Effect of preseasonal enzyme potentiated desensitisation (EPD) on plasma-IL-6 and IL-10 of grass pollen-sensitive asthmatic children.

EPD is a method of preventive immunotherapy which employs b-glucuronidase as a biological response modifier. Plasma IL-6 and IL-10 were measured before a single injection of EPD, 24 hours later and 15 days after in a group of 17 children suffering from grass pollen asthma. 17 normal untreated children were used as controls. Although the study was conducted before the grass pollen season when the allergic children were free of symptoms, their plasma IL-6 and IL-10 were significantly elevated before the injection of EPD. 24 hours after treatment the plasma IL-10 had increased significantly and there was also a slight rise in IL-6. 15 days after treatment IL-6 had fallen to normal but IL-10 was still elevated. These findings suggest antigen-specific and non-specific mechanisms by which EPD may produce clinical improvement.

Enzyme-potentiated desensitization in children with asthma and mite allergy: a double-blind study.

The aim of this study was to evaluate the efficacy and safety of enzyme-potentiated desensitization (EPD) in children with asthma. Twenty asthmatic children (14 males and 6 females; median age: 8.5 years) were included in the study. They had positive skin tests to Dermatophagoides pteronyssinus (Dpt), no history of other allergy and had suffered from asthma for at least two years. The children were examined before starting the trial, at the first EPD dose, after 8 weeks, at the second EPD dose and 3 months after the second EPD dose. Blood samples for PRIST and RAST were drawn before the first and at the second EPD dose, and at the last follow-up. Conjunctival provocation tests (CPT) and skin test endpoint determinations were performed with dilutions of a freeze-dried Dpt extract (10-100,000 SQ-U/ml) at the start of the trial and at the last follow-up. Parents kept a diary record of the days with asthma and daily drug usage. The children were randomized to receive either two intradermal placebo injections or the active material with an 8-week interval (November 1991 and January 1992). Ten children received EPD and 10 children placebo. The intradermal injection of EPD (0.05 ml) contained 0.01 ml of beta-glucuronidase (40 Fishman units) and 0.04 ml of a mixture of inhalant allergens (1 Noon unit). The placebo injection consisted of buffer solution only. The EPD-treated children had significantly fewer days with asthma (p = 0.00000). In addition, the EPD-treated children used significantly less medication for the management of asthma attacks (p = 0.00000). At the start of the trial, three out of 10 children in the EPD group and two out of 10 in the placebo group reacted only to the highest dose of allergen used in the CPT (100,000 SQ/ml) (NS). At the last follow-up, the threshold dose in the CPT was 100,000 SQ/ml or more in nine out of 10 children in the EPD group and in four out of 10 children of the placebo group (p = 0.0349). At the last follow-up, one child in the EPD group had a negative CPT with all doses tested. Global clinical evaluation by the investigators showed that eight out of 10 EPD-treated children improved, in comparison with three out of 10 children in the placebo group (p = 0.0349). Assessment by the parents was six out of 10 and four out of 10 improved, respectively (NS). Specific IgE to Dpt, total IgE and skin prick test endpoints before and after EPD showed no significant changes. One child in the placebo group experienced mild urticaria several hours following the second injection. No other local or systemic side effects were reported. The results of the present study provide further data on the effectiveness and safety of EPD in patients with asthma.

Detection of undegraded beta-lactoglobulins and evaluation of the molecular weight of peptides in hydrolysate cow's milk formulae.

Hydrolysate formulae have been developed with the purpose of reducing the allergenicity of cow's milk proteins, thus providing a suitable formula for feeding babies with cow's milk allergy. More recently, hydrolysate formulae have also been used with babies at high risk of atopy in order to prevent cow's milk allergy. The aim of the present study was to investigate the presence of intact cow's milk proteins and the molecular weights of peptides in several batches of two extensively hydrolyzed formulae and two partially hydrolyzed formulae. The results show the presence of a significant amount of intact beta-lactoglobulin in one partially hydrolyzed formula and of peptides with high molecular weights (>16,900 D) in the two partially hydrolyzed formulae. In conclusion, the present study confirms that partially hydrolysed formulae contain a large proportion of peptides with high molecular weights: in addition, undegraded beta-lactoglobulin was detected in a partially hydrolyzed whey formula. These data strongly indicate that partially hydrolyzed formulae may be not only allergenic in an already sensitized individual, but also immunogenic in a predisposed baby.

Natural history of IgE antibodies in children at risk for atopy.

BACKGROUND: The relationship between atopic diseases and high serum IgE levels has been emphasized since the mid-sixties, when IgE antibodies were discovered. A number of environmental factors, such as the type of feeding, passive smoking, viral infections, early mold, house dust mite and pet fur exposure modulate IgE synthesis and affect the development of atopic diseases. OBJECTIVE: The aim of the present study was to investigate the natural history of total and specific IgE antibodies in babies at risk for atopy, enrolled in a prospective study for the prevention of atopic disease, and follow-up from birth to 4 years of age. METHODS: One hundred seventy-four babies (90 boys and 84 girls) at risk for atopy were enrolled in this study. At the last follow-up the children had a median age of 52 months (range 43 to 74 months), dietary and environmental manipulations for the prevention of atopic diseases were recommended. All the infants were examined at the ages of 1, 3, 6, 9, and 12 months and twice each year subsequently when detailed histories were taken and signs and symptoms of atopic disease were sought. Total and specific IgE to cow milk, egg, soy, wheat, and Dermatophagoides pteronyssinus (Dpt) were measured at 6 and 12 months of life and then every year. RESULTS: During the first 24 months of life, the number of children with specific IgE to foods (n = 30) was significantly higher in comparison to the number of children with specific IgE to Dpt (n = 12) (P = .0006). Cow milk and egg were the most common offending foods. The number of children with IgE to cow milk (n = 14) was significantly higher than that with IgE to soy (n = 9) (P = .0011). Total serum IgE levels were significantly higher in the group of children who developed atopic disease in comparison with the group that did not (P < .01). CONCLUSION: Dietary and environmental measures may influence the IgE response in atopy-prone children, thus confirming the role of environmental factors in the modulation of the phenotypic expression of atopy.

Allergenicity of milk protein hydrolysate formulae in children with cow's milk allergy.

Cow's milk protein hydrolysate formulae have been developed to lower or eliminate the allergenicity of cow's milk proteins, and to reduce the antigenic load and the risk of sensitization. Cross-reactivity between different hydrolysate formulae and cow's milk proteins has been demonstrated. We have studied 20 children (median age 31 months, range 15-76 months) with a history of IgE-mediated cow's milk allergy. All the children had immediate allergic respiratory and/or cutaneous and/or gastro-intestinal reactions to cow's milk ingestion. In addition, the children had positive prick skin tests and positive RAST to cow's milk. Prick skin test, RAST, and double-blind placebo controlled food challenges were performed with three different hydrolysate formulae: a casein hydrolysate formula and two whey formulae, one partially and one extensively hydrolyzed. All 20 children had immediate allergic reactions after the challenge test with cow's milk. Only 2/20 children had a positive challenge test with a casein hydrolysate formula (Alimentum): one developed asthma and one urticaria. Two of the 15 children challenged with an extensively hydrolysed whey formula (Profylac) developed perioral erythema. Nine out of 20 children had a positive challenge test with a partially hydrolysed whey formula (Nidina H.A.): four developed asthma, three urticaria and two lip oedema. All children had positive prick skin tests to cow's milk proteins (casein and/or lactalbumin); 9 to Nidina H.A.; 3 to Profylac, and 3 to Alimentum. Specific IgE antibodies to cow's milk were present in all children; in 13 to Nidina H.A., in 4 to Profylac, and in 3 to Alimentum.

Soy hypersensitivity in children with food allergy.

To evaluate humoral (IgE antibodies) and clinical (positive challenge test) soy hypersensitivity prevalence, we studied 317 children (271 boys and 100 girls) with a median age of 5 months (range 1-120) who visited the Division of Allergy and Clinical Immunology of the Pediatric Department of the University of Roma "La Sapienza" because of histories and symptoms suggestive of food allergy. Atopic dermatitis (AD) was present in 247/317 children (78%), diarrhea in 19 (6%), urticaria in 22 (7%), and rhinitis and/or asthma in 29 (9%). All children underwent diagnostic procedures including family and personal history, physical examination, PRIST, and RAST to cows milk (CM), egg, wheat, soy, and Dermatophagoides pteronyssinus (Dpt). Open challenge tests to soy were performed in the hospital under observation and with emergency equipment at hand. The prevalence of humoral sensitization to CM was 54%, to egg 46%, to Dpt 35%, to wheat 24%, and to soy 22%. Only five children had IgE only to soy; six to soy and egg; and 58 to soy, CM, and egg. Only ten children (3%) had positive challenge to soy and only five of them had IgE to soy. RAST had a sensitivity of 0.69, a specificity of 0.83, a negative predictive value of 0.77, and a positive predictive value of only 0.06.

Efficacy and safety of a soy-protein-formula for feeding babies with atopic dermatitis and cow's milk hypersensitivity.

In this paper we report 21 infants with atopic dermatitis (AD) due to cow's milk (CM) hypersensitivity in 20/21 of whom a CM-free diet using as a CM-substitute a soy-protein formula improved the skin lesions, in addition to insuring a regular growth in all infants. Only one infant failed to complete the trial due to an absolute refusal of the soy protein formula. A possible secondary sensitization to soy was found in one infant, in whom dietary therapy alone was not effective. We conclude that soy-protein formulas represent an effective CM-substitute when CM must be eliminated from the diet of an infant with AD.

Skin eosinophilia from influenza viruses. An experimental histological study.

The authors would first like to stress the increasing frequency of bronchial asthma during or after influenza. To find an explanation for this occurrence they observed tissue reactions following an injection of viral material. In their experiments, they injected into the skin of guinea pigs, strains of the Hong Kong, Texas and USSR influenza viruses using current vaccines, sacrificing groups of animals 2, 6, 24, 48 hours and 7 days after the injection. The histological study revealed the following picture of reaction to influenza viruses. Two hours after the injection: marked and diffuse infiltration of eosinophils in the connective tissue of the skin. After 6 hours: the infiltration shows a predominance of neutrophils. After 24 hours: the neutrophil infiltration is predominant and diffuse. There is evidence of considerable degranulation of eosinophils. The cutaneous histiocytes undergo fibrocytic and marcophagic proliferation. After 28 hours, the same picture. After 7 days there is sever degeneration with a peripheral fibroblastic reaction. The most important finding of this experiment is the early marked infiltration of eosinophils which follows the injection of the influenza viruses. The eosinophil infiltration appears to be related to the release of histamine caused by influenza viruses. The histological examination did not reveal the presence of immune allergic-type cells at any time. Therefore, the onset of asthmatic attacks would appear to be more related to the histamine-releasing action of the influenza viruses rather than to their sensitizing activity. Naturally, the latter may occur in human pathologies.