A consensus protocol for the determination of the threshold doses for allergenic foods: how much is too much?

BACKGROUND: While the ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies, little information is known regarding these threshold doses for specific allergenic foods. While low-dose challenge trials have been conducted on an appreciable number of allergic individuals, a variety of different clinical protocols were used making the estimation of the threshold dose very difficult. OBJECTIVE: A roundtable conference was convened to develop a consensus clinical protocol for low-dose challenge trials for the estimation of threshold doses for specific allergenic foods. METHODS: In May 2002, 20 clinical allergists and other interested parties were invited to participate in a roundtable conference to develop consensus of the key elements of a clinical protocol for low-dose challenge trials. RESULTS: A consensus protocol was developed. Patients with convincing histories of food allergies and supporting diagnostic evidence including past challenge trials or high CAP-RAST scores can be enrolled in low-dose challenge trials. Care must be taken with younger patients to assure that they have not outgrown their food allergy. An approach was developed for the medication status of patients entering such trials. Challenge materials must be standardized, for example, partially defatted peanut flour composed of equal amounts of the three major varieties of peanuts (Florunner, Virginia, Spanish). Challenge materials must be appropriately blinded with sensory evaluation used to confirm the adequacy of blinding. A double-blind, placebo-controlled design should be used for low-dose challenge trials. Low-dose challenge trials would begin at doses of 10 microg of the allergenic food and would continue with doses of 100 microg and 1 mg followed by specific higher doses up to 100 mg depending upon the expert judgement of the physician; even higher doses might be applied to assure that the patient is indeed reactive to the particular food. A 30-min time interval would be used between doses, and reactive doses would be expressed as both discrete and cumulative doses. The goal of each challenge would be to develop objective symptoms; trials should not be discontinued on the basis of subjective symptoms only. Statistically, a minimum of 29 patients would be enrolled in low-dose challenge trials for each allergenic food because 0 reactors out of 29 patients at a particular dose allow the conclusion that there is 95% certainty that 90% of allergic individuals will not react to that dose. CONCLUSION: A consensus protocol was developed. Using this protocol, it will be possible to estimate threshold doses for allergenic foods, the lowest amount that elicits mild, objective symptoms in highly sensitive individuals.

Investigation of the allergenicity of a refined peanut oil-containing topical dermatologic agent in persons who are sensitive to peanuts.

We determined if a topical oil containing 0.01% fluocinolone and refined peanut oil (Derma-Smoothe/FS topical oil), among other ingredients, included materials to which peanut-sensitive individuals were sensitized. No immediate (15-min) or delayed (72-h) skin test reactivity was demonstrated in any of the 14 subjects tested. These results suggest that this refined peanut oil-containing dermatologic preparation is safe to use, even in persons who are sensitive to peanuts.

School attendance and school performance: a population-based study of children with asthma.

OBJECTIVE: To analyze school attendance and school achievement as outcomes of the care of children with asthma. METHODS: A previously identified Rochester, Minnesota, cohort of children with asthma and age- and sex-matched children without asthma were studied. School attendance, standardized achievement test scores, grade point average, grade promotion, and class rank of graduating students for children with asthma and control subjects were obtained from the Rochester Public School system. RESULTS: Children with asthma (n = 92) and age- and sex-matched non-asthmatic control subjects with 640 school-years of observation were studied. Children with asthma had 2.21 (95% CI, 1.41 to 3.01) more days absent than children without asthma. There was no significant difference in standardized achievement test scores (reading percentile difference 1.22% [95% CI, -3.68 to 6.12], mathematics percentile difference 2.36% [95% CI, -2.89 to 7.60], language percentile difference 2.96% [95% CI, -4.03 to 7.15]). There was no significant difference in grade point average, grade promotion, or class rank of graduating students. CONCLUSION: In this community, although children with asthma had 2 excess days of absenteeism, the school performance of children with asthma was similar to that of children without asthma.

The 30th anniversary of the American Board of Allergy and Immunology: then and now.

Thirty years ago the Allergy Subspecialty Boards of the American Board of Pediatrics (ABP) and the American Board of Internal Medicine (ABIM) merged to form the American Board of Allergy and Immunology (ABAI). The ABAI mission was to: establish qualifications and examine physician candidates for certification as specialists in allergy and immunology; serve the public, physicians, hospitals, and medical schools by providing the names of physicians certified by the Board; assist educational and professional organizations to improve the quality of care and availability of allergists to deliver such care, to establish and improve standards for the teaching of allergy and immunology, to establish standards for training programs, and to encourage development of increased opportunities for training of physicians interested in allergy and immunology. This mission statement has guided the activities of the Board ever since by providing a strong focus on the 2 major responsibilities: examining and certifying candidates in a fair objective way, and setting standards for the content and conduct of training programs.

Allergy to iguana.

BACKGROUND: Furry animals produce allergens that can cause allergic rhinitis and asthma. In contrast, scaly animals, such as lizards, are assumed not to be allergenic. OBJECTIVE: We sought to evaluate a 32-year-old man who complained of allergic rhinitis and asthma symptoms that occurred exclusively in his own home. He had dogs and cats at home but denied any increase in symptoms specifically associated with these pets. Skin prick testing initially performed to 42 common aeroallergens, including cat, dog, and house dust mite, elicited negative results. He later reported that the symptoms were worse on exposure to his pet iguanas. METHODS: Skin prick tests were subsequently performed to an extract made from scales from his pet iguana. Extracts were also prepared from several zoo reptiles. Immunoassays for IgE antibody, as well as IgE immunoblots, were performed by using these extracts and the patient's serum. RESULTS: The skin prick test result with the pet iguana scale extract was positive. The patient's serum contained IgE antibody to his own pet iguana and to a zoo iguana. CONCLUSION: Our patient's history, skin test results, and in vitro studies clearly demonstrate that he is allergic to iguana. Physicians should be aware that such allergy to scaly pets may occur and should not restrict history taking to questions about furry pets.

Myiasis due to Hypoderma lineatum infection mimicking the hypereosinophilic syndrome.

Myiasis is the infestation of live humans with larvae of Diptera (true flies). This report describes a protracted illness caused by infestation with Hypoderma lineatum, resembling the hypereosinophilic syndrome. A 35-year-old man had a 9-month multisystemic illness with pronounced eosinophilia, pleuritis, pericarditis, and myositis. Treatments including glucocorticoids did not alter the disease. Diagnostic studies included computed tomography, 2-dimensional echocardiography, leukocyte count, surgical biopsy of skin and muscle, blood immunoglobulin levels, and blood chemistry. Myiasis was recognized when a worm emerged from the patient's skin; after a second worm emerged, the patient's symptoms disappeared rapidly. Other determinations included IgE and IgG levels specific for H lineatum, Western blot, and immunofluorescence for eosinophil major basic protein; IgG antibodies to H lineatum decreased after emergence of the worms. The patient's symptoms mimicked the hypereosinophilic syndrome but resolved when the myiasis became apparent. Specific serologic analyses can identify infected patients, and ivermectin may be useful as treatment.

Quantitative IgE antibody assays in allergic diseases.

During the past several years, immunoassays for specific IgE antibodies have been refined to permit reporting results in mass units. Thus quantitative immunoassays for IgE antibodies may be an adjunct to skin tests. In cases of food allergy among children with atopic dermatitis, cutoff values for IgE antibody concentrations to egg, milk, peanut, and fish have been derived to provide 95% positive and 90% negative predictive values. Food-specific IgE antibody determinations can also be used to predict which food allergies are resolving spontaneously. Elevated egg-specific IgE antibody levels in infancy are associated with significantly increased risk for development of inhalant allergies later in childhood. In cases of inhalant allergy, specific IgE antibody levels correlate closely with results of inhalation challenge studies in cat-sensitive persons. Also, mite-specific IgE antibody levels correlate significantly with the mite allergen contents of reservoir dust in the homes of mite-sensitive persons. Immunoassays for quantitation of specific IgE antibodies may be used to document allergen sensitization over time and to evaluate the risk of reaction on allergen exposure. However, immunoassays and skin tests are not entirely interchangeable, and neither will replace the other in appropriate circumstances.

Detection and quantitation of raw fish aeroallergens from an open-air fish market.

BACKGROUND: IgE-mediated hypersensitivity to fish is a clinically relevant problem, particularly in several European countries. Although most allergic reactions to fish are caused by ingestion, occupational exposures to seafood allergens by inhalation have been correlated with respiratory symptoms. In Madrid, patients with fish allergy have exhibited respiratory symptoms after visits to an open-air fish market. OBJECTIVE: We sought to study the possibility of passively aerosolized fish allergen in an open-air fish market through air sampling and a competitive IgE immunoassay. METHODS: Air samples were collected on polytetrafluoroethylene filters by using air samplers. Samples were collected on 41 different days from both an open-air fish market and an outdoor residential area. Fish allergens were specifically quantified by competitive IgE immunoassay by using pooled sera from fish-sensitive individuals. A raw fish extract (10 mg of dry weight/mL) was used as the reference standard. RESULTS: Allergen was quantified in all 39 fish market air samples (2-25 ng/m(3)). The residential air samples contained no detectable allergen. The analytic limit of detection was 2 ng, allowing detection of 0.4 ng/m(3) for the air volumes collected. A concentrated (30-fold) pool of fish market air samples was tested in serial dilutions and demonstrated an identical regression line to that of the raw fish standard. CONCLUSION: By using air sampling and an immunochemical analytic technique, fish allergen is detectable in the air of an open-air fish market. Avoidance of a food allergen, such as fish, should include preventing exposure to aerosolized particles through inhalation in relevant environments.

Nebulized lidocaine in the treatment of severe asthma in children: a pilot study.

BACKGROUND: Glucocorticoids have been used to treat asthma since the 1950s; however, their adverse systemic effects have limited their duration of use and dosage. Unfortunately, many patients with severe asthma often require oral glucocorticoids in addition to inhaled glucocorticoids. Alternatives to glucocorticoids have been sought with mixed success. Recently, lidocaine has been added to the list of potent glucocorticoid sparing agents for the treatment of severe asthma. OBJECTIVE: We report the first group of pediatric patients with severe asthma treated with nebulized lidocaine. METHODS: The study was performed in an open manner with 6 severely asthmatic patients followed in the Pediatric Allergy and Immunology Section, Mayo Clinic. The only intervention was the institution of nebulized lidocaine (0.8 mg/kg/dose to 2.5 mg/kg/dose t.i.d to q.i.d). The average daily steroid requirement was followed during the administration of the nebulized lidocaine. RESULTS: During a mean of 11.2 months of therapy (range 7 to 16 months) 5 of the 6 patients completely discontinued their oral glucocorticoids within an average time of 3.4 months (range 1 to 7 months). CONCLUSIONS: After further study, lidocaine may prove to be the first non-toxic, steroid alternative to patients with severe steroid-dependent asthma.

Allergic rhinitis in Rochester, Minnesota residents with asthma: frequency and impact on health care charges.

BACKGROUND: Asthma is a common and costly condition. Concomitant asthma and allergic rhinitis (AR) have been shown to increase the medication costs for people with asthma. No studies have compared medical care costs of those with and without concomitant AR. OBJECTIVES: We sought to determine the prevalence and incremental medical care costs of concomitant AR. METHODS: For each member of a population-based asthma cohort, we used all their medical charts within Olmsted County to record age at first diagnosis of asthma; the presence and age of any diagnosis of AR; and the total, ambulatory, and respiratory care-related costs of medical care. Costs were compared for age- and sex-specific strata of people with asthma who did and did not have AR. RESULTS: AR was most commonly diagnosed in people whose asthma was diagnosed before age 25 (prevalence of 59%) and uncommonly diagnosed in anyone after age 40 (prevalence <15%). Yearly medical care charges were on average 46% higher for those with asthma and concomitant AR than for persons with asthma alone, controlling for age and sex. We were unable to assess the impact of treatment of AR on medical care charges. CONCLUSIONS: Physicians should consider the diagnosis of AR (prevalence >50%) in all symptomatic children and young adults with asthma. Further evaluation is necessary to evaluate the ability of treatment to decrease the incremental costs of AR in persons with asthma.

Inhalation challenge testing of latex-sensitive health care workers and the effectiveness of laminar flow HEPA-filtered helmets in reducing rhinoconjunctival and asthmatic reactions.

BACKGROUND: There are few data relating latex aeroallergen concentrations to biologic responses in latex-sensitized persons. OBJECTIVES: We sought to investigate acceptable latex aeroallergen concentrations below which latex-sensitive health care workers do not experience symptoms and to study the effect of high-efficiency particle arrest (HEPA)-filtered laminar flow helmets in preventing latex-induced symptoms. METHODS: Under challenge chamber conditions, latex-sensitive health care workers underwent 7 sequential inhalation challenge tests by donning and discarding either vinyl gloves (challenge 1), low latex-allergen powder-free gloves (challenge 2), or high latex-allergen powdered gloves (challenges 3 to 7) for up to 1 hour. Volunteers wore a laminar flow helmet during all challenges; HEPA filters in the helmet were in place only during challenges 3 and 4. Flow-volume loops, symptom scores, and latex aeroallergen concentrations were measured before and during each test. RESULTS: At 60 minutes, latex aeroallergen concentrations during challenges 3 to 7 (mean, 7600 ng/m3; range, 93 to 54,000 ng/m3 ) were significantly higher than during challenges 1 or 2 (mean, 65 ng/m3; range, nondetectable to 100 ng/m3 ) (P <.001). During challenges 5 and 6, mean maximum percent falls in FEV1 (-16% and -11%, respectively) were significantly greater compared with those measured during challenges 3 and 4 (-3% and -1%, respectively) (P =.03). Mean maximum change from baseline symptom scores during challenges 5 and 6 was significantly higher than that during challenges 3 and 4 (P =.006). During challenges with high latex-allergen gloves, 4 volunteers had reproducible FEV1 falls of 20% or greater at cumulative inhaled latex aeroallergen doses ranging from less than 100 ng to 1500 ng. CONCLUSION: The laminar flow helmets were effective in reducing latex-induced symptoms. Only 1 volunteer exhibited a fall in FEV1 of 20% or greater after a cumulative inhaled latex aeroallergen dose of less than 100 ng, and no volunteer showed a decline in FEV1 after exposure to powder-free low allergen gloves.

Anaphylaxis in a milk-allergic child following ingestion of lemon sorbet containing trace quantities of milk.

Although allergic persons can react to foods containing trace quantities of unlabeled or unintended food allergens, there are few data available on the quantities of these allergens required to evoke allergic symptoms. We report a milk-allergic 3-year-old boy who experienced throat itching, facial angioedema, and vomiting within 20 min of ingesting 4 to 6 oz (ca. 113.4 to 170.1 g) of lemon sorbet. Subsequent analysis of two sorbet samples provided by the parents and a third sample purchased locally by the investigators revealed trace quantities of milk allergens, whey protein (8.8 micrograms/ml), or lactose (200 ppm). The quantity of whey protein ingested was estimated to be 120 to 180 micrograms (equivalent to 23 to 24 microliters of milk). All three sorbet samples had been manufactured in the same plant within a 4-month period; the equipment used to produce and package the sorbet was also used to produce and package ice cream. No milk allergen or whey protein was detected in 38 other marketplace sorbet samples submitted by the manufacturer for testing. We concluded that trace quantities of whey proteins (< 200 micrograms) can elicit systemic reactions in exquisitely milk-allergic individuals. Such individuals should avoid eating frozen desserts prepared using equipment also used for producing or packaging ice cream, unless manufacturers can demonstrate unequivocally that their cleaning practices are sufficient to prevent milk contamination. Adequate tests are not currently available to food manufacturers but are under development.

Attained adult height after childhood asthma: effect of glucocorticoid therapy.

BACKGROUND: Although oral and inhaled glucocorticoid therapy may impair growth in children with asthma, the effect of glucocorticoid therapy and asthma on attained adult height has not been extensively studied in representative children in the community. OBJECTIVES: The study was designed to compare the attained adult height of children with asthma with the attained adult height of nonasthmatic children and to compare the attained adult height of asthmatic children treated with glucocorticoids with the attained adult height of asthmatic children who did not receive glucocorticoids. METHODS: Residents of Rochester, Minnesota, with onset of asthma from 1964 to 1987 and age- and sex-matched non-asthmatic residents of Rochester were studied. Glucocorticoid exposure was assessed from medical records. The mean of 5 stadiometer measurements of adult height, adjusted for sex and parental height, was analyzed. RESULTS: One hundred fifty-three patients with asthma (mean age at onset, 6.1 +/- 4.8 years) and 153 age- and sex-matched nonasthmatic subjects were studied. Adult height of patients with asthma (mean age at measurement, 25.7 +/- 5.2 years) was not significantly different from the adult height of non-asthmatic subjects; the overall difference, adjusted for mid-parental height, was -0.20 cm (95% confidence interval from -0.27 to 1.64). The adult height of asthmatic children treated with glucocorticoids was not significantly different from the adult height of patients with asthma not treated with glucocorticoids; the difference after adjusting for mid-parental height was -0.2 cm (95% confidence interval from -0.1 to 0.6). CONCLUSIONS: We conclude that the attained adult height of patients with asthma is not different from the adult height of age- and sex-matched nonasthmatic subjects and that the attained adult height of asthmatic children treated with glucocorticoids is not significantly different from the adult height of children not treated with glucocorticoids.