Renata Rodrigues Cocco

Clinical Use of Probiotics in Pediatric Allergy (cuppa): A World Allergy Organization Position Paper

BackgroundProbiotic administration has been proposed for the prevention and treatment of specific allergic manifestations such as eczema, rhinitis, gastrointestinal allergy, food allergy, and asthma. However, published statements and scientific opinions disagree about the clinical usefulness.ObjectiveA World Allergy Organization Special Committee on Food Allergy and Nutrition review of the evidence regarding the use of probiotics for the prevention and treatment of allergy.MethodsA qualitative and narrative review of the literature on probiotic treatment of allergic disease was carried out to address the diversity and variable quality of relevant studies. This variability precluded systematization, and an expert panel group discussion method was used to evaluate the literature. In the absence of systematic reviews of treatment, meta-analyses of prevention studies were used to provide data in support of probiotic applications.ResultsDespite the plethora of literature, probiotic research is still in its infancy. There is a need for basic microbiology research on the resident human microbiota. Mechanistic studies from biology, immunology, and genetics are needed before we can claim to harness the potential of immune modulatory effects of microbiota. Meanwhile, clinicians must take a step back and try to link disease state with alterations of the microbiota through well-controlled long-term studies to identify clinical indications.ConclusionsProbiotics do not have an established role in the prevention or treatment of allergy. No single probiotic supplement or class of supplements has been demonstrated to efficiently influence the course of any allergic manifestation or long-term disease or to be sufficient to do so. Further epidemiologic, immunologic, microbiologic, genetic, and clinical studies are necessary to determine whether probiotic supplements will be useful in preventing allergy. Until then, supplementation with probiotics remains empirical in allergy medicine. In the future, basic research should focus on homoeostatic studies, and clinical research should focus on preventive medicine applications, not only in allergy. Collaborations between allergo-immunologists and microbiologists in basic research and a multidisciplinary approach in clinical research are likely to be the most fruitful.

Milk and soy allergy.

Cows milk allergy (CMA) affects 2% to 3% of young children and presents with a wide range of IgE and non-IgE-mediated clinical syndromes, which have a significant economic and lifestyle effect. It is logical that a review of CMA would be linked to a review of soy allergy because soy formula is often an alternative source of nutrition for infants who do not tolerate cows milk. This review examines the epidemiology, pathogenesis, clinical features, natural history, and diagnosis of cows milk and soy allergy. Cross-reactivity and management of milk allergy are also discussed.

Pneumonias de repetição em paciente com deficiência de anticorpos e imunoglobulinas normais

apos imunizacao para todos ossorotipos (1, 3, 5, 6, 9 e 14) testados, embora a paciente apresentasse niveis normais deimunoglobulinas. A avaliacao radiologica, no momento da admissao, demonstrou presenca deatelectasias difusas associadas a bronquiectasias. Apos inicio do tratamento com imunoglobulinaendovenosa e fisioterapia respiratoria houve esvaecimento gradual ate reversao das alteracoesradiologicas. Demonstrou-se, assim, a importância de um diagnostico preciso para inicio detratamento especifico, com melhora gradual do quadro clinico e radiologico, evitando sequelaspulmonares irreversiveis.

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.

Contribution of Molecular Allergen Analysis in Diagnosis of Milk Allergy

Purpose of ReviewWe sought to describe the available evidence supporting the utilization of the molecular allergen analysis (MAA) for diagnosis and management of cow milk protein allergy (CMPA).Recent FindingsCow milk proteins are among the most common food allergens in IgE- and non-IgE-mediated food allergic disorders in children. Most individuals with CMPA are sensitized to both caseins and whey proteins. Caseins are more resistant to high temperatures compared to whey proteins.SummaryMAA is not superior to the conventional diagnostic tests based on the whole allergen extracts for diagnosis of CMPA. However, MAA can be useful in diagnosing tolerance to extensively heated milk proteins in baked foods. Children with CMPA and high levels of casein IgE are less likely to tolerate baked milk compared to children with low levels of casein IgE. Specific IgE-binding patterns to casein and betalactoglobulin peptides may predict the natural course of CMPA and differentiate subjects who are more likely to develop CMPA at a younger age versus those with a more persistent CMPA. Specific IgE-binding patterns to casein and beta-lactoglobulin peptides may also predict response to milk OITand identify patientsmost likely to benefit fromOIT.

Prebióticos, probióticos e simbióticos na prevenção e tratamento das doenças alérgicas

OBJECTIVE: To review current evidence about the effects of probiotics, prebiotics and symbiotics on the immune development as well as on the prevention of allergic diseases in children. DATA SOURCES: Randomized, double-blind clinical trials in humans published in the last five years, in the Medline database, containing the following keywords: prebiotics (oligosaccharides), probiotics, symbiotics and hypersensitivity. DATA SYNTHESIS: For this review three papers with prebiotics were included, all of them using a mixture of GOS:FOS (9:1) in infant formula for the first months of life; 24 papers with probiotics, where L. rhamnosus GG, B. lactis, L. casei, L. paracasei, L. reuteri, L. acidophilus, B. longum, B. breve and P. freudenreichii sp. were the tested bacterial strains; and two papers about symbiotics. CONCLUSIONS: Although there are some evidence of benefits of early supplementation with some specific probiotic strains, prebiotics and symbiotics for the prevention of atopic eczema in children with high risk of allergy development, and probiotic use for the treatment of IgE-mediated moderate and severe atopic dermatitis, further research is needed in order to extended the evaluation of supplemented individuals, safety aspects and long term effectsOBJETIVO: Avaliar o papel dos probioticos, prebioticos e simbioticos no equilibrio do sistema imunologico do lactente, bem como seu efeito preventivo no desenvolvimento de doencas alergicas na crianca. FONTE DE DADOS: A partir do levantamento de todos os ensaios clinicos duplo-cegos e randomicos em seres humanos, publicados nos ultimos cinco anos na base de dados Medline e que contivessem unitermos relacionados a prebioticos (oligossacarideos), probioticos e simbioticos versus hipersensibilidade, analisou-se seu papel quanto a utilizacao em doencas alergicas. SINTESE DE DADOS: Foram incluidos nesta revisao tres trabalhos com prebioticos, os quais utilizaram a mistura GOS:FOS (9:1) em formulas infantis em lactentes nos primeiros meses de vida; 24 trabalhos com probioticos, sendo os micro-organismos utilizados na suplementacao L. rhamnosus GG, B. lactis, L. casei, L. paracasei, L. reuteri, L. acidophilus, B. longum, B. breve e P. freudenreichii sp., e dois estudos com simbioticos. CONCLUSOES: Apesar das evidencias de beneficios da suplementacao precoce de probioticos com algumas cepas especificas, prebioticos e simbioticos na prevencao da dermatite atopica, em criancas de alto risco para alergias, e do uso de probioticos no tratamento das dermatites atopicas moderadas e graves mediadas por IgE, ha necessidade de ampliar os estudos quanto ao tempo de observacao dos individuos suplementados, quanto a seguranca e aos efeitos em longo prazo

Oral food challenges in a specialized allergy outpatient clinic in São Paulo, Brazil

Methods A retrospective study of chart analysis of 171 patients undergone to 220 OFC, between June/2007 and Feb/ 2014. Food tests comprised CM, egg, soy, peanuts, nuts, seafood, meat, chicken, tartrazine, chocolate, wheat and coconut. Patients were evaluated according to the type of CM’s challenge (open or double-blind placebocontrolled), aim of the procedure (diagnosis or follow up tolerance), symptoms, body mass index, time of breastfeeding, age at first reaction, family history of food allergy, presence of other atopic diseases (asthma, allergic rhinitis and atopic dermatitis) and skin prick test.

Increased sensitization to several allergens over a 12-year period in Brazilian children

2. Ruokolainen L, von Hertzen L, Fyhrquist N, et al. Green areas around homes reduce atopic sensitization in children. Allergy. 2015;70:195-202. 3. von Hertzen L, Beutler B, Bienenstock J, et al. Helsinki alert of biodiversity and health. Ann Med. 2015;47:218-225. 4. Lehtimäki J, Karkman A, Laatikainen T, et al. Patterns in the skin microbiota differ in children and teenagers between rural and urban environments. Sci Rep. 2017;7:45651. 5. Maechler M, Rousseeuw P, Struyf A, et al. cluster: “Finding Groups in Data”: Cluster Analysis Extended. https://cran.r-project.org/web/ packages/cluster/index.html. Accessed January 2, 2016. 6. Oksanen J, Blanchet FG, Kindt R, et al. vegan: Community Ecology Package. R package version 2.3-2. 2015. https://CRAN.R-project. org/package=vegan. Accessed January 2, 2016. 7. Anders S, Huber W. Differential expression analysis for sequence count data. Genome Biol. 2010;11:R106. 8. Lax S, Smith DP, Hampton-Marcell J, et al. Longitudinal analysis of microbial interaction between humans and the indoor environment. Science. 2014;345:1048-1052. 9. Kembel SW, Jones E, Kline J, et al. Architectural design influences the diversity and structure of the built environment microbiome. ISME J. 2012;6:1469-1479. 10. Pekkarinen P, von Hertzen L, Laatikainen T, et al. A disparity in the association of asthma, rhinitis, and eczema with allergenspecific IgE between Finnish and Russian Karelia. Allergy. 2007;62: 281-287. 11. Ruokolainen L, Lehtimäki JM, Karkman AV, Haahtela TK, von Hertzen L, Fyhrquist NT. Holistic view on health. Two protective layers of biodiversity. Ann Zool Fenn. 2017;54:39-49. 12. Haahtela T, Valovirta E, Bousquet J, Mäkelä M. The Finnish Allergy Programme 2008–2018 works. Eur Respir J. 2017;49:1700470. 13. Prescott S, Larcombe D, Logan A, et al. The skin microbiome: impact of modern environments on skin ecology, barrier integrity, and systemic immune programming. World Allergy Organ J. 2017; 10:29.

Accuracy of serum IgE concentrations and papule diameter in the diagnosis of cow's milk allergy

OBJECTIVE To compare serum concentrations of specific IgE and mean papule diameters induced in the immediate skin reactivity test with cows milk and its fractions with results of the oral challenge test, and to establish cutoff points capable of predicting clinical reactivity to cows milk in patients treated at a referral service. METHODS One hundred and twenty-two children (median of 17 months) with a history of immediate reactions to cows milk and presence of specific IgE for cows milk and/or its fractions (positive skin and/or IgE serum tests) were submitted to open oral challenge test with cows milk. RESULTS The oral challenge test was positive in 59.8% of the children, 49% of whom were males. Serum levels of specific IgE, as well as mean cows milk papule diameters, were significantly higher in allergic patients (medians: 3.39kUA/L vs. 1.16kUA/L, 2.5mm vs. 0mm). The optimal cutoff points (Youdens index) of serum IgE specific for cows milk and its fractions capable of predicting cows milk reactivity (positive oral challenge test) were: 5.17kUA/L for cows milk, 0.95kUA/L for α-lactalbumin, 0.82kUA/L for β-lactoglobulin, and 0.72kUA/L for casein, whereas for papule diameters the cutoff points were 3.5mm for cows milk and 6.5mm, 9.0mm, and 3.0mm for the α-lactalbumin, β-lactoglobulin, and casein fractions, respectively. CONCLUSIONS The cutoff points capable of predicting clinical reactivity to cows milk were: 5.17kUA/L for serum-specific IgE and 3.5mm for papule diameter measurement, values considered discriminatory for the diagnosis of cows milk allergy.

Are there predictive symptoms/signs for a positive oral cow's milk challenge in patients suspected of cow's milk allergy?

Methods 128 children with suspected CMA were undergone to CMFC (June/2007 to Feb/2014) and comprised two groups according to the result: negative test (passed, PG, n=100) and positive test (failed, FG, n=28). Both groups were analyzed regarding to age at first reaction, gender, nutritional status, breastfeeding, familial history of FA, symptoms reported, presence of asthma, allergic rhinitis or atopic dermatitis and results of skin prick test (SPT). FG was analyzed according to required amount of CM to elicit reaction, symptoms and severity of reaction.