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Take a look at a selection of our recent media coverage:

Gut microbiome changes uniformly linked to allergic disease development in childhood

4th September 2023

Delays in gut microbiome maturation in young children are uniformly associated with distinct allergic diagnoses at five years of age, according to the findings of a study by Canadian researchers.

The study, which was published in the journal Nature Communications, revealed how specific gut microbiome features and early life influences are associated with children developing any of four common allergies: atopic eczema, asthma, food allergy and/or allergic rhinitis.

It is possible, therefore, that these findings could lead to methods for predicting whether a child would develop an allergic disease. They could also form the foundation of strategies to prevent them from developing, especially given that food allergies in particular continue to be a major source of life-threatening reactions in children.

Courtney Hoskinson, PhD candidate at the University of British Columbia (UBC) and the study‘s lead author said: ‘Typically, our bodies tolerate the millions of bacteria living in our guts because they do so many good things for our health. Some of the ways we tolerate them are by keeping a strong barrier between them and our immune cells and by limiting inflammatory signals that would call those immune cells into action.‘

‘We found a common breakdown in these mechanisms in babies prior to the development of allergies.‘

In the study, researchers evaluated the four clinically distinct allergic diseases diagnosed at five years of age in the large, deeply characterised CHILD cohort study. The team adopted a multi-omics approach to profile infant stool collected at study visits scheduled for ages three months and one year.

Gut microbiome and allergic diseases

The study used a deeply phenotyped cohort of 1,115 children. A total of 523 participants could be defined as a ‘healthy‘ control group in that they did not develop allergic sensitisation at any time in their life up to five years of age.

Some 592 children had been diagnosed by an expert physician at the five-year scheduled visit with one or more allergic disorders: atopic eczema (n = 367), asthma (n = 165), food allergy (n = 136) and allergic rhinitis (n = 187). There were gut microbiome features uniformly associated with these allergic diagnoses at five years of age.

When evaluating the association between early-life factors and a diagnosis of allergic disease at age five, male sex, a history of either maternal of paternal atopy and antibiotic usage before age one were all significantly linked with an increased risk of developing an allergic disease.

In contrast, breastfeeding up to age six months and self-identifying as Caucasian were negatively associated with an allergy diagnosis.

Dr Stuart Turvey, professor in the department of pediatrics at UBC, investigator at British Columbia Children‘s Hospital Research Institute and co-senior author on the study, added: ‘There are a lot of potential insights from this robust analysis. From these data we can see that factors such as antibiotic usage in the first year of life are more likely to result in later allergic disorders, while breastfeeding for the first six months is protective. This was universal to all the allergic disorders we studied.

‘Developing therapies that change these interactions during infancy may therefore prevent the development of all sorts of allergic diseases in childhood, which often last a lifetime.‘

Efficacy of Palforzia in childhood peanut allergy increases over time

9th August 2021

Over a two-year period, daily use of Palforzia in those with a childhood peanut allergy led to higher level of allergen desensitisation.

An estimated approximately 2% of the population of Western nations has a peanut allergy. However, the prevalence in the paediatric population is likely to be higher with one study of 3218 finding that 24.8% had a childhood peanut allergy. The presence of a peanut allergy has the potential to cause life-threatening reactions and elicit anaphylaxis in both children and adults.

While the standard approach for those with a peanut allergy is allergen avoidance and the use of adrenaline auto-injection as a treatment for any allergic reactions following accidental ingestion, a peanut allergen powder, Palforzia, has been approved for use in the EU since 2020. Palforzia contains peanut protein as a defatted powder and has a marketing authorisation for the treatment of patients aged 4 to 17 years with a confirmed diagnosis of childhood peanut allergy.

Treatment with Palforzia is a form of oral immunotherapy that involves ingesting, small and controlled amounts of peanut protein with the aim of desensitising children and ultimately reducing the risk of life-threatening allergic reactions. However, continued treatment is required because once therapy is discontinued, reactivity to peanuts reoccurs.

The efficacy of Palforzia in childhood peanut allergy has been demonstrated in two Phase III randomised, controlled trials. In the first trial (PALISADE), 67% of participants who received Palforzia were able to ingest a dose of 600mg of peanut protein without any problems, compared to 4% of those assigned to placebo. In the second and more recent trial (ARTEMIS), 58% of those given Palforzia could tolerate 1000mg of peanut protein without problems compared with only 2% in the placebo group.


The same group have now reported follow-up data for patients who completed the PALISADE study in an open-label extension study. Individuals with childhood peanut allergy received 300mg/day for either 1.5 years (group A) or a total of 2 years (Group B). The primary outcome of the trial was a double-blind, placebo-controlled food challenge (DBPCFC), which involves supervised and gradual ingestion of the suspected food allergen (peanuts) disguised or hidden in another food.

Findings
The extension study included 142 participants aged 4–17 years (110 in Group A). The median age of group A was 10 years (52.7% male) whereas the median age of group B was 8 years (56.2% male). The percentage of participants able to tolerate the highest DBPCFC (2000mg peanut protein) and without any dose-limiting symptoms was 80.8% in group B compared with 48.1% in group A. In addition, the proportion of individuals requiring adrenaline as a rescue medication was 24% (group A) and only 3.8% (group B).

The researchers described how the data indicated that the extent of desensitisation to childhood peanut allergy was clearly time-dependent in how efficacy appeared to increase over time. They concluded that longer-term data will be captured from this ongoing study to determine whether continued therapy improves DBPCFC response.

Citation
Fernandez-Rivas M et al. Open-label follow-on study evaluating the efficacy, safety, and quality of life with extended daily oral immunotherapy in children with peanut allergy. Allergy 2021

Allergy information can be difficult for consumers to interpret

27th July 2021

Effective food safety requires an understanding of allergy information but a study has revealed consumers found this difficult to interpret.

Self-reported food allergy is relatively common, with one European analysis identifying a pooled lifetime prevalence of 17.3%. Furthermore, the presence of a food allergy negatively affects an individuals’ quality of life across all ages, with one study finding that the risk of accidental allergen ingestion and limitations in social life are associated with a worse health-related quality of life. The provision of allergy information has been incorporated into EU law since 2016 and requires that there is a clearer and harmonised presentation of allergens such as nuts, soy etc, on pre-packed foods and mandatory allergy information on non-prepacked foods in outlets such as bars and cafes. The introduction of precautionary allergen labelling (PAL), is the voluntary way used by food producers to warn consumers of the risks from the unintended presence of specific allergens in products, though PAL is not formally regulated in the EU. Despite the legal labelling requirements, allergic reactions remain common, with one study finding that 46% of adults reported an allergic reaction and 41% of these reactions occurred to pre-packed foods. However, it has also been found that consumers find a wide and inconsistent range of ways in which allergy information is presented on labels.

In an attempt to better understand how both allergy and non-allergy sufferers interpret and assess allergen information, a team from the Institute for Health Services Research, Utrecht, The Netherlands, evaluated consumer understanding of allergy information on foods in a controlled, environment. The team looked at how consumers interpreted the information presented in three scenarios. In the first, consumers rated the risk of consumption by someone with an allergy from a mixed set of 18 products which contained the allergy information. Secondly, six of the 18 products were labelled “may contain peanut”, six had “peanut as an ingredient” and for the remaining six, there was no mention of peanut as an ingredient. Finally, individuals were asked to assess three different PAL labels, i.e., “may contain peanut” vs “may contain traces of peanut” vs “produced in a factory which also processes peanut”, using a 5-point scale.

Findings
For the ingredient experiment, 102 individuals with a mean age of 33.9 years (79% female) and 48 nonallergic consumers, similarly rated the risk of eating an allergen containing food. The PAL experiment involved 99 participants and found that those without an allergy judged the risk assessment to higher than those with an allergy (82% vs 58%, p < 0.01). The PAL for which participants expressed the highest preference was “may contain nuts” (65.7%), whereas the least preferred was “produced in a factory which also processes peanuts” (26.3%).

In their discussion, the authors noted how consumers appeared to attribute different risks, depending on the presentation of allergy information on a food label. However, overall, only around 50% of consumers judged that the allergy information was clear. They concluded by calling for allergy information guidelines to ensure that the information is much clearer and understood by consumers.

Citation
Holleman BC et al. Poor understanding of allergen labelling by allergic and non- allergic consumers. Clin Exp Allergy 2021

Early introduction of gluten reduces incidence of coeliac disease

1st October 2020

The enquiring about tolerance (EAT) study is an open-label randomised trial of a dietary intervention for the prevention of food allergy (including coeliac disease) in which potentially allergenic foods were introduced to an infant’s diet at an early age.

In the present study, a team from the Paediatric Allergy Research group, Kings College, London, focused on the development of coeliac disease at 3 years of age, after the introduction of gluten, a protein present in wheat that triggers the disease, from 4 months of age. A total of 1004 infants from the general population of England and Wales, were enrolled in the study and were all breast-fed until 13 weeks of age, after which they were randomised to consume six allergenic foods; cow’s milk, hen’s egg, peanut, sesame, cod fish and wheat in addition to breast milk (intervention group) or to continue with exclusively with breast milk until 6 months of age (control group), as recommended by UK government guidelines. The weekly recommended dose of wheat for a child was set at 4g of wheat protein and this was provided as wheat-based cereal biscuits (Weetabix) or equivalent. The team calculated that this was equivalent to a gluten dose of 3.2g/week and though this was set as the minimum intake, no maximum limits were set. The families were asked to complete weekly questionnaires through to 1 year and then every 3 months until 3 years of age.

Findings
For the 1004 (488 given the allergenic foods) infants included in the final analysis, 514 were male (51.2%) and the mean gluten intake between ages 4 and 6 months was 0.49g/week for the control group compared to 2.66g/week for the intervention group. At 8 months of age, gluten consumption had increased to 8.21g/week in the intervention group. Interesting by 3 years of age, 7 children in the control group but none of those in the gluten group, at developed coeliac disease.

Given the relatively small sample size, the authors called for more studies to confirm whether early introduction of gluten is an effective strategy to prevent the development of coeliac disease.

Reference
Logan K et al. Early gluten introduction and celiac disease in the EAT study. A prespecified analysis of the EAT randomised clinical trial. JAMA Pediatr doi:10.1001/jamapediatrics.2020.2893

Can daily application of an emollient from birth prevent the development of atopic eczema?

5th March 2020

Atopic eczema is characterised by a defective skin barrier and often precedes the development of food allergies and other atopic diseases. Could regular emollient use from birth actually prevent the development of the condition? Rod Tucker finds out.

Atopic eczema is a highly pruritic, inflammatory skin condition which affects 20% of children.1 The condition develops during infancy and classically leads to food allergies, asthma and allergic rhinitis in what has been termed the ‘atopic march’.2 A family history of atopic disease is an important risk factor for the development of atopic eczema. In addition, the presence of atopic eczema increases the risk of IgE-mediated food allergies and for example, infants with the condition are six times more likely to develop egg allergies.3

While the precise cause of eczema remains uncertain, the condition is characterised by a defective skin barrier and there is evidence that genetically determined loss-of-function mutations in the gene that codes for filaggrin, a protein that has an important role in skin barrier function, may contribute to eczema development during infancy.4 The presence of defective skin barrier serves as a possible entry route for allergens and this has been proposed as a possible route to sensitisation and the subsequent development of a peanut allergy.5

Management with emollients

Emollients are the cornerstone of eczema management and are recommended for all patients with the condition.6 An emollient provides a water impermeable barrier over the surface of the skin which serves to both prevent water loss and ingression of potential allergens and irritants.

Given this dual role, is it possible that treatment with emollients soon after birth could actually prevent the development of atopic eczema and the ensuing atopic march? This was the question posed in the barrier enhancement for eczema prevention (BEEP) study published in the Lancet.7

The study was based on the observations of a pilot study undertaken by the same group which found that the incidence of atopic eczema was lower (22% vs 43%) in 124 infants treated with the daily application of an emollient from birth.8 But this was not simply blue sky thinking: several lines of evidence had pointed to a role for emollients in preventing inflammation as well as work which illustrated how the barrier dysfunction in atopic eczema appeared to be a secondary phenomena to subclinical inflammation present in dry atopic skin.9

The BEEP study recruited 1,394 high-risk (that is, where at least one first-degree relative had either eczema, allergic rhinitis or asthma) babies who were randomised to either once daily application of an emollient (Diprobase or Doublebase gel) to the whole body excluding the scalp or best practice skincare advice (the control group). This latter group received advice to use mild cleansers and shampoos specifically formulated for infants but also to avoid soaps, bubble bath and baby wipes.

The primary outcome measure was a diagnosis of eczema at two years of age. The results showed no difference: eczema was present at two years of age in 23% of infants assigned to daily emollient use and 25% in the control group. There were also no significant differences in the incidence of food allergies or other allergic diseases and the authors were at a loss to explain their findings.

Allergenic food exposure

An alternative strategy to reducing food allergies is through early exposure to potentially allergenic foods in order to allow the development of tolerance and this was the subject of the preventing atopic dermatitis and allergies (PreventADALL) study which was also published in the same issue of The Lancet.

In PreventADALL, Norwegian researchers explored the dual approach of daily emollient use and early introduction of potential allergic foodstuffs such as peanut butter, wheat porridge and eggs10 and the incidence of eczema was recorded after 12 months.

The study had four arms: control (no advice); skin emollients; early feeding and finally combined emollient and early feeding. The incidence of eczema at 12 months was 8% (control group), 11% (emollient group), 9% (food group) and 5% (combined group) and these differences were not significant. In other words, neither a combination of daily emollient use and early introduction of potential allergenic foods reduced the development of atopic eczema at 12 months.

The results of both studies, although disappointing, recognise the limited value of these primary prevention strategies. However, these results do not undermine the importance of regular emollient use in the management of established atopic eczema.

Whether changing the composition of an emollient makes any difference remains to be seen and is the subject of the ongoing PEBBLES study.11

References

  1. Nankervis H et al. Scoping systematic review of treatments for eczema. programme Grants for Applied Research 2016;4(7):1–480.
  2. Hill DA, Spergel JM. The atopic march: critical evidence and clinical relevance. Ann Allergy Asthma Immunol 2018;120:131–7.
  3. Martin PE et al. Which infants with eczema are at risk of food allergy? Results from a population-based cohort. Clin Exp Allergy 2015;45:255–64.
  4. Flohr C et al. Fliaggrin loss-of-function mutations are associated with early-onset eczema, eczema severity and transepidermal water loss at 3 months of age. Br J Dermatol 2010;163:1333–6.
  5. Brough HA et al. Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy. J Allergy Clin Immunol 2015;135:164–70.
  6. National Institute for Health and Care Excellence. Atopic eczema in under 12s: diagnosis and management (CG 57) 2007.
  7. Chalmers JR et al. Daily emollient during infancy for prevention of eczema: the BEEP randomised controlled trial. Lancet 2020; online Feb 19.
  8. Simpson EL et al. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. J Allergy Clin Immunol 2014;134:818–23.
  9. Katsuko K, Kobayashi H, Ogoshi K. Impairment of skin barrier function is not inherent in atopic dermatitis patients: a prospective study conducted in newborns. Pediatr Dermatol 2006;23:109–13.
  10. Skjerven HO et al. Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial. Lancet, 2020; online February 19.
  11. Lowe A et al. PEBBLES study protocol: a randomised controlled trial to prevent atopic dermatitis , food allergy and sensitisation in infants with a family history of allergic disease using a skin barrier improvement strategy. BMJ Open 2019;9:e023594.

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