Göran Oldaeus

Hypoallergenicity of an extensively hydrolyzed whey formula.

Several different protein hydrolysate‐based infant formulas have been promoted as hypoallergenic and considered suitable for the dietary management of cows milk allergy (CMA). Accepting that none of the hydrolysate‐based products is completely safe, the American Academy of Pediatrics (AAP) recommends that these formulas should be tested in a double‐blind placebo‐controlled setting and tolerated by at least 90% of children with proven CMA. In principle, this recommendation is also endorsed by the European Society of Paediatric Gastroenterology and Nutrition (ESPGAN) and the European Society of Paediatric Allergy and Clinical Immunology (ESPACI). In this two‐center study, 32 children with proven CMA were tested with the extensive hydrolysate whey formula Nutrilon Pepti, for comparison with Profylac (extensive) and Nan HA (partial) whey hydrolysate products. Skin‐prick tests (SPTs) were, respectively, positive to the three hydrolysate formulas in 19%, 15%, and 32% of children. After oral challenge it was concluded that 97% (95% CI: 85–100%) of the children tolerated Nutrilon Pepti, 94% (95% CI: 75–100%) tolerated Profylac, and 64% (95% CI: 37–81%) tolerated Nan HA. This study demonstrates that the extensive hydrolysates Nutrilon Pepti and Profylac are well tolerated in a population of children with proven CMA and that both products can be considered safe for their intended use. This study confirms that a very small number of children react even to extensively hydrolyzed formulas. SPT prior to oral exposure to the hydrolysate‐based formulas can indicate whether a child is at risk of showing reactions to the product. Introduction of new products to these children should be carried out under a doctors supervision. However, the majority of the SPT‐positive children did tolerate the two extensively hydrolyzed whey‐based formulas tested.

Antigenicity and allergenicity of cow milk hydrolysates intended for infant feeding

Allergenicity and antigenicity of various commercially available cow milk hydrolysates intended for infant feeding were analysed in 45 children with cow milk allergy. The hydrolysates included the whey hydrolysates Beba HA® (Good Start HA®) and Profylac®, and the casein hydrolysates Alimentum® and Nutramigen®. Positive skin prick tests were recorded against Beba HA in 10 of 41 tested children (24%), against Profylac® in 5/34 (15%) and in one each (2.5%) against Alimentum and Nutramigen. Double‐blind placebo‐controlled oral challenge tests were performed in 11 children with cow milk allergy using Alimentum, cow milk (positive control) and their regular well‐tolerated formula (Nutramigen or soy) used as negative control. One child reacted to Alimentum. This patient was the only one with circulating antibodies against the product, as indicated by a positive RAST. High density SDS‐PAGE electrophoresis showed that Beba HA contained a number of unresolved proteins, and non‐degraded or partially degraded whey proteins in the range of 5–20 kD. Profylac contained strongly stained protein material in the low molecular weight region 1–10 kD. No protein bands could be identified in the casein‐based hydrolysates. Residual antigenicity was tested by measuring the content of betalactoglobulin in the hydrolysates. Three of the hydrolysates contained < 0.06 μg/g dry weight, while the concentration in Beba HA was 200 μg/g dry weight. Positive RAST against Beba HA was detected in 11/45 sera (24%) compared to 7–13% against the other hydrolysates. RAST inhibition with the hydrolysates using cow milk discs was very low for all of them. Using dot immuno‐binding assay a weak IgE binding with Alimentum was detected in 4 sera, Beba HA and Profylac in each 2 sera and with Nutramigen in one. The data taken together show that all 4 tested hydrolysates retain some allergenicity. There were differences between the products, one of the whey hydrolysates being substantially more allergenic and antigenic than the other tested formulas. The casein hydrolysate Alimentum showed few reactions in vivo and in vitro in this selected group of children but one child reacted when challenged with Alimentum, indicating that there is a risk for general reactions when using any hydrolysed product in subjects allergic to cow milk.

No effect of probiotics on respiratory allergies : a seven-year follow-up of a randomized controlled trial in infancy

Supplementation with the probiotic Lactobacillus reuteri reduced the incidence of IgE‐associated allergic disease in infancy. This treatment might therefore also reduce the risk of asthma and allergic rhinoconjunctivitis in school age.

Efficacy of once-daily versus twice-daily administration of budesonide by Turbuhaler® in children with stable asthma

We evaluated the efficacy of once‐daily versus twice‐daily treatment with budesonide, delivered by a Turbuhaler®, in the management of children with stable asthma in a randomized, double‐blind, parallel‐group study involving 206 children (age 5–15 years). After a 2‐week run‐in period during which the children were maintained on their usual dose of budesonide (200 μg or 400 μg/day), patients were randomized to receive the same daily dose in either two daily administrations (morning and evening) or as a single dose in the morning over a period of 12 weeks. The primary efficacy variable was morning peak expiratory flow (PEF).

Cow's milk IgE and IgG antibody responses to cow's milk formulas

For comparison of the antigenicity and allergenicity of three cows milk formulas, serum IgE antibodies to cows milk, β‐lactoglobulin and casein, and IgG antibodies to β‐lactoglobulin were analyzed in 94 infants with a family history of allergy. They were participating in a randomized trial comparing the allergy prophylactic effect of feeding an extensively hydrolyzed (N), a partially hydrolyzed (PH), and a regular cows milk formula (RM). Only infants who had been formula‐fed for 3 months or more were included. IgE antibodies to cows milk proteins were more common in the RM group (22/34) than in the N (2/31) and PH groups (3/29). There was a strong correlation between sensitization to cows milk and β‐lactoglobulin (r=0.85, P<0.001). The IgG responses to β‐lactoglobulin were low in the N group, intermediate in the PH group, and high in the RM group. High responses, as well as detection of IgE antibodies, were associated with development of atopic disease. The low antigenicity and allergenicity of the extensively hydrolyzed formula support its use in allergy prophylaxis. The partial hydrolysate seemed to be less suitable for this purpose.

A new model for low-dose food challenge in children with allergy to milk or egg

Background: Atopic eczema and food allergy are common in early childhood. Children seem to gradually develop tolerance to milk and egg, and it is a relief for families when their child can tolerate small amounts of these basic foods, even if larger doses may still cause symptoms. Aim: To develop a model for low‐dose oral food challenge, facilitating re‐/introduction of milk or egg. Methods: In 39 children sensitized to milk and/or egg, we performed 52 challenges using a new standardized model for low‐dose oral food challenge. The recipes were validated for blinding with sensorial tests. Results: Four children challenged to milk had a positive challenge outcome. There were no significant differences with respect to family history, associated atopic manifestations, nutritional supply, eczema severity, or skin‐prick test compared with the non‐reacting children, but total and specific IgE values were significantly higher. All but two of the non‐reacting children were able to introduce milk and egg into their diet without problems.

Significant improvement of eczema with skin care and food elimination in small children.

AIM To evaluate common methods of investigation and treatment in children younger than 2 y of age with eczema, with or without sensitization to food allergens. METHODS One hundred and twenty-three children younger than 2 y of age with eczema and suspected food allergy were included in this prospective study. The children underwent skin-prick test with cows milk, fresh hens egg white and wheat. Specific IgE to milk and egg white was analysed. The eczema extent and severity was estimated with SCORAD before and after treatment. Children with a positive skin-prick test were instructed to exclude that food item from their diet. All children were treated with emollients and topical steroids when needed. RESULTS Sixty-two of the children were skin-prick positive to at least one of the allergens; 62% had mild, 30% moderate and 8% severe eczema at their first visit. After treatment, 90% had mild, 10% moderate and 0% severe eczema. Forty-six per cent of the children had circulating IgE antibodies to milk or egg white. Ten per cent had specific IgE but negative skin-prick test to the same allergen. This subgroup improved their eczema significantly without elimination diet. CONCLUSION The conventional treatments for children with eczema, i.e. skin care and food elimination, are effective. The beneficial effect of skin care as the first step should not be neglected, and it may not be necessary to eliminate food allergens to relieve skin symptoms in all food-sensitized children with eczema.

Severe Eczema in Infancy Can Predict Asthma Development. A Prospective Study to the Age of 10 Years

Background Children with atopic eczema in infancy often develop allergic rhinoconjunctivitis and asthma, but the term “atopic march” has been questioned as the relations between atopic disorders seem more complicated than one condition progressing into another. Objective In this prospective multicenter study we followed children with eczema from infancy to the age of 10 years focusing on sensitization to allergens, severity of eczema and development of allergic airway symptoms at 4.5 and 10 years of age. Methods On inclusion, 123 children were examined. Hanifin-Rajka criteria and SCORAD index were used to describe the eczema. Episodes of wheezing were registered, skin prick tests and IgE tests were conducted and questionnaires were filled out. Procedures were repeated at 4.5 and 10 years of age with additional examinations for ARC and asthma. Results 94 out of 123 completed the entire study. High SCORAD points on inclusion were correlated with the risk of developing ARC, (B = 9.86, P = 0.01) and asthma, (B = 10.17, P = 0.01). For infants with eczema and wheezing at the first visit, the OR for developing asthma was 4.05(P = 0.01). ARC at 4.5 years of age resulted in an OR of 11.28(P = 0.00) for asthma development at 10 years. Conclusion This study indicates that infant eczema with high SCORAD points is associated with an increased risk of asthma at 10 years of age. Children with eczema and wheezing episodes during infancy are more likely to develop asthma than are infants with eczema alone. Eczema in infancy combined with early onset of ARC seems to indicate a more severe allergic disease, which often leads to asthma development. The progression from eczema in infancy to ARC at an early age and asthma later in childhood shown in this study supports the relevance of the term “atopic march”, at least in more severe allergic disease.

Significant improvement of eczema with skin care and food elimination in small children: Eczema, skin care and elimination diet in children

Aim: To evaluate common methods of investigation and treatment in children younger than 2 y of age with eczema, with or without sensitization to food allergens. Methods: One hundred and twenty‐three children younger than 2 y of age with eczema and suspected food allergy were included in this prospective study. The children underwent skin‐prick test with cows milk, fresh hens egg white and wheat. Specific IgE to milk and egg white was analysed. The eczema extent and severity was estimated with SCORAD before and after treatment. Children with a positive skin‐prick test were instructed to exclude that food item from their diet. All children were treated with emollients and topical steroids when needed. Results: Sixty‐two of the children were skin‐prick positive to at least one of the allergens; 62% had mild, 30% moderate and 8% severe eczema at their first visit. After treatment, 90% had mild, 10% moderate and 0% severe eczema. Forty‐six per cent of the children had circulating IgE antibodies to milk or egg white. Ten per cent had specific IgE but negative skin‐prick test to the same allergen. This subgroup improved their eczema significantly without elimination diet.