Specific IgE-profiles and allergy prediction

Presence of antibodies of type Immunoglobulin E (IgE-ab), often called sensitization, is common and often precede development of atopic disease, including food allergy. While not all IgE-sensitized individuals develop food allergy, some seem to be at a higher risk. By studying specific IgE-profiles longitudinally in two different birth cohorts we aimed to identify factors associated with atopic disease development and more severe disease. Firstly, in study I and II, we used the Scandinavian population-based birth cohort PreventADALL, where 2397 infants were randomized into four different groups receiving either preventive skin care with emollient and oil baths from 2 weeks of age, early food introduction (peanut, milk, egg, wheat) from 3 months, both skin/food intervention or control group. In study I the development of IgE in relation to maternal and perinatal factors were studied in 1110 children aged 3 months. We found that 7 % of the infants were sensitized at 3 months of age, mainly against food allergens, but few of them expressed the corresponding molecular allergens. Any positive maternal food sensitization in mid-pregnancy was associated with infant sensitization at 3 months. The aim of study II was to investigate early sensitization to peanut allergen molecules analyzed in children aged 12 months in relation to peanut allergy at 3 years of age. We found that children aged 12 months often were sensitized against peanut extract but few were classified as allergic to peanut at 3 years of age. Children in the food intervention group expressed a different pattern of peanut allergen molecules, with mainly IgE-levels against Ara h 3. Secondly, in study III and IV we used the Swedish population based BAMSE cohort, consisting of 4089 participants from 6 different parts of Stockholm followed longitudinally between 0-24 years of age. In study III participants were examined longitudinally between age 4-24 years with emphasis on peanut IgE development in relation to symptoms and inflammatory markers such as FENO, blood eosinophils and lung function. Peanut allergy seldom appeared after the age of 8 years and few participants outgrew their allergy in adulthood, those who did all had initially low peanut Ara h 2 IgE-levels. Peanut allergic individuals were found to express higher levels of FENO, blood eosinophils and a more severe asthma. Finally, in study IV we studied sensitization to tree nut extract and tree nut molecular allergens in relation to background factors and symptoms of tree nut allergy at 24 years of age. The tree nut sensitized participants were often asymptomatic, and the majority were birch sensitized. Individuals with storage protein sensitization often had an atopic background, were polysensitized and described more severe allergic reactions. Conclusion: Sensitization to peanut develop early, and already at 3 months infants express IgE towards peanut while peanut allergen molecule sensitization increased later on. In adolescence peanut allergy tend to remain, especially in participants with early allergies towards other food as well as childhood asthma and atopic dermatitis. Peanut and tree nut storage protein sensitized participants were found to express higher levels of FENO, blood eosinophils and more prone to severe asthma. As few sensitized infants’ express IgE against storage proteins at this age, it could indicate that the IgE development process is not complete at this age, thus still time for a possible tolerance development. Previous studies have indicated that that an early food introduction is preferred over a delayed one, and this research add new insight in this process. It is possible that atopic infants in particular might benefit the most in terms of preventing a more severe allergic phenotype if early food introduction would be applied

Fetal growth and risk of childhood asthma and allergic disease

Introduction: Early genetic and environmental factors have been discussed as potential causes for the high prevalence of asthma and allergic disease in the western world, and knowledge on fetal growth and its consequence on future health and disease development is emerging. Objective: This review article is an attempt to summarize research on fetal growth and risk of asthma and allergic disease. Current knowledge and novel findings will be reviewed and open research questions identified, to give basic scientists, immunologists and clinicians an overview of an emerging research field. Methods: PubMed-search on pre-defined terms and cross-references. Results: Several studies have shown a correlation between low birth weight and/or gesta- tional age and asthma and high birth weight and/or gestational age and atopy. The exact mechanism is not yet clear but both environmental and genetic factors seem to contribute to fetal growth. Some of these factors are confounders that can be adjusted for, and twin studies have been very helpful in this context. Suggested mechanisms behind fetal growth are often linked to the feto-maternal circulation, including the development of placenta and umbilical cord. However, the causal link between fetal growth restriction and subse- quent asthma and allergic disease remains unexplained. New research regarding the catch-up growth following growth restriction has posited an alternative theory that dis- eases later on in life result from rapid catch-up growth rather than intrauterine growth restriction per se. Several studies have found a correlation between a rapid weight gain after birth and development of asthma or wheezing in childhood. Conclusion and clinical relevance: Asthma and allergic disease are multifactorial. Several mechanisms seem to influence their development. Additional studies are needed before we fully understand the causal links between fetal growth and development of asthma and allergic diseases.Swedish Research CouncilALF KI/SLLStrategic Research Program in Epidemiology at Karolinska InstitutetPublishe

Development of sensitization to peanut and storage proteins and relation to markers of airway and systemic inflammation : A 24-year follow-up

Background Long-time data of peanut allergy over time is sparse. We aimed to study the longitudinal development of sensitization to peanut extract and storage protein allergen molecules and associations with asthma status, airway and systemic inflammation markers. Methods The Swedish birth cohort BAMSE followed 4089 participants with questionnaires, clinical investigations and blood sampling between 0 and 24 years. Information on (i) background factors at 2 months, (ii) peanut allergy symptoms and IgE data (ImmunoCAP) at 4, 8, 16, and 24 years, and (iii) IgE to storage proteins, lung function data including exhaled nitric oxide (FENO) as well as systemic inflammatory markers at 24 years of age were collected. Results The prevalence of peanut extract sensitization, defined as IgE ≥ 0.35 kUA/L, was 5.4%, 8.0%, 7.5%, and 6.2% at 4, 8, 16, and 24 years of age, respectively. Between 8 and 24 years of age, (33/1565) participants developed IgE-ab to peanut extract (median 1,4, range 0.7–2.6 kUA/L), and among those 85% were also sensitized to birch. Only six individuals developed sensitization to Ara h 2 (≥0.1 kUA/L) between 8 and 24 years of age, of whom three had an IgE-ab level between 0.1–0.12 kUA/L. Storage protein sensitization was associated with elevated FENO, blood eosinophils and type 2 inflammation-related systemic proteins. Conclusion Sensitization to peanut extract after 4 years of age is mainly induced by birch cross-sensitization and IgE to Ara h 2 rarely emerges after eight years of age. Storage protein sensitization is associated with respiratory and systemic inflammation

Impaired skin barrier and allergic sensitization in early infancy

Background: Factors predicting allergic sensitization in the first 6 months of life are poorly understood. We aimed to determine whether eczema, dry skin, and high transepidermal water loss (TEWL) at 3 months were associated with allergic sensitization at 6 months of age and, secondarily, to establish whether these characteristics predicted sensitization from 3 to 6 months of age. Methods: At 3 months of age, 1,994 infants from the population-based PreventADALL birth cohort in Norway and Sweden were assessed for eczema and dry skin on the cheeks and/or extensors; impaired skin barrier function, defined as TEWL in the upper quartile (>9.4 g/m(2)/h), and allergen-specific IgE levels <0.1 kU(A)/L, available in 830. At 6 months, we assessed allergic sensitization to any food (egg, cow's milk, peanut, wheat, soy) or inhalant (birch, timothy grass, dog, and cat) allergen by a skin prick test wheal diameter >= 2 mm larger than negative control. Results: Any sensitization was found in 198 of the 1,994 infants (9.9%), the majority to food allergens (n = 177, 8.9%). Eczema, dry skin, and high TEWL at 3 months increased the risk of sensitization at 6 months; adjusted odds ratios 4.20 (95% CI 2.93-6.04), 2.09 (95% CI 1.51-2.90) and 3.67 (95% CI 2.58-5.22), respectively. Eczema predicted sensitization with 55.6% sensitivity and 68.1% specificity; dry skin with 65.3% sensitivity and 57.3% specificity; and high TEWL with 61.7% sensitivity and 78.1% specificity. Conclusion: Eczema, dry skin, and high TEWL at 3 months predicted allergic sensitization at 6 months of age

Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial

acceptedVersio

Extract and molecular-based early infant sensitization and associated factors—A PreventADALL study

Background: More knowledge about sensitization patterns in early infancy, including impact of molecular allergology, is needed to help predict future allergy development more accurately. Objective: We aimed to determine the prevalence and patterns of allergic sensitization at 3 months of age, and explore possible associated factors. Methods: From the Scandinavian antenatally recruited PreventADALL mother–child cohort, we included 1110 3-month infants with available serum. Sensitization was defined as s-IgE of ≥0.1 kUA/L by Phadiatop Infant® (ThermoFisher Scientific) including birch, cat, grass, dog, milk, egg, peanut and wheat. Further ImmunoCAP analyses to ovomucoid, casein, Ara h 1-3, omega-5-gliadin were performed in food extract s-IgE-positive children. Maternal sensitization was defined as s-IgE ≥ 0.35 kUA/L to Phadiatop® (inhalant allergen mix) and/or Fx5 (food allergen mix) at 18-week pregnancy. Results: Overall 79 (7.3%) infants had specific sensitization, many with low s-IgE-levels (IQR 0.16–0.81 kUA/L), with 78 being sensitized to food extract allergens; 41 to egg, 27 to milk, 10 to peanut, and 25 to wheat. A total of 62/78 were further analysed, 18 (29%) had s-IgE to ovomucoid, casein, Ara h 1-3 and/or omega-5-gliadin. Eight infants (0.7%) were sensitized to inhalant allergens. Maternal sensitization to food allergens was associated with infant sensitization, odds ratio 3.64 (95% CI 1.53–8.68). Conclusion: Already at 3 months of age, 7% were sensitized to food, mostly without detectable s-IgE to food allergen molecules, and <1% to inhalant allergens. Maternal food sensitization was associated with infants’ sensitization.publishedVersio

Early food intervention and skin emollients to prevent food allergy in young children (PreventADALL): a factorial, multicentre, cluster-randomised trial

Background: Primary prevention of food allergy by early introduction of allergenic foods seems promising. We aimed to determine whether early food introduction or the application of regular skin emollients in infants from a general population reduced the risk of food allergy. Methods: This 2 × 2 factorial, cluster-randomised trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway, and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine 18-week ultrasound examination were cluster-randomised at birth to the following groups: (1) no intervention group; (2) the skin intervention group (skin emollients; bath additives and facial cream; from age 2 weeks to <9 months, both at least four times per week); (3) the food intervention group (early complementary feeding of peanut, cow's milk, wheat, and egg from age 3 months); or (4) combined intervention group (skin and food interventions). Participants were randomly assigned (1:1:1:1) using computer-generated randomisation based on clusters of 92 geographical areas and eight 3-month time blocks. Study personnel performing clinical assessments were masked to group allocation. The primary outcome was allergy to any interventional food at 36 months of age. The primary efficacy analysis was done by intention-to-treat analysis, which included all participants who were randomly assigned, apart from three individuals who withdrew their consent. This was a study performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the Lung and Environment). This study is registered as ClinicalTrials.gov, NCT02449850. Findings: We recruited 2697 women with 2701 pregnancies, from whom 2397 newborn infants were enrolled between April 14, 2015, and April 11, 2017. Of these infants, 597 were randomly assigned to the no intervention group, 575 to the skin intervention group, 642 to the food intervention group, and 583 to the combined intervention group. One participant in each of the no intervention, food intervention, and skin intervention groups withdrew consent and were therefore not included in any analyses. Food allergy was diagnosed in 44 children; 14 (2·3%) of 596 infants in the non-intervention group, 17 (3·0%) of 574 infants in the skin intervention group, six (0·9%) of 641 infants in the food intervention group, and seven (1·2%) of 583 infants in the combined intervention group. Peanut allergy was diagnosed in 32 children, egg allergy in 12 children, and milk allergy in four children. None had allergy to wheat. Prevalence of food allergy was reduced in the food intervention group compared with the no food intervention group (risk difference -1·6% [95% CI -2·7 to -0·5]; odds ratio [OR] 0·4 [95% CI 0·2 to 0·8]), but not compared with the skin intervention group (0·4% [95% CI -0·6 to 1· 5%]; OR 1·3 [0·7 to 2·3]), with no significant interaction effect (p=1·0). Preventing food allergy in one child required early exposure to allergenic foods in 63 children. No serious adverse events were observed. Interpretation: Exposure to allergenic foods from 3 months of age reduced food allergy at 36 months in a general population. Our results support that early introduction of common allergenic foods is a safe and effective strategy to prevent food allergy