseases among younger school children in Medimurje County (ISAAC Phase I)]. / Prevalencija simptoma alergijskih bolesti u mlade skolske djece na podrucju Medimurske zupanije (ISAAC faza I).

OBJECTIVE: To estimate the prevalence of symptoms of asthma, allergic rhinitis/rhinoconjuctivitis and atopic eczema symptoms in the Medimurje County in Northwest Croatia. SUBJECTS AND METHODS: The study was undertaken between January and April 2005 among school children in 27 randomly selected elementary schools. Data were collected using standardized ISAAC written questionnaire Phase I. RESULTS: A total of 3106 children participated in the study (7-9 yrs) with response rate 96.94%. 712 (22.9%) children had symptoms of allergic diseases at some time in their life. Estimated lifetime (ever) prevalence rates of symptoms were: wheezing 14.91%, allergic rhinitis symptoms 8.88% and atopic dermatitis symptoms 10.66%. Estimated 12-month prevalence rates were: wheezing 6.92%, allergic rhinitis symptoms 8.40%, allergic rhinoconjunctivitis 4.67%, and atopic dermatitis symptoms 5.76%. CONCLUSIONS: The results of this study show that Medimurje County is an area with moderate prevalence of atopic disease symptoms among the pediatric population.

Lung diffusion capacity in children with respiratory symptoms and untreated GERD.

BACKGROUND: Gastroesophageal reflux disease (GERD) is associated with many respiratory disorders, among which, chronic cough, laryngitis, and asthma are among the most common. We investigated lung function, including gas diffusion capacity, in children with poor asthma control or chronic laryngitis with untreated GERD. MATERIAL AND METHODS: A total of 71 children, aged 6-17 years, with chronic respiratory and other symptoms suggestive for GERD, were enrolled and divided into 2 groups: chronic laryngitis and asthma. Participants underwent 24-hour pH monitoring and lung function assessment, measurement of single-breath diffusing capacity of the lung for carbon monoxide (DLCO), and fraction of exhaled nitric oxide (FENO) measurement. RESULTS: 24-hour pH monitoring was positive for GERD in 92.1% of preselected children with asthma and 90.1% of children with chronic recurrent laryngitis. All flows (PEF, MEF75, MEF50, and MEF25) were significantly lower in the asthma group, while FENO and DLCO were significantly lower in the laryngitis group. A significant inverse relationship was found between DLCO and all reflux indexes in the laryngitis group. Each unit change of Johnson-DeMeester score and Boix-Ochoa score increased the odds for significantly lower DLCO in laryngitis patients by 3.9% and 5.5%, respectively. CONCLUSIONS: In children with uncontrolled asthma and chronic laryngitis, the regurgitation of gastric contents due to GERD contributes to poor asthma control and aggravation of chronic laryngitis. Despite having normal lung function, the gas diffusion capacity should be controlled in patients with GERD and chronic laryngitis, and it might be the very first abnormality in distal airways.

Sensitization profile in differential diagnosis: allergic asthma vs. chronic (nonspecific) cough syndrome.

BACKGROUND: In the subgroup of children with chronic cough, distinguishing children with allergic asthma from those with non-specific respiratory symptoms is difficult. We have focused on determination of diagnostic efficiency of serum total IgE, sIgE, and skin prick test in differentiation of asthmatic children from children with nonspecific respiratory symptoms. MATERIAL AND METHODS: A total of 131 children with median age of 7.5 years were enrolled in study and divided into 2 groups; children with allergic asthma (N=71) and children with chronic cough (N=60). Participants underwent the standard allergological examination, including skin prick test and measurement of total IgE, and following 3 allergen-specific IgE antibodies against aeroallergens: Dermatophagoides pteronyssinus, Ambrosia artemisiifolia, and Phleum pratense. RESULTS: The percentage of patients with elevated level of total and sIgE was higher in children with allergic asthma than in children with chronic cough syndrome (P=0.0001). In children with asthma, sIgE had a better diagnostic value than total IgE. The best diagnostic efficiency of cut-off values for sIgE was shown for Der p sIgE. Skin prick test to all allergens had 78.82% sensitivity and 91.3% specificity in differentiating the 2 tested groups. The highest sensitivity and specificity in skin prick test was proved for Dermatophagoides pteronyssinus. CONCLUSIONS: The sensitization profile consisting of total IgE, sIgE levels, and SPT clearly distinguishes children with allergic asthma from children with chronic nonspecific cough, but still with overlap. Therefore, diagnosis should always be confirmed by a thorough allergy investigation.

Inhaled corticosteroids used for the control of asthma in a "real-life" setting do not affect linear growth velocity in prepubertal children.

BACKGROUND: Recent guidelines recommend inhaled corticosteroids as the first-line treatment for persistent asthma. However, long-term corticosteroid treatment in children has raised concerns about potential growth rate deceleration. We aimed to assess the association of growth velocity with the use of inhaled corticosteroids in prepubertal children with asthma in a "real-life" setting. MATERIAL/METHODS: This study included 844 children aged 4-9.5 years coming to the hospital for regular check-ups between October 2006 and February 2009 for asthma with/without allergic rhinitis and no other known constraints of growth. Out of the 844 children, 790 had all data needed for analysis--245 children were not treated with ICS, 545 children received ICS (fluticasone, budesonide) with/without INCS (fluticasone, mometasone or budesonide). During the study period, 48 children with/without ICS received short SCS courses. RESULTS: Mean (SE) height at the first check-up was 123.1 (0.31) cm; range (100.0-147.8 cm). Mean (SE) linear growth velocity (LGV) of the included children was 0.185 (0.0035) mm/day between 2 check-ups. No significant difference was found in LGV between the group not treated with ICS (0.180 mm/day±0.0055) and the group treated with ICS (0.187±0.0044 mm/day). Also, there was no statistical difference between subgroups according to additional therapy with INCS and SCS. No significant correlation was found for LGV and daily dose of ICS (r=0.086, p>0.05). CONCLUSIONS: In our retrospective study using electronic hospital database, ICS and combined use of corticosteroids did not show any association with LGV in prepubertal asthmatic children in a "real-life" setting.

Decreased risk for atopic disorder associated with highly hyperreactive tuberculin skin test reaction in children and adolescents.

BACKGROUND: It is speculated that the exposure to Mycobacterium tuberculosis, either by infection or by Bacillus Calmette-Guérin vaccination, may inhibit the onset of atopy by the modification of immune profiles leading to a shift of T(H)1/T(H)2 balance to the T(H)1 side. OBJECTIVE: One hundred eighty-six patients hyperreactive at tuberculin skin test (TST) were examined in order to investigate the prevalence of atopic disorder, particularly referring to the association between the size of the TST induration and the prevalence of sensitization and manifest atopic disorder. METHODS: The study consisted of a family history record, patients' medical history assessment and clinical examination, skin prick test (SPT), serum total and allergen-specific IgE (sIgE) measurement and eosinophil count. RESULTS: Atopic disorder was present in 49 (26.3%) patients tested. No significant difference between the groups based on the TST induration size (15-24 mm vs. > or =25 mm) was found for gender distribution, family atopy history, total IgE measurement, eosinophil count, positive SPT, and the presence of sIgE. A significant difference was found for the age median (14.0 years vs. 13.0 years), childhood atopy record, and manifest atopic disorder. No association between the size of the TST induration and the incidence of allergic sensitization was demonstrated. However, a significant inverse association between the size of the TST induration and manifest atopic disorder was demonstrated. CONCLUSION: In patients highly hyperreactive at TST, the size of the induration is inversely associated with manifest atopic disorder.

Magnesium and calcium in exhaled breath condensate of children with asthma and gastroesophageal reflux disease.

BACKGROUND: Magnesium and calcium physiologic functions are closely related. Magnesium is primarily an intracellular cation, the action of which also involves maintenance of cellular ionic balance, while influencing calcium homeostasis by blocking calcium channels. The aim of this study was to compare the concentrations of magnesium and calcium in exhaled breath condensate (EBC) of children with asthma and gastroesophageal reflux disease (GERD). SUBJECTS AND METHODS: EBC was collected from 66 children aged 7-14 years (23 children with acute asthma, 17 children with GERD, and 26 healthy children). Determination of magnesium and calcium concentrations was preceded by optimization and validation for low concentrations. RESULTS: No difference was recorded for either magnesium or calcium concentration between study groups. However, the magnesium to calcium ratio was statistically significantly lower in both GERD and asthma children as compared with control group. CONCLUSION: Study results showed the magnesium to calcium ratio to be a statistically significantly better indicator of certain pathologic changes than absolute concentration of either ion.

Normal variation of bronchial reactivity in nonasthmatics is associated with the level of mite-specific IgE.

OBJECTIVE: To investigate association between non-specific bronchial reactivity (NBR) and level of mite specific IgE amongst mite-sensitized non-asthmatic subjects. METHODS: Subjects attending occupational check-up were assessed for: respiratory symptoms, atopic status (skin prick testing [SPT], total and specific IgE), spirometry and NBR. Individuals without history of respiratory disease (N = 234) were included into analysis. RESULTS: All subjects had normal spirometry and 99% had normal NBR while 41.8% had detectable specific IgE to mites. Lung function parameters and NBR were significantly lower in mite sensitized subjects. Multiple regression analysis controlling for age, gender, smoking, family history, SPT, IgE, and lung function showed that NBR was significantly associated only with mite specific IgE level (beta = 0.26; 95% CI, 0.05-0.47; p = 0.018). CONCLUSION: Even in subjects without allergic symptoms, IgE-mediated sensitization does not appear to be all or nothing phenomenon influencing the normal variability of underlying airway reactivity.

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.

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).