bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peanut challenge: a retrospective study of 140 patients
Authors: Pucar F. , Kagan R. , Lim H. , Clarke A.E. 
Published: March 2003

Background Accurate diagnosis of peanut allergy is essential given that it is a lifelong and potentially fatal food allergy. Diagnosis relies on patient history, prick skin test (PST), and in many situations, food challenge. More information is required on the safety of food challenge and the informational value of a PST.Objectives Primary: to assess the safety of peanut challenges. Secondary: to estimate the sensitivity, specificity, and the positive and negative predictive values of PST to peanut performed in those who underwent a peanut challenge.Methods A retrospective study of peanut challenges performed at a tertiary care paediatric hospital allergy clinic between January 1994 and November 1998.Results Of the 140 peanut challenges performed on 140 patients, 18 were positive. The most frequent adverse clinical effects of positive peanut challenges were: urticaria, oropharyngeal irritation, rhinitis, vomiting and abdominal pain. Among the 18 patients who had a positive result, 10 required medical treatment (antihistamines, ± epinephrine, ± salbutamol) to control the allergic reaction. The sensitivity, specificity, and the positive and negative predictive values of PST to peanut in this group of children undergoing a peanut challenge were 100%, 62.3%, 28.1% and 100%, respectively.Conclusions Given the poor positive predictive value and specificity of PST, a peanut challenge is usually required to diagnose peanut allergy with certainty when the PST is positive. In cases of a clear history of anaphylaxis to peanut and a positive PST, challenges are unwarranted. When the history is strongly suggestive and the PST is borderline positive, i.e. 3 or 4 mm, peanut challenge is generally necessary to confirm the diagnosis. Given the excellent negative predictive value and sensitivity of PST, a blinded peanut challenge is usually unnecessary in the context of a negative PST except for patients with a history strongly suggestive of immediate hypersensitivity. These patients should be individually assessed for the need to undergo a blinded challenge. The peanut challenge is a useful and safe diagnostic tool when performed by qualified personnel under appropriate conditions.
Mucosal output of eotaxin in allergic rhinitis and its attenuation by topical glucocorticosteroid treatment
Authors: Greiff L. , Petersen H. , Mattsson E. , Andersson M. , Erjefält J. S. , Linden M. , Svensson C. , Persson C. G. A. 
Published: March 2003

Background Eotaxin is a chemokine that attracts and activates eosinophils. The present study examines the occurrence of eotaxin in nasal mucosal surface liquids in patients with seasonal allergic rhinitis without allergen exposure and during repeat allergen challenge with and without topical glucocorticosteroid treatment. The number of subepithelial eosinophils and mucosal outputs of bulk plasma (α2‐macroglobulin) and eosinophil cationic protein (ECP) are also examined.Methods Twelve patients underwent daily allergen challenges for 6 days. Separately, 14 patients, who were receiving budesonide and placebo in a parallel group design, also underwent allergen challenge for 6 days. Nasal biopsies were obtained before and 24 h after the allergen challenge series, and lavages were carried out before and 15 min after selected allergen challenges.Results At baseline nasal lavage fluid levels of eotaxin correlated to levels of α2‐macroglobulin and ECP. After the first allergen challenge there was a correlation between nasal lavage fluid levels of eotaxin and ECP. Repeat allergen exposure increased the mucosal output of eotaxin (P <0.05) and ECP (P <0.01) as well as eosinophil numbers (P <0.01), but no correlation was found between increased eosinophil numbers and eotaxin. Budesonide reduced eotaxin levels during repeat allergen challenge (P <0.05).Conclusions Repeat allergen exposure in allergic rhinitis is associated with increased mucosal output of eotaxin. Topical budesonide attenuates this effect, suggesting the possibility that inhibitory effects on mucosal eotaxin may contribute to anti‐eosinophilic actions of topical glucocorticosteroids.
The release of histamine is associated with the inactivation of mast cell chymase during immediate allergic wheal reaction in the skin
Authors: Saarinen J. V. , Harvima R. J. , Naukkarinen A. , Horsmanheimo M. , Harvima I. T. 
Published: March 2003

Background Chymase released by mast cells can participate in the immediate allergic wheal. However, chymase may be susceptible to inactivation by protease inhibitors during degranulation.Objective To study the inactivation of chymase and the release of histamine in the immediate allergic wheal reaction.Methods Ten sensitive atopic subjects were prick‐tested with the cow dander allergen, and skin biopsies were taken from the control skin and from the challenge site at 30 and 120 min. Tryptase (Tact) and chymase (Cact) activities in mast cells were measured enzyme‐histochemically. Sequential double‐staining was used to demonstrate the activity and immunoreactivity (Cprot) of chymase in the same mast cell as well as α1‐proteinase inhibitor (α1‐PI) and α1‐antichymotrypsin (α1‐AC) in Tact+ cells. Skin microdialysis was used to monitor histamine release after the allergen challenge for up to 120 minResults The numbers of Tact+ and Cact+ cells were already maximally decreased at 30 min by 37 ± 17% and 61 ± 31%, respectively (mean ± SD, P < 0.0001). At the same time the Cact+/Cprot+ ratio decreased from 82 ± 15% to 43 ± 16% (P < 0.0001). The cumulative histamine release at 30 min correlated negatively with the Cact+/Tact+ (P = 0.047) and Cact+/Cprot+ (P = 0.024) ratios, but positively with the decrease in the number of Cact+ cells (P = 0.024). These data indicate that the higher the histamine release the lower the chymase activity. Also the number of Tact+ cells in the control skin correlated positively with the cumulative histamine release at 120 min (P = 0.043). In the control skin, 95 ± 6% and 76 ± 8% of the Tact+ cells displayed α1‐AC and α1‐PI, respectively.Conclusion In addition to extensive degranulation of mast cells, chymase is also rapidly inactivated after the allergen challenge, possibly by pre‐existing chymase inhibitors in the mast cells. This inactivation is associated with the release of histamine.
Allergen‐induced basophil activation: CD63 cell expression detected by flow cytometry in patients allergic to Dermatophagoides pteronyssinus and Lolium perenne
Authors: Sanz M. L. , Sánchez G. , Gamboa P. M. , Vila L. , Uasuf C. , Chazot M. , Diéguez I. , De Weck A. L. 
Published: March 2003

Background In this study, we determined by flow cytometry the percentage of basophils activated after in vitro stimulation by allergens and expressing the CD63 marker. The diagnostic reliability of the technique was assessed as well as its correlation with other in vitro diagnostic parameters.Methods Fifty‐three patients suffering from asthma and/or allergic rhinitis following sensitization to Dermatophagoides pteronyssinus and 51 patients sensitized to Lolium perenne were investigated. Twenty‐four atopic patients not sensitive to these allergens and 38 healthy subjects were also selected as controls. The basophil activation test determines the percentage of basophils which express CD63 as an activation marker, by means of flow cytometry, after in vitro stimulation with allergen, using double labelling with monoclonal antibody anti‐CD63–PE and anti‐IgE–FITC.Results No differences in basal values (non‐activated control) were found between sensitized patients, atopic controls and healthy controls. On the other hand, sensitized patients showed a significantly higher percentage of activated basophils after stimulation by allergens in vitro than both control groups (P < 0.001). We found a significant correlation between skin tests and basophil activation tests (r = 0.72, P < 0.001). We also found a positive and significant correlation between basophil activation tests and histamine release tests (r = 0.80, P < 0.001), allergen‐specific sulphidoleukotriene production (r = 0.7, P < 0.001) and the occurrence of serum allergen‐specific IgE (r = 0.71, P < 0.001).Conclusion The basophil activation test is a highly reliable technique in the diagnosis of allergy to inhalant allergens. The sensitivity of the basophil activation test was 93.3%, and its specificity 98.4%, when using a cut‐off point of 15% activated basophils as positive result.
Thymus size and head circumference at birth and the development of allergic diseases
Authors: Benn C. S. , Jeppesen D. L. , Hasselbalch H. , Olesen A. B. , Nielsen J. , Björkstén B. , Lisse I. , Aaby P. 
Published: March 2003

Background The positive association between a large head circumference at birth and total serum IgE levels has been suggested to be due to negative associations between head circumference at birth and thymus development and between thymus development and total serum IgE levels.Objectives To examine the associations between head circumference and thymus size at birth and the development of allergic disease.Methods The size of the thymus was assessed by sonography during the first week of life in 149 healthy term infants. Information on birth characteristics and mode of delivery was collected at delivery. The presence of allergic disease was assessed 5 years later by mailed questionnaires, which were returned by 85% of the eligible families.Results At birth, head circumference was positively associated with thymus size (P < 0.001). In all, 27 (23%) of the children had developed at least one allergic disease. Multivariate analysis revealed that both parental allergy (Prevalence Ratio and 95% CI) = 3.18 (1.49–6.78)) and caesarean delivery (2.62 (1.48–4.64)) were independently correlated with allergic disease, whereas thymus size was not.Conclusions Our study does not support that a large head circumference is associated with a small thymus size, nor that a small thymus size is associated with allergic disease. Whether thymus size at birth is related to total serum IgE levels still remains to be elucidated.
Expression of C–C chemokine TARC in human nasal mucosa and its regulation by cytokines
Authors: Terada N. , Nomura T. , Kim W. J. , Otsuka Y. , Takahashi R. , Kishi H. , Yamashita T. , Sugawara N. , Fukuda S. , Ikeda‐Ito T. , Konno A. 
Published: March 2003

Background Although interleukin (IL)‐4 and IL‐5 have been demonstrated to play a critical role in the pathophysiology of allergic diseases such as allergic rhinitis, the mechanism that causes the predominance of Th2 lymphocytes has yet to be clarified. Thymus and activation‐regulated chemokine (TARC) has been known to facilitate the recruitment, activation and development of Th2 polarized cells, leading investigators to suggest a role for TARC in the development of Th2 responses.Objective To gain a better understanding of the role of TARC in the pathogenesis of allergic rhinitis we investigated the cellular sources of this chemokine in nasal mucosa. In addition, the effect of cytokines on TARC production has been investigated.Methods The expression of TARC in human nasal mucosa was assessed by immunohistochemistry. To study the effect of cytokines on TARC production, epithelial cells, endothelial cells and fibroblasts, isolated from inferior nasal mucosa samples, were stimulated by a variety of cytokines including IL‐4, IL‐13, tumour necrosis factor (TNF)‐α and interferon (IFN)‐γ.Results Epithelial cells in nasal mucosa in subjects with allergic rhinitis expressed higher signal level than those in non‐allergy patients. Combined stimulation with IL‐4 and TNF‐α, as well as IL‐13 and TNF‐α, synergistically induced TARC expression in epithelial cells. Furthermore, the amount of TARC induced by these cytokines was higher in epithelial cells obtained from patients with allergic rhinitis than in those from non‐allergic patients.Conclusion These results demonstrate a crucial role of nasal epithelial cells in the expression of TARC, and that Th2 cytokine IL‐4 and IL‐13 may promote Th2 responses by inducing TARC production from epithelial cells.
Differential inhibition of inflammatory effector functions by petasin, isopetasin and neopetasin in human eosinophils
Authors: Thomet O. A. R. , Wiesmann U. N. , Blaser K. , Simon H.‐U. 
Published: March 2003

Background Priming of eosinophils with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and subsequent stimulation with platelet‐activating factor (PAF) or the anaphylatoxin C5a is associated with a rapid production of leukotrienes (LTs) and release of eosinophil cationic protein (ECP).Objective This study was designed to determine the effects of the sesquiterpene esters petasin, isopetasin and neopetasin on LT generation and ECP release in eosinophils in vitro.Methods The model of eosinophil activation described above was used to induce LT production and ECP release. Cells were incubated with petasins and control inhibitors prior to priming and stimulation. To analyse intracellular steps of eosinophil activation and determine potential drug targets, some key signalling events were studied. Activity of cytosolic phospholipase A2 (cPLA2) was measured by analysing the generation of arachidonic acid (AA). Translocation of 5‐lipoxygenase (5‐LO) was observed using immunofluorescence microscopy. Intracellular calcium concentrations [Ca2+]i were measured by a bulk spectrofluorometric assay.Results Whereas all three compounds inhibited LT synthesis, ECP release from eosinophils was blocked by petasin only, but not isopetasin or neopetasin. Similarly, PAF‐ or C5a‐induced increases in [Ca2+]i were completely abrogated by petasin only, whereas isopetasin and neopetasin had significant lower blocking efficacy. Moreover, only petasin, but not isopetasin or neopetasin, prevented increases in cPLA2 activity and 5‐LO translocation from the cytosolic compartment to the nucleus envelope in calcium ionophore‐stimulated eosinophils.Conclusion These data suggest that different petasins may at least partially block different intracellular signalling molecules. To reduce LT synthesis, isopetasin and neopetasin may act at the level of or distal to 5‐LO. In contrast, petasin may inhibit inflammatory effector functions in human eosinophils by disrupting signalling events at the level of or proximal to phospholipase Cβ (PLCβ), besides its potential inhibitory activity within mitogen‐activated protein kinase (MAPK) and LT pathways.
An open audit of montelukast, a leukotriene receptor antagonist, in nasal polyposis associated with asthma
Authors: Ragab S. , Parikh A. , Darby Y. C. , Scadding G. K. 
Published: March 2003

Background Nasal polyposis occurs frequently in patients with intrinsic asthma, especially in those who are aspirin sensitive. It can be difficult to treat effectively, even with surgery and regular topical intranasal corticosteroids many patients are still symptomatic.Objective To investigate the response to montelukast, a leukotriene D4 receptor antagonist, as an add‐on therapy to topical and inhaled corticosteroids in patients, both aspirin sensitive (AS) and aspirin tolerant (AT), with nasal polyposis and asthma.Methods Nasal polyposis symptoms were assessed by visual analogue scales; nasal polyps were assessed by nasendoscopy and via the measurement of nasal volumes by acoustic rhinometry. The nasal airway was assessed by nasal inspiratory peakflow (NIPF). Asthma was monitored using symptom scores and peak expiratory flow measurements. Aspirin sensitivity was assessed by history together with intranasal lysine aspirin challenge. Upper and lower airway nitric oxide measurements were made before and during treatment.Results Clinical subjective improvement in nasal polyposis occurred in 64% AT (P < 0.01), patients and 50% AS patients (P > 0.05); asthma improvement in 87% AT and 61% AS patients (P < 0.05 for both). Objective changes in peak flow occurred only in AT patients (P < 0.05). Acoustic rhinometry, nasal inspiratory peak flow and nitric oxide levels did not change significantly in any group, however, correlations were seen between nitric oxide levels and polyp scores and between nitric oxide levels and acoustic rhinometry changes. Improvement on montelukast therapy was not associated with any of the following variables: age, sex, skin prick test positivity, disease duration or aspirin sensitivity. (P > 0.05 for all).Conclusion The findings are consistent with a subgroup of nasal polyps/asthma patients in whom leukotriene receptor antagonists are effective. This is not related to aspirin sensitivity. Further placebo‐controlled studies need to be undertaken.
Peripheral blood CD4+ and CD8+ T cell type 1 and type 2 cytokine production in atopic asthmatic and normal subjects
Authors: Cho S.‐H. , Stanciu L. A. , Begishivili T. , Bates P. J. , Holgate S. T. , Johnston S. L. 
Published: March 2003

Background Increased production of IL‐4 and IL‐5 and decreased production of IFN‐γ by CD4+ T cells has been implicated in asthma pathogenesis. However, CD8+ T cells also produce type 1 and type 2 cytokines and the relative roles of CD4+ and CD8+ T cell cytokine production in asthma have not been previously studied.Objective To determine the production of the type 1 and type 2 cytokines by CD4+ and CD8+ T cell subsets in asthmatic and normal subjects.Methods Intracellular cytokine staining for IL‐4, ‐5, ‐10, ‐13 and IFN‐γ was analysed in peripheral blood CD4+ and CD8+ T cells from 24 atopic asthmatic and 20 normal subjects.Results Both subsets of T cells produced all cytokines studied and there were no significant differences between CD4+ and CD8+ T cells in their capacity to produce either type 1 or type 2 cytokines. There were significantly increased frequencies of IFN‐γ‐positive CD4+ (13.1 ± 2.4%, vs. 7.3 ± 1.4%) and CD8+ (20.0 ± 2.9%, vs. 9.6 ± 2.1%) T cells in asthmatic subjects compared with normal subjects (P < 0.05), but not in frequencies of CD4+ or CD8+ T cells staining positively for IL‐4, ‐5, ‐10 or ‐13.Conclusion The frequencies of peripheral blood CD8+ T cells producing type 1 and type 2 cytokines are comparable with the frequencies of CD4+ T cells. There was an increased frequency of IFN‐γ producing CD4+ and CD8+ T cells in asthmatic compared with normal subjects. Further studies investigating T cells derived from the airways and investigating various stages within the disease process are required to further elucidate the importance of type 2 and type 1 T cell cytokine production in the pathogenesis of human allergic disease.
Carbohydrates expressed on Aspergillus fumigatus induce in vivo allergic Th2‐type response
Authors: Yamashita Y. , Okano M. , Yoshino T. , Hattori H. , Yamamoto T. , Watanabe T. , Takishita T. , Akagi T. , Nishizaki K. 
Published: March 2003

SummaryBackground  The mould Aspergillus fumigatus (Af) causes several forms of Th2‐biased diseases such as Type I respiratory allergies. This mould contains abundant carbohydrates including glucan, chitin and galactomannan. However, little is known on whether these carbohydrates directly drive Th2 responses in vivo.Objective  We sought to determine the relative role of carbohydrates expressed on crude extracts of Af in the induction of Th2‐type antibody production and local eosinophila in mice.Methods  Carbohydrates on native Af were destroyed by sodium metaperiodate under mild conditions. CBA/J mice were sensitized intranasally with native, periodate‐treated or mock‐treated Af. Histologic changes and production of Af‐specific IgE, IgG1 and IgG2a, as well as serum total IgE were determined. Inhibition ELISA for Af‐specific IgE was performed using periodate‐treated Af as an inhibitor.Results  Mice sensitized with periodate‐treated Af displayed significant decreases in both total and specific IgE levels in comparison to mice sensitized with native or mock‐treated Af. Furthermore, sensitization and subsequent challenge with periodate‐treated Af significantly reduced the degree of eosinophil recruitment into the nasal mucosa, compared to the controls. On the other hand, competitive inhibition showed that periodate‐treated Af could inhibit binding between native Af and specific IgE in a similar manner to that of native and mock‐treated Af.Conclusion  These results suggest that carbohydrates on Af play a key role as internal adjuvants in inducing the allergic Th2‐type response and are not the targets of the induced IgE response.
Lack of association between a polymorphism in the interleukin‐13 gene and total serum immunoglobulin E level among nuclear families in Costa Rica
Authors: Celedón J. C. , Soto‐Quiros M. E. , Palmer L. J. , Senter J. , Mosley J. , Silverman E. K. , Weiss S. T. 
Published: March 2003

Background IL‐13 has been implicated in the pathogenesis of asthma and in the regulation of IgE synthesis in humans. Single nucleotide polymorphisms (SNPs) in the IL‐13 gene have been associated with asthma and total serum IgE level in Caucasian populations.Objective To test for genetic association between an SNP in exon 4 of the IL‐13 gene (IL‐13 + 2044 or Arg130Gln) and total serum IgE level and asthma‐related phenotypes in a population with high prevalence of asthma living in Costa Rica.Methods Family‐based association study.Results Among 83 Costa Rican school children with asthma and their parents (249 individuals), there was no evidence of linkage disequilibrium between the IL‐13 + 2044 SNP and any of the outcomes of interest (total serum IgE level on a logarithmic scale, number of positive skin tests to aeroallergens, and asthma). These results were not significantly changed after adjustment for age and gender.Conclusions No significant evidence of linkage disequilibrium between an SNP in exon 4 of the IL‐13 gene and total serum IgE level, sensitization to allergens or asthma was found in a family‐based association study in Costa Rica.
Mite avoidance can reduce air trapping and airway inflammation in allergic asthmatic children
Authors: Peroni D. G. , Piacentini G. L. , Costella S. , Pietrobelli A. , Bodini A. , Loiacono A. , Aralla R. , Boner A. L. 
Published: March 2003

SummaryBackground We investigated the effects of prolonged allergen avoidance in 18 house dust mite‐sensitized asthmatic children during a prolonged residential period at a high altitude, allergen‐free environment.Methods Evaluations of residual volume (RV) and exhaled nitric oxide (eNO) were performed (i) at admission to the residential house in September, (ii) in December after 3 months of stay, (iii) in January after 15 days at home, exposed to allergens, and (iv) in June after 9 months of stay.Results During the study period RV showed a significant decrease in December (from 117.5 ± 7.7% to 96.5 ± 3.2%) (P < 0.02) and a following increase in January (126.2 ± 17.2%), after allergen re‐exposure (P < 0.03). RV decreased again in June at the end of the study period (91.1 ± 6.0%) (P = 0.001). FEV1, FEF25−75 and VC values did not present significant variations. ENO showed a significant decrease in December after 3 months at high altitude (from 21.3 ± 3.9 p.p.b. to 11.9 ± 1.7 p.p.b.) (P = 0.03), but no further significant change. No correlation was found between lung volumes and eNO, probably reflecting different aspects of asthma.Conclusions Results suggest that RV may be more sensitive than other respiratory function parameters in identifying children with air trapping, being influenced significantly as the inflammatory indices by effective allergen avoidance/exposure regimen.