Lethal food allergy in children.
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Biomedical subjects
Publications and source records attributed to J W Yunginger.
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Interobserver variability during the data collection for a large retrospective study of asthma was assessed. After extensive training by three physician investigators, two nurses collected study data from existing medical records using an explicit protocol. At four time intervals, samples of records already abstracted by one nurse were reviewed and re-abstracted by another nurse assigned to the project. The unweighted kappa coefficient was used to evaluate observer reliability. Most of the kappa coefficients were > or = 0.6, suggesting good to excellent agreement. Agreement was highest for demographic, clinical and medication variables, while judgement variables had the lowest kappa coefficients. The well known dependence of kappa on the prevalence of the variable studied was evident in these data. We strongly recommend periodic monitoring of observer reliability in any study using more than one individual to collect data to ensure reliable data collection.
With the emergence of the acquired immunodeficiency syndrome (AIDS) epidemic and the practice of protecting health-care workers from all body fluids, the use of rubber gloves has increased, as has occupational allergy to latex among health-care workers. During 1991, 49 Mayo Medical Center employees sought assessment and treatment of rhinitis, conjunctivitis, contact urticaria, contact dermatitis, asthma, or eczema thought to be related to exposure to latex. Most of these persons had a history of atopy and worked in areas where rubber gloves were used and changed frequently. Of the 49 subjects, 34 had positive results of skin tests to latex products, and the sera from 19 of 35 persons tested contained increased latex-specific IgE antibodies. Employees with sensitivity to latex (and co-workers in the immediate areas) should use vinyl gloves and should notify their own health-care providers of their sensitization. Changes in job assignment may be necessary for some persons.
Approximately 1 to 3% of the general population has had a systemic reaction to insect stings. Adults whose reactions include urticaria, obstruction of the upper or lower airway, or hypotension and children whose reactions include obstruction of the upper or lower airway or hypotension have an increased risk of future systemic reactions to stings. Allergy skin tests to Hymenoptera venoms can help to identify the offending insect and to classify the reactions as allergic; however, because 15% of the general population may have positive results to such tests, persons who have not experienced a systemic reaction to insect stings should not be tested. Venom immunotherapy is highly effective and confers 98 to 99% protection in patients who have experienced previous systemic reactions to insect stings. Reaction rates to venom skin tests or venom immunotherapy are low and are similar to those in allergy testing and immunotherapy for hay fever. Generally, patients who have had systemic reactions to stings should be assessed by an allergist to determine whether they are candidates for immunotherapy with Hymenoptera venom. The decision to institute venom immunotherapy should be based on the disposition of the patient, the severity of the reaction, and the risk of subsequent stings. Deliberate sting challenges are clinically useful for guiding immunotherapy.
To determine whether the incidence of asthma had increased in Rochester, Minnesota, from January 1, 1964 through December 31, 1983, we used a population-based computer-linked medical diagnosis system to identify individual medical records with diagnosis of asthma or other conditions mimicking asthma. All records were reviewed using explicit predetermined diagnostic criteria; we identified 3,622 incident cases of asthma, including definite asthma (n = 1,547), probable asthma (n = 952), and single wheezing episodes (n = 1,123). The annual age- and sex-adjusted incidence of definite + probable asthma rose from 183 per 100,000 in 1964 to 284 per 100,000 in 1983. This rise was entirely accounted for by increased incidence rates in children and adolescents (age range, 1 to 14 yr); incidence rates for infants younger than 1 yr of age and for adults remained constant. For definite + probable asthma cases, the incidence rates for males were higher than for females from infancy through 9 yr of age and for persons older than 50; incidence rates for females were higher than for males from 15 through 49 yr of age. The median age at onset was 3 yr for males and 8 yr for females. We conclude that asthma begins in early childhood, with a higher incidence and earlier onset in males, and that the increase in incidence rates seen from 1964 to 1983 occurred only in children and in adolescents.
Systemic anaphylaxis results from the sudden release of mediators from a variety of inflammatory cells. Most reactions are due to insect stings, food allergy, immunotherapy injections, or pharmaceutical products. Anaphylaxis is easily recognized in most cases, although persons found unresponsive or who exhibit hypotension without urticaria or cutaneous angioedema present special diagnostic problems. Most reactions respond promptly to aggressive therapy, although fatalities occasionally occur. Optimal long-term care of patients with anaphylaxis involves accurate identification of triggering agents, education regarding allergen avoidance, and self-administration of epinephrine in case of future reactions.
Milk-allergic persons often rely on kosher labeling to select dairy-free foods. A 2-year-old boy experienced multiple generalized reactions after ingestion of milk or milk products; his serum contained elevated levels of milk-specific IgE antibodies, and his milk skin test was strongly positive. An identical reaction occurred after ingestion of "pareve"-labeled raspberry sorbet. Using an inhibition immunoassay with pooled sera from two milk-sensitive persons as the source of IgE antibodies, we found the milk allergen level in sorbet provided by the family to be 11% of the level found in non-fat dry milk. The milk allergen level in three independently purchased containers of sorbet ranged from 2% to undetectable. The presence of milk in three of four of the sorbets was confirmed by immunoblotting studies, by quantitation of milk proteins by polyacrylamide gel electrophoresis, and by quantitation of lactose by gas chromatography. Subsequently, it was discovered that milk was incorporated into the sorbet when equipment used to package ice cream had been used to package the sorbet. Although kosher labeling may provide assurance to milk-sensitive persons that a particular food does or does not contain milk, such labeling is no guarantee that this is indeed the case.
BACKGROUND: Exposure to airborne spores of the common mold Alternaria alternata has been implicated in asthma attacks. Such exposure is particularly frequent in the Midwest during the summer and fall months. To determine the role of A. alternata in triggering severe asthma attacks, we investigated the cases of 11 patients with asthma who had sudden respiratory arrest and determined the frequency of sensitivity to this allergen in these patients. METHODS: The 11 patients (age range, 11 to 25 years) with initial episodes of respiratory arrest, which was fatal in 2 patients, were identified in the course of their care in our pediatric and adult clinical allergy practice and by a retrospective review of all Mayo Clinic records of patients with severe asthma cared for between 1980 and 1989. Skin-test reactivity to A. alternata and levels of IgE antibody against this mold in the 11 patients were compared with those in 99 matched controls with asthma who had no history of respiratory arrest. RESULTS: All the patients came from the upper Midwest, and the episodes of respiratory arrest occurred in the summer or early fall. Ten of the 11 patients with asthma who had respiratory arrest (91 percent) had positive skin-puncture tests for sensitivity to alternaria, as compared with 31 percent of the controls (P less than 0.001), and the serum levels of IgE antibodies to alternaria were elevated in all 9 patients tested. Among the covariates we examined (age, sex, and distance from the Mayo Clinic), only age was a significant confounder. After adjustment for age, alternaria skin-test reactivity was found to be associated with an increase of approximately 200-fold in the risk of respiratory arrest (adjusted odds ratio, 189.5; 95 percent confidence interval, 6.5 to 5535.8). CONCLUSIONS: Exposure to the aeroallergen A. alternata is a risk factor for respiratory arrest in children and young adults with asthma.
We prospectively studied 51 self-selected Hymenoptera sting-sensitive patients to determine (1) whether a minimal or optimal duration for venom immunotherapy (VIT) exists and (2) whether clinical or immunologic parameters exist that are predictive of clinical immunity after VIT was stopped. After 2 to 10 years of VIT, all patients had deliberate sting challenges (DSCs) from live insects. If DSCs were tolerated, patients voluntarily stopped VIT and returned annually for repeat venom skin tests (VSTs) and DSCs. In most patients, it was possible to monitor VST and venom-specific antibody (Ab) levels before and after VIT was stopped. One-year after VIT, VST and venom-specific IgE and IgG Ab level results were variable; 49 patients tolerated DSC, whereas two patients exhibited generalized reactions. These two patients had pre-VIT histories of grade IV field-sting reactions and had received VIT for 2 years and 4 years, respectively. The short-term (1 year) risk of recurrence of clinical allergy to stings after VIT was higher in patients who had experienced grade IV field-sting reactions before VIT versus patients experiencing grade I to III reactions before VIT (2/15, 13% versus 0/36, 0%) and higher in patients who had received VIT for less than 5 years versus patients who received VIT for 5 or more years (2/20, 10% versus 0/31, 0%). We suggest that VIT should be continued for 5 years in patients with pre-VIT field-sting reactions of grade IV severity. VST and venom-specific Ab results do not reliably predict the outcome of DSC or the subsequent clinical course in individual patients stopping VIT.
This study, using an improved histamine assay, repeated previous studies that demonstrated large doses of morphine for induction of anesthesia in patients undergoing coronary artery bypass grafting were associated with histamine release. Thirty randomized patients received infusions of either morphine, 1 mg/kg, oxymorphone, 0.2 mg/kg, or fentanyl, 50 micrograms/kg, over a 10-minute period for induction of anesthesia prior to surgery. There were no significant changes in plasma histamine levels in individual patients or among drug groups. The discrepancy between the present histamine results and those previously reported using similar protocols is due, in part, to variations in plasma histamine measurements that can occur using the less reproducible, older assays for histamine. During routine inductions, large doses of morphine, oxymorphone, or fentanyl administered by infusion do not appear to stimulate release of clinically significant plasma levels of histamine.
To establish a useful laboratory protocol to investigate possible cases of fatal anaphylaxis, we measured mast-cell-derived tryptase levels and allergen-specific immunoglobulin E (IgE) antibody levels in sera obtained prior to or within 24 h after death from 19 anaphylaxis victims. Elevated serum tryptase levels (range = 12 ng/mL to 150 micrograms/mL) were found in nine of nine Hymenoptera sting fatalities, six of eight food-induced fatalities, and two of two reactions to diagnostic therapeutic agents. Tryptase levels were normal (less than 10 ng/mL) in 57 sequential sera obtained postmortem from six control patients. Tryptase could not be measured in pleural or pericardial fluids for technical reasons. Serum IgE antibodies were elevated in five of the nine Hymenoptera sting fatalities and in eight of the eight fatal food reactions; assays were unavailable for the two diagnostic/therapeutic agents. If elevated, the victim's serum IgE antibodies to food could be used to identify allergens in uneaten portions of foods consumed shortly before the anaphylactic event. IgE antibodies were moderately stable during storage in a variety of anticoagulants at room temperature for up to 11 weeks. Elevated mast-cell-derived tryptase levels in postmortem sera reflect antemortem mast cell activation and may be used as a marker for fatal anaphylaxis. If assays are available for IgE antibodies to relevant allergens, such assays provide evidence for antemortem sensitization; these assays may be modified to identify allergens in foods consumed by victims of food-induced anaphylaxis.
Results from three in vitro assays for allergen-specific IgE, the standard Phadebas radioallergosorbent test (PhRAST), modified RAST (mRAST), and the new Pharmacia CAP System (CAP) were compared with skin prick testing (SPT) results in 104 patients with allergic rhinitis and/or asthma and 24 nonatopic controls. Five allergens were evaluated: cat, Dermatophagoides pteronyssinus, Alternaria, June grass, and short ragweed. Using SPT results as the reference standard, the PhRAST had the lowest sensitivity (62%) and highest specificity (99%). The CAP achieved higher sensitivity (74%) with comparable specificity (96%) while the mRAST had even higher sensitivity (90%) but lower specificity (87%). The overall frequency of positive results in controls was 0% for PhRAST, 1.7% for CAP, and 3.3% for mRAST. If the threshold for a positive mRAST was raised to greater than or equal to class 2, this assay achieved performance characteristics similar to the CAP. If the results of these in vitro tests are used as the sole guide to the prescription of environmental control and immunotherapy in unselected patients with rhinitis and asthma, the performance characteristics of the CAP make it the preferred test.
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Recent evidence suggests that interferon-gamma (IFN-gamma) is a potent inhibitor of IgE synthesis in rodents. We conducted a randomized, placebo-controlled, two-period clinical trial of human recombinant IFN-gamma in the treatment of allergic rhinitis. Forty-five adults with well-documented ragweed-allergic rhinitis were randomized into three groups of 15 adults each and received subcutaneous injections three times weekly. The first treatment period (4 weeks during the off season) began on April 18, 1988; the second treatment period (6 weeks during ragweed pollination) began on August 15, 1988. All subjects received the same treatment in both periods. Group 1 received 0.2 mg per injection of IFN, group 2 received 0.02 mg of IFN, and group 3 received placebo. One subject in group 1 and three subjects in group 2 withdrew because of adverse reactions, and three subjects withdrew for personal reasons. There were no significant differences in mean weekly symptom scores or supplemental medication scores among the three groups in either treatment period. Furthermore, there were no significant differences in the changes of serum IgE antibody to crude ragweed extract or in serum total IgE among the three groups during or before the ragweed-pollination season. These results indicate that this treatment regimen with IFN-gamma does not alter IgE production in patients with ragweed hay fever and indicate the need for further clinical research of lymphokine modulation of IgE production.
Africanized honeybees (HBs) pose a hazard to both normal and sting-sensitive subjects in certain areas of Central and South America, and it is predicted that they will soon be present in the southern United States as well. Using an electrical stimulation device, we collected Africanized HB venom (AHV) in Venezuela and European HB venom (EHV) in Louisiana. These venoms, along with commercial European HB venom (CHV), were compared by thin-layer isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The Coomassie brilliant blue and silver-stained banding patterns of AHV and EHV were essentially identical to CHV. Western blots were prepared from SDS-PAGE gels and tested with pooled sera from EHV-sensitive subjects and then radiolabeled antihuman IgE. The resulting autoradiographs revealed similar banding patterns among EHV, AHV, and CHV. RAST-inhibition studies were performed with solid-phase CHV and pooled sera from EHV-sensitive subjects. The specific allergenic activities of the three HB venoms (allergy units per milligram of protein) were comparable. By RAST-inhibition assay with solid-phase, highly purified individual venom components, AHV and EHV both contained phospholipase A2, hyaluronidase, and high-molecular-weight allergens. The increased morbidity after Africanized HB stings is likely related to their more defensive behavior during which many bees react by stinging rather than to biochemical or allergenic differences between AHV and EHV.
Although the floral industry deals with many potential allergens, few examples of occupational asthma exist in this industry. A 22-year-old florist experienced symptoms of rhinitis, conjunctivitis, and asthma on exposure to baby's breath. To determine the contribution of baby's breath to the patient's symptoms, an extract of baby's breath was prepared. Prick skin tests with a 1:10(-5) wt/vol concentration of the extract produced an immediate response, whereas nonexposed atopic and normal control subjects did not react. The patient's asthmatic response to baby's breath was confirmed by bronchial challenge that caused an immediate fall in FEV1 of 26.2% from baseline after inhalation of 88 breath units of the extract. With a direct RAST, the patient's serum bound 38 times the amount of IgE bound by the negative control. IgE binding in the RAST was inhibited by the baby's breath extract but not by unrelated inhibitors (ragweed and tree pollens). Immunoblotting demonstrated IgE binding to 13 protein bands in the extract with molecular weights ranging from 11.5 to 68 kd. Serum from a patient previously reported to have sensitivity to baby's breath recognized five protein bands. Three proteins with molecular weights of 27, 31, and 37 kd were recognized by both patients' sera. We conclude that this patient developed IgE-mediated sensitivity to multiple allergens in baby's breath. This study confirms the importance of this plant as a potential cause of occupational asthma in the floral industry.
To quantitate trace amounts of peanut allergens in food-processing materials and finished foods, we established a solid-phase radioimmunoassay inhibition using pooled sera from five peanut-sensitive subjects and a roasted peanut-meal extract covalently linked to polyacrylamide beads. Test samples were extracted, dialyzed, lyophilized, and reconstituted at 10 to 225 mg of dry weight per milliliter concentrations. The peanut-allergen content of test samples was expressed relative to a reference extract of roasted peanut meal that was assigned an arbitrary potency of 100,000 U/ml. In confectionery products spiked with varying quantities of peanut (0.7% to 0.0175%), the recovery of peanut allergen ranged from 31% to 94%. The sensitivity of the assay was 2.5 U/mg of dry weight from these samples (0.00875% peanut). Peanut allergens were undetectable in virgin vegetable oil used to roast peanuts, but 600 to 7600 U/mg of dry weight were present in oil after varying periods of use. The allergen content of used oil was reduced to 8 U/mg of dry weight by filtration and steam cleaning. The availability of such assays provides a means of monitoring finished food products for potential allergens. This monitoring in turn will provide the means to correlate symptoms experienced by sensitive patients with the exact quantity of allergen ingested. At the present time, there is little information on the quantities of ingested peanut allergen that pose risks to peanut-sensitive subjects.