Marnie Robinson

Administration of a probiotic with peanut oral immunotherapy: A randomized trial

BACKGROUND Coadministration of a bacterial adjuvant with oral immunotherapy (OIT) has been suggested as a potential treatment for food allergy. OBJECTIVE To evaluate a combined therapy comprising a probiotic together with peanut OIT. METHODS We performed a double-blind, placebo-controlled randomized trial of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 and peanut OIT (probiotic and peanut oral immunotherapy [PPOIT]) in children (1-10 years) with peanut allergy. The primary outcome was induction of sustained unresponsiveness 2 to 5 weeks after discontinuation of treatment (referred to as possible sustained unresponsiveness). Secondary outcomes were desensitization, peanut skin prick test, and specific IgE and specific IgG4 measurements. RESULTS Sixty-two children were randomized and stratified by age (≤5 and >5 years) and peanut skin test wheal size (≤10 and >10 mm); 56 reached the trials end. Baseline demographics were similar across groups. Possible sustained unresponsiveness was achieved in 82.1% receiving PPOIT and 3.6% receiving placebo (P < .001). Nine children need to be treated for 7 to achieve sustained unresponsiveness (number needed to treat, 1.27; 95% CI, 1.06-1.59). Of the subjects, 89.7% receiving PPOIT and 7.1% receiving placebo were desensitized (P < .001). PPOIT was associated with reduced peanut skin prick test responses and peanut-specific IgE levels and increased peanut-specific IgG4 levels (all P < .001). PPOIT-treated participants reported a greater number of adverse events, mostly with maintenance home dosing. CONCLUSION This is the first randomized placebo-controlled trial evaluating the novel coadministration of a probiotic and peanut OIT and assessing sustained unresponsiveness in children with peanut allergy. PPOIT was effective in inducing possible sustained unresponsiveness and immune changes that suggest modulation of the peanut-specific immune response. Further work is required to confirm sustained unresponsiveness after a longer period of secondary peanut elimination and to clarify the relative contributions of probiotics versus OIT.

Increasing the accuracy of peanut allergy diagnosis by using Ara h 2

BACKGROUND Measurement of whole peanut-specific IgE (sIgE) is often used to confirm sensitization but does not reliably predict allergy. Ara h 2 is the dominant peanut allergen detected in 90% to 100% of patients with peanut allergy and could help improve diagnosis. OBJECTIVES We sought to determine whether Ara h 2 testing might improve the accuracy of diagnosing peanut allergy and therefore circumvent the need for an oral food challenge (OFC). METHODS Infants from the population-based HealthNuts study underwent skin prick tests to determine peanut sensitization and subsequently underwent a peanut OFC to confirm allergy status. In a stratified random sample of 200 infants (100 with peanut allergy and 100 with peanut tolerance), whole peanut sIgE and Ara h 2 sIgE levels were quantified by using fluorescence enzyme immunoassay. RESULTS By using the previously published 95% positive predictive value of 15 kU(A)/L for whole peanut sIgE, a corresponding specificity of 98% (95% CI, 93% to 100%) was found in this study cohort. At the equivalent specificity of 98%, the sensitivity of Ara h 2 sIgE is 60% (95% CI, 50% to 70%), correctly identifying 60% of subjects with true peanut allergy compared with only 26% correctly identified by using whole peanut sIgE. We report that when using a combined approach of plasma sIgE testing for whole peanut followed by Ara h 2 for the diagnosis of peanut allergy, the number of OFCs required is reduced by almost two thirds. CONCLUSION Ara h 2 plasma sIgE test levels provide higher diagnostic accuracy than whole peanut plasma sIgE levels and could be considered a new diagnostic tool to distinguish peanut allergy from peanut tolerance, which might reduce the need for an OFC.

Vitamin D insufficiency is associated with challenge-proven food allergy in infants

BACKGROUND Epidemiological evidence has shown that pediatric food allergy is more prevalent in regions further from the equator, suggesting that vitamin D insufficiency may play a role in this disease. OBJECTIVE To investigate the role of vitamin D status in infantile food allergy. METHODS A population sample of 5276 one-year-old infants underwent skin prick testing to peanut, egg, sesame, and cows milk or shrimp. All those with a detectable wheal and a random sample of participants with negative skin prick test results attended a hospital-based food challenge clinic. Blood samples were available for 577 infants (344 with challenge-proven food allergy, 74 sensitized but tolerant to food challenge, 159 negative on skin prick test and food challenge). Serum 25-hydroxyvitamin D levels were measured by using liquid chromatography tandem mass spectrometry. Associations between serum 25-hydroxyvitamin D and food allergy were examined by using multiple logistic regression, adjusting for potential risk and confounding factors. RESULTS Infants of Australian-born parents, but not of parents born overseas, with vitamin D insufficiency (≤50 nmol/L) were more likely to be peanut (adjusted odds ratio [aOR], 11.51; 95% CI, 2.01-65.79; P=.006) and/or egg (aOR, 3.79; 95% CI, 1.19-12.08; P=.025) allergic than were those with adequate vitamin D levels independent of eczema status. Among those with Australian-born parents, infants with vitamin D insufficiency were more likely to have multiple food allergies (≥2) rather than a single food allergy (aOR, 10.48; 95% CI, 1.60-68.61 vs aOR, 1.82; 95% CI, 0.38-8.77, respectively). CONCLUSIONS These results provide the first direct evidence that vitamin D sufficiency may be an important protective factor for food allergy in the first year of life.

Magnetic resonance imaging findings in a population-based cohort of children with cerebral palsy.

The purpose of this study was to investigate the frequency and spectrum of magnetic resonance imaging (MRI) abnormalities in a population of children with cerebral palsy (CP) who were born in the years 2000 and 2001 in Victoria, Australia. In 2000 and 2001, 221 children (126 males, 95 females; mean age 6y [SD 7mo], range 5–7y) with CP, excluding those with CP due to postneonatal causes (6% of all cases), were identified through the Victorian Cerebral Palsy Register. All medical records were systematically reviewed and all available brain imaging was comprehensively evaluated by a single senior MRI radiologist. MRI was available for 154 (70%) individuals and abnormalities were identified in 129 (84%). The study group comprised 88% with a spastic motor type CP; the distribution was hemiplegia in 33.5%, diplegia in 28.5%, and quadriplegia in 37.6% of children. Overall, pathological findings were most likely to be identified in children with spastic hemiplegia (92%) and spastic quadriplegia (84%). Abnormalities were less likely to be identified in non‐spastic motor types (72%) and spastic diplegia (52%). The most common abnormalities identified on MRI were periventricular white matter injury (31%), focal ischaemic/haemorrhagic lesions (16%), diffuse encephalopathy (14%), and brain malformations (12%). Dual findings were seen in 3% of patients. This is the first study to document comprehensively the neuroimaging findings of all children identified with CP born over a consecutive 24‐month period in a large geographical area.

The Natural History and Clinical Predictors Of Egg Allergy In The First 2 Years Of Life: A Prospective, Population-Based, Cohort Study

BACKGROUND There is a paucity of data examining the natural history of and risk factors for egg allergy persistence, the most common IgE-mediated food allergy in infants. OBJECTIVE We aimed to assess the natural history of egg allergy and identify clinical predictors for persistent egg allergy in a population-based cohort. METHODS The HealthNuts study is a prospective, population-based cohort study of 5276 infants who underwent skin prick tests to 4 allergens, including egg. Infants with a detectable wheal were offered hospital-based oral food challenges (OFCs) to egg, irrespective of skin prick test wheal sizes. Infants with challenge-confirmed raw egg allergy were offered baked egg OFCs at age 1 year and follow-up at age 2 years, with repeat OFCs to raw egg. RESULTS One hundred forty infants with challenge-confirmed egg allergy at age 1 year participated in the follow-up. Egg allergy resolved in 66 (47%) infants (95% CI, 37% to 56%) by 2 years of age; however, resolution was lower in children with baked egg allergy at age 1 year compared with baked egg tolerance (13% and 56%, respectively; adjusted odds ratio, 5.27; 95% CI, 1.36-20.50; P = .02). In the subgroup of infants who were tolerant to baked egg at age 1 year, frequent ingestion of baked egg (≥5 times per month) compared with infrequent ingestion (0-4 times per month) increased the likelihood of tolerance (adjusted odds ratio, 3.52; 95% CI, 1.38-8.98; P = .009). Mutation in the filaggrin gene was not associated with the resolution of either egg allergy or egg sensitization at age 2 years. CONCLUSION Phenotyping of egg allergy (baked egg tolerant vs allergic) should be considered in the management of this allergy because it has prognostic implications and eases dietary restrictions. Randomized controlled trials for egg oral immunotherapy should consider stratifying at baseline by the baked egg subphenotype to account for the differential rate of tolerance development.

Doctor – How do I use my EpiPen?

Parents and children who have been prescribed an Epipen are often unable to demonstrate its correct administration. One contributory factor may be that doctors are unfamiliar with the EpiPen and are unable to demonstrate the correct administration of the pen to the family. The aim of this study was to determine the rate of correct EpiPen demonstration by junior and Senior Medical Staff at a major tertiary paediatric Hospital. Junior and Senior medical staff were scored on their ability to correctly use the EpiPen trainer. A 6 step scoring system was used. One‐hundred doctors were recruited (Residents n = 31, Senior Residents n = 39, Fellow/Consultants n = 30). Junior and Senior Medical staff had similar scores for EpiPen demonstration, the number that needed to read the EpiPen instructions prior to use and the frequancy of accidental self‐injection into the thumb. Only two doctors (2%) demonstrated all 6 administration steps correctly. The most frequent errors made were not holding the pen in place for >5 seconds (57%), failure to apply pressure to activate (21%), and self‐injection into the thumb (16%). Ninety five doctors needed to read the instructions, and of these, only 39 (41%) then proceeded to correctly demonstrate the remaining 5 steps. Forty‐five doctors had previously dispensed an EpiPen, but only three demonstrated its use to parents/children with a trainer. The majority of doctors do not know how to use an Epipen and are unable to provide appropriate education to parents/children. In 37% of cases, the demonstration would not have delivered adrenaline to a patient.

Environmental and demographic risk factors for egg allergy in a population-based study of infants

Although egg allergy is the most common food allergy in infants and young children, risk factors for egg allergy remain largely unknown. This study examined the relationship between environmental and demographic factors and egg allergy in a population‐based infant cohort.

Predetermined challenge eligibility and cessation criteria for oral food challenges in the HealthNuts population-based study of infants.

epinephrine being delivered intramuscularly, the concern is that it might. Needle lengths of EAIs have already been cited as potentially inadequate to reliably deliver epinephrine to the muscle bed. Any amount of unexpected recoil that occurs while using a real EAI during an emergency might further reduce the likelihood of successful intramuscular administration. On the basis of this pilot study, it might be prudent for practitioners to inform patients that there are indeed differences with regard to how much force is required to activate different brands of EAIs, as well as differences in recoil generated. This might be of particular importance for those patients or providers who have been using one brand of EAI exclusively and then switch to a different brand of EAI. Encouraging patients to practice with real expired EAIs on tissue simulants, such as an orange, might also be beneficial. Regardless of the brand of EAI used, providers should instruct patients to firmly grasp the device and to continually depress the EAI into the thigh after activation occurs. This compression might also help displace subcutaneous fat and reduce the distance to muscle in some patients, potentially increasing the likelihood of intramuscular administration of epinephrine.

The prevalence and socio-demographic risk factors of clinical eczema in infancy: a population-based observational study.

Socio‐demographic predictors for the development of clinically observed, infantile eczema have not been formally examined in a large population‐based study. Few studies of eczema risk factors have included current, objective eczema outcomes as well as parent‐reported history.

Long-term clinical and immunological effects of probiotic and peanut oral immunotherapy after treatment cessation: 4-year follow-up of a randomised, double-blind, placebo-controlled trial

BACKGROUND Oral immunotherapy has attracted much interest as a potential treatment for food allergy, yet little is known about its long-term effects. We aimed to assess long-term outcomes in participants who completed a randomised, double-blind, placebo-controlled trial of combined probiotic and peanut oral immunotherapy (PPOIT), which was previously shown to induce desensitisation and 2-week sustained unresponsiveness. METHODS All participants who completed the PPOIT randomised trial were eligible to participate in this follow-up study 4 years after treatment cessation. Peanut intake and adverse reactions to peanut in the 4 years after treatment cessation were systematically documented with a structured questionnaire administered by allergy nurses. Additionally, participants were invited to undergo peanut skin prick tests, measurement of peanut sIgE and sIgG4 concentrations, and double-blind placebo-controlled peanut challenge to assess 8-week sustained unresponsiveness. FINDINGS 48 (86%) of 56 eligible participants were enrolled in the follow-up study. Mean time since stopping treatment was 4·2 years in both PPOIT (SD 0·6) and placebo (SD 0·7) participants. Participants from the PPOIT group were significantly more likely than those from the placebo group to have continued eating peanut (16 [67%] of 24 vs one [4%] of 24; absolute difference 63% [95% CI 42-83], p=0·001; number needed to treat 1·6 [95% CI 1·2-2·4]). Four PPOIT-treated participants and six placebo participants reported allergic reactions to peanut after intentional or accidental intake since stopping treatment, but none had anaphylaxis. PPOIT-treated participants had smaller wheals in peanut skin prick test (mean 8·1 mm [SD 7·7] vs 13·3 mm [7·6]; absolute difference -5·2 mm [95% CI -10·3 to 0·0]; age-adjusted and sex-adjusted p=0·035) and significantly higher peanut sIgG4:sIgE ratios than placebo participants (geometric mean 67·3 [95% CI 10·3-440·0] vs 5·2 [1·2-21·8]; p=0·031). Seven (58%) of 12 participants from the PPOIT group attained 8-week sustained unresponsiveness, compared with one (7%) of 15 participants from the placebo group (absolute difference 52% [95% CI 21-82), p=0·012; number needed to treat 1·9 [95% CI 1·2-4·8]). INTERPRETATION PPOIT provides long-lasting clinical benefit and persistent suppression of the allergic immune response to peanut. FUNDING Murdoch Childrens Research Institute and Australian Food Allergy Foundation.