Food Oral Immunotherapy Research Articles

Determining optimal prioritization system for food oral immunotherapy in a tertiary care setting

Determining optimal prioritization system for food oral immunotherapy in a tertiary care setting

Anti-IgE treatment with oral immunotherapy in multifood allergic participants: a double-blind, randomised, controlled trial

SummaryBACKGROUNDDespite progress in single food oral immunotherapy (OIT), there is little evidence concerning the safety and efficacy of treating individuals with multiple food (multifood) allergies. We conducted a pilot study testing whether anti-IgE (omalizumab) combined with multifood OIT benefitted multifood allergic patients.METHODSIn this blinded, phase 2 clinical trial conducted at Stanford University, 48 participants, aged 4-15 years, with multifood allergies validated by double-blind, placebo-controlled food challenges (DBPCFCs) to their offending foods were block randomized (3:1) to receive multifood OIT to 2-5 foods, together with omalizumab (n=36) or placebo (n=12). Omalizumab or placebo was administered subcutaneously for 16 weeks with OIT starting at week 8; omalizumab or placebo was stopped 20 weeks before exit DBPCFCs (week 36) to determine the primary endpoint: the proportion of participants who passed DBPCFCs to at least 2 of their offending foods. This completed trial is registered with ClinicalTrials.gov, .FINDINGSAt week 36, a significantly greater proportion of the omalizumab (30/36, 83%) vs. placebo (4/12, 33%) participants passed DBPCFCs to 2 g protein for ≥ 2 of their offending foods (odds ratio (OR): 10, 95% confidence interval (CI): 1·8, 58·3, P=0·004). The same individuals also tolerated 4 g protein of ≥ 2 foods (secondary endpoint, P=0·004). A greater proportion of omalizumab (13/17, 77%) vs. placebo (0/5, 0%) participants passed a DBPCFC to 2 g protein for ≥ 4 of their offending foods (OR: 33, 95% CI: 1·9, ∞, P=0·01). All participants completed the study. There were no serious or severe (≥ grade 3) adverse events.INTERPRETATIONIn multifood allergic patients, omalizumab improves the efficacy of multifood OIT and enables safe and rapid desensitization.FUNDINGNIH U19 AADCRC and Opportunity Fund, Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Simons Foundation, Myra Reinhard Foundation, FARE Center of Excellence, Department of Pathology, and Department of Pediatrics, Stanford University.

Observational long-term follow-up study of rapid food oral immunotherapy with omalizumab

BackgroundA number of clinical studies focused on treating a single food allergy through oral immunotherapy (OIT) with adjunctive omalizumab treatment have been published. We previously demonstrated safety and tolerability of a rapid OIT protocol using omalizumab in a phase 1 study to achieve desensitization to multiple (up to 5) food allergens in parallel, rapidly (7–36 weeks; median = 18 weeks). In the current long-term, observational study, we followed 34 food allergic participants for over 5 years, who had originally undergone the phase 1 rapid OIT protocol.MethodsAfter reaching the maintenance dose of 2 g protein for each of their respective food allergens as a part of the phase 1 study, the long-term maintenance dose was reduced for some participants based on a pragmatic team-based decision. Participants were followed up to 62 months through standard oral food challenges (OFCs), skin prick tests, and blood tests.ResultsEach participant passed the 2 g OFC to each of their offending food allergens (up to 5 food allergens in total) at the end of the long-term follow-up (LTFU) study.ConclusionOur data demonstrate the feasibility of long-term maintenance dosing of a food allergen without compromising the desensitized status conferred through rapid-OIT.Trial registration Registry: Clinicaltrials.gov. Registration numbers: NCT01510626 (original study), NCT03234764 (LTFU study). Date of registration: November 29, 2011 (original study); July 26, 2017 (LTFU study, retrospectively registered)

Feasibility of sustained response through long-term dosing in food allergy immunotherapy

BackgroundClinical trials using oral immunotherapy (OIT) for the treatment of food allergies have shown promising results. We previously demonstrated the feasibility of desensitization for up to 5 food allergens simultaneously through OIT. In this observational study, we report the findings of long-term follow-up (LTFU) of the participants treated through a single site OIT phase 1 trial.MethodsThe participants (n = 46) were followed up to 72 months since the time they reached 2 g maintenance dose per food in the initial phase 1 trial. During the long-term maintenance dosing, participants continued or reduced the initial maintenance dose of food allergen protein to high (median 2 g protein) vs. low (median 300 mg protein). Participant follow-up included clinical monitoring, standardized OFCs, and in some cases, skin prick tests and measurement of allergen-specific IgE and IgG4.ResultsIrrespective of the high vs. low long-term maintenance dose during LTFU, all participants were able to ingest 2 g protein of each food allergen protein during OFCs performed at the end of our LTFU.ConclusionOur LTFU cohort of food OIT participants from a single site, phase 1 OIT study, supports the feasibility of sustained desensitization through long-term maintenance dosing.Trial registration Registry: Clinicaltrial.gov. Registration numbers: NCT01490177 (original study); NCT03234764 (LTFU study). Date of registration: November 29, 2011 (original study); July 26, 2017 (LTFU study, registered)

Oral Immunotherapy for Food Allergy : What Have We Achieved So Far?

The burden of food allergy is significant, multi-faceted, and well documented. In an effort to improve food-allergic patients’ quality of life, there is a continuous effort to provide novel treatment options for food allergy. Food immunotherapy is an exciting area of research that has seen tremendous progress over the last decade. This review examines the current literature and provides insights into key oral immunotherapy studies published so far. Areas requiring further study, the role of food oral immunotherapy, and its potential future applications for patient care are also discussed.

Elimination diet and the development of multiple tree-nut allergies

BackgroundDespite its high prevalence, relatively little is known about the characteristics of patients with multiple tree-nut allergies.MethodsPatients (n=60, aged 4-15 years), recruited for a multiple food (tree nuts, peanut, milk, egg, soy, sesame, and wheat) oral immunotherapy (OIT) study, filled a questionnaire on their initial allergy evaluation. Medical records were reviewed. At OIT enrollment (median interval, 7.5 years), patients underwent oral food challenges (OFCs) to foods still eliminated.ResultsThere was significantly less evidence for eliminating tree nuts compared with other foods, as reflected by a lower rate of acute reaction to the offending food, either as the trigger for initial allergy evaluation (5.9% for tree-nuts vs. 20-40% for other foods, respectively P<0.001) or later in life (14.5% vs. 38-75%, respectively P=0.001), and a higher rate of negative skin prick test (SPT)/specific IgE (sIgE) at initial diagnosis (25% vs. <10%, P<0.001). SPT/sIgE increased significantly from past initial levels to present for tree nuts (P<0.001) and peanut (P=0.001) but not for other foods, and most OFCs performed at present were positive.ConclusionsTree nuts are often eliminated from the diet of multiple-food-allergic patients, despite their low probability for allergy. Sensitization and allergy to most tree nuts exist years later, suggesting that it developed during the period of elimination.

Recovery from desensitization of IgE-dependent responses in human lung mast cells.

Clinical desensitization and oral food immunotherapy are therapeutic interventions that allow individuals who react adversely to an allergen (drug or food) to be made tolerant to the allergen. However, tolerance is brief, and allergen hypersensitivity can recur within days following allergen withdrawal. We hypothesize that the reason these treatments are temporary reflects rapid recovery of mast cells from a desensitized state. We sought to test this. Desensitization of IgE-mediated histamine release from human lung mast cells was explored by methods that partially replicate the pattern of treatment during clinical desensitization. Specific and non-specific desensitization and changes in surface IgE were examined following desensitization. Recovery from desensitization was also studied. Desensitization of mast cell responses was readily induced with concentrations of antigen or anti-IgE that were suboptimal for secretion. There was little or no non-specific desensitization when lung mast cells were exposed to antigens. There was no loss of cell surface IgE following desensitization. Removing the desensitizing stimulus from the media following desensitization allowed the cells to recover with half-point of recovery of ~1.5 days and complete recovery after 5 days. Both the functional response and histamine content recovered within this time frame. The recovery appeared possible because both antigens and anti-IgE dissociated rapidly from cells after washing to remove excess stimulus. Human lung mast cells readily recover from a desensitized state following removal of desensitizing antigen. This finding provides a potential explanation for the ephemeral nature of clinical desensitization.

Sustained Unresponsiveness Following Food Oral Immunotherapy (FOIT)

Sustained Unresponsiveness Following Food Oral Immunotherapy (FOIT)

Food Oral Immunotherapy (FOIT) Failures: Who and Why

Food Oral Immunotherapy (FOIT) Failures: Who and Why

The Use of Omalizumab in Food Oral Immunotherapy

Food allergy is an important health issue that affects up to 8% of the population. The management of allergic patients involves allergen avoidance and prompts the treatment of accidental reactions, as no curative treatment is available so far in routine practice. Oral immunotherapy (OIT) is a promising therapeutic alternative, but it is associated with frequent allergic reactions and cost-effectiveness issues. In hopes of reducing such reactions, a number of trials have used omalizumab, an anti-IgE monoclonal humanized antibody, as adjunctive therapy in OIT. The allergens studied in these omalizumab-enabled OIT trials include peanuts, milk, eggs, or mixes of multiple foods. In this article, we review the major findings from these studies and discuss potential benefits and issues related to omalizumab-enabled OIT. Results from the previous trials suggest that the use of omalizumab could potentially lead to safer and more efficient OIT protocols, by reducing the number and severity of reactions, and increasing allergen tolerance threshold. While more evidence is needed with regard to the maintenance of the long-term tolerance after OIT, omalizumab's potential immunomodulatory role could be of benefit. More studies are needed to further document this new indication for omalizumab.

Safety profile of oral immunotherapy with cow's milk and hen egg: A 10-year experience in controlled trials.

Oral immunotherapy (OIT) for food allergy is gaining interest due to the favorable clinical results reported with cow's milk, hen egg and peanut. The safety of the procedure remains a critical aspect that can limit the introduction of OIT in clinical practice. We described herein, in detail, the occurrence and characteristics of adverse events (AE) with OIT in children who participated in controlled trials at our unit. The clinical records of 68 children who received active treatment (40 for cow's milk and 28 for hen egg) were carefully reviewed. The inclusion and exclusion criteria, and the grading of AEs were the same across the trials. Of the 68 children involved, 6 (9%) had to discontinue the OIT procedure due to severe AEs. Fifty percent of the children underwent the buildup and maintenance phases without AEs. Mild-to-moderate AEs were documented in 28 patients, who could complete the desensitization. The majority of reactions were mild or moderate, occurred during an acute intercurrent illness and required only symptomatic treatment. A careful review of the patients who received food OIT in controlled trials confirmed that AEs were not rare but that ∼90% of children could achieve an effective desensitization. The procedure remains investigational and should be performed only by trained physicians, especially in the pediatric setting.

Primary eosinophilic gastrointestinal disorders in children who have received food oral immunotherapy

BackgroundFood oral immunotherapy (OIT) involves the administration of the food allergen causing the symptoms, in order to induce tolerance. Primary eosinophilic gastrointestinal disorders (PEGDs) are characterised by an eosinophil-rich inflammation affecting different locations of the digestive tract. We present a series of patients with PEGDs in a group of children following OIT with milk and/or egg. Material and methodsA prospective study during the period 2006–2014 was performed in paediatric patients subjected to OIT with milk and/or egg. When these children present persistent gastrointestinal symptoms, they are referred to the Paediatric Gastroenterology Unit for evaluation. ResultsPrimary eosinophilic gastrointestinal disorders were diagnosed in eight of the 128 cases of OIT (6.25%). The time to PEGDs development was variable: two cases showed symptoms during OIT, and the rest with a median time of 29 months (15–48 months). Food treatment discontinuation was not required in four of the five cases of eosinophilic oesophagitis, although food removal was necessary in patients with eosinophilic gastroenteritis. ConclusionsWe report the highest prevalence of PEGDs in children subjected to OIT, and the first cases of eosinophilic gastroenteritis following food OIT.The monitoring of new digestive signs and symptoms after OIT is crucial for the diagnosis of these disorders, and prolonged follow-up is required. The management of such patients and the need or not to eliminate the food should be assessed on an individualised basis, according to the severity of the condition, its evolution and response to different treatment alternatives.

Allergen immunotherapy: an update on protocols of administration.

Allergen immunotherapy (AIT) is still the only causal treatment for allergic rhinitis and asthma. However, conventional subcutaneous AIT administration schedules are time-consuming and safety issues still play a role; for sublingual AIT, the best efficacy is still investigated and for food allergy the best efficacy-safety balance is not yet completely discovered. Investigators have made progress in these fields lately. (Figure is included in full-text article.) Since January 2014, several (ultra) rush or cluster build-up phases with hypoallergic variants of extracts have been explored with success. Also, the efficacy of only preseasonal subcutaneous AIT was demonstrated for tree and grass pollen. Sublingual AIT was shown to be effective and well tolerated in allergic rhinitis and asthma with tablets and with highly concentrated liquid formulations (ragweed, house dust mite), but not cockroach. For food allergy, oral immunotherapy is promising, but close attention should be paid to the exact administration schedule, maintenance dose, and the definition of efficacy (desensitization or real tolerance, as defined by a negative challenge test at least 4 months off treatment). The practicing physician should be watchful for advances in the field of aeroallergen AIT and food oral immunotherapy, analyzing the presented information in detail and interpreting conclusions product specifically, without generalizing.

A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy

Although studies of oral immunotherapy (OIT) for food allergy have shown promise, treatment is frequently complicated by adverse reactions and, even when successful, has limited long-term efficacy because benefits usually diminish when treatment is discontinued. We sought to examine whether the addition of omalizumab to milk OIT reduces treatment-related reactions, improves outcomes, or both. This was a double-blind, placebo-controlled trial with subjects randomized to omalizumab or placebo. Open-label milk OIT was initiated after 4 months of omalizumab/placebo with escalation to maintenance over 22 to 40 weeks, followed by daily maintenance dosing through month 28. At month 28, omalizumab was discontinued, and subjects passing an oral food challenge (OFC) continued OIT for 8 weeks, after which OIT was discontinued with rechallenge at month 32 to assess sustained unresponsiveness (SU). Fifty-seven subjects (7-32 years) were randomized, with no significant baseline differences in age, milk-specific IgE levels, skin test results, or OFC results. At month 28, 24 (88.9%) omalizumab-treated subjects and 20 (71.4%) placebo-treated subjects passed the 10-g "desensitization" OFC (P = .18). At month 32, SU was demonstrated in 48.1% in the omalizumab group and 35.7% in the placebo group (P = .42). Adverse reactions were markedly reduced during OIT escalation in omalizumab-treated subjects for percentages of doses per subject provoking symptoms (2.1% vs 16.1%, P = .0005), dose-related reactions requiring treatment (0.0% vs 3.8%, P = .0008), and doses required to achieve maintenance (198 vs 225, P = .008). In this first randomized, double-blind, placebo-controlled trial of omalizumab in combination with food OIT, we found significant improvements in measurements of safety but not in outcomes of efficacy (desensitization and SU).

Prevalence of celiac disease in patients with severe food allergy.

The association between food allergy and celiac disease (CD) is still to be clarified. We screened for CD 319 patients with severe food allergy (IgE>85kU/l against food proteins and a history of severe allergic reactions) who underwent specific food oral immunotherapy (OIT), together with 128 children with mild allergy who recovered without OIT, and compared the prevalence data with our historical data regarding healthy schoolchildren. Sixteen patients (5%) with severe allergy and one (0.8%) with mild allergy tested positive for both genetic and serological CD markers, while the prevalence among the schoolchildren was 1%. Intestinal biopsies were obtained in 13/16 patients with severe allergy and in the one with mild allergy, confirming the diagnosis of CD. Sufferers from severe food allergy seem to be at a fivefold increased risk of CD. Our findings suggest that routine screening for CD should be recommended in patients with severe food allergy.

Clinical efficacy and immunological changes subjacent to egg oral immunotherapy

BackgroundEvidence of the efficacy of food oral immunotherapy (OIT) is not robust enough to change clinical practice from current standard management. Furthermore, the immunologic changes underlying food desensitization are unknown. ObjectiveTo establish the immunologic basal status and differences between an egg-allergic group of children and a population of nonallergic children and to investigate the safety and efficacy of a specific egg OIT protocol to induce clinical desensitization and the associated immune responses. MethodsChildren with or without egg allergy were recruited. Allergic subjects underwent an OIT protocol based on weekly doses of egg protein and a maintenance phase. Immune profile and changes in all subjects were investigated by measuring T-helper cells types 1 and 2 (TH1 and TH2) and T-regulatory cytokines and transcription factors and egg-specific IgE and IgG4 levels. ResultsAt baseline, a significantly lower production of ovalbumin-specific interleukin (IL)-10 and tumor necrosis factor-α and a trend toward higher IL-5 and IL-13 were found in allergic children. The egg OIT protocol enabled 60% of them to ingest 32 mL of egg white. Significant increases in egg-specific IgG4 levels and IL-10 production, with a trend toward lower IL-5 and IL-13 and higher tumor necrosis factor-α and interferon-γ levels, and significant decreases in egg-specific IgE concentration were observed. ConclusionEgg-allergic individuals display a bias toward TH2 type cytokine production and decreased TH1 and IL-10 responses compared with nonallergic individuals. The OIT protocol was safe and effective in inducing egg desensitization, leading to a shift in the immune profile of allergic individuals toward a nonallergic phenotype.

Simultaneous quantification of multiple specific food allergen proteins indicates varied allergen content in diagnostic and therapeutic preparations

In order to help allergic patients manage often severe symptoms, food manufacturers are required to list allergens on labels whereas researchers are working to improve diagnostics and develop effective immunotherapies. Existing tools using generic immunoassays do not provide precise identification or quantification of specific food allergens. Our goal was to develop an accurate, sensitive and high throughput assay that would enable simultaneous quantification of multiple allergens in foods and in allergen preparations used for oral food immunotherapy (OIT). Fluorescent beads coupled to allergen specific monoclonal antibodies were used to develop a multiplex array for simultaneous quantification of major allergens from peanut (Ara h 1, Ara h 2, Ara h 6), milk (Bos d 5), egg (Gal d 1), and shrimp tropomyosin. Target allergens were detected using biotinylated antibodies and streptavidin conjugated fluorochrome. The array was quantified using highly purified natural allergens as standards. Allergen content was measured in NIST Standard Reference Material (SRM) peanut butter, diagnostic extracts, and extracts used for OIT. The results were compared to ELISA. There was a high correlation between the multiplex array and allergen specific ELISA (R2= 0.82 to 0.98). The sensitivity of the array was increased by up to 40fold compared to ELISA, demonstrating accuracy as low as 20 pg/ml. Significant differences were found between specific peanut allergen levels (Ara h1: Ara h 2: Ara h 6 ratio) in NIST SRM peanut butter (4:1:1) compared with peanut flour extracts used for OIT (1:3:3) and diagnostic peanut extract (1:5:6). In conclusion, an accurate and sensitive multiplex array for major food allergens was developed, revealing the varied allergen content of diagnostic and therapeutic preparations. The flexibility of the microsphere technology allows for further expansion to produce a comprehensive array for the most important food allergens. Ultimately, this quantitative multiplex array will enable more effective assessment of the potency of food extracts used for immunotherapy and allergy diagnosis and may also help to reduce the risk of inadvertent contamination of food.

Tolerance to Allergenic Foods Following Food Oral Immunotherapy (FOIT)

RationaleFOIT treatment desensitizes most food allergic individuals, but the achievement of tolerance is uncertain. We report on 21 selected patients who underwent food challenges (FC) after FOIT was withheld for at least 30 days.MethodsRetrospective record review of FOIT patients approved by the North Texas IRB. After 453-1752 days of maintenance dosing selected patients stopped ingesting the allergenic food for 1 month and then were subjected to an open, graded FC.Results19/21 patients passed the FC (FCP) (5/5 egg, 6/7 milk, 7/8 peanut, 1/1 cashew). 15/19 FCP and 0/2 who failed the FC (FCF) had a history of anaphylaxis to the allergenic food prior to starting FOIT. Median IgE (kU/L) before beginning FOIT for FCP were egg 5.04 (0.37-49.97), milk 5.23 (1.52-10.93), peanut 10.39 (2.44-61.33), cashew 4.53; and for FCF: milk 54.24, peanut >100. Median IgE values before FC for FCP were egg 0.35 (0.1-15.9), milk 0.17 (0.08-0.3), peanut 0.96 (0.08-7.38), and cashew 1.14; and milk 1.16, peanut 11.5 for FCF. There were 0.26 epinephrine treated reactions per patient (ETRpp) during FOIT escalation and 0.05 ETRpp during maintenance for FCP. There were 2 ETRs in escalation and none in maintenance for the 2 FCF patients.Conclusions90% of selected FOIT patients achieved tolerance to their allergenic food. These data suggest that patients with high pre-OIT IgE values, high pre-FC values, and more ETRs during escalation are less likely to pass FC. More FOIT patients will need to undergo FC before meaningful conclusions may be drawn concerning tolerance. RationaleFOIT treatment desensitizes most food allergic individuals, but the achievement of tolerance is uncertain. We report on 21 selected patients who underwent food challenges (FC) after FOIT was withheld for at least 30 days. FOIT treatment desensitizes most food allergic individuals, but the achievement of tolerance is uncertain. We report on 21 selected patients who underwent food challenges (FC) after FOIT was withheld for at least 30 days. MethodsRetrospective record review of FOIT patients approved by the North Texas IRB. After 453-1752 days of maintenance dosing selected patients stopped ingesting the allergenic food for 1 month and then were subjected to an open, graded FC. Retrospective record review of FOIT patients approved by the North Texas IRB. After 453-1752 days of maintenance dosing selected patients stopped ingesting the allergenic food for 1 month and then were subjected to an open, graded FC. Results19/21 patients passed the FC (FCP) (5/5 egg, 6/7 milk, 7/8 peanut, 1/1 cashew). 15/19 FCP and 0/2 who failed the FC (FCF) had a history of anaphylaxis to the allergenic food prior to starting FOIT. Median IgE (kU/L) before beginning FOIT for FCP were egg 5.04 (0.37-49.97), milk 5.23 (1.52-10.93), peanut 10.39 (2.44-61.33), cashew 4.53; and for FCF: milk 54.24, peanut >100. Median IgE values before FC for FCP were egg 0.35 (0.1-15.9), milk 0.17 (0.08-0.3), peanut 0.96 (0.08-7.38), and cashew 1.14; and milk 1.16, peanut 11.5 for FCF. There were 0.26 epinephrine treated reactions per patient (ETRpp) during FOIT escalation and 0.05 ETRpp during maintenance for FCP. There were 2 ETRs in escalation and none in maintenance for the 2 FCF patients. 19/21 patients passed the FC (FCP) (5/5 egg, 6/7 milk, 7/8 peanut, 1/1 cashew). 15/19 FCP and 0/2 who failed the FC (FCF) had a history of anaphylaxis to the allergenic food prior to starting FOIT. Median IgE (kU/L) before beginning FOIT for FCP were egg 5.04 (0.37-49.97), milk 5.23 (1.52-10.93), peanut 10.39 (2.44-61.33), cashew 4.53; and for FCF: milk 54.24, peanut >100. Median IgE values before FC for FCP were egg 0.35 (0.1-15.9), milk 0.17 (0.08-0.3), peanut 0.96 (0.08-7.38), and cashew 1.14; and milk 1.16, peanut 11.5 for FCF. There were 0.26 epinephrine treated reactions per patient (ETRpp) during FOIT escalation and 0.05 ETRpp during maintenance for FCP. There were 2 ETRs in escalation and none in maintenance for the 2 FCF patients. Conclusions90% of selected FOIT patients achieved tolerance to their allergenic food. These data suggest that patients with high pre-OIT IgE values, high pre-FC values, and more ETRs during escalation are less likely to pass FC. More FOIT patients will need to undergo FC before meaningful conclusions may be drawn concerning tolerance. 90% of selected FOIT patients achieved tolerance to their allergenic food. These data suggest that patients with high pre-OIT IgE values, high pre-FC values, and more ETRs during escalation are less likely to pass FC. More FOIT patients will need to undergo FC before meaningful conclusions may be drawn concerning tolerance.

Oral immunotherapy for food allergy: mechanisms and role in management.

With the emergence of food allergy as an important public health problem, it has become clear that there is an unmet need in regard to treatment. In particular, IgE-mediated food allergy that is associated with risk of fatal anaphylaxis has been the subject of multiple studies in the past decade. The growing body of evidence derived from multiple centres and various study designs indicates that for IgE-mediated food allergy, immunomodulation through food immunotherapy is possible; however, the extent of protection afforded by such treatment is highly variable. At this time, the capacity for food immunotherapy to restore permanent tolerance to food has not been demonstrated conclusively. This review will discuss these topics as they apply to the most important studies of food oral immunotherapy.

Oral immunotherapy in cow's milk allergic patients: course and long-term outcome according to asthma status

BackgroundPatients with asthma and food allergy comprise a high-risk group for life-threatening reactions at accidental exposure. ObjectiveTo examine the course and long-term outcome of patients with asthma completing milk oral immunotherapy. MethodsChildren at least 6 years old with (n = 101) and without (n = 93) asthma and IgE-mediated cow's milk allergy, undergoing milk oral immunotherapy from April 2010 to December 2011, were compared. Milk dose escalations were performed until patients reached full (>7.2 g of milk protein) or partial desensitization. Skin prick tests in all patients and spirometry in those with asthma were performed. Patients who completed treatment were followed for longer than 6 months. ResultsBefore immunotherapy, patients with asthma, regardless of severity, had more anaphylactic reactions (84.2% vs 64.5%, P = .003), emergency department visits (68.3% vs 51.6%, P = .02), and hospital admissions (32.7% vs 18.3%, P = .03) compared with patients without asthma. Patients with asthma, regardless of severity, had more reactions and injectable epinephrine use during induction (P = .004) and home treatments (P = .007) of immunotherapy. Moderate to severe asthma was associated with a lower likelihood of reaching full desensitization (51.5% vs 68.8%, P = .019), but most patients with asthma (87 of 101, 86.1%), regardless of severity, reached a dose likely to protect them against accidental exposure. Most patients with asthma continued to consume milk protein freely after completion of immunotherapy. Although adverse reactions were still observed, severe reactions appeared to subside with time. ConclusionPatients with asthma are at risk for more severe reactions and are less likely to reach full desensitization during food oral immunotherapy. However, most reach limited daily consumption and most who achieve full desensitization continue to consume milk protein freely after treatment.