Pamela E. Martin

Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants

BACKGROUND Several indicators suggest that food allergy in infants is common and possibly increasing. Few studies have used oral food challenge to measure this phenomenon at the population level. OBJECTIVE To measure the prevalence of common IgE-mediated childhood food allergies in a population-based sample of 12-month-old infants by using predetermined food challenge criteria to measure outcomes. METHODS A sampling frame was used to select recruitment areas to attain a representative population base. Recruitment occurred at childhood immunization sessions in Melbourne, Australia. Infants underwent skin prick testing, and those with any sensitization (wheal size ≥ 1 mm) to 1 or more foods (raw egg, peanut, sesame, shellfish, or cows milk) were invited to attend an allergy research clinic. Those who registered a wheal size ≥ 1 mm to raw egg, peanut, or sesame underwent oral food challenge. RESULTS Amongst 2848 infants (73% participation rate), the prevalence of any sensitization to peanut was 8.9% (95% CI, 7.9-10.0); raw egg white, 16.5% (95% CI, 15.1-17.9); sesame, 2.5% (95% CI, 2.0-3.1); cows milk, 5.6% (95% CI, 3.2-8.0); and shellfish, 0.9% (95% CI, 0.6-1.5). The prevalence of challenge-proven peanut allergy was 3.0% (95% CI, 2.4-3.8); raw egg allergy, 8.9% (95% CI, 7.8-10.0); and sesame allergy, 0.8% (95% CI, 0.5-1.1). Oral food challenges to cows milk and shellfish were not performed. Of those with raw egg allergy, 80.3% could tolerate baked egg. CONCLUSION More than 10% of 1-year-old infants had challenge-proven IgE-mediated food allergy to one of the common allergenic foods of infancy. The high prevalence of allergic disease in Australia requires further investigation and may be related to modifiable environmental factors.

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.

An update on epidemiology of anaphylaxis in children and adults

Purpose of reviewThe purpose of the present review is to describe the epidemiology of food-induced, medication-induced, drug-induced, and insect sting-induced anaphylaxis; to summarize recent changes in the incidence of anaphylaxis internationally; and to discuss recent insights into potential risk factors for anaphylaxis. Recent findingsRecent studies confirm that the incidence of anaphylaxis, particularly food-induced anaphylaxis, is increasing world-wide. The rise in anaphylaxis incidence appears most pronounced in children under the age of 5 years, which is also the age group most at risk of hospitalization for food-induced anaphylaxis. Identification of factors that may increase the risk of episodes of anaphylaxis remains an important research priority. Recently, two large cohort studies using data from electronic medical records confirmed that individuals with asthma are at higher risk of anaphylaxis and those with severe asthma have the highest risk of all. With respect to modifiable lifestyle factors, several studies have demonstrated a link between latitude and anaphylaxis, with areas with less year-round sunlight reporting a higher prevalence of food-induced anaphylaxis. SummaryReports of an increasing incidence of anaphylaxis internationally highlight the need for identification of modifiable risk factors for anaphylaxis. Emerging evidence suggests that low vitamin D levels may be associated with risk of anaphylaxis and food allergy; however, further studies are required to confirm this.

The HealthNuts population-based study of paediatric food allergy: validity, safety and acceptability

Background The incidence of hospital admissions for food allergy‐related anaphylaxis in Australia has increased, in line with world‐wide trends. However, a valid measure of food allergy prevalence and risk factor data from a population‐based study is still lacking.

Which infants with eczema are at risk of food allergy? Results from a population‐based cohort

The relationship between early onset eczema and food allergy among infants has never been examined in a population‐based sample using the gold standard for diagnosis, oral food challenge.

Childhood eczema and rhinitis predict atopic but not nonatopic adult asthma: A prospective cohort study over 4 decades

BACKGROUND The evidence on whether the atopic march observed in childhood (ie, the progression from eczema to allergic rhinitis and asthma) extends to adulthood is sparse, and there is no evidence on whether the progression leads to a specific phenotype of asthma. OBJECTIVE We sought to assess whether childhood eczema and rhinitis are risk factors for specific phenotypes of adult asthma. METHODS Participants of the Tasmanian Longitudinal Health Study recruited in 1968 (age range, 6.0-7.0 years) were followed up at age 44 years. The risk of current atopic or nonatopic asthma in middle age characterized by sensitization to aeroallergens given childhood eczema, rhinitis, or both was calculated by using multinomial logistic regression. RESULTS No association was found between childhood eczema or rhinitis and nonatopic adult asthma. In contrast, childhood eczema and rhinitis in combination predicted both new-onset atopic asthma by middle age (adjusted multinomial odds ratio [aMOR], 6.3; 95% CI, 1.7-23.2) and the persistence of childhood asthma to adult atopic asthma (aMOR, 11.7; 95% CI, 3.6-37.9). Participants with childhood eczema alone were at increased risk of new-onset atopic asthma (aMOR, 4.1; 95% CI, 1.9-8.8), whereas rhinitis alone predicted the persistence of childhood asthma to atopic asthma (aMOR, 2.7; 95% CI, 1.3-5.6). Of all asthma, 29.7% of persistent atopic asthma and 18.1% of new-onset atopic asthma could be attributed to having childhood eczema and rhinitis. CONCLUSION Childhood eczema and rhinitis are strongly associated with the incidence and persistence of adult atopic asthma.

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.

Filaggrin loss-of-function mutations do not predict food allergy over and above the risk of food sensitization among infants.

Diagnosed allergic disease (any) 1.26 0.67-2.37 .47 1.34 0.68-2.63 .40 0.956 0.44-2.08 .91 1.07 0.80-1.44 .63 Doctor-diagnosed eczema (any) 1.11 0.59-2.11 .74 1.49 0.74-2.99 .26 1.95 0.76-5.03 .17 1.17 0.83-1.63 .37 Sensitized (SPT1) 2.0§ 1.05-4.09§ .04§ 1.32 0.62-2.78 .47 1.27 0.55-2.93 .58 1.27 0.91-1.78 .17 SPT1 and eczema 2.0§ 0.89-4.48§ .10§ 1.48 0.63-3.50 .37 1.70 0.59-4.92 .33 1.5§ 0.96-2.42§ .07§ Food allergy (IgE mediated) 1.65 0.65-4.22 .30 0.85 0.33-2.20 .73 1.83 0.43-7.78 .41 1.17 0.67-2.02 .58 Diagnosed asthma — — — 1.55 0.38-6.23 .54 1.40 0.39-5.00 .61 — — — Allergic rhinitis and inhalant SPT1 — — — — — — 0.506 0.16-1.61 .25 — — —

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.