Background: Allergic sensitization is the most important risk factor for asthma and rhinitis among children, adolescents and young adults. Less is known about the incidence and remission of allergic sensitization, particularly in older adults. Furthermore, it is not clear if the earlier documented increase in prevalence of allergic sensitization continues. This thesis is focused on prevalence, incidence and remission of allergic sensitization to airborne allergens among adolescents and adults as well as on time trends in prevalence among adults. Furthermore, associated risk factors and the relation of allergic sensitization to asthma and rhinitis were assessed. Methods: In the study of children and adolescents, incidence, remission and prevalence of allergic sensitization were assessed in a cohort study of schoolchildren, aged 7-8 years (y) at baseline. In the studies of adults, incidence and remission of allergic sensitization were assessed in a randomly selected adult population sample in 1994 (n=664) aged 20-69 y, which was followed up in 2004 (n=555). Trends in prevalence of allergic sensitization were assessed by comparing two cross-sectional studies; the cohort from 1994 and another randomly selsected population sample examined in 2009 (n=737). The relation of allergic sensitization to asthma and rhinitis was determined in the adult cohort in 2009. Allergic sensitization was assessed by skin prick test (SPT) with ten common airborne allergens at ages 7-8, 11-12 and 19 y in the cohort of children and in the participants ≤ 60 y in the adult cohorts. Specific IgE to nine airborne allergens was analyzed in the adult cohorts in 2004 and 2009. Risk factors for allergic sensitization and variables defining respiratory disease and symptoms were assessed by questionnaires in the cohort of children and by structured interviews in the adult cohorts. Results: The 10-year cumulative incidence of allergic sensitization among the adults from 1994 to 2004 was 5%, while remission was 32%. In both adult cohorts, the prevalence of allergic sensitization was highest among young adults, aged 20-29 y, 55% and 61% and decreased significantly with increasing age. Among children and adolescents, both incidence and persistence of allergic sensitization were high, and the prevalence of allergic sensitization increased by age from 21% at age 7-8 y to 42% at age 19 y. Multisensitization at age 19 y was strongly associated with early onset of sensitization. The prevalence of sensitization to the major specific allergens birch, timothy, cat and dog as well as multisensitization (from 40% in 1994 to 56% in 2009, p=0.002) increased significantly from 1994 to 2009 among the adults. Sensitization to any allergen increased from 35% to 39%, however not significantly (p=0.13). A family history of allergic rhinitis was strongly and consistently associated with allergic sensitization in all ages. Male sex and urban living were significantly positively and birth order and furry animals at home in childhood were negatively associated with onset of sensitization before the age of 7-8 y, but not with onset of sensitization from 11-12y to 19 y. Young adult age and urban living were significant factors associated with allergic sensitization in adult age. Sensitization to any animal was significantly positively associated with current asthma (OR4.80 (95% CI 2.68-8.60)), whereas both sensitization to any pollen (OR 4.25 (2.55-7.06)) and any animal (OR 3.90 (95% CI 2.31-6.58)) were associated with current allergic rhinitis. The association between allergic sensitization and allergic rhinitis was strongest in young adult age and decreased with increasing age, while asthma was similarly associated with sensitization to any animal across all adult ages. Among asthmatics, the prevalence of allergic sensitization decreased with increasing age of asthma onset. Conclusion: Both incidence and persistence of allergic sensitization were high among children and adolescents explaining the increase in prevalence by increasing age. An inverse pattern with low incidence and high remission of allergic sensitization was seen among adults. The decrease in prevalence of allergic sensitization by increasing adult age might at least partly be explained by normal ageing and not only by an effect of year of birth (cohort effect). The significant increase in prevalence of sensitization to the specific allergens explained the significant increase in multisensitization over 15 years. A family history of allergy was the strongest and the only consistent risk factor for allergic sensitization in all ages. The prevalence of allergic sensitization decreased with increasing age of asthma onset among adult asthmatics.

A imunoglobulina E (IgE) tem papel central na patogênese das doenças alérgicas. É parte da resposta do tipo 2, e as citocinas IL-4 e IL-13 são essenciais para que haja produção deste isotipo de imunoglobulina. Produção de IgE é também induzida por parasitas intestinais, particularmente helmintos. O objetivo do presente estudo foi avaliar a contribuição de IgE específica para ácaros, barata, gato, cachorro e para o parasita Ascaris lumbricoides sobre os níveis de IgE total entre crianças de áreas distintas no Brasil. Anticorpos IgE para ácaros Dermatophagoides pteronyssinus e Blomia tropicalis; barata Blattella germanica; gato; cachorro; e A. lumbricoides foram medidos usando o sistema ImmunoCAP, e comparados à IgE total no soro de 150 crianças de 3-6 anos de idade vivendo na cidade de Natal, endêmica para parasitoses intestinais, e de 54 crianças de 3-6 anos de idade com asma e/ou rinite, vivendo em Ribeirão Preto. Níveis de IgE total foram significantemente mais elevados em crianças de Natal quando comparados aqueles em crianças de Ribeirão Preto (média geométrica 630,9 kU/L, faixa 19,6-63.290 kU/L; e 398,1 kU/L, faixa 35,7-4.803 kU/L, respectivamente). Entre as 150 crianças de Natal, 52(34,6%) apresentaram IgE positiva para D.pteronyssinus; 70(46,6%) para B.tropicalis; 45(30%) para barata; 19(12,6%) para gato; 17(11,3%) para cachorro; e 125(83,3%) para A.lumbricoides. Entre as 54 crianças com asma e/ou rinite de Ribeirão Preto, 41(75,9%) apresentaram IgE positiva para D.pteronyssinus; 34(62,9%) para B.tropicalis; 22(40,7%) para barata; 11(20,3%) para gato; 12(22,2%) para cachorro. Embora estas crianças fossem negativas para parasitas à inclusão no estudo, 22(40,7%) tinham IgE para A.lumbricoides. Anticorpos IgE para A. lumbricoides foram mais elevados entre crianças de Natal, quando comparados a IgE para alérgenos inalantes (p<0,01). Níveis de IgE para D. pteronyssinus entre crianças de Ribeirão Preto foram mais altos que IgE para outros inalantes e A.lumbricoides (p<0,01). Em Natal, a porcentagem de IgE para A. lumbricoides em relação à IgE total foi maior em comparação a IgE para D.pteronyssinus e B.germanica (mediana 0,41%; 0,08%; e 0,04% respectivamente, p<0,01). Em Ribeirão Preto, a porcentagem de IgE para D.pteronyssinus e para B.tropicalis em relação à IgE total foi maiorem comparação a IgE para A.lumbricoides e barata (mediana 9,8%; 0,6%; 0,3%; e 0,2%, respectivamente, p<0,05). Regressão linear revelou que a associação mais forte foi para IgE para A.lumbricoides com IgE total em Natal (R²=0,56; p<0,01); associação significante foi também observada para IgE para ácaros com IgE total em Ribeirão Preto (R2=0,35; p<0,01 para D.pteronyssinus; R2=0,33; p<0,01 para B.tropicalis, respectivamente). Nossos resultados demonstraram que anticorpos IgE para ácaros contribuem fortemente para a IgE total entre crianças com asma e/ou rinite, vivendo em uma área de baixa taxa de infecções parasitárias em nosso meio. Por outro lado, entre crianças vivendo em uma área em que parasitas são encontrados em abundância, infecções parasitárias induzem uma forte resposta IgE policlonal, e anticorpos IgE específicos para parasita, além de ácaros, barata, gato e cachorro representam uma modesta proporção da IgE total. A especificidade desta IgE, e os efeitos a longo prazo desta resposta cedo na vida, permanecem desconhecidos. / Immunoglobulin E (IgE) plays a central role in the pathogenesis of allergic diseases. It is part of the type 2 response, and the cytokines IL-4 and IL-13 are essential for the production of this immunoglobulin isotype. IgE production is also induced by intestinal parasites, particularly helminths. The aim of the present study was to evaluate the contribution of specific IgE to mites, cockroach, cat, dog and parasite Ascaris lumbricoides on total IgE levels among children living in different areas in Brazil. IgE antibodies to mites Dermatophagoides pteronyssinus and Blomia tropicalis; cockroach Blattella germanica; cat; dog; and A. lumbricoides were measured using the ImmunoCAP system and compared to total serum IgE of 150 children 3-6 year-old living in the city of Natal, endemic for intestinal parasites, and 54 children 3-6 years of age with asthma and /or rhinitis, living in Ribeirão Preto. Total IgE levels were significantly higher in children from Natal as compared to those among children in Ribeirão Preto (geometric mean 630,9 kU/L, range 19,6-63.290 kU/L; e 398,1 kU/L, range 35,7-4.803 kU/L, respectively). Among the 150 children from Natal, 52(34.6%) presented IgE positive to D.pteronyssinus; 70(46.6%) to B. tropicalis; 45(30%) to cockroach; 19 (12.6%) to cat; 17(11.3%) to dog; and 125(83.3%) to A. lumbricoides. Among the 54 children with asthma and /or rhinitis from Ribeirão Preto, 41(75.9%) had IgE positive to D.pteronyssinus; 34(62.9%) to B.tropicalis; 22(40.7%) to cockroach; 11(20.3%) to cat; 12(22.2%) to dog. Although these children were negative for parasites at inclusion in the study, 22(40.7%) had IgE to A.lumbricoides. IgE antibodies to A.lumbricoides were higher among children from Natal, as compared to IgE to inhalant allergens (p<0.01). IgE levels to D.pteronyssinus among children living in Ribeirão Preto were higher than IgE to other inhalants and A.lumbricoides (p<0.01). In Natal, the percentage of IgE to A.lumbricoides in relation to total IgE was higher in comparison to IgE to D.pteronyssinus e B.germanica (median 0.41%, 0.08%, and 0.04% respectively, p<0.01). In Ribeirão Preto, the percentage of IgE to D.pteronyssinus and to B.tropicalis in relation to total IgE was higher in comparison to IgE to A.lumbricoides and cockroach (median 9.8%, 0,6%, 0.3%, and 0.2%, respectively, p <0.05). Linear regression analysis revealed that the strongest association was for IgE to A.lumbricoides with total IgE in Natal (R²=0.56, p<0.01); significantassociation was also observed for IgE to mites with total IgE in Ribeirão Preto (R2=0.35, p<0.01 for D. pteronyssinus, R2=0.33, p<0.01 for B.tropicalis, respectively). Our results demonstrated that IgE antibodies to mites contribute strongly to total IgE among children with asthma and /or rhinitis, living in an area of low parasite infection rates in our country. On the contrary, among children living in an area where parasites are found in abundance, parasitic infections induce a strong polyclonal IgE response, and IgE antibodies specific for parasite, and also for mites, cockroaches, cat and dog represent a modest proportion of total IgE. The specificity of these IgE antibodies and the implications of this response occurring early in life remain unknown.

A imunoglobulina E (IgE) tem papel central na patogênese das doenças alérgicas. É parte da resposta do tipo 2, e as citocinas IL-4 e IL-13 são essenciais para que haja produção deste isotipo de imunoglobulina. Produção de IgE é também induzida por parasitas intestinais, particularmente helmintos. O objetivo do presente estudo foi avaliar a contribuição de IgE específica para ácaros, barata, gato, cachorro e para o parasita Ascaris lumbricoides sobre os níveis de IgE total entre crianças de áreas distintas no Brasil. Anticorpos IgE para ácaros Dermatophagoides pteronyssinus e Blomia tropicalis; barata Blattella germanica; gato; cachorro; e A. lumbricoides foram medidos usando o sistema ImmunoCAP, e comparados à IgE total no soro de 150 crianças de 3-6 anos de idade vivendo na cidade de Natal, endêmica para parasitoses intestinais, e de 54 crianças de 3-6 anos de idade com asma e/ou rinite, vivendo em Ribeirão Preto. Níveis de IgE total foram significantemente mais elevados em crianças de Natal quando comparados aqueles em crianças de Ribeirão Preto (média geométrica 630,9 kU/L, faixa 19,6-63.290 kU/L; e 398,1 kU/L, faixa 35,7-4.803 kU/L, respectivamente). Entre as 150 crianças de Natal, 52(34,6%) apresentaram IgE positiva para D.pteronyssinus; 70(46,6%) para B.tropicalis; 45(30%) para barata; 19(12,6%) para gato; 17(11,3%) para cachorro; e 125(83,3%) para A.lumbricoides. Entre as 54 crianças com asma e/ou rinite de Ribeirão Preto, 41(75,9%) apresentaram IgE positiva para D.pteronyssinus; 34(62,9%) para B.tropicalis; 22(40,7%) para barata; 11(20,3%) para gato; 12(22,2%) para cachorro. Embora estas crianças fossem negativas para parasitas à inclusão no estudo, 22(40,7%) tinham IgE para A.lumbricoides. Anticorpos IgE para A. lumbricoides foram mais elevados entre crianças de Natal, quando comparados a IgE para alérgenos inalantes (p<0,01). Níveis de IgE para D. pteronyssinus entre crianças de Ribeirão Preto foram mais altos que IgE para outros inalantes e A.lumbricoides (p<0,01). Em Natal, a porcentagem de IgE para A. lumbricoides em relação à IgE total foi maior em comparação a IgE para D.pteronyssinus e B.germanica (mediana 0,41%; 0,08%; e 0,04% respectivamente, p<0,01). Em Ribeirão Preto, a porcentagem de IgE para D.pteronyssinus e para B.tropicalis em relação à IgE total foi maiorem comparação a IgE para A.lumbricoides e barata (mediana 9,8%; 0,6%; 0,3%; e 0,2%, respectivamente, p<0,05). Regressão linear revelou que a associação mais forte foi para IgE para A.lumbricoides com IgE total em Natal (R²=0,56; p<0,01); associação significante foi também observada para IgE para ácaros com IgE total em Ribeirão Preto (R2=0,35; p<0,01 para D.pteronyssinus; R2=0,33; p<0,01 para B.tropicalis, respectivamente). Nossos resultados demonstraram que anticorpos IgE para ácaros contribuem fortemente para a IgE total entre crianças com asma e/ou rinite, vivendo em uma área de baixa taxa de infecções parasitárias em nosso meio. Por outro lado, entre crianças vivendo em uma área em que parasitas são encontrados em abundância, infecções parasitárias induzem uma forte resposta IgE policlonal, e anticorpos IgE específicos para parasita, além de ácaros, barata, gato e cachorro representam uma modesta proporção da IgE total. A especificidade desta IgE, e os efeitos a longo prazo desta resposta cedo na vida, permanecem desconhecidos. / Immunoglobulin E (IgE) plays a central role in the pathogenesis of allergic diseases. It is part of the type 2 response, and the cytokines IL-4 and IL-13 are essential for the production of this immunoglobulin isotype. IgE production is also induced by intestinal parasites, particularly helminths. The aim of the present study was to evaluate the contribution of specific IgE to mites, cockroach, cat, dog and parasite Ascaris lumbricoides on total IgE levels among children living in different areas in Brazil. IgE antibodies to mites Dermatophagoides pteronyssinus and Blomia tropicalis; cockroach Blattella germanica; cat; dog; and A. lumbricoides were measured using the ImmunoCAP system and compared to total serum IgE of 150 children 3-6 year-old living in the city of Natal, endemic for intestinal parasites, and 54 children 3-6 years of age with asthma and /or rhinitis, living in Ribeirão Preto. Total IgE levels were significantly higher in children from Natal as compared to those among children in Ribeirão Preto (geometric mean 630,9 kU/L, range 19,6-63.290 kU/L; e 398,1 kU/L, range 35,7-4.803 kU/L, respectively). Among the 150 children from Natal, 52(34.6%) presented IgE positive to D.pteronyssinus; 70(46.6%) to B. tropicalis; 45(30%) to cockroach; 19 (12.6%) to cat; 17(11.3%) to dog; and 125(83.3%) to A. lumbricoides. Among the 54 children with asthma and /or rhinitis from Ribeirão Preto, 41(75.9%) had IgE positive to D.pteronyssinus; 34(62.9%) to B.tropicalis; 22(40.7%) to cockroach; 11(20.3%) to cat; 12(22.2%) to dog. Although these children were negative for parasites at inclusion in the study, 22(40.7%) had IgE to A.lumbricoides. IgE antibodies to A.lumbricoides were higher among children from Natal, as compared to IgE to inhalant allergens (p<0.01). IgE levels to D.pteronyssinus among children living in Ribeirão Preto were higher than IgE to other inhalants and A.lumbricoides (p<0.01). In Natal, the percentage of IgE to A.lumbricoides in relation to total IgE was higher in comparison to IgE to D.pteronyssinus e B.germanica (median 0.41%, 0.08%, and 0.04% respectively, p<0.01). In Ribeirão Preto, the percentage of IgE to D.pteronyssinus and to B.tropicalis in relation to total IgE was higher in comparison to IgE to A.lumbricoides and cockroach (median 9.8%, 0,6%, 0.3%, and 0.2%, respectively, p <0.05). Linear regression analysis revealed that the strongest association was for IgE to A.lumbricoides with total IgE in Natal (R²=0.56, p<0.01); significantassociation was also observed for IgE to mites with total IgE in Ribeirão Preto (R2=0.35, p<0.01 for D. pteronyssinus, R2=0.33, p<0.01 for B.tropicalis, respectively). Our results demonstrated that IgE antibodies to mites contribute strongly to total IgE among children with asthma and /or rhinitis, living in an area of low parasite infection rates in our country. On the contrary, among children living in an area where parasites are found in abundance, parasitic infections induce a strong polyclonal IgE response, and IgE antibodies specific for parasite, and also for mites, cockroaches, cat and dog represent a modest proportion of total IgE. The specificity of these IgE antibodies and the implications of this response occurring early in life remain unknown.

Charles University Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Author: Bc. Petra Porubová Supervisor: prof. RNDr. Ctirad Andrýs, Ph.D. Title of diploma thesis: Allergic phenotypes in patients with respiratory allergy evaluated by microchip ISAC technique Key words: allergic inflammation, allergen specific IgE, component resolved diagnostics, microchip, ISAC Background: The aim of this diploma thesis was to evaluate the sensitization profile in the group of pacients with allergic rhinitis and/or bronhial asthma and to identify possible differences between patients with different disease severity. Methods: ImmunoCAP ISAC was used to determine specific IgE antibodies against 112 allergen components. The evaluated group included 152 patients (57.9 % women) from the allergology outpatient office of the Department of Clinical Immunology and Allergology, University Hospital Hradec Králové. Results: The most common allergens in this group of patients were the components Phl p 1 (68,4 %) and Bet v 1 (65,1 %). Differences in the number of positive and negative reactions were demonstrated between patients with different severity of allergic rhinitis. Correlations were found between the number of positive/negative reactions and the severity of bronchial asthma. And the...

p. 1-157 / Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-04-24T21:12:07Z No. of bitstreams: 1 22222222222tttt.pdf: 2420212 bytes, checksum: d208a267b6fe5b14ae33b31fc9319a4a (MD5) / Approved for entry into archive by Maria Creuza Silva(mariakreuza@yahoo.com.br) on 2013-05-04T17:08:10Z (GMT) No. of bitstreams: 1 22222222222tttt.pdf: 2420212 bytes, checksum: d208a267b6fe5b14ae33b31fc9319a4a (MD5) / Made available in DSpace on 2013-05-04T17:08:10Z (GMT). No. of bitstreams: 1 22222222222tttt.pdf: 2420212 bytes, checksum: d208a267b6fe5b14ae33b31fc9319a4a (MD5) Previous issue date: 2011 / O objetivo deste estudo foi investigar a influência de fatores ambientais, antropométricos e de estilo de vida em asma e atopia em uma área rural do Equador. Foi conduzido um estudo transversal, a partir do qual foram identificadas crianças e adolescentes, com e sem chiado no peito no ultimo ano, para serem incluídas no estudo caso-controle. Inicialmente, um estudo exploratório foi realizado para identificar se diferentes fatores (sócioeconômicos, ambientais, famíliares, estilo de vida, infecção por helmintos) estariam associados com sibilo atópico e não-atópico na área rural. Os resultados mostraram que sibilo não-atópico foi o fenótipo mais comum nesta área, e foi observado um padrão diferente de fatores de risco para sibilância atópica e não-atópica, o que pode sugerir que diferentes mecanismos podem estar envolvidos. Vários estudos nas áreas rurais e urbanas pobres na América Latina têm reportado que a asma não é atribuída a atopia. Da mesma forma, uma dissociação entre a IgE específica e reatividade ao teste cutâneo tem sido observada. Assim, testamos a hipótese de que na nossa população, infecções por helmintos, poderiam estar modificando estas associações. Os resultados mostram uma relação complexa entre helmintos, asma e atopia. Notou-se que a associação entre os marcadores de atopia foi mais débil nos indivíduos com presença de sensibilização para Ascaris, e a associação entre o teste cutâneo e sibilo, foi atenuada em indivíduos com infecção ativa com Ascaris e / ou Trichuris. Adicionalmente a IgE anti-Ascaris, mas não infecção ativa, incrementou o risco de sibilo, independentemente de IgE específica a alérgenos. Finalmente, uma nova hipótese sugere que a adoção de novos estilos de vida estaria conduzindo a um aumento da asma e atopia. Assim, estudou-se excesso de peso, por ser considerado um marcador de recentes mudanças nos padrões de vida e que, por sua vez, estaria associado com asma e atopia. A presença de teste cutâneo e IgE específica a alérgenos foi de 1,85 e 2,20 vezes maior em crianças com excesso de peso do que em crianças eutróficas/déficit, respectivamente. No entanto, o efeito em sibilo foi decorrente de um mecanismo não-atópico. Embora esses resultados precisem ser confirmados por estudos longitudinais, certamente contribuirão para uma melhor compreensão dos mecanismos da asma não-atopica nas aéreas rurais, que tem sido muito pouco compreendidos. / Salvador

Contexte. Les premières années de vie apparaissent particulièrement propices au développement de la sensibilisation allergénique. Objectifs. Cette thèse vise à : i) décrire les profils de sensibilisation allergénique chez le nourrisson et l’enfant, ii) étudier l’association entre ces profils et la morbidité allergique et iii) identifier les facteurs de risque de cette sensibilisation. Méthodes. Dans le cadre du suivi de la cohorte prospective de naissances en population générale Pollution and Asthma Risk: an Infant Study (PARIS), la sensibilisation allergénique a été évaluée chez 1 860 nourrissons à 18 mois et 1 007 enfants à 8/9 ans par dosage des IgE spécifiques dirigées contre 16 et 19 allergènes, respectivement. Les informations concernant la santé et le cadre de vie des enfants ont été recueillies par questionnaires standardisés répétés. Des profils de sensibilisation et des profils de morbidité ont été identifiés par classification non supervisée et mis en relation par régression logistique multinomiale. Enfin, les facteurs associés à la sensibilisation allergénique chez le nourrisson ont été étudiés par régression logistique multivariée. Résultats. Dès 18 mois, 13,8% des enfants étaient sensibilisés et 6,2%, multi-sensibilisés. À 8/9 ans, ces prévalences étaient de 34,5% et 19,8%, respectivement. Les profils de sensibilisation identifiés chez le nourrisson (3) et dans l’enfance (5) différaient au regard de la morbidité allergique. L’analyse étiologique a permis de préciser le rôle des expositions précoces aux allergènes et aux microorganismes sur la sensibilisation allergénique. Conclusion. Cette thèse contribue à une meilleure compréhension de l’histoire naturelle de la sensibilisation allergénique, et ce, dès les premières années de vie. Cette connaissance est essentielle à la prévention des maladies allergiques qui en découlent. / Background. The first years of life appear to be critical for the development of allergic sensitization. Objectives. This thesis aims: i) to describe allergic sensitization profiles in infants and children, ii) to assess the link between these sensitization profiles and allergic morbidity, and iii) to identify risk factors for allergic sensitization. Methods. This work concerns children involved in the Pollution and Asthma Risk: an Infant Study (PARIS) population-based prospective birth cohort. Allergic sensitization was assessed in 1,860 18-month-old infants and 1,007 8/9-year-old children by specific IgE measurements towards 16 and 19 allergens, respectively. Lifelong health and living condition data were collected by repeated standardized questionnaires. Sensitization profiles and morbidity profiles were identified using unsupervised classification, and related to each other by multinomial logistic regression. Finally, risk factors for early allergic sensitization were assessed by multivariate logistic regression. Results. As soon as 18 months of age, 13.8% of children were sensitized and 6.2%, multi-sensitized. When 8/9 years old, corresponding prevalence was 34.5% and 19.8%, respectively. Sensitization profiles identified in infancy (3) and in childhood (5) differed in terms of allergic morbidity. Risk factor analysis allowed to clarify the role of early exposure to allergens and microorganisms on allergic sensitization. Conclusion. This thesis improves the natural history of allergic sensitization understanding, as soon as the first years of life. This knowledge is essential for subsequent disease preventing.