Summary PROTEGO is a Chilean cluster‐randomised crossover trial of vernix caseosa retention to prevent atopic dermatitis. 1383 mother‐infant dyads will be enrolled and followed for atopic dermatitis until 12 months.
ABSTRACT Background Increased basal serum tryptase level (BST) is associated with anaphylaxis. In the absence of clonal mast cell disease and hereditary α‐tryptasemia (HαT), the contribution of the tryptase locus variation to BST and anaphylaxis remains undefined. Objective To determine the impact of tryptase locus variation on BST and anaphylaxis. Methods Individuals with systemic Hymenoptera venom allergic reactions, large local reactions and asymptomatic sensitization underwent a novel ddPCR‐based tryptase genotyping to quantify active tryptase alleles. Individuals positive for KIT p.D816V or HαT were excluded. Results The cohort consisted of 295 individuals with systemic reactions, 140 with large local reactions, and 29 asymptomatically sensitized individuals. Active tryptase allele number, excluding the inactive βIIIFS allele, correlated with BST levels ( r = 0.34, p < 0.0001); all BST values were within the normal range. Patients with systemic reactions had higher BST compared with those with large local reactions and asymptomatic sensitization (median, 4.5 ng/mL vs. 3.5 ng/mL; p < 0.0001). Individuals carrying four active β‐tryptase alleles were less likely to experience anaphylaxis than those carrying two or three active β‐tryptase alleles (26.7% vs. 42.3%; p = 0.024). A trend towards more severe reactions was observed in individuals carrying α‐tryptase allele together with a higher number of active β‐tryptase alleles. Conclusion Variation at the tryptase locus explains differences in BST levels within the normal range. Four active β‐tryptase alleles were associated with a lower frequency of anaphylaxis.
ABSTRACT Background Infants with non‐specific symptoms are sometimes labelled as cow's milk allergic and managed with specialized formula. These products differ from standard infant formula in protein and carbohydrate source, typically containing lower quality protein and free/added sugars such as glucose polymers or sucrose. We evaluated the frequency, timing, duration and estimated volume of specialized formula prescribed to young children. Methods We undertook a retrospective population‐based cohort study of children up to age 2 years born between 2009 and 2021 who were registered with a contributing UK general practice, predominantly in England. Community prescribing and demographic data were obtained from the Clinical Practice Research Datalink (CPRD) Aurum, a de‐identified primary care database representing approximately 24% of the population. National prescribing data for England were used to estimate community prescribing rates for 2022–2025. Results Of 4,203,276 children born between 2009–2021 in the database, 1,944,323 (46.3%) were registered by age 3 months with complete data to age 2 years and were included. Of these, 111,478 (5.7%) were prescribed specialized formula, rising from 1.7% of children born in 2009 to 7.9% in 2021 and an estimated 9.7% in 2025. Prescriptions were most commonly initiated at age 0–2 months. Multiple prescriptions were documented for 85,370 (76.6%) of these children. Children with multiple amino‐acid formula prescriptions consumed an estimated mean total of 242 L; those with multiple extensively hydrolysed formula prescriptions 203 L; and those with multiple soya formula prescriptions 137 L. Among these children, the median interval between first and last prescription was 257 days for amino‐acid formula, 213 days for extensively hydrolysed formula and 152 days for soya formula. Conclusions Community prescribing of specialized formula in England increased approximately five‐fold over the study period, potentially triggering significant free sugars exposure during infancy.
ABSTRACT Background Wheat allergy dependent on augmentation factors (WALDA) represents the most common form of IgE‐mediated wheat allergy in adults. Although ω5‐gliadin is the major allergen in WALDA, sIgE reactivity to non‐gluten wheat proteins remains poorly characterized. Methods Serum samples from 54 adults with challenge‐confirmed WALDA and 21 tolerant controls (including 5 with positive sIgE to ω5‐gliadin) from two German centres were analysed for sIgE reactivity to 19 recombinant wheat proteins and the cross‐reactive carbohydrate determinant (CCD) MUXF3. Results sIgE to α−/β‐gliadin (Tri a 21.0101) was highly specific for WALDA, present in 29/54 patients (53.7%) but absent in controls (100% specificity, p < 0.001). Receiver operating characteristic analysis revealed excellent discriminatory ability (area under the curve = 0.85) with an optimal cut‐off of 0.22 kU/l. Reactivity to non‐gluten wheat proteins was limited, with 24.1% of patients showing sIgE to thioredoxin, 11.3% to dehydrin, 9.3% to any α‐amylase/trypsin inhibitor subunit, and minimal sIgE to non‐specific lipid transfer proteins (Tri a 14), thiol reductase, triosephosphate isomerase, peroxiredoxin, serpin, glyceraldehyde‐3‐phosphate dehydrogenase, serine protease inhibitor‐like allergen, and peroxidase. Non‐gluten reactivity correlated strongly with MUXF3 CCD (ρ = 0.776), total IgE (ρ = 0.646), and wheat extract sIgE (ρ = 0.534; all p < 0.001). Grass pollen‐sensitized individuals showed increased non‐gluten protein reactivity ( p < 0.001). Controls demonstrated higher MUXF3 CCD reactivity (38.1% vs. 11.6%, p < 0.05). Conclusion The data suggest that WALDA is characterized by highly specific reactivity to gliadin proteins, with limited sensitization to non‐gluten wheat components. sIgE to α−/β‐gliadin represents a promising diagnostic biomarker with superior specificity compared with ω5‐gliadin alone.
