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R G Hamilton
Clinical & Experimental Allergy 08/2011; 41(8):1048-9. · 5.03 Impact Factor
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ABSTRACT: Basophil histamine release (BHR) to allergen has been used as a confirmatory test to support the clinical diagnosis of allergic disease.
Among subjects reporting respiratory cat allergy, we hypothesized that cat-induced BHR in vitro would predict nasal allergen challenge (NAC) response in that same individual. We therefore compared the magnitude of cat allergen-induced BHR to NAC outcome and serological measures of cat-specific IgE and the ratio of cat-specific IgE to total IgE.
Forty-two subjects with a history of cat allergy, positive cat puncture skin test (PST) and detectable cat-specific IgE (> 0.1 kAU/L, ImmunoCap) participated with consent. Subjects were grouped as positive or negative cat allergen-induced BHR, with a positive result defined as the release of ≥ 20% of the total cellular histamine content. The majority of subjects also underwent a NAC with a positive result defined as ≥ 5 total sneezes.
Subjects with a positive compared with a negative cat allergen BHR had higher cat-specific IgE levels at 5.40 ± 1.24 kAU/L (n=25) vs. 1.55 ± 0.73 kAU/L (n=17, P=0.01) as well as a higher cat-specific IgE/total IgE ratio [6.1 ± 1.4% (n=25) vs. 1.6 ± 0.9% (n=17, P=0.01)]. Of the 31 subjects who underwent a NAC, a positive NAC was observed in 78% (18/23) with a positive cat allergen BHR compared with 37% (3/8) with a negative cat allergen BHR, giving a positive predictive value of 78% and a negative predictive value of 63%. The diagnostic sensitivity and specificity of a positive BHR to predict a positive NAC was 86% and 50%, respectively.
A positive cat allergen-induced BHR is associated with higher cat-specific IgE levels, a higher cat-specific to total IgE ratio and is predictive of a positive cat-induced NAC [ClinicalTrials.gov NCT00604786].
Clinical & Experimental Allergy 07/2011; 41(7):963-9. · 5.03 Impact Factor
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ABSTRACT: We recently reported that human blood dendritic cells from allergic subjects have impaired IFN-alpha production following toll-like receptor 9 (TLR9)-dependent innate immune stimulation. It is not known how subcutaneous allergen immunotherapy (SCIT) affects dendritic cell immune responses.
The aim of this study is to determine how SCIT affects human dendritic cell function.
Peripheral blood mononuclear cell (PBMC) and plasmacytoid dendritic cells (pDCs) were isolated from the blood of seven dust mite allergic subjects at baseline and upon reaching a standard SCIT maintenance dose that included dust mite and other aeroallergens. Cells were stimulated with various adaptive and innate immune receptor stimuli, or media alone for 20 h with secreted cytokine levels determined by ELISA. A portion of the cells were used to measure intracellular signalling proteins by flow cytometry. Humoral immune responses were measured from plasma.
SCIT resulted in a threefold increase in PBMC production of IFN-alpha in response to CpG at 100 nM (P=0.015) and at 500 nM (P=0.015), n=7. The predominant cell type known to produce IFN-alpha in response to CpG (CpG ODN-2216) and other TLR9 agonists is the pDC. As expected, a robust innate immune response from isolated pDCs was re-established among allergic subjects undergoing SCIT resulting in a fivefold increase in IFN-alpha production in response to CpG at 500 nM (P=0.046), n=7. In contrast, IL-6 production was unaffected by SCIT (P=0.468). Consistent with published reports, IgG4 blocking antibody increased 10-fold with SCIT (P=0.031), n=7. There was no significant increase in the frequency of pDCs or the expression of TLR9 that would account for the rise in IFN-alpha production.
Allergen immunotherapy increases dendritic cell TLR9-mediated innate immune function, which has previously been shown to be impaired at baseline in allergic subjects.
Clinical & Experimental Allergy 01/2010; 40(1):94-102. · 5.03 Impact Factor
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ABSTRACT: Basophil activation has been implicated in the pathogenesis of aspirin-exacerbated respiratory disease (AERD). However, a comprehensive analysis of basophil responses to aspirin in terms of mediator release, cytokine secretion and increased expression of surface activation markers has not been performed.
To study the in vitro effects of aspirin on the concurrent release of histamine, leukotriene C4 (LTC4) and IL-4 from human basophils and to also evaluate changes in surface activation markers (CD63, CD69 and CD203c) expressed by these cells.
Basophil-enriched cell suspensions from 10 patients with AERD and 10 healthy volunteers were incubated with lysine-aspirin for up to 3 h. Cells were analysed for expression of CD63, CD69 and CD203c using flow cytometry. Cell-free supernatants were evaluated for histamine, and LTC4 release and for IL-4 secretion.
Aspirin-induced expression of CD63, CD69 and CD203c yielded 30%, 80% and 70% sensitivity, respectively, but with poor specificity. There was no significant difference in LTC4 synthesis between groups. None of the patients with AERD (or controls) released IL-4 in response to aspirin. A higher dose of 5 mg/mL aspirin-mediated non-specific effects on basophils.
Basophil responses to in vitro aspirin challenge are poor indicators of clinical sensitivity. Aspirin activates some basophils by means of mechanisms that differ from the classical IgE-mediated pathway. Our study also shows that the use of 27 mm of aspirin (5 mg/mL) by previous investigators causes non-specific basophil activation, thereby eliminating its usefulness in a cell-based diagnostic test for AERD. Evaluation of in vitro basophil activation has low clinical value in identifying aspirin-induced respiratory reactions.
Clinical & Experimental Allergy 06/2009; 39(10):1522-31. · 5.03 Impact Factor
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R G Hamilton
Allergy 03/2009; 64(2):317-8. · 6.27 Impact Factor
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ABSTRACT: High-affinity IgE receptor (Fc epsilon RI) expression on blood dendritic cells reportedly correlates with serum IgE levels. Our studies demonstrate that plasmacytoid dendritic cells (pDCs) secrete pro-inflammatory cytokines (IL-6, TNF-alpha) following Fc epsilon RI stimulation - a mode of activation that simultaneously reduces expression of Toll-like receptor 9 (TLR9). Whether or not TLR9 and/or Fc epsilon RI levels and their function on dendritic cells relate to allergic status is unknown.
The aim of this study is to compare the innate (TLR9-mediated) immune response of human pDCs to TLR9 and Fc epsilon RI alpha receptor expression in allergic and non-allergic subjects.
Basophil-depleted mononuclear cell fractions containing pDCs were prepared from peripheral blood of allergic and non-allergic subjects. Intracellular TLR9 and surface Fc epsilon RI alpha expression in blood dendritic cell antigen-2-positive cells were determined by flow cytometry. Activating anti-IgE antibody, anti-Fc epsilon RI alpha antibody, and TLR9 agonist were used to stimulate cell suspensions, with cytokine levels determined by ELISA.
No difference in the frequency of pDCs was detected among allergic (n=9) vs. non-allergic (n=11) subjects (P=0.261). While there was also no difference in the baseline expression of TLR9, pDCs from allergic subjects produced sixfold less IFN-alpha when stimulated with CpG (P=0.002). Conversely, there was higher Fc epsilon RI alpha expression (P=0.01) on the pDCs of allergic subjects.
Impaired TLR9-dependent immune responses in human pDCs are associated with allergic status and inversely correlated with Fc epsilon RI alpha expression. This impaired innate immune response among dendritic cells of allergic subjects may lead to more targeted therapeutic approaches and could provide a better understanding of the mechanisms underlying conventional and CpG-based immunotherapy.
Clinical & Experimental Allergy 06/2008; 38(5):781-8. · 5.03 Impact Factor
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M Raulf-Heimsoth,
H-P Rihs,
P Rozynek,
R Cremer,
A Gaspar,
G Pires,
H Y Yeang,
S A M Arif, R G Hamilton,
I Sander,
M Lundberg,
T Brüning
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ABSTRACT: Characterized native and recombinant Hevea brasiliensis (rHev b) natural rubber latex (NRL) allergens are available to assess patient allergen sensitization profiles.
Quantification of individual IgE responses to the spectrum of documented NRL allergens and evaluation of cross-reactive carbohydrate determinants (CCDs) for more definitive diagnosis.
Sera of 104 healthcare workers (HCW; 51 German, 21 Portuguese, 32 American), 31 spina bifida patients (SB; 11 German, 20 Portuguese) and 10 Portuguese with multiple surgeries (MS) were analysed for allergen-specific IgE antibody (sIgE) to NRL, single Hev b allergens and CCDs with ImmunoCAP technology.
In all patient groups rHev b 5-sIgE concentrations were the most pronounced. Hev b 2, 5, 6.01 and 13 were identified as the major allergens in HCW and combined with Hev b 1 and Hev b 3 in SB. In MS Hev b 1 displayed an intermediate relevance. Different sIgE antibody levels to native Hevea brasiliensis (nHev b) 2 and rHev b 6.01 allowed discrimination of SB with clinical relevant latex allergy vs. those with latex sensitization. Sensitization profiles of German, Portuguese and American patients were equivalent. rHev b 5, 6.01 and nHev b 13 combined detected 100% of the latex-allergic HCW and 80.1% of the SB. Only 8.3% of the sera showed sIgE response to CCDs.
Hev b 1, 2, 5, 6.01 and 13 were identified as the major Hev b allergens and they should be present in standardized latex extracts and in vitro allergosorbents. CCDs are only of minor relevance in patients with clinical relevant latex allergy. Component-resolved diagnostic analyses for latex allergy set the stage for an allergen-directed immunotherapy strategy.
Clinical & Experimental Allergy 12/2007; 37(11):1657-67. · 5.03 Impact Factor
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ABSTRACT: Long-term avoidance of natural rubber latex [Hevea brasiliensis (Hev b)] is currently recommended for health-care workers (HCWs) with established natural rubber latex (NRL) allergy. Percutaneous sensitivity to eight Hev b NRL allergens was evaluated in HCWs in 2000. To date, no studies have evaluated the longitudinal effects of NRL avoidance on percutaneous sensitivity to NRL allergens.
The aims of this study were to evaluate changes in percutaneous reactivity to non-ammoniated latex (NAL) and NRL allergens in HCWs 5 years after a recommendation to avoid NRL and to evaluate factors that predict the persistence of in vivo sensitivity to NAL and NRL allergens.
Skin prick testing was performed with NAL, seven NRL allergens (Hev b 1, 2, 3, 4, 6.01, 7.01, and 13), and recombinant Hev b 5 (rHev b 5) in 34 HCWs who were initially evaluated in 2000 for occupationally related NRL allergy. Serial 10-fold dilutions of NAL and NRL allergens were employed in skin testing. Sera from the HCWs were assayed for latex and enhanced latex (rHev b 5-enriched allergosorbent)-specific IgE antibodies using the ImmunoCAP assay.
The prevalence of work-related symptoms significantly decreased between 2000 and 2005 with avoidance of NRL (P<0.05). A >/=100-fold reduction in percutaneous sensitivity to Hev b 2 and Hev b 7 was less likely in those with prior history of systemic reactions to NRL (P=0.0053), reported history of reaction to cross-reactive foods (P=0.014), continued local reactions to NRL gloves (P<0.0001), or high NRL glove exposure since the initial study (P=0.0075). The diagnostic sensitivity and specificity of the latex-specific IgE serology was 54% and 87.5%, respectively, in comparison with NAL skin tests. The addition of rHev b 5 to the ImmunoCAP (enhanced latex) allergosorbent altered the diagnostic sensitivity and specificity of the ImmunoCAP to 77% and 75%, respectively.
While symptoms may resolve quickly with NRL avoidance therapy, detectable IgE indicating continued sensitization remains beyond 5 years, and thus continued avoidance of NRL should be recommended.
Clinical & Experimental Allergy 09/2007; 37(9):1349-56. · 5.03 Impact Factor
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ABSTRACT: Hevea brasiliensis latex serum is commonly used as the in vivo and in vitro reference antigen for latex allergy diagnosis as it contains the full complement of latex allergens.
This study quantifies the concentrations of the significant allergens in latex serum and examines its suitability as an antigen source in latex allergy diagnosis and immunotherapy.
The serum phase was extracted from centrifuged latex that was repeatedly freeze-thawed or glycerinated. Quantitation of latex allergens was performed by two-site immunoenzymetric assays. The abundance of RNA transcripts of the latex allergens was estimated from the number of their clones in an Expressed Sequence Tags library.
The latex allergens, Hev b 1, 2, 3, 4, 5, 6, 7 and 13, were detected in freeze-thawed and glycerinated latex serum at levels ranging from 75 (Hev b 6) to 0.06 nmol/mg total proteins (Hev b 4). Hev b 6 content in the latex was up to a thousand times higher than the other seven latex allergens, depending on source and/or preparation procedure. Allergen concentration was reflected in the abundance of mRNA transcripts. When used as the antigen, latex serum may bias the outcome of latex allergy diagnostic tests towards sensitization to Hev b 6. Tests that make use of latex serum may fail to detect latex-specific IgE reactivity in subjects who are sensitized only to allergens that are present at low concentrations.
Latex allergy diagnostics and immunotherapy that use whole latex serum as the antigen source may not be optimal because of the marked imbalance of its constituent allergens.
Clinical & Experimental Allergy 09/2006; 36(8):1078-86. · 5.03 Impact Factor
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ABSTRACT: Hev b 4 is an allergenic natural rubber latex (NRL) protein complex that is reactive in skin prick tests and in vitro immunoassays. On SDS-polyacrylamide gel electrophoresis (SDS-PAGE), Hev b 4 is discerned predominantly at 53-55 kDa together with a 57 kDa minor component previously identified as a cyanogenic glucosidase. Of the 13 NRL allergens recognized by the International Union of Immunological Societies, the 53-55 kDa Hev b 4 major protein is the only candidate that lacks complete cDNA and protein sequence information.
We sought to clone the transcript encoding the Hev b 4 major protein, and characterize the native protein and its recombinant form in relation to IgE binding.
The 5'/3' rapid amplification of cDNA ends method was employed to obtain the complete cDNA of the Hev b 4 major protein. A recombinant form of the protein was over-expressed in Escherichia coli. The native Hev b 4 major protein was deglycosylated by trifluoromethane sulphonic acid. Western immunoblots of the native, deglycosylated and recombinant proteins were performed using both polyclonal antibodies and sera from latex-allergic patients.
The cDNA encoding the Hev b 4 major protein was cloned. Its open reading frame matched lecithinases in the conserved domain database and contained 10 predicted glycosylation sites. Detection of glycans on the Hev b 4 lecithinase homologue confirmed it to be a glycoprotein. The deglycosylated lecithinase homologue was discerned at 40 kDa on SDS-PAGE, this being comparable to the 38.53 kDa mass predicted by its cDNA. Deglycosylation of the lecithinase homologue resulted in the loss of IgE recognition, although reactivity to polyclonal rabbit anti-Hev b 4 was retained. IgE from latex-allergic patients also failed to recognize the non-glycosylated E. coli recombinant lecithinase homologue.
The IgE epitopes of the Hev b 4 lecithinase homologue reside mainly in its carbohydrate moiety, which also account for the discrepancy between the observed molecular weight of the protein and the value calculated from its cDNA.
Clinical & Experimental Allergy 12/2005; 35(11):1490-5. · 5.03 Impact Factor
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ABSTRACT: Receiver operating characteristics (ROC) analyses to evaluate and compare the diagnostic accuracy of Food and Drug Administration (510K)-cleared natural rubber latex (NRL)-specific immunoglobulin E (IgE) antibody immunoassays have not been performed using well-characterized skin-testing reagents. Sera were collected from 311 subjects (131 latex puncture skin test [PST] positive and 180 PST negative). All masked, coded sera were analyzed for latex-specific IgE antibodies in the Diagnostic Products Corporation microplate AlaSTAT, HYCOR HY-TEC RAST, and Pharmacia-Upjohn CAP System RAST FEIA (CAP). Diagnostic accuracy was evaluated using GraphRoc for Windows software to construct and analyze ROC curves in relation to the subjects' PST status and the results of the immunoassays. The ROC areas under the curve (AUCs) +/- standard error based on PST for the three diagnostic tests were 0.858 +/- 0.024, 0.869 +/- 0.024, and 0.924 +/- 0.017, respectively, for AlaSTAT, CAP, and HY-TEC. The HY-TEC system had a significantly greater AUC based on PST than those observed for AlaSTAT (P < 0.05) and CAP (P < 0.05) analyses. When the diagnostic tests were probed as to the cutoffs giving maximal diagnostic efficiency compared to PST, CAP and AlaSTAT yielded values of <0.35 kU of allergen IgE (kU(A))/liter and <0.35 kU/liter while the HY-TEC assay yielded 0.11 kU/liter. The diagnostic efficiencies based on PST in our cohort at these cutoffs were 87.1, 88.1, and 88.7%, respectively. The HY-TEC assay had a significantly greater AUC than CAP and AlaSTAT using PST as a diagnostic discriminator in our cohort. When the HY-TEC system was probed at its maximally efficient cutoff (0.11 kU/liter) versus HYCOR's recommended cutoff of 0.05 kU/liter, a loss of sensitivity of 8.4% was observed with a gain in specificity of 19.5%.
Clinical and Diagnostic Laboratory Immunology 11/2001; 8(6):1145-9. · 2.51 Impact Factor
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ABSTRACT: 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).
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.
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.
The results of this study indicate that repeated HEC latex-allergen challenges are both reproducible and safe, and do not increase latex sensitivity.
Allergy 10/2001; 56(9):857-61. · 6.27 Impact Factor
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ABSTRACT: Inadvertent Hymenoptera stings reportedly elicit large local reactions in up to 17% of the general population. Current practice parameters do not recommend venom immunotherapy (IT) for these cases.
The goal of this case study was to investigate the clinical and immunologic consequences of venom IT in a newly sensitized individual with large local reactions using an intentional sting challenge before and after treatment to document changes in reaction severity.
A 47-year-old man became honeybee venom (HBV)-allergic with progressively larger reactions at honeybee sting sites with subsequent stings. Then, a sting on his forefinger produced a large (62 cm) local reaction with swelling throughout the arm that persisted for more than 4 weeks with severe pain. He refused steroid therapy and voluntarily requested venom IT with honeybee-sting challenges to monitor clinical parameters and immunologic changes in his skin and serum before and 7 months post-HBV maintenance IT.
A single pre-IT bee sting challenge produced an 11.4-cm wheal with 13-cm erythema at the sting site after 15 minutes, followed by several weeks of edema that involved the entire arm. After rapid escalation of venom IT to maintenance in 7 weeks, a post-maintenance IT sting challenge with two honeybees produced a 3-cm diameter erythema with no wheal at 15 minutes and no late-phase induration. Complete loss of any visible reaction at the field sting site resulted after 13 months of maintenance venom IT. A HBV-specific IgG antibody level >3.5 microg/mL and IgG/IgE antibody molar ratio >500 persisted over the period of venom IT, with venom skin reactivity diminishing 100-fold.
These results support venom IT use in the treatment of Hymenoptera venom-sensitive individuals who experience large local reactions and are at risk for repetitive inadvertent stings.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 08/2001; 87(2):134-7. · 2.83 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
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.
Journal of Allergy and Clinical Immunology 07/2001; 107(6):958-62. · 11.00 Impact Factor
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ABSTRACT: The mechanisms behind airway hyperresponsiveness in asthma are unknown. Airway wall edema has been proposed as one possible culprit of this phenomenon.
To test the hypothesis that airway edema may be the cause of allergen-induced increases in airway responsiveness in asthma, this trial aimed at determining the relationship between allergen-induced changes in airway responsiveness to inhaled methacholine and indirect indices of edema, namely peripheral airway resistance and the levels of the plasma protein fibrinogen in bronchoalveolar lavage (BAL) fluids.
Twenty-six atopic individuals with mild asthma were subjected to bronchoscopy at baseline and 28 hours after allergen inhalation. Before each bronchoscopy, methacholine bronchoprovocation was performed. During bronchoscopy, peripheral airway resistance measurements were obtained by wedged bronchoscopy. BAL fluids were analyzed for fibrinogen, as well as for eosinophilic cationic protein. Cytology was performed, and cytokine gene expression was assessed with competitive reverse transcriptase PCR from cell pellets.
A significant increase in airway responsiveness to methacholine was recorded after allergen, but this did not correlate with changes in peripheral airway resistance (which was not affected) or with BAL fibrinogen (which decreased after allergen). Other BAL outcomes confirmed that airway inflammation was produced and was characterized by a T(H)2 cytokine pattern.
Airway responsiveness in asthma increases after exposure to allergen in the absence of increased indirect indices of edema. The role of edema in this phenomenon should therefore be tested more vigorously.
Journal of Allergy and Clinical Immunology 06/2001; 107(5):805-11. · 11.00 Impact Factor
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ABSTRACT: In our 1976 controlled venom immuno rapy trial, 33% of 182 patients with a history of systemic reactions to insect stings were excluded because of negative venom skin test responses. There have been reports of patients with negative skin test responses who have had severe reactions to subsequent stings.
Our aim is to increase awareness about the patient with a negative skin test response and insect sting allergy and to determine the frequency and significance of negative skin test responses in patients with a history of systemic reactions to insect stings.
We prospectively examined the prevalence of negative venom skin test responses in patients with a history of systemic reactions to stings. In patients who gave informed consent, we analyzed the outcome of retesting and sting challenge.
Of 307 patients with positive histories screened for our sting challenge study, 208 (68%) had positive venom skin test responses (up to 1 microg/mL concentration), and 99 (32%) had negative venom skin test responses. In 36 (36%) of the 99 patients with negative skin test responses, the venom RAST result was a low positive (1-3 ng/mL), or repeat venom skin test responses were positive; another 7 (7%) patients had high venom-specific IgE antibody levels (4-243 ng/mL). Notably, 56 (57%) of 99 patients with positive histories and negative skin test responses had negative RAST results. In patients with positive skin test responses, sting challenges were performed in 141 of 196 patients, with 30 systemic reactions. Sting challenges were performed on 37 of 43 patients with negative skin test responses and positive venom-specific IgE and in 14 of 56 patients with negative skin test responses and negative RAST results. There were 11 patients with negative skin test responses who had systemic reactions to the challenge sting: 2 had negative RAST results, and 9 had positive RAST results at 1 ng/mL. The frequency of systemic reaction was 21% in patients with positive skin test responses and 22% in patients with negative skin test responses (24% in those with positive RAST results and 14% in those with negative RAST results).
Venom skin test responses can be negative in patients who will subsequently experience another systemic sting reaction. Venom skin test responses are negative in many patients with a history of systemic allergic reactions to insect stings and may be associated with positive serologic test responses for venom-specific IgE antibodies (sometimes strongly positive results). Venom skin test responses should be repeated when negative, along with a serologic IgE antivenom test. Better diagnostic skin test reagents are urgently needed.
Journal of Allergy and Clinical Immunology 06/2001; 107(5):897-901. · 11.00 Impact Factor
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ABSTRACT: Although asthma can be associated with significant airflow obstruction in those over the age of 65, it is often underdiagnosed and undertreated.
To describe severity of asthma, allergy skin test sensitivities, indoor allergen exposures, and the impact on quality of life (QOL) and health status in elderly persons with asthma.
A cross-sectional data analysis with 80 elderly persons with asthma recruited from medical, geriatric, and allergy/immunology tertiary care centers. Asthma severity was determined by symptoms and measurements of lung function. House dust specimens were collected from mattresses and bedroom carpets and analyzed separately for the major allergens of house dust, using monoclonal antibody-based immunoenzymetric assays. QOL was measured using Juniper's Asthma Quality of Life Questionnaire. Health status was measured using the Short Form Health Survey Medical Outcome Questionnaire which included Ferrans and Powers' Quality of Life Index subscales.
Two-thirds of participants had either moderate or severe persistent asthma. Skin tests to a battery of common airborne allergens were positive to at least one allergen in 56 of the 75 participants tested (74.7%). Reservoir dust allergen levels were often high enough to place participants at risk of symptoms or at risk of developing sensitization. Increased asthma severity was associated with significantly lower QOL and a trend toward decreased health status.
Asthma is a significant chronic problem in the elderly. Atopy was common. Asthma severity impacts on these participants' QOL and health status. Results support interventions aimed at identifying allergens precipitating attacks and reducing them in the home.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 06/2001; 86(5):524-30. · 2.83 Impact Factor
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ABSTRACT: The mechanism(s) leading to the development of late phase allergic reactions is (are) unknown. Previous studies have indicated that a relationship between serum IgE and the late phase exists. To explore the relationships between allergen-specific immunoglobulins in bronchoalveolar lavage (BAL) fluids and the magnitude of airflow limitation during the late phase response to inhaled allergen. Ragweed-specific IgE, IgA, secretory IgA (sIgA) and IgG were measured in BAL fluid and in the serum 1-5 weeks before whole lung antigen challenge with ragweed extract, in 16 ragweed allergic asthmatics. In addition, BAL and serum eosinophil cationic protein (ECP) and BAL fibrinogen levels were determined and BAL cells counted and differentiated. The latter procedures were repeated in a second BAL performed 24 h after the end of the ragweed challenge. After the challenge, lung function was monitored hourly for 8 h, to record the magnitude of airflow limitation. Ragweed-specific immunoglobulins were detected in 25% to 37.5% of BAL samples. Compared to the subjects with undetectable BAL fluid ragweed-specific IgE levels at baseline, those with detectable antibodies had stronger late phase reactions as determined by the nadir of FEV1 between hours 4 and 8 after the ragweed inhalation challenge (P = 0.0007). Allergen-induced changes in BAL ECP and fibrinogen levels were also higher in those subjects with detectable ragweed-specific IgE in baseline fluids (P = 0.03 and P = 0.005, respectively). Significant relationships between BAL antigen-specific IgA, serum ragweed-specific IgE and IgA and the late phase reaction were also found. The results of this study point towards the possibility that allergen-specific IgE and IgA may be independently involved in the pathogenesis of the late phase reaction. This notion merits further exploration.
Clinical & Experimental Allergy 03/2001; 31(2):239-48. · 5.03 Impact Factor
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ABSTRACT: 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.
We sought to develop a novel hooded exposure chamber (HEC) system to allow safe, sensitive, and semiquantitative evaluation of respiratory latex allergy.
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.
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.
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.
Journal of Allergy and Clinical Immunology 02/2001; 107(1):178-84. · 11.00 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
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.
Journal of Allergy and Clinical Immunology 01/2001; 107(1):48-54. · 11.00 Impact Factor
