Cold Urticaria and Infectious Mononucleosis in Children

Physical urticaria includes a heterogeneous group of disorders characterized by the development of urticarial lesions and/or angioedema after exposure to certain physical stimuli. The authors present the case of a child with severe acquired cold urticaria secondary to infectious mononucleosis. Avoidance of exposure to cold was recommended; prophylactic treatment with ketotifen and cetirizine was begun and a self-administered epinephrine kit was prescribed. The results of ice cube test and symptoms significantly improved. Physical urticaria, which involves complex pathogenesis, clinical course and therapy, may be potentially life threatening. Evaluation and diagnosis are especially important in children. To our knowledge this is the first description of persistent severe cold-induced urticaria associated with infectious mononucleosis in a child.

Risk Factors for Latex Sensitization in Children with Spina Bifida

Background: Children with spina bifida represent the major risk group for latex sensitization. Purpose: To determine the prevalence of latex sensitization in these children and to identify risk factors. Material and methods: We studied 57 patients with spina bifida. The mean age was 5.6 years and the male/female ratio was 0.8/1. In all patients a questionnaire, skin prick test (SPT) with latex (UCBStallergènes, Lofarma and ALK-Abelló), common aeroallergens and fruits (UCB-Stallergènes) and serum determination of total IgE (AlaSTAT) were performed. Results: The prevalence of latex sensitization was 30 %; only two sensitized children (12 %) had symptoms after exposure. Risk factors for latex sensitization were age 5 years (p = 0.008; OR = 6.0; 95% CI = 1.7-22.1), having at least four previous surgical interventions (p < 0.0001; OR = 18.5; 95% CI = 3.6-94.8), having undergone surgery in the first 3 months of life (p = 0.008; OR = 5.4; 95% CI = 0.7-29.2) and total serum IgE 44 IU/ml (p = 0.03; OR = 3.8; 95 %CI = 1.1-13.1). Multiple logistic regression analysis showed that only a history of four or more surgical interventions (p < 0.0001; OR = 26.3; 95 %CI = 2.9-234.2) and total serum IgE 44 IU/ml (p = 0.02; OR = 8.6; 95% CI = 1.4-53.4) were independently associated with latex sensitization. Sex, family and personal allergic history, hydrocephalus with ventriculoperitoneal shunt, cystourethrograms, intermittent bladder catheterization and atopy were not related to latex sensitization. Conclusions: In children with spina bifida, significant and independent risk factors identified for latex sensitization were multiple interventions and higher levels of total serum IgE. A prospective study will clarify the clinical evolution of assymptomatic children sensitized to latex.

Stenosis of the Branches of the Neopulmonary Artery after the Arterial Switch Operation: a Cardiac Magnetic Resonance Imaging Study

Background : The neonatal arterial switch operation (ASO) is now the standard of care for children born with transposition of the great arteries. Stenosis of the neopulmonary artery on long‑term follow up is a known complication. Methods : We performed a retrospective analysis of eleven patients who underwent a cardiac magnetic resonance imaging (MRI) due to echocardiographic evidence suggestive of stenosis of the neopulmonary artery or its branches (mean estimated Doppler gradient 48 mmHg, min 30 mmHg, max 70 mmHg). A comprehensive evaluation of anatomy and perfusion was done by cardiac MRI. Results : The branches of the neopulmonary artery (neo PA) showed decreased caliber in three patients unilaterally and in two patients, bilaterally. Magnetic resonance (MR) perfusion studies showed concomitant decreased flow, with discrepancy between the two lungs of 35/65% or worse, only in the three patients with unilateral obstruction, by two different MR perfusion methods. Conclusions : Cardiac MR can be used as a comprehensive non‑invasive imaging technique to diagnose stenosis of the branches of the neopulmonary after the ASO, allowing evaluation of anatomy and function of the neoPA, its branches, and the differential perfusion to each lung, thus facilitating clinical decision making.

Methacholine Dose-Response Slopes from Maximal Bronchial Challenge Tests in Asthmatic Children: Methodological Aspects

To determine whether the slope of a maximal bronchial challenge test (in which FEV1 falls by over 50%) could be extrapolated from a standard bronchial challenge test (in which FEV1 falls up to 20%), 14 asthmatic children performed a single maximal bronchial challenge test with methacholin(dose range: 0.097–30.08 umol) by the dosimeter method. Maximal dose-response curves were included according to the following criteria: (1) at least one more dose beyond a FEV1 ù 20%; and (2) a MFEV1 ù 50%. PD20 FEV1 was calculated, and the slopes of the early part of the dose-response curve (standard dose-response slopes) and of the entire curve (maximal dose-response slopes) were calculated by two methods: the two-point slope (DRR) and the least squares method (LSS) in % FEV1 × umol−1. Maximal dose-response slopes were compared with the corresponding standard dose-response slopes by a paired Student’s t test after logarithmic transformation of the data; the goodness of fit of the LSS was also determined. Maximal dose-response slopes were significantly different (p < 0.0001) from those calculated on the early part of the curve: DRR20% (91.2 ± 2.7 FEV1% z umol−1)was 2.88 times higher than DRR50% (31.6 ± 3.4 DFEV1% z umol−1), and the LSS20% (89.1 ± 2.8% FEV1 z umol−1) was 3.10 times higher than LSS 50% (28.8 ± 1.5%FEV1 z umol−1). The goodness of fit of LSS 50% was significant in all cases, whereas LSS 20% failed to be significant in one. These results suggest that maximal dose-response slopes cannot be predicted from the data of standard bronchial challenge tests.

Development of The Viking Speech Scale to Classify the Speech of Children with Cerebral Palsy

Surveillance registers monitor the prevalence of cerebral palsy and the severity of resulting impairments across time and place. The motor disorders of cerebral palsy can affect children’s speech production and limit their intelligibility. We describe the development of a scale to classify children’s speech performance for use in cerebral palsy surveillance registers, and its reliability across raters and across time. Speech and language therapists, other healthcare professionals and parents classified the speech of 139 children with cerebral palsy (85 boys, 54 girls; mean age 6.03 years, SD 1.09) from observation and previous knowledge of the children. Another group of health professionals rated children’s speech from information in their medical notes. With the exception of parents, raters reclassified children’s speech at least four weeks after their initial classification. Raters were asked to rate how easy the scale was to use and how well the scale described the child’s speech production using Likert scales. Inter-rater reliability was moderate to substantial (k > .58 for all comparisons). Test–retest reliability was substantial to almost perfect for all groups (k > .68). Over 74% of raters found the scale easy or very easy to use; 66% of parents and over 70% of health care professionals judged the scale to describe children’s speech well or very well. We conclude that the Viking Speech Scale is a reliable tool to describe the speech performance of children with cerebral palsy, which can be applied through direct observation of children or through case note review.

CO2 Concentration in Day Care Centres is Related to Wheezing in Attending Children

Poor ventilation at day care centres (DCCs) was already reported, although its effects on attending children are not clear. This study aimed to evaluate the association between wheezing in children and indoor CO2 (a ventilation surrogate marker) in DCC and to identify behaviours and building characteristics potentially related to CO2. In phase I, 45 DCCs from Lisbon and Oporto (Portugal) were selected through a proportional stratified random sampling. In phase II, 3 months later, 19 DCCs were further reassessed after cluster analysis for the greatest difference comparison. In both phases, children’s respiratory health was assessed by ISAAC-derived questionnaires. Indoor CO2 concentrations and building characteristics of the DCC were evaluated in both phases, using complementary methods. Mixed effect models were used to analyze the data. In phase I, which included 3,186 children (mean age 3.1±1.5 years), indoor CO2 concentration in the DCC rooms was associated with reported wheezing in the past 12months (27.5 %) (adjusted odds ratio (OR) for each increase of 200 ppm 1.04, 95 % CI 1:01 to 1:07). In phase II, the association in the subsample of 1,196 children seen in 19 out of the initial 45 DCCs was not significant (adjusted OR 1.02, 95 % CI 0.96 to 1.08). Indoor CO2 concentration was inversely associated with the practices of opening Windows and internal doors and with higher wind velocity. A positive trend was observed between CO2 and prevalence of reported asthma (4.7 %). Conclusion: Improved ventilation is needed to achieve a healthier indoor environment in DCC.

Environment and Health in Children Day Care Centres (ENVIRH) - Study Rationale and Protocol

Background: Indoor air quality (IAQ) is considered an important determinant of human health. The association between exposure to volatile organic compounds, particulate matter, house dust mite, molds and bacteria in day care centers (DCC) is not completely clear. The aim of this project was to study these effects. Methods --- study design: This study comprised two phases. Phase I included an evaluation of 45 DCCs (25 from Lisbon and 20 from Oporto, targeting 5161 children). In this phase, building characteristics, indoor CO2 and air temperature/relative humidity, were assessed. A children’s respiratory health questionnaire derived from the ISAAC (International Study on Asthma and Allergies in Children) was also distributed. Phase II encompassed two evaluations and included 20 DCCs selected from phase I after a cluster analysis (11 from Lisbon and 9 from Oporto, targeting 2287 children). In this phase, data on ventilation, IAQ, thermal comfort parameters, respiratory and allergic health, airway inflammation biomarkers, respiratory virus infection patterns and parental and child stress were collected. Results: In Phase I, building characteristics, occupant behavior and ventilation surrogates were collected from all DCCs. The response rate of the questionnaire was 61.7% (3186 children). Phase II included 1221 children. Association results between DCC characteristics, IAQ and health outcomes will be provided in order to support recommendations on IAQ and children’s health. A building ventilation model will also be developed. Discussion: This paper outlines methods that might be implemented by other investigators conducting studies on the association between respiratory health and indoor air quality at DCC.

Food Allergy and Anaphylaxis in Infants and Preschool-Age Children

Food allergy (FA) prevalence data in infants and preschool-age children are sparse, and proposed risk factors lack confirmation. In this study, 19 children’s day care centers (DCC) from 2 main Portuguese cities were selected after stratification and cluster analysis. An ISAAC’s (International Study of Asthma and Allergies in Childhood) derived health questionnaire was applied to a sample of children attending DCCs. Outcomes were FA parental report and anaphylaxis. Logistic regression was used to explore potential risk factors for reported FA. From the 2228 distributed questionnaires, 1217 were included in the analysis (54.6%). Children’s median age was 3.5 years, and 10.8% were described as ever having had FA. Current FA was reported in 5.7%. Three (0.2%) reports compatible with anaphylaxis were identified. Reported parental history of FA, personal history of atopic dermatitis, and preterm birth increased the odds for reported current FA. A high prevalence of parental-perceived FA in preschool-age children was identified. Risk factor identification may enhance better prevention.

Numerical Evaluation of Ventilation Performance in Children Day Care Centres

Modelling of ventilation is strongly dependent on the physical characteristics of the building of which precise evaluation is a complex and time consuming task. In the frame of a research project, two children day care centres (CDCC) have been selected in order to measure the envelope air permeability, the flow rate of mechanical ventilation systems and indoor and outdoor temperature. The data obtained was used as input to the computer code CONTAM for ventilation simulations. The results obtained were compared with direct measurements of ventilation flow from short term measurements with CO2 tracer gas and medium term measurements with perfluorocarbon tracer (PFT) gas decay method. After validation, in order to analyse the main parameters that affect ventilation, the model was used to predict the ventilation rates for a wide range of conditions. The purpose of this assessment was to find the best practices to improve natural ventilation. A simple analytical method to predict the ventilation flow rate of rooms is also presented. The method is based on the estimation of wind effect on the room through the evaluation of an average factor and on the assessment of relevant cross section of gaps and openings combined in series or in parallel. It is shown that it may be applied with acceptable accuracy for this type of buildings when ventilation is due essentially to wind action.

Regulatory Cells, Cytokine Pattern and Clinical Risk Factors for Asthma in Infants and Young Children with Recurrent Wheeze

Several risk factors for asthma have been identified in infants and young children with recurrent wheeze. However, published literature has reported contradictory findings regarding the underlying immunological mechanisms. OBJECTIVES: This study was designed to assess and compare the immunological status during the first 2 years in steroid-naive young children with >or= three episodes of physician-confirmed wheeze (n=50), with and without clinical risk factors for developing subsequent asthma (i.e. parental asthma or a personal history of eczema and/or two of the following: wheezing without colds, a personal history of allergic rhinitis and peripheral blood eosinophilia >4%), with age-matched healthy controls (n=30). METHODS: Peripheral blood CD4(+)CD25(+) and CD4(+)CD25(high) T cells and their cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), GITR and Foxp3 expression were analysed by flow cytometry. Cytokine (IFN-gamma, TGF-beta and IL-10), CTLA-4 and Foxp3 mRNA expression were evaluated (real-time PCR) after peripheral blood mononuclear cell stimulation with phorbol 12-myristate 13-acetate (PMA) (24 h) and house dust mite (HDM) extracts (7th day). RESULTS: Flow cytometry results showed a significant reduction in the absolute number of CD4(+)CD25(high) and the absolute and percentage numbers of CD4(+)CD25(+)CTLA-4(+) in wheezy children compared with healthy controls. Wheezy children at a high risk of developing asthma had a significantly lower absolute number of CD4(+)CD25(+) (P=0.01) and CD4(+)CD25(high) (P=0.04), compared with those at a low risk. After PMA stimulation, CTLA-4 (P=0.03) and Foxp3 (P=0.02) expression was diminished in wheezy children compared with the healthy children. After HDM stimulation, CTLA-4 (P=0.03) and IFN-gamma (P=0.04) expression was diminished in wheezy children compared with healthy children. High-risk children had lower expression of IFN-gamma (P=0.03) compared with low-risk and healthy children and lower expression of CTLA-4 (P=0.01) compared with healthy children. CONCLUSIONS: Although our findings suggest that some immunological parameters are impaired in children with recurrent wheeze, particularly with a high risk for asthma, further studies are needed in order to assess their potential as surrogate predictor factors for asthma in early life.

Fractures in Children and Adolescents with Spina Bifida: The Experience of a Portuguese Tertiary-Care Hospital

AIM: The morbidity associated with osteoporosis and fractures in children and adolescents with spina bifida highlights the importance of osteoporosis prevention and treatment in these patients. The aim of this study was to examine the occurrence and pattern of bone fractures in paediatric patients with spina bifida. METHOD: We reviewed the data of all paediatric patients with spina bifida who were treated in our centre between 1999 and 2008. RESULTS: One hundred and thirteen patients were included in the study (63 females, 50 males; mean age 10y 8mo, SD 4y 10mo, range 6mo-18y). The motor levels were thoracic in six, upper lumbar in 22, lower lumbar in 42, and sacral in 43 patients. Of the 113 patients, 58 (51.3%) had shunted hydrocephalus. Thirty-six (31.8%) were non-ambulatory (wheelchair-dependent [unable to self-propel wheelchair] n=3, wheelchair-independent [able to self-propel wheelchair] n=33), 13 were partial ambulators, 61 were full ambulators, and three were below the age of walking. Forty-five fractures were reported in 25 patients. The distal femur was the most common fracture site. Statistical analyses showed that patients with higher levels of involvement and in wheelchairs had a significantly increased risk of having a [corrected] fracture (p<0.001). Spontaneous fractures were the principal mechanism of injury, and an association was identified between fracture mechanism, type of ambulation, and lesion level: the fractures of patients with higher levels of motor functioning and those in wheelchairs were mainly pathological (p=0.01). We identified an association between risk of a second fracture, higher motor level lesion, and non-ambulation. There was an increased risk of having a second fracture after a previous spontaneous fracture (p=0.004). INTERPRETATION: Data in this study indicate a high prevalence of fractures in patients with spina bifida.

Long-Term Lamivudine Treatment of Children with Chronic Hepatitis B: Durability of Therapeutic Responses and Safety

Lamivudine has been demonstrated safe and efficacious in the short term in a large cohort of children with chronic hepatitis B (CHB), but optimal duration of treatment has not been elucidated and limited data on the safety of long-term lamivudine administration have been reported. In addition, the durability of favourable therapeutic outcomes after lamivudine therapy in children has not been well characterized. The aim of this study was to examine the safety of lamivudine and the durability of clinical responses in a group of children who received up to 3 years of treatment for CHB. One hundred and fifty-one children from centres in nine countries who had previously received lamivudine in a large prospective trial were enrolled. During the first year, children had been randomized to either lamivudine or placebo treatment. Subsequently, in a separate extension study, those who remained hepatitis B e antigen (HBeAg) positive were given lamivudine for up to 2 years and those who were HBeAg negative were observed for additional 2 years. Results of these studies have been previously reported. In this study, these children were followed for 2 additional years. Data gathered from medical record review included weight, height, signs and symptoms of hepatitis, alanine aminotransferase (ALT) levels, serologic markers, hepatitis B virus (HBV) DNA levels and serious adverse events (SAEs). Other pharmacological treatments for CHB were allowed according to the practices of individual investigators and were documented. Subjects were divided into two groups for analysis, those who had achieved virological response (VR), defined as HBeAg negative and undetectable HBV DNA by the bDNA assay by the end of the extension study at 3 years, and those who had not. In those who had achieved VR by the end of the extension study, long-term durability of HBeAg seroconversion was 82% and >90% in those who had received lamivudine for 52 weeks and at least 2 years respectively. This compares to 75% for those who had achieved seroconversion after placebo. In those who had not achieved VR by the end of the extension study, an additional 11% did so by the end of the study; they had all received lamivudine in the previous trial, and none had received further treatment during the study. Eight children lost hepatitis B surface antigen during the study and all had received lamivudine at some point during the previous trials. Evaluation of safety data revealed no SAEs related to lamivudine. There was no effect of treatment on weight or height z scores. Clinically benign ALT flares (>10 times normal) were seen in 2% of children. Favourable outcomes from lamivudine treatment of CHB in children are maintained for at least several years after completion of treatment. Up to 3 years of lamivudine treatment is safe in children.