Ana Paula Beltran Moschione Castro

Risk factors for asthma in adolescents in a large urban region of Brazil.

Background. Identify risk factors for asthma in adolescents from São Paulo, Brazil. Methods. total of 528 adolescents (141 asthmatics, 387 control subjects) from the ISAAC study (phase III) were submitted to a complementary questionnaire to evaluate risk factors, through response to questions regarding personal history, environment, and diet and an agreement to undergo the skin prick test (SPT) for aeroallergens. Results. Positive SPT to at least one allergen occurred in 49.4% adolescents. The risk factors for asthma were: prematurity (OR: 3.84, 95% CI: 1.54–9.64), rhinitis (OR: 3.18, 95% CI: 1.71–5.91), positivity in the SPT (OR: 2.81, 95% CI: 1.48–5.32), eczema in characteristic skin-folds (OR: 2.86, 95% CI: 1.13–7.26), and an allergic mother (OR: 2.01, 95% CI: 1.02–3.93). The consumption of cooked vegetables was a protective factor for asthma (OR: 0.37, 95% CI: 0.18–0.79) Conclusions. Asthma is a multifatorial disease. An allergic mother, aeroallergen sensitization, rhinitis, eczema and prematurity were considered risk factors and the consumption of cooked vegetables was considered a protective factor for asthma in this population.

Avaliação dos fatores associados a infecções recorrentes e/ou graves em pacientes com síndrome de Down

OBJECTIVES: to evaluate epidemiological, clinical and laboratorial aspects of patients with Down syndrome, who present recurrent and/or severe infections, as well as to evaluate the presence of immunodeficiency in this population. METHODS: patients with Down syndrome diagnosed by chromosome analysis with recurrent and/or severe infections, followed at the Allergy and Immunology Unit of Childrens Institute from 1990 to 1999, were submitted to an epidemiological, clinical and laboratorial protocol, including immunological aspects.| RESULTS: sex distribution was 1.6 M:1 F, with age ranging from 1 to 12 years and 10 months (average = 2y7m). Forty patients reported recurrent infections and five, sepsis. Out of all patients with recurrent infection, 31 fulfilled the repeated infection criteria, with pneumonia and rhinopharyngitis as the most common infections. Congenital heart diseases were found in 62.2% of cases, more frequent in the repeated pneumonia group. Immunological evaluation showed two cases with IgG2 deficiency, two with low lymphocytes CD4+ count, and two cases with reduced blastogenic response to mitogens. Five cases had reduced NK cells function. Seropositivity for CMV was found in 22 of 36 cases analyzed (61.1%). CONCLUSIONS: although the data found in this study are valid for this specific population, the authors point out the necessity of the immunodeficiency research in Down syndrome patients with maintenance of infection besides the appropriated control of associated diseases.

Secondary hypogammaglobilinemia after use of carbamazepine: case report and review

Immunologic disorders related to anticonvulsant therapy have been described in the last three decades, including cellular and humoral alterations that result in recurrent infections; however, the physiopathologic mechanisms are not completely understood. This report describes a patient with complex partial epilepsy and hypogammaglobulinemia while in treatment with carbamazepine, with significant improvement in clinical signs and laboratory tests after substitution to sodium valproate. The authors stress the importance of clinical and laboratory evaluation of patients in continuous anticonvulsant therapy, including immunoglobulins levels and peripheral blood evaluations.

Calcineurin inhibitors in the treatment of allergic dermatitis.

OBJECTIVE To review the role of calcineurin inhibitors in the treatment of allergic dermatitis, focusing on mechanisms of action, efficacy and topical and systemic adverse effects. SOURCES Articles written in English and published in MEDLINE using the following keywords: pimecrolimus, tacrolimus, calcineurin inhibitors. Original articles that presented controlled and open studies for assessing efficacy, tolerability and adverse effects were selected. Review articles and case series were also evaluated; the latter was only considered for assessing adverse effects. The official websites of the Food and Drug Administration and of manufacturers of calcineurin inhibitors were also used. SUMMARY OF THE FINDINGS The data showed that calcineurin inhibitors are efficient in the treatment of mild to severe atopic dermatitis, leading to improvement in symptoms, reduction in number of attacks and need of topical corticotherapy. Calcineurin inhibitors have good tolerability and few topical adverse effects. To date, there has been no evidence to support higher prevalence of neoplasia in patients using these drugs; however, an adequate pharmacovigilance system has been set up to assess this aspect. CONCLUSIONS Calcineurin inhibitors, which are a new drug class in the treatment of allergic dermatitis, are efficient, well tolerated and have few adverse effects. Calcineurin inhibitors should always be used according to recommended guidelines, and patients should always be followed by the physician during and after their administration.

Ideal Vial Size for Bortezomib: Real-World Data on Waste and Cost Reduction in Treatment of Multiple Myeloma in Brazil

OBJECTIVES Single-size vials of drugs may be a source of waste and increase in treatment costs. Bortezomib, indicated for multiple myeloma (MM) treatment, is available in 3.5-mg vials, a quantity higher than the average dose commonly prescribed. This analysis aimed to demonstrate, through real-world data, which would be the optimal vial presentation for bortezomib in Brazil and quantify the reduction in medication waste related to this option. METHODS From November 2007 to October 2009 all patients with MM treated with bortezomib were identified via the Evidências database. Analysis of prescribed, dispensed, and wasted doses, their costs and projections of the ideal vial size were performed. RESULTS Thirty-five patients (mean body surface area of 1.73 m(2)) received 509 infusions in 131 cycles of treatment (average of 3.77 cycles per patient). The average dose prescribed was 2.1 mg per infusion (95% confidence interval [CI] 1.97-2.26) with average waste of 39.5% of the vial content (95% CI 35.35-43.76). The mean waste per patient per day was 1.38 mg (95% CI 1.24-1.52). If a 3-mg vial were available, the average drug waste per patient per day would be 0.88 mg (95% CI 0.74-1.03) or 36.2% less. With a 2.5-mg vial the waste would be 1.05 mg (95% CI 0.81-1.29) or 23.9% less. If two presentations were available (2.5 mg and 0.5 mg), the waste would be 0.52 mg (95% CI 0.4-0.63) or 62.5% less. Considering the price of the different vials to be proportional to the original 3.5-mg vial, the cost would be also reduced by the same rates described above. CONCLUSIONS A simple adjustment in vial size may reduce the waste of bortezomib by 36% to 62% and can also reduce the cost of treatment.

Neutropenia in antibody-deficient patients under IVIG replacement therapy

Patients with antibody deficiencies are more prone to develop acute neutropenic episodes even during immunoglobulin replacement. The aims of this study were to evaluate the presence of acute neutropenia in 42 patients with primary antibody immunodeficiencies, currently receiving intravenous immunoglobulin (IVIG), and to describe the clinical and laboratory findings during neutropenic episodes. Of all patients, 10 (23.8%) presented acute neutropenia (absolute neutrophil count <1500 cells/mm3) during follow up (mean of 6.4 yr). The absolute neutrophil count ranged from 71 to 1488 cells/mm3. Neutropenia was not clearly associated with antibiotic prophylactic therapy or immunoglobulin levels, while infections were associated with neutropenia in the majority of episodes. Most acute neutropenia episodes were mild or moderate, except in CVID patients who present more severe neutropenia. Although IVIG may have contributed to reducing the severity of neutropenia, it does not prevent its occurrence in all patients. In conclusion, primary immunodeficient patients, even submitted to IVIG replacement therapy, must be regularly evaluated for neutropenia in order to minimize the risk of infections and its appropriate approach.

Pediatric allergy and immunology in Brazil

The subspecialty of pediatric allergy and immunology in Brazil is in its early years and progressing steadily. This review highlights the research developed in the past years aiming to show the characteristics of allergic and immunologic diseases in this vast country. Epidemiologic studies demonstrated the high prevalence of asthma in infants, children, and adolescents. Mortality rates and average annual variation of asthma hospitalization have reduced in all pediatric age groups. Indoor aeroallergen exposure is excessively high and contributes to the high rates of allergy sensitization. Prevalence of food allergy has increased to epidemic levels. Foods (35%), insect stings (30%), and drugs (23%) are the main etiological agents of anaphylaxis in children and adolescents. Molecular diagnosis of primary immunodeficiencies (PID) showed a high incidence of fungal infections including paracoccidioidomycosis in X‐linked hyper‐IgM syndrome, and the occurrence of BCG adverse reactions or other mycobacterial infections in patients with chronic granulomatous disease. Education in pediatric allergy and immunology is deficient for medical students, but residency programs are effective in training internists and pediatricians for the practice of allergy. The field of PID requires further training. Last, this review is a tribute to Prof. Dr. Charles Naspitz, one of the pioneers of our specialty in Brazil.

Double-blind, placebo-controlled food challenges in Brazilian children: Adaptation to clinical practice

BACKGROUND A double-blind, placebo-controlled food challenge (DBPCFC) is considered the gold standard for diagnosing food allergy, but because of methodological difficulties it is rarely conducted in clinical practice, especially in paediatric patients. The purpose of the study was to propose a DBPCFC protocol that is adapted to our conditions for the diagnosis of an IgE-mediated cows milk allergy (CMA) in a Brazilian reference centre for paediatric allergies. METHODS This study includes the experimental phase (choice of materials, adjustments made to protocols described in the literature) and the test execution phase. DBPCFCs were performed in 58 patients aged 1-15 years who were separated into two groups: Group 1 (n=39), sex 1.6 M:F, 5.3 years median age, suggestive history of IgE-mediated CMA; and Group 2 (n=19), sex 1.4 M:F, 8.3 years median age with symptoms not associated with milk ingestion and laboratory data not compatible with IgE-mediated CMA. RESULTS The materials were standardised for testing: containers and disposable products, low-lactose cows milk (CM) and vehicles, such as natural fruit juice, vegetable soup and soybean-based beverages. Each DBPCFC was performed in a single day with two blind, randomised phases with a 2-h interval between them. The milk doses were gradually increased and offered in regular intervals of 15-30 min. Following negative or inconclusive results, patients underwent an open oral challenge test with 200 mL of low-lactose CM. CONCLUSIONS The proposed adaptation for the DBPCFC allowed to implement this important test for the diagnosis of IgE-mediated CMA in a reference centre for paediatric allergies. It was considered feasible and safe if performed in an appropriate setting with physician supervision.

Fatores associados ao controle da asma em pacientes pediátricos em centro de referência

Objective: To describe the epidemiological and clinical data and factors associated with asthma control of asthmatic patients followed at a pediatric reference center. Methods: Cross-sectional study including asthmatic outpatients receiving prophylactic medications from the institution. For classification of asthma, steps of treatment and control evaluation, the IV Brazilian Guidelines for the Management of Asthma (2006) were adopted. The presence of other allergies, obesity, immunodeficiency, gastro esophageal reflux and allergic sensitization were evaluated and compared between patients with or without asthma control according to the treatment step, obesity and allergic sensitization. Results: 300 patients with asthma (1.38M:1F) were included; median age=10.8 years; median age at onset of symptoms=1.0 year. Among parents and/or siblings, 78% reported atopy. Personal history showed other allergic diseases in 292 patients (96% rhinitis, 27% atopic dermatitis, 18% allergic conjunctivitis, 6% food allergy). IgA deficiency was diagnosed in seven cases and IgG2 deficiency in four. Obesity was noted in 34/233 patients (15%) and overweight/obesity were associated with asthma poor control (p<0.023). Among 118 patients multisensitizated, the frequency of poor asthma control was greater (22 (19%) cases; p=0.049, OR 1.9; 95%CI 1.03-3.50). Among the patients, 180 (60%) were treated according steps 3 and 4; 122 children (45%) were considered controlled and 112 (41%) were partially controlled. Conclusions: Allergic rhinitis was the allergic disease more associated with asthma. The prevalence of IgA defi ciency was 20 times higher than in the general population. Total or partial control of asthma symptoms was obtained in 85% of the cases. Overweight/obesity and multisensitization were associated to poor asthma control.OBJETIVO: Descrever os dados epidemiologicos, clinicos e os fatores associados ao controle da asma em pacientes asmaticos seguidos em um ambulatorio pediatrico especializado. METODOS: Estudo transversal de pacientes asmaticos ambulatoriais, para os quais eram fornecidas medicacoes profilaticas. A classificacao da asma, as etapa de tratamento e a avaliacao do controle seguiram a IV Diretrizes Brasileiras para o Manejo da Asma, de 2006. Os fatores avaliados foram: outras alergias, obesidade, imunodeficiencias, refluxo gastresofagico e sensibilizacao alergica, sendo comparados pacientes com asma controlada ou nao com relacao a etapa do tratamento, a obesidade e a sensibilizacao alergica. RESULTADOS: Foram analisados 300 pacientes com asma (1,38M:1F), com mediana de idade de 10,8 anos, e de inicio dos sintomas de 1,0 ano. A atopia estava presente em 78% dos pais e/ou irmaos. Antecedentes pessoais de doencas alergicas ocorreram em 292 pacientes (96% rinite, 27% dermatite atopica, 18% conjuntivite alergica, 6% alergia alimentar). Foram diagnosticados sete casos de deficiencia de IgA (DIgA) e quatro de IgG2; obesidade em 37/253 (15%), sendo que sobrepeso e obesidade estiveram associados a falta de controle (p=0,023). Em 118 pacientes com multissensibilizacao, predominaram casos nao controlados (22 (19%) casos; p=0,049; OR 1,9; IC95% 1,03-3,50). Entre os 180 casos (60%) em tratamento nas etapas 3 e 4, 122 (45%) estavam controlados e 112 (41%) parcialmente controlados. CONCLUSOES: A rinite foi a alergia mais associada a asma e a prevalencia de DIgA foi 20 vezes maior do que na populacao geral. O controle parcial ou total dos sintomas da asma foi obtido em 85% dos casos. Obesidade/sobrepeso e multissensibilizacao foram associadas a falta de controle da asma.

Obesidade e asma: associação ou epifenômeno?

OBJECTIVE To relate obesity and asthma by comparing gender, age, initial classification of asthma, clinical control, basal forced expiratory volume in one second (FEV1) and forced expiratory flow between 25 and 75% (FEF25-75%) with rates of body mass index (BMI) in asthmatic adolescents. METHODS Cross-sectional study involving 120 asthmatics patients (1.9 male: 1 female) with a mean age of 14.1 years (9 to 20.1 years of age), classified according to asthma severity and control, and evaluated by spirometry using their basal FEV1 and FEF25-75%. The data were described by frequency, mean and standard deviation or median and range and analyzed by ANOVA, unpaired t test, Fischers exact test, Kruskal-Wallis and Pearsons correlation, considering significant p<0.05. RESULTS There was no difference between gender in relation to the initial classification and the level of asthma control; 91.7% (100 cases) received initial classification as persistent and 106 cases (88.3%) were partially or totally controlled. There was no statistical difference between controlled patients and the others in relation to BMI. No significant correlations were found between zBMI and FEV1 and between zBMI and FEF25-75%, analyzing all patients and only patients with overweight or obese. CONCLUSIONS In this study, no significant correlation was found between overweight/obesity and asthma using clinical, anthropometric and spirometric parameters.OBJETIVO: Evaluar la asociacion entre obesidad y asma por la comparacion entre edad, genero, clasificacion inicial y control del asma, valores de volumen espiratorio forzado en el primer segundo (VEF1) y flujo espiratorio forzado entre 25 y 75% basal (FEF25-75%) con los indices de masa corporal (IMC) en adolescentes asmaticos. METODOS: Estudio transversal implicando a 120 pacientes (1,9M:1F) asmaticos con mediana de edad de edad de 14,1 anos (9 a 20,1 anos), clasificados respecto al control y gravedad del asma, y evaluados por la espirometria utilizando su VEF1 y FEF25-75% basales. Estos datos fueron descriptos por la frecuencia, promedios y desviaciones estandar o medianas y variacion y analizados por las pruebas de ANOVA, prueba t no pareada, Prueba exacto de Fisher, Kruskal-Wallis y por la correlacion de Pearson considerandose significantes valores de p<0,05. RESULTADOS: No hubo diferencia entre los generos respecto a la clasificacion inicial del asma y el nivel de control. Recibieron clasificacion inicial persistente 91,7% (100 casos), siendo que 106 casos (88,3%) estaban parcial o totalmente controlados. No hubo diferencia estadistica entre los pacientes controlados y los restantes respecto al IMC. No se encontraron correlaciones significantes entre zIMC y VEF y entre zIMC y FEF25-75% al analizar todos los pacientes y solamente los pacientes con sobrepeso u obesos. CONCLUSIONES: En este estudio, no fue encontrada correlacion significante entre sobrepeso/obesidad y asma, utilizandose parametros clinicos, antropometricos y espirometricos.