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1.
NEJM Evid ; 3(6): EVIDoa2300311, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38804779

RESUMO

BACKGROUND: A randomized trial demonstrated consumption of peanut from infancy to age 5 years prevented the development of peanut allergy. An extension of that trial demonstrated the effect persisted after 1 year of peanut avoidance. This follow-up trial examined the durability of peanut tolerance at age 144 months after years of ad libitum peanut consumption. METHODS: Participants from a randomized peanut consumption trial were assessed for peanut allergy following an extended period of eating or avoiding peanuts as desired. The primary end point was the rate of peanut allergy at age 144 months. RESULTS: We enrolled 508 of the original 640 participants (79.4%); 497 had complete primary end point data. At age 144 months, peanut allergy remained significantly more prevalent in participants in the original peanut avoidance group than in the original peanut consumption group (15.4% [38 of 246 participants] vs. 4.4% [11 of 251 participants]; P<0.001). Participants in both groups reported avoiding peanuts for prolonged periods of time between 72 and 144 months. Participants at 144 months in the peanut consumption group had levels of Ara h2-specific immunoglobulin E (a peanut allergen associated with anaphylaxis) of 0.03 ± 3.42 kU/l and levels of peanut-specific immunoglobulin G4 of 535.5 ± 4.98 µg/l, whereas participants in the peanut avoidance group had levels of Ara h2-specific immunoglobulin E of 0.06 ± 11.21 kU/l and levels of peanut-specific immunoglobulin G4 of 209.3 ± 3.84 µg/l. Adverse events were uncommon, and the majority were related to the food challenge. CONCLUSIONS: Peanut consumption, starting in infancy and continuing to age 5 years, provided lasting tolerance to peanut into adolescence irrespective of subsequent peanut consumption, demonstrating that long-term prevention and tolerance can be achieved in food allergy. (Funded by the National Institute of Allergy and Infectious Diseases and others; ITN070AD, ClinicalTrials.gov number, NCT03546413.).


Assuntos
Arachis , Hipersensibilidade a Amendoim , Humanos , Hipersensibilidade a Amendoim/prevenção & controle , Hipersensibilidade a Amendoim/imunologia , Hipersensibilidade a Amendoim/epidemiologia , Seguimentos , Arachis/imunologia , Feminino , Masculino , Pré-Escolar , Lactente , Adolescente , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Criança , Tolerância Imunológica
2.
J Allergy Clin Immunol ; 146(2): 344-355, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32311390

RESUMO

BACKGROUND: Oral food challenge (OFC) is the criterion standard to assess peanut allergy (PA), but it involves a risk of allergic reactions of unpredictable severity. OBJECTIVE: Our aim was to identify biomarkers for risk of severe reactions or low dose threshold during OFC to peanut. METHODS: We assessed Learning Early about Peanut Allergy study, Persistance of Oral Tolerance to Peanut study, and Peanut Allergy Sensitization study participants by administering the basophil activation test (BAT) and the skin prick test (SPT) and measuring the levels of peanut-specific IgE, Arachis hypogaea 2-specific IgE, and peanut-specific IgG4, and we analyzed the utility of the different biomarkers in relation to PA status, severity, and threshold dose of allergic reactions to peanut during OFC. RESULTS: When a previously defined optimal cutoff was used, the BAT diagnosed PA with 98% specificity and 75% sensitivity. The BAT identified severe reactions with 97% specificity and 100% sensitivity. The SPT, level of Arachis hypogaea 2-specific IgE, level of peanut-specific IgE, and IgG4/IgE ratio also had 100% sensitivity but slightly lower specificity (92%, 93%, 90%, and 88%, respectively) to predict severity. Participants with lower thresholds of reactivity had higher basophil activation to peanut in vitro. The SPT and the BAT were the best individual predictors of threshold. Multivariate models were superior to individual biomarkers and were used to generate nomograms to calculate the probability of serious adverse events during OFC for individual patients. CONCLUSIONS: The BAT diagnosed PA with high specificity and identified severe reactors and low threshold with high specificity and high sensitivity. The BAT was the best biomarker for severity, surpassed only by the SPT in predicting threshold. Nomograms can help estimate the likelihood of severe reactions and reactions to a low dose of allergen in individual patients with PA.


Assuntos
Anafilaxia/diagnóstico , Basófilos/imunologia , Hipersensibilidade a Amendoim/diagnóstico , Administração Oral , Alérgenos/imunologia , Arachis/imunologia , Teste de Degranulação de Basófilos , Basófilos/química , Biomarcadores , Criança , Progressão da Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Imunização , Masculino , Sensibilidade e Especificidade , Índice de Gravidade de Doença
3.
J Allergy Clin Immunol ; 144(2): 494-503, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31160034

RESUMO

BACKGROUND: Staphylococcus aureus has been implicated in the pathophysiology of eczema, allergic rhinitis, asthma, and food allergy. S aureus is a marker of more severe eczema, which is a risk factor for food sensitization/allergy. Therefore it might be that the association between S aureus and food allergy in eczematous patients is related to eczema severity. OBJECTIVE: We sought to investigate the association of S aureus colonization with specific IgE (sIgE) production to common food allergens and allergies in early childhood independent of eczema severity. We additionally determined the association of S aureus colonization with eczema severity and persistence. METHODS: In Learning Early About Peanut Allergy (LEAP) study participants eczema severity was assessed, and skin/nasal swabs were cultured for S aureus. Sensitization was identified by measuring sIgE levels. Peanut allergy was primarily determined by means of oral food challenge, and persistent egg allergy was primarily determined by using skin prick tests. RESULTS: Skin S aureus colonization was significantly associated with eczema severity across the LEAP study, whereas at 12 and 60 months of age, it was related to subsequent eczema deterioration. Skin S aureus colonization at any time point was associated with increased levels of hen's egg white and peanut sIgE independent of eczema severity. Participants with S aureus were more likely to have persistent egg allergy and peanut allergy at 60 and 72 months of age independent of eczema severity. All but one of the 9 LEAP study consumers with peanut allergy (9/312) were colonized at least once with S aureus. CONCLUSION: S aureus, independent of eczema severity, is associated with food sensitization and allergy and can impair tolerance to foods. This could be an important consideration in future interventions aimed at inducing and maintaining tolerance to food allergens in eczematous infants.


Assuntos
Asma , Dermatite Atópica , Hipersensibilidade a Ovo , Hipersensibilidade a Amendoim , Rinite Alérgica , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Asma/imunologia , Asma/microbiologia , Criança , Pré-Escolar , Dermatite Atópica/imunologia , Dermatite Atópica/microbiologia , Hipersensibilidade a Ovo/imunologia , Hipersensibilidade a Ovo/microbiologia , Feminino , Humanos , Lactente , Masculino , Hipersensibilidade a Amendoim/imunologia , Hipersensibilidade a Amendoim/microbiologia , Rinite Alérgica/imunologia , Rinite Alérgica/microbiologia , Índice de Gravidade de Doença
4.
J Allergy Clin Immunol ; 141(4): 1343-1353, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29097103

RESUMO

BACKGROUND: Early introduction of dietary peanut in high-risk infants with severe eczema, egg allergy, or both prevented peanut allergy at 5 years of age in the Learning Early About Peanut Allergy (LEAP) study. The protective effect persisted after 12 months of avoiding peanuts in the 12-month extension of the LEAP study (LEAP-On). It is unclear whether this benefit is allergen and allergic disease specific. OBJECTIVE: We sought to assess the effect of early introduction of peanut on the development of allergic disease, food sensitization, and aeroallergen sensitization. METHODS: Asthma, eczema, and rhinoconjunctivitis were diagnosed based on clinical assessment. Reported allergic reactions and consumption of tree nuts and sesame were recorded by questionnaire. Sensitization to food allergens and aeroallergens was determined by means of skin prick testing and specific IgE measurement. RESULTS: A high and increasing burden of food allergen and aeroallergen sensitization and allergic disease was noted across study time points; 76% of LEAP participants had at least 1 allergic disease at 60 months of age. There were no differences in allergic disease between LEAP groups. There were small differences in sensitization and reported allergic reactions for select tree nuts, with levels being higher in the LEAP consumption group. Significant resolution of eczema and sensitization to egg and milk occurred in LEAP participants and was not affected by peanut consumption. CONCLUSION: Early consumption of peanut in infants at high risk of peanut allergy is allergen specific and does not prevent the development of other allergic disease, sensitization to other food allergens and aeroallergens, or reported allergic reactions to tree nuts and sesame. Furthermore, peanut consumption does not hasten the resolution of eczema or egg allergy.


Assuntos
Alérgenos/imunologia , Arachis/imunologia , Dermatite Atópica/prevenção & controle , Hipersensibilidade Alimentar/prevenção & controle , Fenômenos Fisiológicos da Nutrição do Lactente/imunologia , Hipersensibilidade Respiratória/prevenção & controle , Pré-Escolar , Dermatite Atópica/etiologia , Dermatite Atópica/imunologia , Feminino , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/imunologia , Humanos , Lactente , Masculino , Fatores de Proteção , Hipersensibilidade Respiratória/etiologia , Hipersensibilidade Respiratória/imunologia , Fatores de Risco
5.
N Engl J Med ; 374(15): 1435-43, 2016 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-26942922

RESUMO

BACKGROUND: In a randomized trial, the early introduction of peanuts in infants at high risk for allergy was shown to prevent peanut allergy. In this follow-up study, we investigated whether the rate of peanut allergy remained low after 12 months of peanut avoidance among participants who had consumed peanuts during the primary trial (peanut-consumption group), as compared with those who had avoided peanuts (peanut-avoidance group). METHODS: At the end of the primary trial, we instructed all the participants to avoid peanuts for 12 months. The primary outcome was the percentage of participants with peanut allergy at the end of the 12-month period, when the participants were 72 months of age. RESULTS: We enrolled 556 of 628 eligible participants (88.5%) from the primary trial; 550 participants (98.9%) had complete primary-outcome data. The rate of adherence to avoidance in the follow-up study was high (90.4% in the peanut-avoidance group and 69.3% in the peanut-consumption group). Peanut allergy at 72 months was significantly more prevalent among participants in the peanut-avoidance group than among those in the peanut-consumption group (18.6% [52 of 280 participants] vs. 4.8% [13 of 270], P<0.001). Three new cases of allergy developed in each group, but after 12 months of avoidance there was no significant increase in the prevalence of allergy among participants in the consumption group (3.6% [10 of 274 participants] at 60 months and 4.8% [13 of 270] at 72 months, P=0.25). Fewer participants in the peanut-consumption group than in the peanut-avoidance group had high levels of Ara h2 (a component of peanut protein)-specific IgE and peanut-specific IgE; in addition, participants in the peanut-consumption group continued to have a higher level of peanut-specific IgG4 and a higher peanut-specific IgG4:IgE ratio. CONCLUSIONS: Among children at high risk for allergy in whom peanuts had been introduced in the first year of life and continued until 5 years of age, a 12-month period of peanut avoidance was not associated with an increase in the prevalence of peanut allergy. Longer-term effects are not known. (Funded by the National Institute of Allergy and Infectious Diseases and others; LEAP-On ClinicalTrials.gov number, NCT01366846.).


Assuntos
Arachis , Hipersensibilidade a Amendoim/imunologia , Arachis/imunologia , Pré-Escolar , Feminino , Seguimentos , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Lactente , Análise de Intenção de Tratamento , Masculino , Cooperação do Paciente , Hipersensibilidade a Amendoim/epidemiologia , Hipersensibilidade a Amendoim/prevenção & controle
6.
N Engl J Med ; 372(9): 803-13, 2015 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-25705822

RESUMO

BACKGROUND: The prevalence of peanut allergy among children in Western countries has doubled in the past 10 years, and peanut allergy is becoming apparent in Africa and Asia. We evaluated strategies of peanut consumption and avoidance to determine which strategy is most effective in preventing the development of peanut allergy in infants at high risk for the allergy. METHODS: We randomly assigned 640 infants with severe eczema, egg allergy, or both to consume or avoid peanuts until 60 months of age. Participants, who were at least 4 months but younger than 11 months of age at randomization, were assigned to separate study cohorts on the basis of preexisting sensitivity to peanut extract, which was determined with the use of a skin-prick test--one consisting of participants with no measurable wheal after testing and the other consisting of those with a wheal measuring 1 to 4 mm in diameter. The primary outcome, which was assessed independently in each cohort, was the proportion of participants with peanut allergy at 60 months of age. RESULTS: Among the 530 infants in the intention-to-treat population who initially had negative results on the skin-prick test, the prevalence of peanut allergy at 60 months of age was 13.7% in the avoidance group and 1.9% in the consumption group (P<0.001). Among the 98 participants in the intention-to-treat population who initially had positive test results, the prevalence of peanut allergy was 35.3% in the avoidance group and 10.6% in the consumption group (P=0.004). There was no significant between-group difference in the incidence of serious adverse events. Increases in levels of peanut-specific IgG4 antibody occurred predominantly in the consumption group; a greater percentage of participants in the avoidance group had elevated titers of peanut-specific IgE antibody. A larger wheal on the skin-prick test and a lower ratio of peanut-specific IgG4:IgE were associated with peanut allergy. CONCLUSIONS: The early introduction of peanuts significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy and modulated immune responses to peanuts. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00329784.).


Assuntos
Arachis , Dieta , Hipersensibilidade a Amendoim/prevenção & controle , Arachis/imunologia , Distribuição de Qui-Quadrado , Eczema/imunologia , Hipersensibilidade a Ovo/imunologia , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Lactente , Análise de Intenção de Tratamento , Masculino , Hipersensibilidade a Amendoim/epidemiologia , Hipersensibilidade a Amendoim/imunologia , Prevalência , Risco , Testes Cutâneos
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