RESUMO
BACKGROUND: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process. OBJECTIVE: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form. METHODS: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed. RESULTS: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form. CONCLUSION: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life.
Assuntos
Consenso , Técnica Delphi , Dessensibilização Imunológica , Hipersensibilidade Alimentar , Consentimento Livre e Esclarecido , Humanos , Dessensibilização Imunológica/métodos , Administração Oral , Hipersensibilidade Alimentar/terapia , Hipersensibilidade Alimentar/imunologiaRESUMO
BACKGROUND: Early detection of cognitive disability is challenging. We assessed the domain-specific, concurrent validity of the ages and stages questionnaire (ASQ-3) and the Bayley Scales of Infant and Toddler Development (BSID-III), and their ability to predict cognitive delay at school age. METHODS: Within a longitudinal birth cohort study, a nested cohort of children was assessed using ASQ-3 and BSID-III at 24 months, and at 5 years using the Kaufmann brief IQ test (KBIT). RESULTS: 278 children were assessed using BSID-III and ASQ-3 at 24-months; mean(SD) BW = 3445(506) grams, M:F ratio=52:48. ASQ-3 had reasonable predictive ability (AUROC, p value, sensitivity:specificity) of same domain delay for motor (0.630, p = 0.008, 50%:76.1%) and language (0.623, p = 0.010, 25%:99.5%) at 2 years, but poor ability to detect cognitive delay compared to BSID-III (0.587, p = 0.124, 20.7%/96.8%;). 204/278 children were assessed at 5 years. BSID-III language and cognition domains showed better correlation with verbal and nonverbal IQ (R = 0.435, p < 0.001 and 0.388, p < 0.001 respectively). Both assessments showed high specificity and low sensitivity for predicting delay at 5 years. CONCLUSIONS: The ASQ-3 cognitive domain showed poor concurrent validity with BSID-III cognitive score. Both ASQ-3 and BSID-III at 2 years poorly predict cognitive delay at 5 years. IMPACT: The ASQ-3 does not adequately detect cognitive delay or predict cognitive delay at 5 years, particularly for children with mild to moderate delay. The ASQ-3 shows reasonable concurrent validity with the motor and language subscales of the BSID-III. Neither early screening nor formal developmental testing demonstrated significant predictive validity to screen for cognitive delay at school age. This article highlights the need to analyse our existing model of using the ASQ-3 to screen for cognitive delay in children aged 2 years.
Assuntos
Desenvolvimento Infantil , Deficiências do Desenvolvimento , Lactente , Criança , Humanos , Deficiências do Desenvolvimento/diagnóstico , Estudos de Coortes , Inquéritos e Questionários , CogniçãoRESUMO
BACKGROUND: Skin barrier dysfunction is a key component of the pathogenesis of atopic dermatitis (AD). Recent research on barrier optimization to prevent AD has shown mixed results. The aim of this study was to assess the relationship between emollient bathing at 2 months and the trajectory of AD in the first 2 years of life in a large unselected observational birth cohort study. METHODS: The Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints Birth Cohort study enrolled 2183 infants. Variables extracted from the database related to early skincare, skin barrier function, parental history of atopy, and AD outcomes. Statistical analysis was performed to adjust for potential confounding variables. RESULTS: One thousand five hundred five children had data on AD status available at 6, 12, and 24 months. Prevalence of AD was 18.6% at 6 months, 15.2% at 12 months, and 16.5% at 24 months. Adjusted for potential confounding variables, the odds of AD at any point were higher among infants who had emollient baths at 2 months (OR (95% CI): 2.41 (1.56 to 3.72), p < .001). Following multivariable analysis, the odds of AD were higher among infants who had both emollient baths and frequent emollient application at 2 months, compared with infants who had neither (OR (95% CI) at 6 months 1.74 (1.18-2.58), p = .038), (OR (95% CI) at 12 months 2.59 (1.69-3.94), p < .001), (OR (95% CI) at 24 months 1.87 (1.21-2.90), p = .009). CONCLUSION: Early emollient bathing was associated with greater development of AD by 2 years of age in this population-based birth cohort study.
Assuntos
Dermatite Atópica , Lactente , Criança , Humanos , Dermatite Atópica/epidemiologia , Dermatite Atópica/prevenção & controle , Emolientes/uso terapêutico , Estudos de Coortes , Banhos , Coorte de NascimentoRESUMO
BACKGROUND: Peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; previously known as AR101) is a daily oral immunotherapy approved to mitigate allergic reactions after accidental peanut exposure in peanut-allergic individuals aged 4-17 years. OBJECTIVE: We sought to comprehensively summarize the PTAH safety profile for up to â¼2 years of treatment. METHODS: Safety and adverse event (AE) data from participants aged 4-17 years from 3 controlled, phase 3 and 2 open-label extension trials were pooled and assessed. RESULTS: Of the 944 individuals receiving ≥1 PTAH dose, median exposure was â¼49 weeks; most participants experienced ≥1 treatment-related AE (TRAE; n = 853; 90.4%). A total of 829 participants experienced TRAEs with a maximum severity of mild (497, 52.6%) or moderate (332, 35.2%); 24 participants (2.5%) experienced TRAEs graded as severe. Overall, 80 participants (9.5%) discontinued as a result of AEs; most experienced gastrointestinal symptoms and discontinued during the first 6 months. When adjusted for exposure, AEs and TRAEs occurred at a rate of 76.4 and 58.7 events per participant-year of exposure (PYE), respectively, during updosing; AEs and TRAEs decreased to 23.0 and 14.2, respectively, during 300 mg maintenance. Overall, exposure-adjusted rates of systemic allergic reactions were 0.12 events/PYE (mild), 0.11 events/PYE (moderate), and 0.01 events/PYE (severe [anaphylaxis]). CONCLUSION: The safety profile of PTAH was consistent across trials, manageable, and improved over time. AEs were predominantly mild to moderate, and all grades declined in frequency with continued treatment. These data can be used to facilitate shared decision-making discussions with patients and families considering treatment with PTAH.
Assuntos
Hipersensibilidade a Amendoim , Administração Oral , Adolescente , Alérgenos , Arachis/efeitos adversos , Criança , Dessensibilização Imunológica/efeitos adversos , Emolientes , Humanos , Hiperplasia , Hipersensibilidade a Amendoim/etiologia , Hipersensibilidade a Amendoim/terapia , PósRESUMO
Anaphylaxis is a rare side-effect of COVID-19 vaccines. To (a) provide direct advice and reassurance to certain persons with a history of anaphylaxis/complex allergy, in addition to that available in national guidelines, and (b) to provide a medically supervised vaccination, a specialist regional vaccine allergy clinic was established. The main objective was to determine if risk stratification through history can lead to safe COVID-19 vaccination for maximum population coverage. A focused history was taken to establish contraindications to giving COVID-19 vaccines. People who reported a high-risk allergy history were given a vaccine not containing the excipient thought to have directly caused previous anaphylaxis. All vaccines were monitored for 30 min after administration. A total of 206 people were vaccinated between 6 July 2021 and 31 August 2021; Comirnaty (Pfizer-BioNTech) (n = 34), and Janssen (n = 172). In total, 78% were women. Ninety-two people (45%) reported a high-risk allergy history. There were no cases of anaphylaxis. Three people developed urticaria and one of these also developed transient tachycardia. One vaccinee developed a pseudoseizure. Two of 208 people (<1%) referred during this time declined vaccination based on personal preference, despite the assessment of low clinical risk. In our experience, all vaccines with high-risk allergy histories were administered Pfizer BioNTech or Janssen Covid-19 vaccines uneventfully following screening based on allergy-focussed history. Our data support that drug allergy is not associated with a higher risk of vaccine-related anaphylaxis but may act to guide the administration of alternate vaccines to people with polyethylene glycol/polysorbate 80/trometamol allergies or anaphylaxis after the first dose.
Assuntos
Anafilaxia , Vacinas contra COVID-19 , COVID-19 , Vacinas , Anafilaxia/etiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Masculino , Medição de RiscoRESUMO
BACKGROUND: Atopic dermatitis (AD) is the most common chronic inflammatory skin condition in childhood. Most (50-60%) children with AD report sleep disturbance, which is secondary to itch, dry skin, inflammation, and abnormal circadian rhythm. Sleep is essential for brain development, learning, and growth. Sleep disruption in early life is associated with cognitive and psychological dysfunction in later life. The aim of this study is to describe in detail the sleep architecture of infants with early-onset atopic dermatitis (AD), compared to controls, by using EEG polysomnography, sleep actigraphy, and parental reporting. METHODS: This observational study will recruit six- to eight-month old infants with moderate to severe AD and age-matched control infants who do not have AD. At six-eight months diurnal sleep electroencephalography and polysomnography will be performed in our research center. Nocturnal sleep actigraphy will be performed at home for five consecutive nights at six-eight months and 12 months. Between six and 12 months, monthly questionnaires will capture data on quantitative sleep and parental sleep. Skin barrier and immune profiles will be captured at six-eight and 12 months. AD will be assessed using standardized severity assessment tools and treated according to protocol. A neurodevelopmental assessment will be performed at 18 months to assess cognition and behaviour. An estimated sample size of 50 participants in each group is required to power the primary outcome of disturbed macrostructure of sleep and secondary outcomes of disturbed microstructure of sleep, and disturbed parental sleep, assuming an attrition rate of 60%. Potential confounding factors which will be controlled for in the data analysis will include parental educational level, parental depression, feeding practice, and number of siblings. DISCUSSION: This study will provide a rich analysis of sleep in infants with AD in the first year of life using detailed electroencephalography, novel actigraphy techniques, and longitudinal parent-reported data. It may provide guidance on the optimal treatment of AD to prevent or reduce sleep disruption. TRIAL REGISTRATION: clinicaltrials.gov NCT05031754 , retrospectively registered on September 2nd, 2021.
Assuntos
Dermatite Atópica , Transtornos do Sono-Vigília , Actigrafia , Dermatite Atópica/complicações , Dermatite Atópica/diagnóstico , Humanos , Lactente , Polissonografia , Sono , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/etiologiaRESUMO
BACKGROUND: Venom-induced anaphylaxis (VIA) is a common, potentially life-threatening hypersensitivity reaction associated with (1) a specific symptom profile, 2) specific cofactors, and 3) specific management. Identifying the differences in phenotypes of anaphylaxis is crucial for future management guidelines and development of a personalized medicine approach. OBJECTIVE: This study aimed to evaluate the phenotype and risk factors of VIA. METHODS: Using data from the European Anaphylaxis Registry (12,874 cases), we identified 3,612 patients with VIA and analyzed their cases in comparison with sex- and age-matched anaphylaxis cases triggered by other elicitors (non-VIA cases [n = 3,605]). RESULTS: VIA more frequently involved more than 3 organ systems and was associated with cardiovascular symptoms. The absence of skin symptoms during anaphylaxis was correlated with baseline serum tryptase level and was associated with an increased risk of a severe reaction. Intramuscular or intravenous epinephrine was administered significantly less often in VIA, in particular, in patients without a history of anaphylaxis. A baseline serum tryptase level within the upper normal range (8-11.5 ng/mL) was more frequently associated with severe anaphylaxis. CONCLUSION: Using a large cohort of VIA cases, we have validated that patients with intermediate baseline serum tryptase levels (8-11 ng/mL) and without skin involvement have a higher risk of severe VIA. Patients receiving ß-blockers or angiotensin-converting enzyme inhibitors had a higher risk of developing severe cardiovascular symptoms (including cardiac arrest) in VIA and non-VIA cases. Patients experiencing VIA received epinephrine less frequently than did cases with non-VIA.
Assuntos
Anafilaxia/etiologia , Anafilaxia/fisiopatologia , Anafilaxia/terapia , Venenos de Artrópodes/efeitos adversos , Mordeduras e Picadas de Insetos/complicações , Adulto , Estudos de Casos e Controles , Criança , Estudos de Coortes , Europa (Continente) , Feminino , Humanos , Masculino , Fenótipo , Sistema de Registros , Fatores de RiscoRESUMO
BACKGROUND: Insect venom is the second most common cause of anaphylaxis outside of medical encounters. Stings cause over 20% of all anaphylactic deaths and 7% of anaphylaxis in children. To date, there have been no longitudinal studies of insect sting events or allergy in preschool children. METHODS: A prospective longitudinal nested observational study in the BASELINE Birth Cohort Study (n = 2137). Sting-related questions were asked at 6 and 12 months and 2 and 5 years. Skin prick testing (SPT) was performed at 2 and 5 years. SpIgE testing was performed on selected cases at 2 years. RESULTS: Seventy-seven children (6.8%) were stung by the age of 2. Of these, 25 (32.5%) reported adverse reactions (four systemic). Eleven (0.9%) had positive SPT at 2 years (eight bee, two wasp, one both). Four stung children had positive SPT. Two (one stung, one never stung) had positive spIgE to a venom component at 2 years. A total of 268 children (21.9%) were stung by 5 years, 144 (52.1%) reporting local reactions and none systemic. Four children (0.4%) had positive SPT at 5 years: one bee and three wasp. Of the 11 SPT-positive children at 2 years, none were still positive at 5 years. CONCLUSION: This is the first longitudinal study of the natural history of hymenoptera stings and allergy in preschool children. Hymenoptera venom allergy is less common in this cohort than in adults. Systemic reactions were not medically documented in this population, in keeping with previous literature. This study confirms the poor correlation of IgE sensitization to venom with sting allergy and does not support the common parental request to screen children for sting allergy.
Assuntos
Himenópteros/imunologia , Hipersensibilidade/etiologia , Mordeduras e Picadas de Insetos/epidemiologia , Animais , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Hipersensibilidade/epidemiologia , Imunoglobulina E/sangue , Lactente , Mordeduras e Picadas de Insetos/imunologia , Irlanda/epidemiologia , Estudos Longitudinais , Masculino , Estudos Prospectivos , Testes Cutâneos/estatística & dados numéricos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Many breastfed babies in Ireland receive formula supplementation within 24 hours of birth. We explored (a) impact of formula supplementation on the likelihood of developing cow's milk protein allergy (CMPA) and (b) current practice of formula supplementation (<24 hours) among mothers intending to breastfeed. METHOD: Fifty-five CMPA-diagnosed children, fed at <24 hours of age (breast only, formula only or breast with formula supplementation), were recruited, and 55 milk-tolerant age- and sex-matched controls were identified retrospectively in Cork University Maternity Hospital. Two logistic regressions (LoR) examined neonatal feed types on likelihood of developing CMPA while controlling for parental atopy and infant sex. Formula supplementation was then prospectively measured among a separate group of 179 breastfeeding mothers. Linear regression (LiR) analysis was used to examine the subjective and objective reasons for formula supplementation, in addition to examining pre-existing factors. RESULTS: Two LoR examined the infant groups: exclusively breastfed, exclusively formula-fed or breastfed with formula supplementation. The first LoR model which showed only formula supplementation was significant in prediction of development of CMPA (χ2 (3) = 25.74, P < .05), with 74% diagnostic accuracy when parental atopy and infant sex were controlled for. Breastfed infants given formula supplements were 7.03 (95% CI, 1.82-27.25) times more likely to exhibit CMPA than those who were exclusively breastfed. Formula supplementation was significant (OR 16.62, 95% CI 3.89-71.11), indicating that breastfed infants who were given formula supplements were 16 times more likely to exhibit CMPA than those who were exclusively bottle-fed. Exclusively formula-fed infants (odds ratio 0.42, 95% CI, 0.16-1.07) were not significantly more likely to exhibit CMPA than those who were exclusively breastfed in either model (P > .05). About 45.8% of breastfed infants (<24 hours) received supplemental formula. LiR investigated importance of the subjective and objective reasons, in predicting formula supplementation. This model was significant F(8,170) = 66.95, P < .05) explaining 75% of total variance. The subjective factors 'no latch' and 'mum unwell' were the strongest predictors (ß > .45). Objective factors and pre-existing factors had lower ß values with only mode of delivery and infant hypoglycaemia being significant. CONCLUSION: Breastfed babies are still being put at significantly increased risk of CMPA by receiving supplemental formula in the first 24 hours of life, despite the major predictors of supplementation being subjective and remediable in other ways. Mothers and healthcare providers should be better educated on the benefits of exclusive breastfeeding and resourced adequately to avoid unnecessary formula supplementation to reduce risk of development of CMPA.
Assuntos
Fórmulas Infantis , Hipersensibilidade a Leite/dietoterapia , Alérgenos/imunologia , Animais , Aleitamento Materno , Bovinos , Suplementos Nutricionais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/epidemiologia , Proteínas do Leite/imunologia , Estudos Retrospectivos , RiscoAssuntos
Hipersensibilidade Alimentar , Hipersensibilidade , Hipersensibilidade a Amendoim , Humanos , Lactente , Irlanda , Alérgenos , ArachisRESUMO
Background: Although animal studies show evidence for a role of vitamin D during brain development, data from human studies show conflicting signals. Objective: We aimed to explore associations between maternal and neonatal vitamin D status with childhood neurodevelopmental outcomes. Methods: Comprehensive clinical, demographic, and lifestyle data were collected prospectively in 734 maternal-infant dyads from the Cork BASELINE Birth Cohort Study. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were quantified at 15 weeks of gestation and in umbilical cord sera at birth via a CDC-accredited liquid chromatography-tandem mass spectrometry method. Children were assessed at age 5 y through the use of the Kaufman Brief Intelligence Test (2nd Edition, KBIT-2) and the Child Behaviour Checklist (CBCL). Linear regression was used to explore associations between 25(OH)D and neurodevelopmental outcomes. Results: 25(OH)D concentrations were <30 nmol/L in 15% of maternal and 45% of umbilical cord sera and <50 nmol/L in 42% of mothers and 80% of cords. At age 5 y, the mean ± SD KBIT-2 intelligence quotient (IQ) composite score was 104.6 ± 8.6; scores were 107.2 ± 10.0 in verbal and 99.8 ± 8.8 in nonverbal tasks. Developmental delay (scores <85) was seen in <3% of children across all domains. The mean ± SD CBCL total problem score was 21.3 ± 17.5; scores in the abnormal/clinical range for internal, external, and total problem scales were present in 12%, 4%, and 6% of participants, respectively. KBIT-2 and CBCL subscale scores at 5 y were not different between children exposed to low antenatal vitamin D status, either at 30 or 50 nmol/L 25(OH)D thresholds. Neither maternal nor cord 25(OH)D (per 10 nmol/L) were associated with KBIT-2 IQ composite scores [adjusted ß (95% CI): maternal -0.01 (-0.03, 0.02); cord 0.01 (-0.03, 0.04] or CBCL total problem scores [maternal 0.01 (-0.04, 0.05); cord 0.01 (-0.07, 0.09)]. Conclusion: In this well-characterized prospective maternal-infant cohort, we found no evidence that antenatal 25(OH)D concentrations are associated with neurodevelopmental outcomes at 5 y. The BASELINE Study was registered at www.clinicaltrials.gov as NCT01498965; the SCOPE Study was registered at http://www.anzctr.org.au as ACTRN12607000551493.
Assuntos
Desenvolvimento Infantil , Sangue Fetal/metabolismo , Inteligência , Complicações na Gravidez/sangue , Fenômenos Fisiológicos da Nutrição Pré-Natal , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Adulto , Pré-Escolar , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/etiologia , Feminino , Humanos , Lactente , Modelos Lineares , Masculino , Mães , Estado Nutricional , Gravidez , Complicações na Gravidez/epidemiologia , Estudos Prospectivos , Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologiaRESUMO
BACKGROUND: Early nutrition and adiposity have been linked to atopic dermatitis (AD) development. OBJECTIVE: We sought to describe risk factors for AD in the first year of life in infants participating in the Cork BASELINE birth cohort study (n = 1537). METHODS: Prospective data on early-life events, infant feeding, and nutritional and environmental exposures were collected at 15 weeks' gestation, birth, and 2, 6, and 12 months of age. Body composition was assessed by using air displacement plethysmography at day 2 and 2 months. The primary outcome, persistent AD, was determined if the U.K. Working Party Diagnostic Criteria were satisfied at both 6 and 12 months. RESULTS: At 6 and 12 months, the point prevalence of AD was 14.2% (99% CI, 10.5% to 17.8%) and 13.7% (99% CI, 10.3% to 17.6%), respectively; 7.5% (99% CI, 5.0% to 9.9%) of infants had AD at both 6 and 12 months of age. At hospital discharge, 35% of infants were exclusively breast-fed, decreasing to 14% by 2 months. Complementary feeding was commenced at a median of 19 weeks (interquartile range, 17-22 weeks; 19% at <17 weeks and 6% at ≥26 weeks). Median fat mass at day 2 was 0.35 kg (interquartile range, 0.25-0.48 kg). A parental history of atopic disease was self-reported by 43% of mothers and 34% of fathers. Risk factors for AD at 6 and 12 months were maternal atopy (adjusted odds ratio, 2.99; 99% CI, 1.35-6.59; P = .0004) and fat mass of the 80th percentile or greater at day 2 (adjusted odds ratio, 2.31; 99% CI, 1.02-2.25; P = .009). CONCLUSION: This is the first report of neonatal adiposity as a predictor of AD at 6 and 12 months of age in a well-characterized atopic disease-specific birth cohort.
Assuntos
Adiposidade , Dermatite Atópica/epidemiologia , Fenômenos Fisiológicos da Nutrição do Lactente , Adulto , Composição Corporal , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Mães , Fatores de RiscoRESUMO
BACKGROUND: Anaphylaxis has been increasing in recent years, with common triggers in infants being milk and eggs. Currently, the mainstay of treatment for milk and/or egg allergy is strict avoidance. Recently, new therapies have emerged including stepwise introduction of allergens via a ladder approach. The suitability of infants for the ladders is debated. OBJECTIVE: This study aims to focus on the use of food ladders in children with anaphylaxis to egg or milk. METHODS: Retrospective review of pediatric patients diagnosed with immunoglobulin E-mediated milk and/or egg allergy between 2011 and 2021. Inclusion and exclusion criteria were applied. Anaphylaxis was defined as per the World Allergy Organization-amended criteria 2020. Data analysis utilized SPSS Version 28. RESULTS: We reviewed 1,552 patient charts, and excluded 1,094, leaving a total sample size of 458. Seventy infants had anaphylaxis at diagnosis (milk n = 36; egg n = 34). A range of 77.8% to 85.2% of infants with anaphylaxis successfully completed the ladder, 88.9% to 92.9% without anaphylaxis were successful. Children who successfully completed the ladder did so at similar rates. A range of 20.6% to 50% children presenting with anaphylaxis at diagnosis experienced allergic symptoms during treatment, compared with 17.3% to 40.7% without anaphylaxis. Reactions were mild, mostly cutaneous and not requiring medical attention. Patients experiencing allergic symptoms while on the ladder were less likely to successfully complete treatment. CONCLUSIONS: Milk and egg ladders are a safe and effective way of inducing tolerance in infants, including those with a history of anaphylaxis at diagnosis. There are no obvious predictors for who will experience allergic reactions while on the ladder; however, these children are less likely to complete the ladder, so parents should be educated in management of mild allergic reactions at home.
Assuntos
Anafilaxia , Hipersensibilidade a Ovo , Hipersensibilidade a Leite , Humanos , Anafilaxia/diagnóstico , Hipersensibilidade a Ovo/imunologia , Hipersensibilidade a Ovo/terapia , Hipersensibilidade a Leite/dietoterapia , Hipersensibilidade a Leite/imunologia , Hipersensibilidade a Leite/terapia , Hipersensibilidade a Leite/diagnóstico , Estudos Retrospectivos , Lactente , Feminino , Masculino , Pré-Escolar , Imunoglobulina E/sangue , Alérgenos/imunologia , Criança , Animais , Leite/efeitos adversos , Leite/imunologia , Ovos/efeitos adversosAssuntos
Promoção da Saúde/métodos , Hipersensibilidade a Amendoim/prevenção & controle , Pré-Escolar , Dermatite Atópica/complicações , Dermatite Atópica/diagnóstico , Dermatite Atópica/epidemiologia , Hipersensibilidade a Ovo/complicações , Hipersensibilidade a Ovo/diagnóstico , Hipersensibilidade a Ovo/epidemiologia , Humanos , Incidência , Lactente , Irlanda/epidemiologia , Hipersensibilidade a Amendoim/complicações , Hipersensibilidade a Amendoim/epidemiologia , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: Examine the association between alcohol consumption before and during pregnancy and neurodevelopmental outcomes in the offspring at two and five years. STUDY DESIGN: Retrospective analysis of a prospective longitudinal cohort; SCOPE-BASELINE. Data on pre-conception and prenatal alcohol consumption were obtained at 15 weeks' gestation and categorised as abstinent, occasional-low (1-7units/week) and moderate-heavy (≥8units/week). Binge drinking was defined as ≥6 units/session. Outcome measures (Child Behaviour Checklist and Kaufman Brief Intelligence Test) were obtained at two and five years. Linear regression examined an alcohol consumption and Child Behaviour Checklist and Kaufman Brief Intelligence Test relationship, adjusting for several potential confounders. RESULTS: Data on alcohol consumption was available for 1,507 women. Adjusted linear regression suggested few associations: pre-pregnancy occasional-low alcohol consumption was associated with lower log externalizing Child Behaviour Checklist scores (-0.264, 95% CI: -0.009, -0.520), while pre-pregnancy moderate-high levels of alcohol consumption was associated with lower Kaufman Brief Intelligence Test verbal standard scores (-0.034, 95% CI: -0.001, -0.068) and composite IQ scores (-0.028, 95% CI: -0.056, -0.0004) at five-years. In the first trimester, moderate-high levels of alcohol consumption was associated with lower internalizing Child Behaviour Checklist scores at two-years (-0.252, 95% CI: -0.074, -0.430). No significant associations were observed between number of binge episodes pre-pregnancy or binge drinking in the first trimester and Child Behaviour Checklist or Kaufman Brief Intelligence Test. CONCLUSIONS: We did not find strong evidence of associations between pre-pregnancy and early pregnancy maternal alcohol consumption and adverse neurodevelopmental outcomes at age two and five years overall. Further research examining alcohol consumption (including binge drinking) beyond 15 weeks' gestation and subsequent neurodevelopmental outcomes is needed to examine the potential effect of alcohol consumption in later pregnancy.
Assuntos
Consumo Excessivo de Bebidas Alcoólicas , Efeitos Tardios da Exposição Pré-Natal , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo Excessivo de Bebidas Alcoólicas/complicações , Criança , Pré-Escolar , Etanol , Feminino , Humanos , Testes Neuropsicológicos , Gravidez , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: Food allergy quality of life (FAQL) is impaired in children with peanut allergy. Food Allergy Quality of Life Questionnaires (FAQLQs) provide disease-specific insight into the burden of peanut allergy and potential FAQL changes after peanut immunotherapy. OBJECTIVE: To examine FAQL changes in children after treatment with epicutaneous immunotherapy for peanut allergy (250 µg, daily epicutaneous peanut protein; DBV712 250 µg). METHODS: FAQL was prospectively measured using the FAQLQ parent proxy form (Food Allergy Quality of Life Questionnaire-Parent Proxy Form [FAQLQ-PF], for children aged ≤12 years) and child form (Food Allergy Quality of Life Questionnaire-Child Form [FAQLQ-CF], child rated if aged ≥8 years) during the 12-month double-blind, randomized, controlled Peanut EPIT Efficacy and Safety Study (PEPITES) trial and the initial 12 months of the open-label PEPITES Open Label Extension Study (PEOPLE) follow-up study. Data were analyzed for between-group differences after treatment unblinding. RESULTS: FAQLQs from placebo participants (FAQLQ-PF: 96; FAQLQ-CF: 47) and treatment group participants (FAQLQ-PF: 209; FAQLQ-CF: 105) were analyzed. Twenty-four-month global FAQL scores (FAQLQ-PF/FAQLQ-CF) were significantly improved in the treatment group versus the placebo group (least squares mean, 0.34, P = .008, and 0.46, P = .023, respectively). At 24 months, there was significant FAQLQ-PF score improvement in participants initially randomized to treatment who met the efficacy primary end point (n = 74; least squares mean, 0.55; P < .001) and in participants with any eliciting dose increase (n = 127; least squares mean, 0.66; P < .001). FAQLQ-PF improvements were observed in social dietary limitations (P = .002), food-related anxiety (P = .029), and emotional impact (P = .048) domains. FAQLQ-CF improvements were observed in risk of accidental exposure (P = .002) and allergen avoidance (P = .04) domains. Nearly all outcomes met a nontreatment context minimal clinically important difference previously cited for FAQLQ. CONCLUSIONS: Epicutaneous immunotherapy treatment was observed to be associated with significant global and domain-specific FAQL improvement (FAQLQ-PF/FAQLQ-CF), largely driven by increases in eliciting dose, in children with peanut allergy.
Assuntos
Hipersensibilidade Alimentar , Hipersensibilidade a Amendoim , Alérgenos , Criança , Dessensibilização Imunológica , Seguimentos , Humanos , Imunoterapia , Hipersensibilidade a Amendoim/terapia , Qualidade de VidaRESUMO
BACKGROUND: The randomized, controlled PALISADE trial demonstrated the benefit of daily oral immunotherapy with Peanut (Arachis Hypogaea) allergen powder-dnfp (PTAH, formerly AR101) in peanut-allergic children and adolescents. OBJECTIVE: ARC004, the open-label follow-on study to PALISADE, used 5 dosing cohorts to explore PTAH treatment beyond 1 year and alternative dosing regimens in peanut-allergic individuals. METHODS: Active arm (PTAH-continuing) PALISADE participants who tolerated 300-mg peanut protein at the exit double-blind placebo-controlled food challenge and placebo arm (PTAH-naive) participants could enter ARC004. PTAH-continuing participants were assigned to receive daily (cohorts 1 and 3A) or non-daily (cohorts 2, 3B, and 3C) dosing regimens; PTAH-naive participants were built up to 300 mg/d PTAH, followed by maintenance dosing. At study completion, participants underwent an exit double-blind placebo-controlled food challenge with doses up to 2000 mg peanut protein. Data were assessed using descriptive statistics. RESULTS: Overall, 358 (87.5%) eligible participants (4-17 years) entered ARC004 (PTAH-continuing, n = 256; PTAH-naive, n = 102). Among PTAH-continuing participants, exposure-adjusted adverse event rates were 12.94 to 17.54/participant-year and 25.95 to 42.49/participant-year in daily and non-daily dosing cohorts, respectively; most participants (83%) experienced mild or moderate adverse events. Daily dosing cohorts appeared to have higher desensitization rates than non-daily dosing cohorts. Of all PTAH-continuing cohorts, cohort 3A had the longest daily dosing duration and the highest desensitization rates. Changes in immune markers with PTAH continuation demonstrated ongoing immunomodulation. Outcomes in PTAH-naive participants mirrored those of the PALISADE active arm. CONCLUSIONS: Continued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment.
Assuntos
Hipersensibilidade a Amendoim , Administração Oral , Adolescente , Alérgenos , Arachis , Criança , Dessensibilização Imunológica , Método Duplo-Cego , Humanos , Hipersensibilidade a Amendoim/terapiaRESUMO
Cytokines can affect the quantity and class of allergen-specific immunoglobulins through the T cell polarization that accompanies atopy. Antigen-specific IgG subclasses and IgE antibodies were compared with intracellular T cell cytokine changes to sensitizing antigens in 23 children with multiple food allergies and 20 healthy controls. Allergic children showed higher levels of total and food-specific IgE, IgG1 and IgG4 to peanut, milk and egg than non-atopic children or adults, coinciding with a TH2 cytokine response to sensitizing antigens. IgG1 and IgG4 antibodies specific to milk and egg and peanut protein were elevated relative to age-matched healthy children (p Assuntos
Hipersensibilidade Alimentar/imunologia
, Imunoglobulina G/sangue
, Interferon gama/biossíntese
, Interleucina-4/biossíntese
, Linfócitos T/metabolismo
, Alérgenos/imunologia
, Animais
, Antígenos CD4/biossíntese
, Criança
, Pré-Escolar
, Proteínas do Ovo/efeitos adversos
, Proteínas do Ovo/imunologia
, Hipersensibilidade Alimentar/sangue
, Humanos
, Imunidade Humoral
, Interferon gama/genética
, Interferon gama/metabolismo
, Interleucina-4/genética
, Interleucina-4/metabolismo
, Antígenos Comuns de Leucócito/biossíntese
, Ativação Linfocitária
, Leite/efeitos adversos
, Leite/imunologia
, Linfócitos T/imunologia
, Linfócitos T/patologia
, Equilíbrio Th1-Th2
RESUMO
BACKGROUND: Peanut allergy is the leading cause of food-related anaphylaxis. Current management options can negatively affect food allergy-related quality of life. We aimed to investigate the efficacy of an investigational oral biologic drug (AR101). METHODS: The AR101 Trial in Europe Measuring Oral Immunotherapy Success in peanut-allergic children (ARTEMIS) trial was a multicentre, double-blind, randomised, placebo-controlled phase 3 trial done at 18 hospitals in Ireland, France, Germany, Italy, Spain, Sweden, and the UK. Children and adolescents with peanut allergy, aged 4-17 years, who developed dose-limiting symptoms to 300 mg or less peanut protein (equivalent to approximately one peanut kernel) during a double-blind placebo-controlled food challenge test at study entry were enrolled. Participants were randomly assigned (3:1) to receive daily doses of either AR101 oral immunotherapy (AR101 group) or a taste-masked placebo (placebo group). All participants, investigators, and care providers were masked to treatment allocation until the study was completed. Doses were increased every 2 weeks over 6 months until a dose of 300 mg was reached and maintained for 3 months. The primary endpoint was the proportion of participants in the intention-to-treat or safety population (defined as those participants who had been randomly assigned and had received at least one dose of the assigned drug) who could consume a single dose of 1000 mg (cumulative dose 2043 mg) peanut protein without developing dose-limiting allergic symptoms at an exit double-blind placebo-controlled food challenge after 9 months of treatment. Additional endpoints included safety (ie, the frequency and severity of adverse events) and changes in food allergy-related quality of life, assessed by use of age-appropriate Food Allergy Quality of Life Questionnaires (FAQLQs) and the Food Allergy Independent Measure (FAIM). The study is registered with ClinicalTrials.gov, NCT03201003, and is completed. FINDINGS: Between June 12, 2017, and Feb 15, 2018, 227 patients were screened, of whom 175 were randomly assigned to the AR101 group (n=132) and the placebo group (n=43). All primary and secondary endpoints were met. 77 (58%) of 132 participants in the AR101 group tolerated 1000 mg peanut protein at the exit food challenge versus one (2%) of 43 participants in the placebo group (AR101-placebo treatment difference 56·0% [95% CI 44·1-65·2], p<0·0001). Adverse events were reported by almost all participants. The maximum severity of adverse events reported was mild or moderate for most participants who received AR101 (mild, 66 [50%] of 132 participants; moderate, 63 [48%]; and severe, one [1%]) or placebo (mild, 24 [56%] of 43 participants; moderate, 18 [42%]; severe, none). Participants aged 8-12 years in the AR101 group reported improvements that exceeded the minimum clinically important difference between the two groups across all FAQLQ domains. Additionally, participants in the AR101 group and their caregivers reported improvements that exceeded the minimum clinically important difference in FAIM domains related to the perceived likelihood and outcomes of a severe allergic reaction. INTERPRETATION: AR101 oral immunotherapy treatment led to rapid desensitisation to peanut protein, with a predictable safety profile that improved with treatment, and an associated improvement in self-reported and caregiver-reported food allergy-related quality of life. These patient-oriented outcomes provide invaluable data to help physicians, patients, and caregivers make informed, shared decisions on the management of peanut allergy. FUNDING: Aimmune Therapeutics.