Con: Immunotherapy is not clinically indicated in the management of allergic asthma.
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Asthma↗
Biomedical subjects
N F Adkinson
Publications and source records attributed to N F Adkinson.
Repeated latex aeroallergen challenges employing a hooded exposure chamber: safety and reproducibility.
BACKGROUND: Bronchial, nasal, and conjunctival challenges are useful for clarifying discordant clinical history (Hx) and skin and/or serologic tests and in assessing semiquantitative changes in biologic sensitivity over time. The objective of this study was to determine the safety and reproducibility of repeated latex-allergen challenges with a hooded exposure chamber (HEC). METHODS: The HEC system comprises a powered forced-air respirator with a fitted face shield and hood that uses glove-derived latex-allergen associated cornstarch particles (LAC) to expose simultaneously the conjunctiva, nose, and lungs. Serial control and incremental LAC challenges are conducted until an endpoint based on upper and/or lower respiratory tract symptoms and peak expiratory flow rates is reached. Six latex-allergic (Hx and puncture skin test [PST]- and 5/6 radioallergosorbent test [RAST]-positive) subjects were challenged on three separate occasions at least 2 weeks apart. Serial latex PST midpoints and serum anti-latex IgE by RAST were monitored at each visit and at a fourth follow-up visit. RESULTS: All subjects responded to LAC, but not to air or control cornstarch administered as controls. All responses were confined to mild symptoms of allergic rhinoconjunctivitis and/or asthma that either resolved spontaneously or were reversed with inhaled albuterol. No subject experienced a systemic or delayed reaction. There were no significant changes in the endpoint LAC doses over the three challenge visits (P>0.2). The mean coefficient of variation for log2 endpoints within-subjects was 17.3+/-17.2% (SD). The serum latex-specific IgE was not significantly boosted by the three challenges (P>0.2). The concentration of latex extract necessary to produce an 8-mm wheal by PST was not significantly changed during the study (P>0.1), indicating that latex sensitivity was not affected by the repeated LAC exposures. CONCLUSIONS: The results of this study indicate that repeated HEC latex-allergen challenges are both reproducible and safe, and do not increase latex sensitivity.
Administration, Inhalation↗
House dust mite and cockroach exposure are strong risk factors for positive allergy skin test responses in the Childhood Asthma Management Program.
BACKGROUND: Children with asthma have a high prevalence of environmental allergies, especially to indoor allergens. The relationships of exposure to indoor allergens (dust mites, cat, dog, cockroach, and molds) and other host factors to allergy sensitization have not been evaluated simultaneously in a large cohort. OBJECTIVES: We studied 1041 children aged 5 to 12 years with mild-to-moderate asthma to determine risk factors associated with having positive allergy skin test responses to indoor allergens. Also, we described, compared, and contrasted 6 allergens in the home environments of these children from 8 North American cities. METHODS: Data were used from baseline visits of the Childhood Asthma Management Program. Patients' sensitivities to house dust mites (Dermatophagoides farinae and Dermatophagoides pteronyssinus), cats, dogs, cockroaches, and molds were examined for relationships to demographic variables, home dust allergen exposures, number of other positive allergy skin test responses, total serum IgE levels, and smoking in the home. RESULTS: San Diego (78.5%) and Toronto (59.3%) had the topmost percentages of homes with moderate-to-high house dust mite levels. Boston (21.5%), St Louis (16.3%), and Baltimore (13.4%) had the highest percentages of homes with detectable levels of cockroach allergen. For house dust mites, the higher the level of allergen exposure, the more likely patients were to have positive allergy skin test responses, with relative odds of 9.0 (95% confidence interval, 5.4-15.1) for those exposed to high mite levels (>10.0 microg/g dust) relative to those unexposed. Even exposure to low levels of mite allergen (0.020-2.0 microg/g) was found to be a significant risk factor for sensitization. For cockroach allergen, those with detectable home exposure were more likely to have positive skin test responses (relative odds, 2.2; 95% confidence interval, 1.3-3.8) than those with undetectable exposure. In contrast, levels of exposure to cat, dog, and mold allergens were not related to sensitization rates. For cat allergen, this may reflect lower rates of cat ownership among highly sensitized subjects. Furthermore, the number of allergy skin test responses that were positive, excluding the test for the outcome of interest for each model, and total serum IgE levels were strong independent predictors of sensitization. CONCLUSIONS: Levels of exposure determined by house dust analysis are important determinants of sensitization for dust mite and cockroach allergen. This relationship was not demonstrable for cat, dog, or mold allergens, possibly because of confounding factors. For all allergens studied, the degree of atopy, determined by the total number of positive skin test responses or by total serum IgE levels, is an important contributing risk factor for sensitization.
Air Pollution, Indoor↗
A hooded exposure chamber method for semiquantitative latex aeroallergen challenge.
BACKGROUND: Allergen challenges are useful in adjudicating discordant clinical histories and skin test responses, serologic test responses, or both, as well as in determining the degree of allergic reactivity. Latex allergen challenges have been developed but have limitations that reduce their usefulness. OBJECTIVE: We sought to develop a novel hooded exposure chamber (HEC) system to allow safe, sensitive, and semiquantitative evaluation of respiratory latex allergy. METHODS: The HEC system uses an impinger to produce a particle cloud of cornstarch isolated from powdered latex gloves. The particles are air driven into a face shield and hood to simultaneously challenge the subject's conjunctiva, nose, and lungs during 3 minutes of normal tidal breathing. A cloud of respirable latex allergen-associated cornstarch particles (LACs) is consistently produced in the HEC during challenges. Twenty-three subjects with latex allergy (history and positive skin test response, positive serologic test response, or both) and 3 atopic control subjects not allergic to latex (history and negative skin test response, negative serologic test response, or both) were sequentially exposed to air, control cornstarch, and then progressive 2-fold increments of LACs in a single-masked fashion. A positive challenge result was defined as (1) a peak expiratory flow rate decline of 15% or greater from baseline; (2) a peak expiratory flow rate decline of 10% or greater and an increase of either the rhinoconjunctivitis or chest symptom score scale of 3 or more points from baseline; or (3) an increase of either the rhinoconjunctivitis or chest symptom score scale of 6 or more points from baseline. RESULTS: Twenty-two of the 23 subjects with latex allergy reached threshold criteria for a positive challenge at LAC titers of 1:8 or greater, giving a sensitivity of 0.96. Challenge endpoints were moderately corrected with skin test sensitivity (r (s) = -0.55, P =.01) but not with RAST reactivity. None of the 3 control subjects responded to LACs at the 1:8 dilution. No patient or control subject responded to the air or control cornstarch control exposures. All responses were confined to mild symptoms of allergic rhinoconjunctivitis, asthma, or both that either resolved spontaneously or were easily reversed with inhaled albuterol. No subject experienced a systemic or late-phase reaction. CONCLUSION: The HEC procedure is a safe, sensitive, and specific method for masked semiquantitative latex aeroallergen challenges that mimic occupational latex exposure to powdered latex gloves.
Administration, Inhalation↗
Natural rubber pharmaceutical vial closures release latex allergens that produce skin reactions.
BACKGROUND: The release of allergenic proteins from natural rubber vial closures (stoppers) into aqueous pharmaceuticals may induce allergic reactions in individuals with latex allergy (LA) receiving medications from such vials. OBJECTIVE: The goal of this study was to determine whether solutions stored in vials containing natural rubber closures release allergenic proteins detectable by skin testing of subjects with LA. METHODS: Five pharmaceutical vial closures (2 natural rubber and 3 synthetic) were coded, inserted onto vials containing phenol-saline-human serum albumin, and stored in an inverted position before use. Twelve volunteers with and 11 volunteers without LA underwent skin testing with solutions from each of the 5 vials, either those not punctured (0P) or those punctured 40 times with a 21-gauge needle 12 to 24 hours before testing (40P). RESULTS: All intradermal skin test responses in the group without LA were negative. Two and 5 of the 12 subjects with LA had positive intradermal skin reactions to 0P and 40P solutions, respectively, from vials containing rubber closures. Two subjects with LA had inexplicable, positive, nonreproducible intradermal skin test reactions to solutions from vials containing bromobutyl but not vials with isoprene synthetic closures. In vitro inhibition analysis detected 6 to 7 AU/g latex allergen in extracts of cut natural rubber containing closures but not in extracts of synthetic closures. CONCLUSION: Natural rubber vial closures released allergenic latex proteins into the tested solutions in direct contact during storage in sufficient quantities to elicit positive intradermal skin reactions in some individuals with LA. These data support a recommendation to eliminate natural rubber from closures of pharmaceutical vials.
Adolescent↗
Recent advances in the diagnosis of drug allergy.
The diagnosis of immunologic drug reactions is based primarily on a detailed clinical history and historical data on relative immunogenicity of the culprit drugs. Except for a few standardized skin tests, most of the other methods for diagnosing drug allergy have unproven diagnostic or predictive clinical utility. Many tests for drug-specific immune responses are suggestive if positive, but have unknown negative predictive values. The present review addresses the most recent published literature regarding the diagnosis of drug allergy. Recent advances in the use of the lymphocyte transformation test, and delayed intradermal skin tests and patch tests for the diagnosis of delayed cutaneous reactions to penicillins suggest that these tests may have clinical utility, although confirmatory reports are still missing. For the diagnosis of acute vaccine reactions, gelatin-specific IgE as measured by radioallergosorbent test has now been shown to be reliably associated with allergic reactions to gelatin-containing vaccines.
Drug Hypersensitivity↗
Evidence for familial aggregation of immunologic drug reactions.
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Drug Hypersensitivity↗
Immunotherapy for allergic rhinitis.
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Allergens↗
Role and application of provocation in the diagnosis of occupational latex allergy.
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Humans↗
Diagnosis of natural rubber latex allergy: multicenter latex skin testing efficacy study. Multicenter Latex Skin Testing Study Task Force.
BACKGROUND: No characterized diagnostic natural rubber latex skin testing material is licensed for use in the United States. OBJECTIVE: We have conducted a multicenter clinical skin testing study to document the safety and diagnostic sensitivity and specificity of a candidate Hevea brasiliensis nonammoniated latex (NAL) extract. These data are intended to support the licensing of this reagent for the diagnosis of latex allergy in high-risk populations. METHODS: Three hundred twenty-four subjects (304 adults and 20 children) were classified by their clinical history as having latex allergy (LA group, 124 adults and 10 children) or having no latex allergy (NLA group, 180 adults and 10 children). All subjects provided blood samples and then received sequential puncture skin tests (PSTs) at 1, 100, or 1000 microg/mL protein with a bifurcated needle and NAL (Greer Laboratories) from Malaysian Hevea brasiliensis (clone 600) sap. A 2-stage glove provocation test was used to clarify latex allergy status of individuals with positive history/negative PST result and negative history/positive PST result mismatches. RESULTS: Twenty-four subjects (15%) originally designated as having LA on the basis of their initial clinical history were reclassified to the NLA group on the basis of a negative glove provocation test result. Of the 134 subjects with LA, 54 (40%) were highly sensitive to latex, with a positive PST result at 1 microg/mL NAL. The Greer NAL reagent produced a positive PST rate (sensitivity) of 95% and 99% in subjects with LA at 100 microg/mL and 1 mg/mL, respectively. The negative PST rate (specificity) in 190 subjects with a negative history with the NAL extract at 100 microg/mL and 1 mg/mL, was 100% and 96%, respectively. Immediately after the PST, mild systemic reactions (mainly pruritus) were recorded in 16.1 % of the adults in the LA group and 4.4% of the adults in the NLA group. No reactions required treatment with epinephrine. Only mild delayed reactions were observed in 9.6% (LA group) and 2.8% (NLA group) of subjects 24 to 48 hours after PST. Mean wheal and erythema diameters measured in the 10 children in the LA group with spina bifida at 100 microg/mL and 1 mg/mL were similar to those observed in the adults in the LA group, suggesting that children are not at increased risk for systemic reactions compared with adults. CONCLUSIONS: A suggestive clinical history is necessary but not sufficient for a definitive diagnosis of IgE-dependent latex allergy. These data support the safety and diagnostic efficacy of the Greer NAL, skin test reagent at 100 micro/mL and 1 mg/mL for confirmatory PSTs.
Adolescent↗
Ragweed-specific antibodies in bronchoalveolar lavage fluids and serum before and after segmental lung challenge: IgE and IgA associated with eosinophil degranulation.
BACKGROUND: Migration of eosinophils and release of eosinophil degranulation products into bronchoalveolar lavage fluid is a consistent finding in studies of late responses to allergen challenge in the lung. However, the mechanism of eosinophil activation and release of eosinophil products in vivo is unclear. OBJECTIVE: We investigated the hypothesis that antigen-specific IgG, IgA, secretory IgA, or IgE is responsible for the eosinophil activation observed in the late-phase pulmonary reaction. METHODS: Ragweed-specific IgE, IgA, secretory IgA, and IgG were measured by monoclonal antibody-based immunoassays in bronchoalveolar lavage (BAL) fluid and in serum from 19 asthmatic subjects allergic to ragweed and six healthy nonallergic control subjects before and 20 hours after segmental lung challenge with ragweed extract. Eosinophil cationic protein (ECP) was also measured in BAL fluid as a marker of eosinophil activation. RESULTS: Most allergic asthmatic subjects had detectable levels of ragweed-specific IgE, IgA, and IgG in their serum and BAL fluid, whereas normal subjects had ragweed-specific IgA with no ragweed-specific IgE and little ragweed-specific IgG. IgA was the dominant ragweed-specific antibody isotype in BAL fluids. Ragweed-specific sIgA (r[s] = 0.52, p = 0.02) and IgA (r[s] = 0.50, p = 0.03) in BAL fluid after segmental lung challenge were significantly correlated with ECP. Ragweed-specific IgE and IgA in serum also correlated with ECP (r[s] = 0.74, p < 0.001 and r[s] = 0.48, p = 0.04, respectively). CONCLUSIONS: The correlation of allergen-specific IgA and IgE antibody levels with ECP as a marker of eosinophil degranulation suggests an important role for IgE antibodies in allergic pulmonary inflammation and a potential role for antigen-specific IgA in eosinophil degranulation in the lung after antigen challenge.
Adult↗
Pathophysiology of contrast media anaphylactoid reactions: new perspectives on an old problem.
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Anaphylaxis↗
Repeated aerosol exposure to small doses of allergen. A model for chronic allergic asthma.
To improve our understanding of the pathophysiology of chronic allergic asthma, we mimicked natural allergen exposure by giving tiny doses of dust-mite extract (equivalent to estimated daily exposure in a typical bedroom) in three weekly sessions for 4 wk. Nine mild asthmatic adults who were highly sensitive to dust-mite allergen participated in the study. Serial assessments of bronchial reactivity by methacholine challenge, pulmonary function, symptoms, and bronchodilator requirements were obtained. Seven of nine subjects had a twofold or more (median: 6, range: 2.7 to 25) reduction (p = 0.008) in PC20, after which saline inhalations were substituted for dust-mite extract. Bronchial reactivity returned to normal within 2 to 3 wk after cessation of dust-mite inhalations in all but one subject. Predosing FEV1 dropped 10% over 4 wk of provocation (p = 0.001) and 7 of 9 returned to prestudy level within 2 wk after dosing was stopped. Late-phase responses were seen in 6 of 9 subjects. We conclude that repeated aerosol exposure to dust-mite allergen in doses comparable to natural bedroom exposure is sufficient to adversely affect pulmonary function and bronchial hyperractivity in sensitized individuals. These changes are rapidly reversible. This low-dose provocational strategy provides an attractive model for the experimental study of allergic asthma. Arshad SH, Hamilton RG, Adkinson NF, Jr. Repeated aerosol exposure to small doses of allergen: a model for chronic allergic asthma.
Adolescent↗
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.
Adolescent↗
Nasal provocation with allergen induces a secondary serum IgE antibody response.
The study of the IgE response to seasonal antigen exposure is limited by its occurrence once a year and by the variability of patient exposure to pollens. To overcome these problems, we investigated whether nasal challenge with antigen causes an increase in serum anti-ragweed IgE levels. We challenged individuals with ragweed allergy intranasally with nanogram quantities of ragweed antigen extract and measured their serum anti-ragweed IgE levels before and at weekly intervals after challenge. In a series of studies we found that there was a reproducible rise in antigen-specific serum IgE levels beginning the first week after challenge that plateaued at about 180% of baseline levels during the fourth week and remained elevated for 8 weeks. Not all individuals showed this response. The magnitude of the allergen-specific IgE response to nasal challenge appeared to be greater than the response to seasonal exposure. Treatment with intranasal beclomethasone before challenge did not affect the response. The results demonstrate a human in vivo model for the study of the antigen-specific secondary IgE response to allergen.
Administration, Intranasal↗
Validation of the latex glove provocation procedure in latex-allergic subjects.
BACKGROUND: A latex provocation test is needed to clarify the allergic status of patients who present with a positive clinical history for latex allergy and a negative latex skin test and/or serologic test. OBJECTIVE: In the present study, we aimed to optimize and validate the performance and safety of a latex glove provocation protocol and to employ it to verify the barrier properties of the Dermapor expanded polytetrafluorethylene (ePTFE) glove liner (liner) for latex glove allergen. METHODS: Twenty-one skin test positive latex-allergic subjects donned goggles and a silicone mask, washed their hands and then put high allergen-containing latex gloves (mean = 15,072 AU/mL) on a moist, bare and liner-covered hand. Due to an absence of verifiable reactions on the bare hand in the first five subjects, the protocol was modified to puncture the skin in three sites on the hand prior to donning the liner/glove or latex glove alone. Subjects were observed for 30 minutes for localized allergic symptoms (pruritus and hives). Lined and unlined hands were compared for reactions. RESULTS: Application of highly allergenic latex gloves onto the bare hands of five skin test-positive, latex-allergic subjects produced some mild pruritus but no visually detectable dermatitis. In contrast, all 17 latex-allergic subjects who underwent the modified glove challenge protocol involving a puncture prior to glove application experienced intense pruritus with measurable wheals and erythema at sites where their skin was punctured. Equivalent wheal and erythema reactions were observed at a site where a puncture was performed directly through the glove. These same subjects experienced no pruritus or hives on their opposite hands that received a liner prior to latex glove application. CONCLUSIONS: Direct application of highly allergenic latex gloves onto the hands of skin test-positive, latex-allergic individuals does not commonly produce localized allergic symptoms after minutes, especially if the subject has successfully avoided latex and has no evidence of dermatitis. By puncturing the skin prior to latex glove donning, quantifiable hives are produced within 15 minutes following glove application. A Dermapor ePTFE liner prevents the transfer of allergen from gloves onto the skin and therefore can serve to minimize contact exposure as part of avoidance therapy.
Adult↗
Ragweed immunotherapy in adult asthma.
BACKGROUND: Although allergen immunotherapy is effective for allergic rhinitis, its role in treating asthma is unclear. METHODS: We examined the efficacy of immunotherapy for asthma exacerbated by seasonal ragweed exposure. During an observation phase, adults with asthma who were sensitive to ragweed kept daily diaries and recorded peak expiratory flow rates between July and October. Those who reported seasonal asthma symptoms and medication use as well as decreased peak expiratory flow were randomly assigned to receive placebo or ragweed-extract immunotherapy in doses that increased weekly for an additional two years. RESULTS: During the observation phase, the mean (+/- SE) peak expiratory flow rate measured in the morning during the three weeks representing the height of the pollination season was 454 +/- 20 liters per minute in the immunotherapy group and 444 +/- 16 liters per minute in the placebo group. Of the 77 patients who began the treatment phase, 64 completed one year of the study treatment and 53 completed two years. During the two treatment years, the mean peak expiratory flow rate was higher in the immunotherapy group (489 +/- 16 liters per minute, vs. 453 +/- 17 in the placebo group [P = 0.06] during the first year, and 480 +/- 12 liters per minute, vs. 461 +/- 13 in the placebo group [P = 0.03] during the second). Medication use was higher in the immunotherapy group than in the placebo group during observation and lower during the first treatment year (P = 0.01) but did not differ in the two groups during the second year (P = 0.7). Asthma-symptom scores were similar in the two groups (P = 0.08 in year 1 and P = 0.3 in year 2). The immunotherapy group had reduced hay-fever symptoms, skin-test sensitivity to ragweed, and sensitivity to bronchial challenges and increased IgG antibodies to ragweed as compared with the placebo group; there was no longer a seasonal increase in IgE antibodies to ragweed allergen in the immunotherapy group after two years of treatment. Reduced medication costs were counterbalanced by the costs of immunotherapy. CONCLUSIONS: Although immunotherapy for adults with asthma exacerbated by seasonal ragweed exposure had positive effects on objective measures of asthma and allergy, the clinical effects were limited and many were not sustained for two years.
Adult↗