Background

The majority (∼75%) of cow's milk-allergic children tolerate extensively heated-(baked-) milk products. Long-term effects of inclusion of dietary baked-milk have not been reported.

Objective

We report on the outcomes of children who incorporated baked-milk products into their diets.

Methods

Children evaluated for tolerance to baked-milk (muffin) underwent sequential food challenges to baked-cheese (pizza) followed by unheated-milk. Immunologic parameters were measured at challenge visits. The comparison group were matched to active subjects (using age, sex, and baseline milk-specific IgE) to evaluate the natural history of tolerance development.

Results

Over a median of 37 months (range 8-75 months), 88 children underwent challenges at varying intervals (range 6-54 months). Among 65 subjects initially tolerant to baked-milk, 39 (60%) now tolerate unheated-milk, 18 (28%) tolerate baked-milk/baked-cheese and 8 (12%) chose to avoid milk strictly. Among the baked-milk-reactive subgroup (n=23), 2 (9%) tolerate unheated-milk, 3 (13%) tolerate baked-milk/baked-cheese, while the majority (78%) avoid milk strictly. Subjects who were initially tolerant to baked-milk were 28 times more likely to become unheated-milk-tolerant compared to baked-milk-reactive subjects (P<.001). Subjects who incorporated dietary baked-milk were 16 times more likely than the comparison group to become unheated-milk-tolerant (P<.001). Median casein IgG4 levels in the baked-milk-tolerant group increased significantly (P<.001); median milk IgE values did not change significantly.

Conclusions

Tolerance of baked-milk is a marker of transient IgE-mediated cow's milk allergy whereas reactivity to baked-milk portends a more persistent phenotype. The addition of baked-milk to the diet of children tolerating such foods appears to accelerate development of unheated-milk tolerance compared to strict avoidance.

Clinical implications

Addition of dietary baked-milk is safe, convenient, and well-accepted by patients. Prescribing baked-milk products to milk-allergic children represents an important shift in the treatment paradigm for milk allergy.

Capsule summary

The majority of cow's milk-allergic children tolerate extensively baked-milk products, which is a marker of transient IgE-mediated cow's milk allergy. Dietary baked-milk appears to accelerate development of unheated-milk tolerance compared to strict avoidance.

Background

Food allergy is a common and increasing health concern in westernized countries. No effective treatment is available and accidental ingestion can be life threatening. Food allergy herbal formula-2 (FAHF-2) blocks peanut anaphylaxis in a murine model of peanut-induced anaphylaxis. It was found to be safe, and well tolerated in an acute phase I study of food allergic patients.

Objective

To assess the safety of FAHF-2 in an extended phase I clinical trial and determine potential effects on peripheral blood basophils from food allergic patients.

Methods

Patients in an open-label study received 3.3 grams (6 tablets) of FAHF-2 three times a day for 6 months. Vital signs, physical examinations, laboratory data, pulmonary function tests and electrocardiographic data were acquired at baseline and at 2 month intervals. During the course of the study, basophil activation and basophil and eosinophil numbers were evaluated using CCR3/ CD63 staining and flow cytometry.

Results

Of eighteen patients enrolled, 14 completed the study. No significant drug-associated differences in laboratory parameters, pulmonary function studies, or electrocardiographic findings before and after treatment were found. There was a significant reduction (p<.010) in basophil CD63 expression in response to ex vivo stimulation at month 6. There was also a trend towards a reduction of eosinophil and basophil numbers after treatment.

Conclusion

FAHF-2 was safe, well-tolerated, and had an inhibitory effects on basophils in an extended phase I clinical study. A controlled phase II study is warranted.

Clinical Implications

FAHF-2 was safe, well-tolerated and inhibited basophils numbers and activation in a 6 month clinical trial for food allergic patients. FAHF-2 may provide a safe immunotherapeutic option for food allergic patients.

Capsule Summary

FAHF-2 was safe and well-tolerated in a six-month phase-I open label clinical trial for food allergy patients. Immunological beneficial effects of FAHF-2 were decreased basophil numbers and inhibition of activation.

Background

Food allergy is a common and serious health problem. A new herbal product, called food allergy herbal formula 2 (FAHF-2), has been demonstrated to have a high safety profile and potent long-term efficacy in a murine model of peanut-induced anaphylaxis.

Objective

To evaluate the safety and tolerability of FAHF-2 in patients with food allergy.

Methods

In this randomized, double-blinded, placebo-controlled, dose escalation, phase 1 trial, patients received 1 of 3 doses of FAHF-2 or placebo: 2.2 g (4 tablets), 3.3 g (6 tablets), or 6.6 g (12 tablets) 3 times a day for 7 days. Four active and 2 placebo patients were treated at each dose level. Vital signs, physical examination results, laboratory data, pulmonary function test results, and electrocardiogram data were monitored. Immunomodulatory studies were also performed.

Results

Nineteen food allergic participants were included in the study. Two patients (1 in the FAHF-2 group and 1 in the placebo group) reported mild gastrointestinal symptoms. One patient withdrew from the study because of an allergic reaction that was unlikely related to the study medication. No significant differences were found in vital signs, physical examination results, laboratory data, pulmonary function test results, and electrocardiogram data obtained before and after treatment visits. Significantly decreased interleukin (IL) 5 levels were found in the active treatment group after 7 days. In vitro studies of peripheral blood mononuclear cells cultured with FAHF-2 also demonstrated a significant decrease in IL-5 and an increase in culture supernatant interferon γ and IL-10 levels.

Conclusions

FAHF-2 appeared to be safe and well tolerated in patients with food allergy.

Background

Data about epinephrine utilization and biphasic reactions in childhood food-induced anaphylaxis during oral food challenges are scarce.

Objective

To determine the prevalence and risk factors of reactions requiring epinephrine and the rate of biphasic reactions during oral food challenges (OFCs) in children.

Methods

Reaction details of positive OFCs in children between 1999 and 2007 were collected using a computerized database. Selection of patients for OFCs was generally predicated on ≤50% likelihood of a positive challenge and a low likelihood of a severe reaction based on the clinical history, specific IgE levels, and skin prick tests (SPTs).

Results

A total of 436 of 1273 OFCs resulted in a reaction (34%). Epinephrine was administered in 50 challenges (11% of positive challenges, 3.9% overall); for egg (n=15, 16% of positive OFCs to egg), milk (n=14, 12%), peanut (n=10, 26%), tree nuts (n=4, 33%), soy (n=3, 7%), wheat (n=3, 9%), and fish (n=1, 9%). Reactions requiring epinephrine occurred in older children (median 7.9 vs. 5.8 years, P<0.001), and were more often caused by peanuts (P=0.006) when compared to reactions not treated with epinephrine. There was no difference in the gender, prevalence of asthma, history of anaphylaxis, specific IgE level, SPTs, or amount of food administered. Two doses of epinephrine were required in 3/50 patients (6%) reacting to wheat, cow’s milk, and pistachio. There was one (2%) biphasic reaction. No reaction resulted in life-threatening respiratory or cardiovascular compromise.

Conclusion

Older age and reactions to peanuts were risk factors for anaphylaxis during oral food challenges. Reactions requiring multiple doses of epinephrine and biphasic reactions were infrequent.