Blind Placebo Controlled Food Challenge Research Articles

The result of desensitization of children with severe Ig-E mediated cow’s milk allergy

Materials and methods 10 children from 6 to 10 year of age were desensitize by introducing increasing doses of cow milk (CM) till 200 ml or the highest tolerated quality for approximally 6 months. Ig-E mediated cow’s milk allergy was convinced by skin prick test and/or specific IgE. Double – blind placebo controlled food challenge has confirmed the diagnosis. All children were observed on the first and the third months after concluding the desensitization.

Fish allergy-natural history and crossreactivity between fish species

Material and methods 105 children with a diagnosis of type I allergy to fish, based on history, specific IgE (sIgE, CAP) to codfish (f3) and skin prick tests (SPT) with commercial fish extracts, are included so far. All children undergo open food challenges (OFC) with canned tuna, fresh swordfish or fresh tuna in order to evaluate whether these fishes are tolerated or not by fish allergic children. Subsequently, those children showing signs of reduced clinical reactivity are subjected to double blind placebo controlled food challenges (DBPCFC) with codfish, followed by OFC to codfish in those with a negative DBPCFC, to evaluate the natural history.

Is Aboriginal Food Less Allergenic? Comparing IgE-Reactivity of Eggs from Modern and Ancient Chicken Breeds in a Cohort of Allergic Children

BackgroundHen's egg allergy ranks among the most frequent primary food allergies in children. We aimed to investigate sensitization profiles of egg allergic patients and compare in vitro IgE reactivities of eggs from ancient chicken breeds (Araucana and Maran) with those from conventional laying hen hybrids.MethodologyEgg allergic children (n = 25) were subjected to skin prick test, double blind placebo controlled food challenge, and sensitization profiles to Gal d 1–5 were determined by allergen microarray. IgE binding and biological activity of eggs from different chicken breeds were investigated by immunoblot, ELISA, and mediator release assays.Principal FindingsWe found that Gal d 1 and Gal d 2 are generally major egg allergens, whereas Gal d 3–5 displayed high sensitization prevalence only in patients reacting to both, egg white and yolk. It seems that the onset of egg allergy is mediated by egg white allergens expanding to yolk sensitization in later stages of disease. Of note, egg white/yolk weight ratios were reduced in eggs from Auraucana and Maran chicken. As determined in IgE immunoblots and mass analysis, eggs from ancient chicken breeds did not differ in their protein composition. Similar IgE-binding was observed for all egg white preparations, while an elevated allergenicity was detected in egg yolk from Araucana chicken.Conclusion/SignificanceOur results on allergenicity and biological activity do not confirm the common assumption that aboriginal food might be less allergenic. Comprehensive diagnosis of egg allergy should distinguish between reactivity to hen's egg white and yolk fractions to avoid unnecessary dietary restrictions to improve life quality of the allergic child and its family.

Relationship Between Clinical and Laboratory Criteria and Results of Double Blind Placebo Controlled Food challenge (DBPCFC) for the IgE Mediated Cow's Milk Allergy Diagnosis in Pediatric Patients

RATIONALE: To describe the relationship between clinical, epidemiological, laboratory data and the DBPCFC for the IgE mediated cow's milk allergy (CMA) diagnosis. METHODS: It was performed 58 DBPCFC in patients aged 1-18 years, divided into two groups: group 1 (n = 39), 1.6 M:F, with a suggestive CMA and group 2 (n = 19), 1.4 M:F with inconsistent complaints of CMA. It was excluded patients with recent anaphylaxis or uncontrolled asthma. The criterium adopted for positive SPT was a wheal ≥ to 3 mm and ImmunoCAP ≥ 3.5 kU/L. The personal and family history of atopy were described in frequency and confidence interval and compared by Fisher's test. The eosinophil count, IgE levels and specific IgE to cow's milk and fractions: skin prick test (SPT) and ImmunoCAP were described by medians and the comparison between groups was done by Mann-Whitney test. The significance level was 5%. RESULTS: There was a significant association between positive DBPCFC and history of atopic disease (p= 0.037), positive DBPCFC and SPT: fresh LV (p <0.001), LV (p <0.001), betalactoglobulin (p <0.001) and casein (p = 0.04) and positive DBPCFC and ImmunoCAP for LV, betalactoglobulin and casein (p <0.001); besides alphalactoalbumin (p = 0.001). CONCLUSION: This study suggests the possibility of developing a score for CMA diagnosis including epidemiological, clinical and laboratorial findings that could eliminate the need to perform DBPCFC in a significant number of children.

The EuroPrevall surveys on the prevalence of food allergies in children and adults: background and study methodology

The epidemiological surveys in children and adults of the EU-funded multidisciplinary Integrated Project EuroPrevall, launched in June 2005, were designed to estimate the currently unknown prevalence of food allergy and exposure to known or suspected risk factors for food allergy across Europe. We describe the protocol for the epidemiological surveys in children and adults. This protocol provides specific instructions on the sampling strategy, the use of questionnaires, and collection of blood samples for immunological analyses. The surveys were performed as multi-centre, cross-sectional studies in general populations. Case-control studies were nested within these surveys. The studies in children aged 7-10 years and adults aged 20-54 years were undertaken in eight centres representing different social and climatic regions in Europe. After a community-based survey collecting basic information on adverse reactions to foods, all those stating they had experienced such reactions, as well as of a random sample of those stating 'no reactions' to foods, completed a detailed questionnaire on potential risks and exposures. Also a blood sample was taken to allow serological analysis to establish patterns of food and aeroallergen sensitization. We also included a questionnaire to schools on their preparedness for dealing with food allergy amongst pupils. Subjects reporting adverse reactions to foods and sensitized to the same food(s) were called in for a full clinical evaluation that included a double blind placebo controlled food challenge (DBPCFC), following a protocol which is described in detail elsewhere. The outcome of these studies will help to improve our understanding of several important aspects of food allergies in the European Community, providing for more well-informed policies and effective measures of disease prevention, diagnosis and management.

The Role of Diet in Symptoms of Irritable Bowel Syndrome in Adults: A Narrative Review

This review summarizes what is known about the effect of diet on irritable bowel syndrome (IBS) symptoms emphasizing data from randomized, controlled clinical trials. Studies suggest that IBS symptoms in one quarter of patients may be caused or exacerbated by one or more dietary components. Recent studies indicate that a diet restricted in fermentable, poorly absorbed carbohydrates, including fructose, fructans (present in wheat and onions), sorbitol, and other sugar alcohols is beneficial, but confirmatory studies are needed. Despite a long history of enthusiastic use, fiber is marginally beneficial. Insoluble fiber may worsen symptoms. Some patients with IBS, especially those with constipation, will improve with increased intake of soluble fiber. Prebiotic fibers have not been adequately tested. Daily use of peppermint oil is effective in relieving IBS symptoms. The usefulness of probiotics in the form of foods such as live-culture yogurt and buttermilk for IBS symptoms is not established. In clinical practice, it is very difficult to establish that a patient's symptoms result from an adverse reaction to food. A double blind placebo-controlled food challenge is the most reliable method, but it is not suitable for routine clinical use. A modified exclusion diet and stepwise reintroduction of foods or trials of eliminating classes of food may be useful.

Rice ( Oryza sativa) allergy in rhinitis and asthma patients: A clinico-immunological study

Sensitization to foods varies in different countries reflecting a possible interaction of genetic factors, cultural and dietary habits. Rice is a major food consumed world wide and needs evaluation for IgE mediated reactions. The present study was carried out to identify rice allergy in patients of rhinitis and asthma and identify the allergenic proteins in raw and cooked rice. Of 1200 patients screened using standard questionnaire, 165 presented with history of rice allergy. Of these, 20 (12.1%) patients demonstrated marked positive skin prick test (SPT) and 13 showed significantly raised specific IgE to rice compared to normal controls. Double blind placebo controlled food challenge (DBPCFC) confirmed rice allergy in 6/10 patients. Immunoblot with hypersensitive individual patients’ sera showed 14–16, 33, 56 and 60 kDa proteins as major IgE-binding components in rice. Boiled rice retained four IgE reactive proteins of 16, 23, 33 and 53 kDa. In summary, IgE-mediated rice allergy affects 0.8% [(0.42–1.58) at 95% CI] of asthma and rhinitis cases. The subjects with severe SPT reactions (4 mm or above) and specific IgE, 6.9 ng/ml to rice demonstrated positive blinded food challenge with clinical symptoms.

Prise en charge clinique d’une allergie alimentaire (AA)

Food allergy is of difficult diagnosis relying on clinical history, skin prick tests and specific IgE antibodies measurements. Therefore, a double blind placebo-controlled oral food challenge is sometimes necessary. The primordial treatment consists in dietetic elimination which is only required for 2% or 3% of adults, and for 6% or 8% of children, who are really allergic because of the risk of anaphylactic reaction after an unintended ingestion. In future, new treatments (immunotherapy, monoclonal antibodies against IgE) and dietary prevention (breast-feeding, delayed introduction of solid foods) should limit the constant increase of these allergies, and facilitated the management, especially for the most frequent and powerful allergens (peanuts).

The clinical investigation of kiwi fruit allergy

Rationale Allergy to kiwi fruit appears increasingly common, but few studies have evaluated its clinical characteristics. Methods 273 subjects with a history suggestive of allergy to kiwi completed a questionnaire. 45 were investigated by double blind placebo controlled food challenge (DBPCFC), prick-to-prick skin testing with fresh kiwi pulp, and measuring CAP specific IgE. 19 subjects were also skin tested using a commercially available solution. Results The most frequently reported symptom was oral pruritus (65%), but severe symptoms (wheeze, cyanosis or collapse) were reported by 18% of subjects. Young children were significantly more likely than adults to react on their first known exposure (p<0.001), and to report severe symptoms (p=0.008). 23 of 45 subjects (50%) had allergy confirmed by DBPCFC. Prick to prick skin test with fresh kiwi was positive in 95% of subjects who had allergy confirmed by DBPCFC, but also in 69% of subjects with a negative food challenge. The commercial extract was significantly less sensitive, but with fewer false positive reactions. CAP sIgE was only positive in 60% of subjects who had a positive challenge. Conclusions DBPCFC confirmed allergy to kiwi fruit in 50% of the subjects tested, who had a previous history suggestive of kiwi allergy. Skin testing with fresh fruit has good sensitivity (95%), but poor specificity (31%) in this population. CAP sIgE and a commercially available skin test solution were both much less sensitive (60%; 72%) but had better specificity (83%; 67%). Kiwi fruit should be considered a significant food allergen particularly for young children.

Presence of allergenic food in the diet of children given a prophylactic allergen-restricted diet

Rationale Infants at high risk for developing food allergy are advised to delay the introduction of highly allergenic foods. The purpose of this study was to verify the complete avoidance of these foods as reported by the parents. Methods In 22 children double blind placebo-controlled food challenges (DBPCFC's) were performed with foods which had been eliminated from the diet from birth. The presence of the eliminated allergenic foods in the diet was ascertained by an experienced dietitian. Specific food frequency questionnaires for foods containing either milk, egg, soy, peanut or nuts were developed (but not validated) and adapted to foods and brands frequently used in the Netherlands. Special attention was paid to the correct reading of labels on commercial products. The composition of manufactured foods was verified by inquiring with the manufacturers or obtaining data available from the Allergen Databank Alba (TNO Nutrition and Food Research, the Netherlands). Results The detailed dietary history was inconclusive in 9 children (41%), revealed no allergenic foods in the diets of 4 children (18%), but showed incidental presence of the allergenic foods in the diets of 9 children (41%). None of these unintentional ingestions resulted in clinical reactions. However, in 4 of the 9 children who inadvertently ingested small amounts of the allergenic food by history, DBPCFC with the same food was positive. Conclusion Complete dietary avoidance of allergenic foods is difficult and often incomplete. Ascertainment of previous asymptomatic ingestion of small amounts of allergenic foods does not preclude positive challenge reactions.

Different kinetics of mediator release can be detected during allergic reactions after oral provocation (double blind placebo-controlled food challenge).

Different kinetics of mediator release can be detected during allergic reactions after oral provocation (double blind placebo-controlled food challenge).

Anaphylaxis Caused by Mannitol in Pomegranate

Immediate hypersensitivity reactions resembling anaphylaxis have been reported in some patients during intravenous infusion of 20% mannitol (1100 mM), an osmotically active agent. An unusual case of anaphylaxis to mannitol arising out of ingestion of pomegranate (Punica granatum) fruit is presented here. Immediate (type I) hypersensitivity to pomegranate was confirmed by skin prick test (SPT) and double- blind placebo-controlled food challenge (DBPCFC). The allergen was identified as mannitol by SPT, following its isolation from pomegranate juice by ion-moderated cation-exchange chromatography. As little as 0.25 ml of pomegranate juice (derived from ~0.4 g pomegranate fruit), containing mannitol at a concentration of 0.22 mM, caused subjective and objective symptoms of immunoglobulin E (IgE)-mediated allergy in DBPCFC.

Allergen recognition patterns in a Dutch hazelnut allergic population in relation to reactivity patterns as observed during double blind placebo controlled food challenges (DBPCFC)

Allergen recognition patterns in a Dutch hazelnut allergic population in relation to reactivity patterns as observed during double blind placebo controlled food challenges (DBPCFC)

Cyclic vomiting syndrome and food allergy/intolerance in seven children: a possible association.

Cyclic vomiting syndrome (CVS) is characterized by repeated unpredictable, explosive and unexplained bouts of vomiting. The episodes have a rapid onset, persist over a number of hours or days, and are separated by symptom-free intervals. Despite the recent interest in this disorder, its aetiology, pathogenesis and even its target organ remain unknown. The purpose of this study is to investigate the role played by food allergy in CVS. The report concerns eight children (five male, three female), mean age 8 years (3-13 years), suffering from CVS for 2 years at least. The diagnosis of CVS was based on characteristic history, normal physical examination and negative laboratory, radiographic, neurological and endoscopic studies. Despite the absence of clinical signs typical of food allergy, skin prick tests were positive in six of the eight patients (75%). Specific IgE were present in 4/8 (50%) of the patients. Skin tests and specific IgE were positive for cow's milk proteins, egg white and soya. IgE levels were higher than the mean + 2SD in 5/8 (63%) of the patients. A double blind placebo controlled food challenge (DBPCFC) was carried out on seven of the eight patients who displayed clinical improvement after an elimination diet for cow's milk (and other foodstuffs indicated by positive skin tests). The DBPCFC was positive in all seven children. Clinical follow-up revealed a state of well-being over the 6 months of observation. It appears reasonable to suggest that food allergy plays a role in cyclic vomiting syndrome.

Food allergy and intolerance in children and adolescents, an update.

Epidemiological surveys demonstrate that rapid increase in allergic diseases is a real phenomenon. In developed countries they are about the commonest chronic diseases, reaching between 15% and 30% of the population. Adverse reaction to food can be divided into toxic reaction and non-toxic reactions. The non-toxic reactions are divided into non-immune mediated and immune mediated, these are considered food allergic reactions. We showed our experience in a 4 y survey, individualized by food allergens during the first two years of life. In Spain egg white protein is the most common allergen followed by cow's milk and peanuts. These three food items represent half of the sensitizations in children under 2 y of age. After 4 y sensitivities to vegetable allergens such as nuts, fruits and legumes are most frequent. The diagnosis of food allergy is still problematic, even in the case of atopy or IgE mediated hypersensitivity. There is a lack of standardized diagnostic procedures; the only test accepted as 'gold standard' for confirmation of food allergy and in general for food intolerance, is a properly performed double blind placebo-controlled oral food challenge. Negative results should be always followed by an open food challenge. This test should only be conducted in patients with a good medical condition and in a clinic or hospital setting, and only if trained personal and equipment for treating systemic anaphylaxis are present. Contraindications to a challenge test are limited to those situations that can be hazardous for the patient in relationship to the studied food. The treatment of food allergy and intolerance is avoiding the implicated food as long as necessary, until tolerance appears. Prevention of food allergy is the first goal of every pediatric allergologist. Controlled trials of food allergy prevention have been performed only in high allergic risk children.

Effects of Structure Modifications on IgE Binding Properties of Serum Albumins

Background: Bovine serum albumin (BSA) is one of the most widely studied proteins; its structure is well–known and its antigenic characteristics have been described in studies performed in in vitro and animal models. The aim of our work was to evaluate the role of BSA conformation in its antigenicity (recognition by circulating IgEs from allergic children). Methods: This study was performed using electrophoresis associated with the immunoblotting technique, where sera from children sensitized to BSA (as shown by double–blind placebo–controlled food challenge) were used. Results and Discussion: Heat treatment and chemical denaturation (SDS treatment) are not able to decrease the BSA capability to bind circulating IgEs. Only by reducing treatment with 2–mercaptoethanol is it possible to modify but not to eliminate the antigenicity of this protein. The reactivity to other serum albumins from different animal species was also investigated and in this study we show a direct correlation between the number of IgE–mediated responses observed in immunoblotting and the percentage of sequence identity (phylogenetic similarity) of serum albumins. Conclusion: Data obtained in this research indicate that serum albumin antigenicity is only partially correlated to its native three–dimensional structure.

CLINICAL EVALUATION OF OPEN FOOD CHALLENGE TEST USING DRIED FOOD (JUICE) CONTAINING FREEZE-DRIED EGG WHITE IN CHIDREN WITH EGG ALLERGY

A dried food (juice) containing freeze-dried egg white and a placebo were obtained. The usefulness of the dried food in pediatric allergy practice was evaluated in 50 infants and children who had eliminated consumption of eggs and egg products due to confirmed or suspected egg allergy. The purpose of the challenge test with the dried food was to assess the degree of immediate-type hypersensitivity and/or tolerance to egg.This test was carried out using the single open food challenge method. Because the amount of the dried food administered as the test dose depends on the degree of hypersensitivity, 1 to 10mg of dried food (0.38-3.8mg freeze dried egg white) was set as the initial dose. If no reaction occurred within 30 minutes, the dose was increased 5-fold to 10-fold in subsequent tests until 7, 700mg was reached. No reaction at 7, 700mg was defined as negative test to egg. Results were as follows.1. Immediate-type reaction was found in 25 patients, and the amount of dried food administered by onset of apparent immediate reaction ranged from 10 to 7, 700mg.2. Non-immediate type of reaction was revealed respectively in 2 and 3 cases, and biphasic reaction of immediate and late types was observed in 2 patients.3. Negative test to egg was observed in 18 patients.4. No patient experienced esystemic anaphylactic reaction due to those challenge test.5. Placebo-food was adopted, when in presumption of uncertain result, and was used in 23 for single blind and in 13 cases for double blind placebo-controlled food challenge tests.Though there were some aspects of this procedure of this test with dried food containing freeze dried egg white that should be improved, it was thought that when by the above-mentioned method, this food was adapted for clinical evaluation of hypersensitivity to egg, particularly for purposes of assessing the degree of hyper-sensitivity and/or tolerance to egg.

Evaluation of a multiple food specific IgE antibody test compared to parental perception, allergy skin tests and RAST

This study was set up to evaluate the food panel of a multiple specific IgE antibody assay in 67 atopic asthmatic children by comparing it to the conventional radioallergosorbent test (RAST) and skin-prick tests (SPT) and then comparing the results of these investigations with the parents' perceptions of food related problems. Fifteen food specific IgE antibodies were measured using the multiple chemiluminescence assay (MAST-CLA). IgE antibodies to five of these food allergens were also measured by conventional RAST and SPTs were performed in 43 using 11 standardized food extracts matched to the multiple allergosorbent chemiluminescent assay (MAST-CLA) profile. SPT and MAST-CLA results showed good agreement with one another, range 68.8-96.7% (average 87%), with significant correlation for most allergens tested. MAST-CLA was discrepant with RAST and/or SPTs in 58/210 (27.6%). A questionnaire was sent to the parents to determine their perception of food related symptoms. Sixty-two (92%) questionnaire replies were received, of which 56% reported symptoms with food. The most frequent symptom perceived to be due to food intolerance was behavioural disturbance. The commonest foods implicated were additives (39%), egg (27%), milk (26%), chocolate (23%) and orange (15%). History, SPT, MAST-CLA and RAST were compared for five allergens in 42 patients (210 values). In 14/210 (6.7%), all the tests were negative despite reported symptoms. Conversely in 49/210 (23.3%) at least one test was positive without symptoms. This study did not support a benefit of multipole testing instead of individually selected RASTs or SPTs.(ABSTRACT TRUNCATED AT 250 WORDS)

68 Nasal mediator release following double blind placebo-controlled oral food challenges (DBPCFC)

68 Nasal mediator release following double blind placebo-controlled oral food challenges (DBPCFC)