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

Abstract

Background

Patients with asthma and food allergy comprise a high-risk group for life-threatening reactions at accidental exposure.

Objective

To examine the course and long-term outcome of patients with asthma completing milk oral immunotherapy.

Methods

Children 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.

Results

Before 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.

Conclusion

Patients 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.

Introduction

Food allergy is a major health problem with an increasing prevalence (range 1–2% to >10%), depending on the location and the diagnostic methods used.¹ Prevalence and major allergenic food products vary geographically. Peanuts and tree nuts are the major allergenic foods in children in the United States,² Australia,³ and Great Britain,⁴ whereas shellfish is more frequent in adults. Cow's milk has been most frequently incriminated as the offending food in children in Israel⁵ and as the most common cause of fatal food anaphylaxis in the United Kingdom.⁶ Although most patients allergic to cow's milk outgrow their allergy during the first years of life, some remain allergic into adulthood.[7], [8], [9]

The standard of care for patients with food allergy is strict avoidance of the offending food and the administration of injectable epinephrine in case of anaphylactic reaction.¹⁰ However, accidental exposures attributed to unintentional ingestion, label-reading errors, and cross-contact still occur, and severe and even fatal reactions can result from underuse of epinephrine owing to fear, lack of availability, or misperception of the reaction severity.¹¹ Patients with asthma form a unique subgroup among children and adults with food allergy, with increased risk for more severe reactions and even death. For example, in 1 study examining emergency department visits because of food-related allergic reactions, symptoms from the lower airways occurred more frequently in children with anaphylaxis who had asthma compared with children without underlying asthma.¹² Coexisting asthma was associated with increased severity of food-related reactions, including fatalities, compared with other types of allergic reactions in a study from the United Kingdom.¹³ In another study, children with asthma reported more severe reactions at accidental exposure to allergenic food than did those without asthma. Moreover, the level of asthma control did not seem to be associated with the severity of allergic reactions reported.¹⁴ Taken together, these studies suggest that a child with food allergy and asthma is at higher risk for severe food-related reactions.

In recent years, several reports have emerged on the use of milk oral immunotherapy (MOIT) demonstrating efficacy and safety in most, but not all, patients, even those with severe cow's milk protein (CMP)-induced reactions.[15], [16] MOIT also might reverse IgE-mediated cow's milk allergy associated decreased bone mineral density.[17], [18], [19], [20] However, data on the course and long-term outcome of patients with asthma during food oral immunotherapy are limited. In a recent study by Vázquez-Ortiz et al,²¹ patients with asthma had more frequent and persistent reactions during MOIT, but data on controller therapy and lung function were lacking. Unfortunately, in many cases, the small number of participants or the exclusion of high-risk patients, including those with severe asthma, does not enable the specific examination of the course and outcome of MOIT in patients with asthma.[16], [20], [22], [23], [24], [25] Given their increased risk for fatal reactions at accidental exposures, it is of paramount importance to examine the course of MOIT in patients with asthma to decide whether to exclude them from such programs. MOIT was initiated at Assaf Harofeh Medical Center (Zerifin, Israel) on April 2010.¹⁸ This report describes the results of MOIT in all patients older than 6 years with and without asthma who began treatment from April 2010 through December 2011.