Justifying a mechanism-based specialty.
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Allergy and Immunology↗
Biomedical subjects
N F Adkinson
Publications and source records attributed to N F Adkinson.
Socioeconomic status and race as risk factors for cockroach allergen exposure and sensitization in children with asthma.
BACKGROUND: The domestic cockroach has been identified as an important source of indoor aeroallergens worldwide in both temperate and tropical climates. Because cockroach populations are highest in crowded urban areas, some have suggested that the increased asthma morbidity and mortality rates in inner cities could be related in part to cockroach allergen exposure. We have examined cockroach allergen exposure in the homes of children with asthma in both urban and suburban locations and have related the rates of exposure and sensitization to socioeconomic, racial, and demographic factors. OBJECTIVE: The study was designed to determine the independent contribution of race, socioeconomic status, and place of residence to the risk of cockroach allergen exposure and sensitization in children with asthma. METHODS: Eighty-seven children with moderate to severe allergic asthma, aged 5 to 17 years, participating in a prospective trial of immunotherapy, were evaluated. Extracted dust samples from three home locations were analyzed by using two-site monoclonal immunoassays for major cockroach allergens (Bla g 1 and Bla g 2). A puncture skin test with a mixed cockroach allergen extract was performed in 81 of the 87 subjects. RESULTS: In the 87 homes evaluated, 26% of the bedroom dust samples had detectable levels of cockroach allergen. In homes with detectable bedroom cockroach allergen levels, mean Bla g 1 and Bla g 2 concentrations in urban and suburban homes were similar. Over 80% of children with bedroom Bla g 1 or Bla g 2 of 1 U/gm or greater demonstrated skin sensitivity to cockroach allergen. The rate of cockroach sensitization was directly related to the level of bedroom exposure. African-American race was the only factor that was independently associated with cockroach allergen exposure (p = 0.05). Lower socioeconomic status, age greater than 11 years, cockroach exposure, and African-American race were all independently associated with cockroach allergen sensitization on the basis of stepwise multiple linear regression analysis. CONCLUSIONS: African-American race and low socioeconomic status were both independent, significant risk factors for cockroach allergen sensitization in children with atopic asthma. Cockroach allergen is detectable throughout the house, including the critical bedroom environment.
Adolescent↗
Pain and dermal reaction caused by injected glycerin in immunotherapy solutions.
BACKGROUND: Fifty percent glycerin preserves immunotherapy solution potency for at least 3 years but must be diluted before injection to reduce glycerin-induced pain and inflammation. We studied pain, erythema, induration, and bruises caused by glycerin (0% to 30%). METHODS: In 15 healthy subjects we compared, in double-blind fashion, pain scores, injection site erythema, induration, and bruising caused by subcutaneous injections in randomized order of 0.1, 0.5, and 1 ml of glycerin 0%, 10%, 20%, and 30%. RESULTS: Injection volume did not significantly influence pain scores from diluent alone (0% glycerin) (p greater than 0.1). Pain scores of subjects given glycerin (0.1 to 1 ml, 10% to 30%) increased significantly as both injection volume (p less than 0.001) and glycerin concentration (p less than 0.001) increased. Pain scores correlated with total glycerin dose administered (volume x concentration) (rs = 0.67, p less than 0.0005) but varied widely, from minimal to severe, in those given the same dose. Injection site erythema, induration, and bruising occurred in some subjects with significant positive correlations between total glycerin dose and both frequency and diameters of erythema and induration. However, these dermal reactions were of trivial clinical importance. CONCLUSION: Injected glycerin produces pain that is proportional to total injected dose of glycerin, but individual variation in perceived discomfort is substantial. Total glycerin doses of less than 0.05 ml rarely produce clinically important pain.
Contusions↗
Increased plasma IgE levels in patients with sepsis after traumatic injury.
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Adult↗
Natural rubber latex skin testing reagents: safety and diagnostic accuracy of nonammoniated latex, ammoniated latex, and latex rubber glove extracts.
BACKGROUND: Nonammoniated latex, ammoniated latex, and rubber glove extracts are the only sources of natural rubber (Hevea brasiliensis) latex that have potential for use as skin testing reagents in the diagnosis of latex allergy. Their diagnostic sensitivity and specificity as skin test reagents are unknown. OBJECTIVE: We conducted a phase 1/2 clinical study to examine the safety and diagnostic accuracy (sensitivity and specificity) of nonammoniated latex, ammoniated latex, and rubber glove extracts as skin test extracts to identify the most efficacious source material for future skin test reagent development. METHODS: Twenty-four adults not allergic to latex, 19 adults with hand dermatitis or pruritus, and 59 adults with a latex allergy were identified by clinical history. All provided blood and then received puncture skin tests and intradermal skin tests with nonammoniated latex, ammoniated latex, and rubber glove extracts from Malaysian H. brasiliensis latex by use of sequential titration. A glove provocation test and IgE anti-latex RAST were used to clarify positive history-negative skin test response and negative history-positive skin test response mismatches. RESULTS: All three extracts were biologically safe and sterile. After normalization to 1 mg/ml of total protein, all three extracts produced equivalent diagnostic sensitivity and specificity in puncture skin tests and intradermal skin tests at various extract concentrations. Optimal diagnostic accuracy was safely achieved at 100 micrograms/ml for intradermal skin tests (e.g., nonammoniated latex: puncture skin test sensitivity 96%, specificity 100%; intradermal skin test sensitivity 93%, specificity 96%). The presence of IgE antibody in skin was highly correlated with IgE anti-latex in serum (nonammoniated latex: r = 0.98, p < 0.001; ammoniated latex: r = 0.94, p < 0.001; rubber glove extract: r = 0.96, p < 0.001). All five available subjects with a positive history, negative skin test response, and absence of IgE antibody in serum had a negative glove provocation test response, indicating no clinical evidence of latex allergy. No systemic or large local allergic reactions were observed with puncture skin tests or intradermal skin tests. CONCLUSIONS: Equivalent diagnostic sensitivity and specificity were observed with the nonammoniated latex, ammoniated latex, and rubber glove extract skin test reagents after normalization for total protein; nonammoniated latex may be considered the reagent of choice on the basis of practical quality control and reproducibility considerations.
Adult↗
Single doses of intravenous protamine result in the formation of protamine-specific IgE and IgG antibodies.
BACKGROUND: Protamine reactions are a well-recognized and serious complication of intravenous protamine administration. IgE-mediated anaphylaxis occurs after initial sensitization and subsequent re-exposure to antigens. Subcutaneous protamine in insulin preparations is associated with protamine-specific IgE and IgG antibody production. In contrast, the influence of intravenous protamine administration on protamine-specific IgE and IgG antibody formation has never been investigated. METHODS: Sera from 93 patients were analyzed for protamine-specific IgE and IgG antibodies both before and 4 to 6 weeks after exposure to single doses of intravenous protamine. Specific clinical variables were assessed by univariate and multivariate analyses to determine independent predictors of protamine-specific antibody production. RESULTS: In patients who were previously seronegative, intravenous protamine administration resulted in protamine-specific IgE and IgG antibody production in 17 of 93 (18%) and 15 of 93 (16%) patients, respectively. As determined by multivariate analysis, male gender (p = 0.06) and insulin-dependent diabetes mellitus (p = 0.002) were associated with protamine-specific IgG but not IgE antibody production. CONCLUSION: Single-dose intravenous protamine resulted in protamine-specific IgE and/or IgG antibody production in 26 of 93 (28%) of patients. Seroconversion was associated with male gender and insulin-dependent diabetes mellitus. Patients responding immunologically to protamine may be at increased risk for experiencing reactions on subsequent exposure.
Aged↗
Psyllium laxative-induced anaphylaxis, asthma, and rhinitis.
A 69-year-old nurse was evaluated for a recent episode of anaphylaxis that had occurred after psyllium ingestion. She had experienced recurrent rhinitis and asthma related to psyllium exposure for the past 15 years. The diagnosis of psyllium hypersensitivity was established by a positive psyllium puncture skin test, an elevated psyllium-specific IgE level in serum, and a confirmatory soluble-antigen competitive inhibition test. The patient was symptomatic for several years, and this diagnosis was not considered until she suffered potentially life-threatening anaphylaxis. Psyllium hypersensitivity may be a more common phenomenon than is currently appreciated by physicians and other health-care providers.
Aged↗
Environmental challenge studies in laboratory animal allergy. Effect of different airborne allergen concentrations.
In order to examine the dose-dependence of the airway response to animal allergens we performed environmental challenges on 17 workers with documented IgE-mediated allergic reactions to laboratory rats. The 1-h environmental challenges were conducted in a vivarium during cage cleaning (high-allergen challenge), quiet sitting (low-allergen challenge), or in a remote location (sham challenge). During the high antigen conditions, mean Rat n 1 concentration was 166 +/- 28 ng/m3 compared with 9.6 +/- 3 ng/m3 in the low-allergen conditions. Nasal symptoms and nasal lavage mediator concentrations were significantly lower during the low-allergen conditions, but the pulmonary response was similar in terms of symptom scores, coughs, or FEV1 change. Using covariate analysis to examine the interaction of airborne allergen concentration, IgE-mediated sensitivity, and airway hyperresponsiveness, it could be shown that both upper and lower airway responses were strongly dependent on airborne allergen concentration but not on the degree of IgE sensitivity to rat allergen. We concluded that within sensitized workers, acute airway response is determined almost entirely by the intensity of environmental allergen exposure and the degree of bronchial hyperresponsiveness but not by the degree of IgE-mediated sensitivity.
Adult↗
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.
Asthma↗
Cornstarch powder on latex products is an allergen carrier.
Allergic reactions of the upper respiratory tract during use of powdered latex rubber gloves have been recently associated with sensitivity to latex. We have studied the ability of cornstarch powder to bind latex proteins and evaluated allergenic properties of the bound protein. Allergenicity was determined by competitive inhibition of human anti-latex IgE binding to solid-phase latex antigen. Cornstarch extracted from powdered latex products and clean cornstarch exposed to latex protein extracts were evaluated in comparison with clean unexposed cornstarch. Both exposed cornstarch preparations inhibited specific binding of anti-latex IgE antibodies to latex proteins in a dose-response manner. Latex-exposed cornstarch diluted 50% vol/vol produced complete inhibition, whereas greater dilutions exhibited variable levels of inhibition, depending on the source of cornstarch-bound proteins, insolubilized latex proteins, and IgE antibody-containing human serum used. Cornstarch not exposed to latex had no inhibitory activity. The study demonstrates that cornstarch indeed binds allergenic latex proteins and supports the causative relationship between allergic reactions in individuals with latex sensitivity and the exposure to airborne particles from powdered latex products.
Adsorption↗
Lipopolysaccharide-reactive immunoglobulin E is associated with lower mortality and organ failure in traumatically injured patients.
Antilipopolysaccharide (anti-LPS) immunoglobulin G (IgG) and IgM have been associated with protection from LPS effects in vivo. We investigated the presence of IgE and anti-LPS in 32 patients that had experienced severe traumatic injury and in 35 healthy volunteers; we also investigated whether IgE anti-LPS was associated with important clinical events. Plasma samples were collected daily from patients in the intensive care unit and on one occasion from volunteers; the samples were assayed for IgE anti-LPS. IgE anti-LPS was assayed by enzyme-linked immunosorbent assay with monoclonal anti-human IgE as the capture antibody. Detection was accomplished with biotin-labeled LPS (Escherichia coli J5 mutant) followed by streptavidin-peroxidase with 2,2'-azino(3-ethylbenzthiazoline)sulfonic acid as the substrate. The assay was demonstrated to be specific for IgE and LPS-biotin by nonreactivity of control sera with high-titer anti-LPS IgG and IgM and by inhibition with unlabeled LPS. IgE anti-LPS was detected in 1 of 35 healthy controls (2.9%) and 25 of 32 traumatically injured patients (78%) (P < 0.001). The presence of IgE anti-LPS was associated with a lower incidence of death (P = 0.026) and of renal failure (P = 0.0012). There was no apparent temporal relationship between detection of IgE anti-LPS and clinical events. IgG anti-LPS was detected more frequently in patients that were positive for IgE anti-LPS (P = 0.06) but was not associated with clinical events. The inability to detect IgE anti-LPS may be related to adverse clinical events through depletion of specific IgE due to LPS exposure after trauma or through saturation of the assay by IgE with other specificities. We have reported increased total IgE concentrations in these patients. (J.T. DiPiro, R.G. Hamilton, T. R. Howdieshell, N. F. Adkinson, and A. R. Mansberger, Ann. Surg. 215:460-466, 1992).
Acute Kidney Injury↗
Dry air- and hypertonic aerosol-induced bronchoconstriction and cellular responses in the canine lung periphery.
Dry air and hypertonic saline both create an osmotic stress to the airways, whilst dry air alone induces transient cooling of the airway mucosa. It is unclear whether these two stimuli lead to bronchoconstriction via the same mechanisms. We compared airflow- and hypertonic aerosol-induced bronchoconstriction (AIB and HIB, respectively) in the canine lung periphery, using a wedged bronchoscope to measure collateral system resistance (Rcs). Bronchoalveolar lavage (BAL) was used to examine changes in cells and mediators during AIB and HIB. We found that: 1) peripheral airways are not refractory to either dry air or hypertonic aerosols, and do not exhibit cross-refractoriness to these stimuli; 2) differences in strength of stimulus can alter the magnitude but not the time course of HIB; 3) within an individual, AIB and HIB are significantly correlated; 4) epithelial cells recovered in BAL fluid (BALF) are significantly elevated after AIB, and are similarly increased after HIB; 5) when compared to control, mediators recovered in BALF are significantly elevated after AIB but not HIB; 6) HIB is not altered by cyclo-oxygenase inhibition; and 7) lavage with hypertonic fluid does not affect the number of epithelial cells recovered, although the concentrations of some mediators are increased. We speculate that differences in cell and mediator profiles reflect differences in the time course of AIB and HIB that result from the modulation of temperature sensitive pathways that occurs during dry air, but not during hypertonic aerosol challenge.
Aerosols↗
Multi-centre comparison of ABBOTT MATRIX Aero to Pharmacia Standard RAST, Modified RAST and skin puncture tests.
ABBOTT MATRIX Aero is an enzyme immunoassay which measures specific IgE antibodies to 14 individually calibrated airborne allergens using a single serum specimen. In this study, ABBOTT MATRIX performance was evaluated in comparison to the results of skin puncture test and the Standard and Modified RAST procedures. The ABBOTT MATRIX demonstrated overall sensitivity of 89% vs. Standard RAST and Modified RAST, with specificity greater than 92% vs. both methods. ABBOTT MATRIX sensitivity vs. skin test (71%) exceeded that of the Standard and Modified RAST procedures (62% and 67% respectively). Positive results reported by ABBOTT MATRIX but not RAST were corroborated by skin test results for 3 of 5 allergens evaluated. All in vitro systems demonstrated specificity of approximately 90% vs. skin test. The ABBOTT MATRIX system provided results which compared favorably with the results of skin test and RAST, but required less hands-on time to obtain quantitative specific IgE measurements to multiple allergens.
Adolescent↗
Serologic methods in the laboratory diagnosis of latex rubber allergy: study of nonammoniated, ammoniated latex, and glove (end-product) extracts as allergen reagent sources.
In the absence of approved natural rubber latex skin testing reagents, serologic methods for the detection of latex-specific immunoglobulin E (IgE) antibody are useful in the definitive diagnosis of latex allergy. In this study we examined extracts from two nonammoniated latex (NAL), two ammoniated latex (AL), and three diverse latex rubber gloves as sources of allergen for their utility in solid phase radioimmunoassays (SPRIAs) for latex-specific IgE. Serum samples were collected from 46 healthcare workers (HCWs), one beautician, two clerks, and seven children with spina bifida who exhibited clinical evidence of latex-associated contact dermatitis (CD, n = 8), contact urticaria (CU) with or without CD (n = 15), or systemic reactions involving respiratory symptoms with or without anaphylaxis (n = 33) and from 10 latex-exposed HCW control subjects with no latex allergy symptoms. Serum samples were coded and analyzed in a blinded manner in two laboratories by three particulate and four nonparticulate SPRIAs with different latex extracts on the allergosorbent. Intraassay coefficient of variation as assessed with 44 split, randomized, blinded serum specimens was < 20%. Agreement within a source of latex (e.g., NAL, AL, or gloves) and between laboratories was > 90% concordant for Glove 1/Glove 2 and NAL1/2. Specific IgE antilatex was detected in one of 10 latex-exposed control serum samples by five of the seven SPRIAs, despite a lack of clinical evidence for latex allergy in this otherwise atopic individual. Latex-specific IgE was detected in the serum of 22% of subjects with CU with or without CD, suggesting that IgE antibody may not be the primary factor involved in the induction of these local reactions. Approximately two thirds of the systemic reactor group had detectable latex-specific IgE in their serum, with levels ranging from 0.7 to 338 ng/ml. The predictive characteristics of these assays will await future provocation testing. We conclude that glove extracts contain as complete a repertoire of allergens as the NAL and AL. Of the three source latex materials, NAL and glove extracts provided the most sensitive and greatest consistency of IgE antibody results between laboratories.
Adult↗
Clinical experience with penicillin skin testing in a large inner-city STD clinic.
OBJECTIVE: To establish (1) the prevalence of positive penicillin skin tests among outpatients with well-defined but variable history of penicillin allergy and (2) the reproducibility, safety, and negative predictive value of skin testing with benzylpenicilloyl polylysine (PPL) and a minor-determinant mixture (MDM). DESIGN: Serial consenting outpatients with current indications for penicillin therapy were skin-tested in duplicate with PPL and MDM. Subjects with negative skin tests (93% of those positive by history and 95% of those negative by history) received therapeutic courses of benzylpenicillin (81%) or ampicillin (19%). Negative predictive value of skin testing was established by 72-hour follow-up for adverse reactions to drug. SETTING/PATIENTS: A total of 5063 consecutive, qualifying outpatients in a Baltimore, Md, sexually transmitted disease (STD) clinic. The study group was young (73% between 20 and 40 years old), 66% male, and 90% black; 25% had history of atopy. Follow-up was 94% complete. RESULTS: Positive skin tests were observed in 7.1% of 776 individuals with previous history of penicillin allergy and in 1.7% of 4287 subjects negative by history (P << .001). Previous history of anaphylaxis or urticaria was associated with significantly higher rates of positive skin tests of 17.3% and 12.4%, respectively (P<<.001). Only 4% with history of exanthem had positive skin tests (P = .03). The coefficient of variation for duplicate skin tests was 11%. Time intervals since last penicillin treatment did not influence the rate of positive skin tests. Adverse reactions to skin tests occurred in 13 (1.2% of patients positive by history; 9.4% of those with positive skin tests). A mild anaphylactic reaction occurred in one individual whose preliminary scratch testing was inadvertently omitted; systemic pruritus or urticaria occurred in 11 subjects; one had a large local reaction. After penicillin administration to individuals with negative skin tests, acute allergic reactions occurred in 0.5% of subjects negative by history compared with 2.9% of subjects positive by history (chi 2 = 33.3; P = .0001). Reactions were generally mild and self-limited; only two cases of mild anaphylactic reaction occurred, both in patients with history of severe IgE-mediated reaction. CONCLUSIONS: Skin testing with both major and minor penicillin determinants is safe using current recommendations, and both reagents are necessary for maximizing the identification of sensitized subjects. Routine penicillin skin testing can facilitate the safe use of penicillin in 90% of individuals with a previous history of penicillin allergy.
Adult↗
Selection of Hymenoptera venoms for immunotherapy on the basis of patient's IgE antibody cross-reactivity.
BACKGROUND: Positive skin test results to multiple venoms in patients with Hymenoptera venom allergy may result from IgE antibody cross-reactivity among venom proteins. To avoid treatment with unnecessary and costly venoms, we have developed a venom RAST inhibition test that identifies individuals in whom a positive venom IgE RAST result is due to cross-reactive venom-specific IgE antibody. METHODS: Serum samples (n = 412) were collected over 5 years from patients with clinically characterized Hymenoptera venom allergy who had positive skin test results to more than one venom. Venom allergosorbent was added to serum containing IgE antivenin and buffer or 100 micrograms of homologous or heterologous venom. Bound IgE was detected with radiolabeled anti-human IgE. Intraassay variation less than 10% coefficient of variation and homologous venom inhibition greater than 80% were required for acceptance of data. A "cross-reactivity index" (CRI) was computed as a ratio of percent inhibition produced by heterologous versus homologous venom. RESULTS: Of the 412 sera-venom combinations analyzed, 41 (10%) were excluded because of incomplete homologous venom inhibition. Of the 371 remaining sera, 82% (n = 305) were studied for IgE anti-Polistes wasp venom (PWV) cross-reactivity with yellow jacket venom (YJV) and the other 66 for other venom specificity cross-inhibitions. Of the serum samples tested, 36.4% (111 of 305) contained IgE anti-PWV venom of which the binding to solid-phase PWV was inhibited with soluble YJV to a level that produced CRIs greater than 95%. We believe that this constitutes complete inhibition and demonstrates exclusively YJV cross-reactive antibody in these samples. The remaining 63.6% had CRIs from 0% to 95%, indicating IgE specific for a spectrum of unique and cross-reactive PWV allergens. Only 4.3% (13 of 305) had CRIs less than 5%, which is consistent with IgE restricted to PWV unique allergens. The degree of the IgE anti-PWV inhibition to solid-phase PWV by YJV was independent of the IgE anti-PWV level. CONCLUSIONS: This study shows that one third of patients with Hymenoptera venom allergy evaluated with positive YJV- and PWV-reactive IgE in the skin and/or serum were identified as candidates for exclusion of PWV from their immunotherapy regimen because their IgE anti-PWV was more than 95% cross-inhibitable with YJV. Cost analysis of the venom RAST inhibition test and a conventional 5-year Hymenoptera venom immunotherapy program indicates that this serologic evaluation is cost-effective.
Animals↗
Intranasal steroids inhibit seasonal increases in ragweed-specific immunoglobulin E antibodies.
We performed two seasonal studies to evaluate the effect of continuous treatment with intranasal steroids, beginning approximately 1 week before the appearance of ragweed pollen, on the level of ragweed-specific IgE antibodies in serum. In both studies the control groups showed the anticipated rise in ragweed-specific IgE antibodies after the ragweed season. In the first study, employing aqueous beclomethasone dipropionate (168 micrograms twice daily), no rise occurred in serum ragweed IgE after seasonal exposure and the level actually decreased in eight of 12 treated subjects. In the second study, with triamcinolone acetonide (220 micrograms twice daily), the expected rise in ragweed IgE antibody was also reduced, although less dramatically, probably as a result of the lower potency of the dose delivered. Our studies not only support the benefits of intranasal steroids in the treatment of seasonal allergic rhinitis but also suggest that specific IgE production may be down-regulated by their continuous use, which may alter the subsequent clinical course of the disease.
Administration, Intranasal↗
High-titer protamine-specific IgG antibody associated with anaphylaxis: report of a case and quantitative analysis of antibody in vasectomized men.
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Adult↗