A controlled trial of immunotherapy for asthma in allergic children.

BACKGROUND: Injections of allergens are widely prescribed for patients with asthma, but little is known about the effectiveness of immunotherapy. METHODS: We conducted a double-blind, placebo-controlled trial of multiple-allergen immunotherapy in 121 allergic children with moderate-to-severe, perennial asthma. The children, who required daily medication for their asthma, were randomly assigned to receive subcutaneous injections of either a mixture of up to seven aeroallergen extracts or a placebo. Maintenance injections were continued for 18 months or longer. Medications were adjusted every two to three weeks on the basis of peak flow rates and symptoms. The principal outcome was the daily medication score. Bronchial sensitivity to methacholine (the concentration provoking a 20 percent decrease in the forced expiratory volume in one second [PC20]) was measured twice yearly. RESULTS: The median medication score declined from 5.4 to 4.9 in the immunotherapy group (P<0.001) and from 5.2 to 5.0 in the placebo group (P<0.001), but there was no significant difference between the groups (P>0.6). The number of days on which oral corticosteroids were used was similar in the two groups. Partial or complete remission of asthma occurred in 31 percent of the immunotherapy group and in 28 percent of the placebo group (P>0.5). There was no difference between the groups in the use of medical care, symptoms, or peak flow rates. The median PC20 increased significantly in both groups, but again with no difference between the two groups. CONCLUSIONS: Immunotherapy with injections of allergens for over two years was of no discernible benefit in allergic children with perennial asthma who were receiving appropriate medical treatment.

Peak flow variation in childhood asthma: a three-year analysis.

Measuring peak expiratory flow (PEF) variation has been suggested as a indicator of asthma disease severity and also of nonspecific bronchial hyperreactivity. To test these assumptions, we examined the relationships between PEF variation, methacholine reactivity, symptom scores, and medication requirements in 74 children with tightly controlled allergic asthma. The level of mean diurnal variation (MDV) for the group was 7.1%, which is generally regarded as normal. We found statistically significant correlations between MDV and both methacholine reactivity (r = 0.43, p = 0.0001) and symptom scores (r = 0.28, p = 0.016). These asthma variables were analyzed longitudinally in 33 children who were followed up at 6-month intervals for at least 36 months. Visit-to-visit changes in MDV were generally not reflective of changes in other variables. However, group levels of MDV gradually decreased over time, especially in children with initial MDV of more than 8%. This reduction in group MDV coincided with similar reductions in group medication requirements and methacholine reactivity. We conclude that children with moderately severe asthma that is tightly controlled may have normal levels of PEF variation. The correlation between PEF variation and other asthma variables is statistically significant but too weak to be useful in the treatment of individual patients. In contrast, measurement of MDV may be a useful indicator of disease severity in group studies of asthma.

Atopic disease, rhinitis and conjunctivitis, upper respiratory tract infections, and insect stings and snake bites.

In this section we review four broad topics in pediatrics: atopic disease, rhinitis and conjunctivitis, upper respiratory tract infections, and insect stings and snake bites. The first three topics comprise three of the most commonly encountered problems in pediatric practice. Although the fourth topic accounts for a relatively small number of office visits, it generates a great deal of concern among our patients and their parents. There have been significant contributions to the pediatric literature in each of these areas over the past year and we review those of particular interest.

Value of a multiantigen radioallergosorbent test in diagnosing atopic disease in young children.

The purpose of this study was to investigate the value of a new multiantigen radioallergosorbent test, Phadiatop Paediatric, in the diagnosis of atopy in children less than 7 years of age. The diagnosis of atopic disease was established by history, physical examination, total serum IgE concentration, and the results of prick skin tests or radioallergosorbent tests or both, and then compared with the result of the Phadiatop Paediatric test for each patient. One hundred two patients (62 boys) between the ages of 4 months and 7.3 years were enrolled (median age 3.2 years). After the history and physical examination, 42% of the patients were believed to be atopic and 32% to be nonatopic; the diagnosis was uncertain in 26%. Skin prick test reactions to a variety of foods and inhalants were positive in 41 of 63 children tested; results of radioallergosorbent tests were positive in 35 of 61 children. Overall, atopy was diagnosed in 53 children and 49 were found to be nonatopic. When the clinical diagnosis was used as the gold standard, the Phadiatop test resulted in a correct diagnosis of atopy in 49 of 53 cases and of no atopy in 43 of 49 cases: sensitivity = 92%, specificity = 88%, and efficiency = 90%. Although the Phadiatop Paediatric test does not indicate specific sensitivities, it provides the clinician with a useful screening test for atopic disease in children 7 years of age or less, and the researcher with a means of validating atopic populations.

The value of immunotherapy with venom in children with allergy to insect stings.

BACKGROUND: The treatment of patients allergic to insect stings with insect-venom injections has been shown to be 97 percent effective in reducing the risk of sting-induced anaphylaxis. However, the frequency of systemic reactions to subsequent stings in unimmunized adults with previous reactions is approximately 60 percent. To determine which factors, in addition to a history of reaction and evidence of venom-specific IgE antibody, predispose patients to future insect-sting reactions, we studied a venom-sensitive group of children who were deemed to be at relatively low risk for severe reactions; 28 percent of them received venom therapy. METHODS: We studied 242 children, 2 through 16 years of age, each of whom had had a systemic allergic reaction, affecting only the skin, to an insect sting. Each child had a positive skin-test reaction to one or more of five hymenopteran venoms. Sixty-eight children received immunotherapy with insect venom and 174 did not; about half were randomly assigned to treatment groups, and the rest were assigned on the basis of the patient's (or the parents') choice. The results of accidental stings during four years of observation were evaluated. RESULTS: In the treated group, 84 stings in 36 patients resulted in one systemic reaction (1.2 percent of stings). In contrast, 196 stings in 86 untreated children resulted in 18 systemic reactions (9.2 percent of stings, P less than 0.001). Sixteen of these 18 reactions were judged to be milder than the patient's reaction to the first sting, 2 were similar in severity, and none were more severe. CONCLUSIONS: These data confirm that immunotherapy with insect venom prevents recurrences of systemic reactions after subsequent insect stings. Because of the surprisingly low rate of reactions among untreated children, we could not identify any characteristics that were predictive of repeat reactions. Since only 9.2 percent of stings in the untreated children led to a systemic reaction and since there was no progression to a more severe reaction, we conclude that venom immunotherapy is unnecessary for most children who are allergic to insect stings.

Assessment of prolonged venom immunotherapy in children.

Venom immunotherapy was initiated in 94 children from April 1977 to October 1979. As of February 1983, 66 children had continued receiving treatment and had recent immunologic evaluation. Assessment of prolonged venom treatment included analysis of immunologic parameters, efficacy of treatment, and long-term safety. Venom skin tests, venom-specific IgE antibody levels, and venom-specific IgG antibody levels comprised the immunologic parameters evaluated. A decrease in allergic sensitivity was demonstrated over time in the skin and serum. Forty-three of 57 (75%) children had less positive vespid venom skin tests, and the mean venom-specific IgE antibody level declined to less than the pretreatment value with 3 or more years of yellow jacket venom therapy. Venom-specific IgG antibody measurements rose rapidly after the initiation of venom injections and were maintained for the duration of this evaluation. During a 3- to 6-year period, 200 stings in 49 treated children resulted in only four mild systemic reactions (98% efficacy). The benign nature of interval histories, physical examinations, and laboratory analyses in these children argues optimistically for the safety of prolonged venom immunotherapy.

Insect sting allergy in children: what is the real cost of the disease?

The impact of insect sting allergies on the quality of life of 118 children and their parents is assessed using attitudinal and psychometric questionnaires. Children, ranging in age from 7-15 years, manifested more anxiety in the clinical setting (state anxiety) than usual (trait anxiety), whereas for parents the trend was reversed. Most children believed that they could control being stung, and restrictions imposed by two-thirds of the parents assisted in preventing stinging episodes. Parents perceived their child's academic achievement, social abilities and extracurricular involvement as superior to that of their peers and closest aged siblings.

A prospective study of the natural history of large local reactions after Hymenoptera stings in children.

Large local reactions are a frequent occurrence after insect stings. We prospectively studied the demography, immunology, and significance of these reactions in the pediatric age group. Most children (83%) who have had large local reactions have positive skin test results to one or more venoms. Elevated amounts of venom-specific IgE antibody are usually present. Over 3 to 5 years, allergic sensitivity declines, as evidenced by less positive skin test results and lower levels of antivenom IgE antibodies. Most significantly, of 113 repeat stings, only 2% resulted in a systemic reaction.

The development of negative skin tests in children treated with venom immunotherapy.

Twenty-eight of 62 children (45%) with a history of sting-induced anaphylaxis and initially positive skin tests to venom(s) developed negative venom skin tests to one or more of the venoms used in their treatment after 3 yr or more of immunotherapy. Children who developed negative venom skin tests were less sensitive prior to treatment, as judged by venom skin tests and venom-specific IgE antibody determinations, than children who maintained positive venom skin tests. Levels of venom-specific IgE antibodies declined with time in most children, but to lower levels in those with negative skin tests. Venom-specific IgG antibody levels were similar in both patients with negative skin tests and those with persistently positive skin tests. The development of negative skin tests may reflect a loss of allergic sensitivity, which is sufficient to allow the physician to consider the discontinuation of venom injections.

Epidemiologic study of insect allergy in children. II. Effect of accidental stings in allergic children.

One hundred eighty-one children with non-life-threatening reactions to insect stings and positive venom skin tests were randomized to treatment (53) or no-treatment (128) groups and followed up clinically and immunologically for at least two years to assess the results of accidental stings. Twenty-eight stings in 17 treated patients and 74 stings in 47 untreated children occurred, leading to one mild reaction in a treated patient, and eight in the no-treatment group (P = NS). No reaction was more serious than the original. Based on IgE antibody changes and skin test results, 87% of the untreated children were stung by an insect to which they had clinical sensitivity by skin test. Vespid skin test sensitivity decreased 10-fold or more in both treated (72%) and untreated (44%) children. Of those with increased sensitivity, congruent to 70% had been stung. These data indicate that the incidence of severe reactions on resting is low in insect-allergic children, and that the majority show decreased skin test sensitivity over time.

An epidemiologic study of insect allergy in children. I. Characteristics of the disease.

Of 235 children with a history of allergic reactions to insect stings studied, 59 had severe life-threatening systemic reactions, 123 had mild, non-life-threatening systemic reactions, and 53 had large local reactions. The overall male-female ratio was 2:1. Venom skin tests were positive in approximately 89% of each group. Prior whole body extract therapy increased the likelihood of venom skin test reactivity to multiple insect venoms from 51 to 78%. Venom skin test results did not correlate with the severity of previous allergic reactions. One hundred and nine children with NLTR and positive venom skin tests were entered into one of two groups--venom immunotherapy or observation only. During the first six months the treatment group had the expected fourfold rise in venom-specific IgE antibody titers, whereas the observation group had a decline of the mean IgE titer. Patients in the observation group who were accidentally stung had a transient rise in IgE antibody titers. The small number of accidental stings which occurred in both groups resulted in reactions milder than the original reactions. Although based on preliminary data, venom immunotherapy may not be necessary for some children with previously mild systemic symptoms.

Diurnal variation of air and helium-oxygen flow-volume curves in asthmatic children.

In order to assess diurnal variation of flow-volume curves and to determine whether small airways are involved in the diurnal variation of pulmonary function in asthmatic children, we studied eight asthmatics who were attending an asthma summer camp. Spirometry and maximal expiratory flow-volume curves with air and a helium-oxygen mixture were obtained in the morning and afternoon over a 10-day period. We found that significant increases in maximal expiratory flows at all lung volumes occurred in the afternoon. However, the increase in flows with helium (helium response) was unchanged from morning to afternoon. These results suggest that both large and small airways are involved in the diurnal variation of pulmonary function in asthmatic children.

Diagnosis and treatment of anaphylactic reactions to Hymenoptera stings in children.

Forty-four children (mean age 9.6 years) with a history of an allergic reaction(s) to an insect sting and with positive insect venom skin tests were studied. IgE antibodies (RAST) to honeybee phospholipase A and to yellow jacket venom were found in the sera of 78% and 77%, respectively, of these patients. The patients were immunized with the appropriate venoms over a 15-week course and most were then subjected to an in-hospital sting; there was a 3% reaction rate (1/37). Clinical protection as associated with a fivefold increase in anti-venom IgG. Five patients did not develop a significant increase in IgG antibody and they were treated more vigorously; four were stung subsequently without reaction. Two patients did not react when stung in the field; positive identification of the culprit insect was obtained. Twenty patients were re-stung after one year of maintenance therapy; there was a single mild, delayed reaction. Immunotherapy also increased the IgE antibody against venom 3.7-fold at three months; after one year of therapy the IgE antibody level had decreased but was still 40% greater than at the outset. Immunotherapy was associated with a 25% incidence of local pain and swelling and a 6% incidence of systemic reactions. We conclude that venom therapy in children is safe and effective. The indications for initiating immunotherapy require further definition.

Nocturnal oxygen saturation in normal and asthmatic children.

At sea level, it appears that oxygen desaturation does not occur in normal children at night and that the desaturation that occurs in moderately severe asthmatic children with therapeutic levels of theophylline does not approach dangerously low levels.

Factors influencing mothers' compliance with a medication regimen for asthmatic children.

This study lends support to the utility of a compliance-adapted health belief framework for exploring mothers' differential adherence to medication regiments prescribed for their asthmatic children. Most of the Model components behaved as hypothesized in predicting mothers' drug administration. The findings offer empirical evidence which can be applied to the purposes of identifying potential noncompliers and designating those specific, health-related orientations of the mother which are related to poor cooperation with therapy. Based on an educational diagnosis, the clinician may thus intervene to alter inappropriate health beliefs in order to enhance the likelihood of compliance for the asthmatic patient.