bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of pyrazolone drug hypersensitivity with HLA‐DQ and DR antigens
Authors: Kowalski  , Woszczek  , Bienkiewicz  , Mis  
Published: March 2003

BackgroundIn sensitive patients pyrazolone drugs can precipitate adverse reactions ranging from urticaria and angioedema to anaphylactic shock, presumably by immunological, IgE‐mediated mechanism. However, up to now no genetic factors influencing the development of allergic reaction have been reported in this type of hypersensitivity.ObjectiveThe aim of our study was the investigation whether the susceptibility to development of pyrazolone drugs hypersensitivity (PDH) reactions was associated with HLA class II antigens.MethodsTo test this hypothesis we studied the distribution of HLA‐DR and DQ antigens in 26 pyrazolone sensitive patients and control groups including unselected general population and clearly defined atopic and non‐atopic groups.ResultsSignificantly higher frequencies of DQ 7 and DR11 antigens were found in PDH group as compared with control unselected population (RR= 16.48, P < 0.0001; Pcor < 0.002 and RR = 4.57, P = 0.0002; Pcor = 0.003 for DQ and DR antigen respectively). Similarly, statistically significant increased frequencies of DQ 7 and DR11 in patients with PDH were observed compared with atopic control group (RR = 18.43, P < 0.0001; Pcor < 0.002 and RR = 6.33, P = 0.0007; Pcor = 0.01, for DQ and DR antigen respectively). However, in comparison to non‐atopic control group only the frequency of DQ 7 antigen was significantly increased (RR = 15.42, P = 0.0001; Pcor = 0.0015). DQ 7 antigen was present in 46.1% of PDH patients compared with 4.9%, 4.4% and 5.3% in the general population, atopic and non‐atopic groups respectively, suggesting pyrazolone hypersensitivity as a trait positively correlated with this HLA antigen.ConclusionOur data suggest a genetic predisposition to pyrazolone hypersensitivity reactions, linked to HLA‐DQ locus.
Food allergy to peanuts in France–evaluation of 142 observations
Authors: Moneret‐Vautrin  , Rance  , Kanny  , Olsewski  , Gueant  , Dutau  , Guerin  
Published: March 2003

BackgroundThe increase in frequency of peanut allergy and fatal cases have been reported.ObjectivesThe objective of this study is to document the severity of food allergy to peanuts by evaluating the reactive dose of peanuts and to search for the role of peanut oil.MethodsThis study is carried out on the basis of 142 observations collected according to the same diagnostic methodology in two allergy centres in France. Skin‐prick‐tests were performed with peanut powder, peanut oil and peanut oil proteinic extract. Labial provocation tests were performed on 121 patients. The reactive dose of peanuts and the role of peanut oil were determined by standardized oral provocation tests in 50 and 62 patients respectively. The data are computerized and the data bank includes 509 food allergic patients.ResultsAllergy to peanuts represents 28% of food allergies and occurs under 1 year of age in 46% of cases, under 15 years of age in 93%. The clinical features were atopic dermatitis (40%), angioedema (37%), asthma (14%), anaphylactic shock (6%) and digestive symptoms (1.4%). The specific IgE were class 3 or higher in 80% of cases. The total reactive dose was less than 100 mg in 25% of cases, from 100 mg to 1 g in 62.5%. All patients reacted to a dose of less than 7.1 g. The threshold of peanut reactivity was lower than the threshold of egg reactivity. An allergy to peanut oil was demonstrated in 14 patients.Conclusion:The severity of peanut allergy and the early onset of the occurrence of this allergy is documented. The role of residual allergenic proteins in peanut oil is established by positive skin‐prick tests to proteic extracts from peanut oil and by double‐blind placebo‐ controlled challenges to peanut oil. The increased consumption of allergens in the form of peanut oil and fats can contribute to the occurrence or persistence of symptoms and may be suspected to increase the risk of sensitisation.
The International Study of Asthma and Allergies in Childhood (ISAAC)
Authors: Asher  , Weiland  
Published: March 2003

Despite considerable research, the aetiology of asthma and allergic disease remains poorly understood. The International Study of Asthma and Allergies In Childhood (ISAAC), was founded to maximize the value of epidemiological research into asthma and allergic disease by establishing a standardized methodology and facilitating international collaboration. It has achieved its specific aims which are to describe the prevalence and severity of asthma, rhinitis and eczema in children living in different centres and to make comparisons within and between countries; to obtain baseline measures for assessment of future trends in the prevalence and severity of these diseases; and to provide a framework for further aetiological research into genetic, lifestyle, environmental and medical care factors affecting these diseases. The ISAAC design comprises three phases. Phase One used simple core written questionnaires for two age groups, and was completed in 156 collaborating centres in 56 countries and a total of 721 601 children participated. In the 13–14 years age group 155 centres from 56 countries participated, of which 99 centres completed a video questionnaire. For the 6–7 years age group there were 91 collaborating centres in 38 countries. ISAAC Phase One has demonstrated a large variation in the prevalence of asthma symptoms in children throughout the world including hitherto unstudied populations. It is likely that environmental factors were responsible for major differences between countries. The results provide a framework for studies between populations in contrasting environ‐ments which are likely to yield new clues about the aetiology of asthma. ISAAC Phase Two will investigate possible aetiological factors, particularly those suggested by the findings of Phase One. ISAAC Phase Three will be a repetition of Phase One in the year 2000 to assess trends in prevalence.
The effect of montelukast (MK‐0476), a cysteinyl leukotriene receptor antagonist, on allergen‐induced airway responses and sputum cell counts in asthma
Authors: DIAMANT  , GROOTENDORST  , VESELIC‐CHARVAT  , TIMMERS  , DE SMET  , LEFF  , SEIDENBERG  , ZWINDERMAN  , PESZEK  , STERK  
Published: March 2003

BackgroundCysteinyl leukotrienes are capable of inducing chemotaxis of eosinophils in vitro and within the airways of animals and humans in vivo.ObjectiveWe hypothesized that montelukast (MK‐0476), a potent cysLT1 receptor antagonist, would protect against allergen‐induced early (EAR) and late (LAR) asthmatic responses by virtue of anti‐inflammatory properties. Hence, we studied the effect of pretreatment with oral montelukast on allergen‐induced airway responses. As an exploratory endpoint, changes in inflammatory cell differentials and eosinophil cationic protein (ECP) were evaluated in hypertonic saline‐induced sputum.MethodsTwelve asthmatic men (20–34 years, FEV1 79–109% predicted, histamine PC20FEV1 < 4 mg/mL) with dual responses to inhaled house dust mite extract participated in a two‐period, double‐blind, placebo‐controlled, crossover study. Three oral doses of montelukast (10 mg) or matching placebo were administered 36 and 12 h before, and 12 h post‐allergen. The airway response to allergen was measured by FEV1, and the EAR and LAR were expressed as the corresponding areas under the time‐response curves (AUC0–3 h and AUC3–8 h, respectively). During each study period, sputum was induced with 4.5% NaCl 24 h before and 24 h after a standardized allergen challenge. Processed whole sputum cytospins were stained with Giemsa, and cell counts expressed as percentage nonsquamous cells. ECP was measured by FEIA in sputum supernatants.ResultsAll subjects completed the study. The changes in baseline FEV1 were not significantly different between the two pretreatments (P = 0.183). Montelukast significantly inhibited the EAR and LAR, reducing the AUC0–3 h by 75.4% (P < 0.001) and the AUC3–8 h by 56.9% (P = 0.003) as compared with placebo. Sputa of nine subjects could be included in the analysis (< 80% squamous cells). Allergen challenge significantly increased sputum eosinophils after placebo (mean change ±sd: 4.8 ± 5.8%, P = 0.038), with a similar trend after montelukast (mean change ±sd: 4.1 ± 5.4%; P = 0.056). The allergen‐induced changes in sputum eosinophils and ECP, however, were not significantly different between the two pretreatments (P = 0.652 and P = 0.506, respectively).ConclusionWe conclude that oral montelukast protects against allergen‐induced early and late airway responses in asthma. However, using the present dosing and sample size, this protection was not accompanied with changes in sputum eosinophil percentage or activity, which may require more prolonged pretreatment with cysLT1 receptor antagonists.
Soluble cytokine receptor CD30 in atopic disorders: a case‐control study
Authors: LATZA  , DAVIS  , WILHELM  , McKNIGHT  , SEYFARTH  , STEIN  
Published: March 2003

BackgroundThe cytokine receptor CD30 is an activation marker of T cells which preferentially associates with the production of the TH2 cytokine IL‐4. Therefore, it may potentially be a candidate marker for atopic disorders and a target molecule for new therapeutic approaches.ObjectiveTo test the hypothesis that elevated levels of soluble CD30 (sCD30) are significantly associated with atopic disorders after adjustment for other predictors of atopy.MethodsThe presence of elevated sCD30 (≥ 20 U/mL) in atopic disorders was evaluated in a nested case‐control study. Cases (n = 60) were blood donors with specific IgE antibodies, total serum levels of IgE ≥ 100 kU/L and presence or history of allergic symptoms. Controls (n = 59) were blood donors without presence or history of allergic symptoms and serum levels of IgE < 50 kU/L. sCD30 was determined from serum samples by an enzyme‐linked immunosorbent assay. Odds ratios (OR) and confidence intervals (CI) were calculated from logistic regression coefficients.ResultsMean sCD30 levels for cases were 75 U/mL ( sd 110 U/mL) as compared with 35 U/mL (
sd 59 U/mL) for controls. Serum levels of sCD30 were elevated in 65% of cases and 32% of controls (OR 3.9, 95% CI 1.8–8.4). The odds ratio for elevated sCD30 as a predictor of atopic disorders slightly decreased to 3.7 after controlling for smoking, age and gender. Blood eosinophilia which was a strong predictor of atopy (OR 11.7) was a weak confounder of the association between sCD30 levels and atopic disorders. Family history of allergy, another strong predictor of atopy (OR 8.6), did not confound the association.ConclusionsThe results are consistent with the hypothesis that CD30 is involved in the pathogenesis of atopic disorders independent of eosinophilia and family history of allergy.
Epicutaneous administration of hapten through patch application augments TH2 responses which can downregulate the elicitation of murine contact hypersensitivity
Authors: Wang  , Sun  , Wu  , Lin  
Published: March 2003

Background and objectiveAllergic contact dermatitis and its animal model, contact hypersensitivity (CHS), have long been documented as type 1 T‐cell‐predominant immune responses. Although type 1/type 2 T‐cell deviation has been repeatedly demonstrated to play an important role in many human diseases and their animal models, the potential of tilting type 1/type 2 T‐cell differentiation of CHS by modulating the manner of administration and dosage of hapten remains unexplored. This study examined the effect of these two factors on type 1/type 2 balance of CHS.MethodsELISA methods for detection of isotypes of hapten‐specific antibodies and cytokine profiles of in vitro reactivation culture as well as ear‐swelling assay were used to indicate type 1 or type 2 T‐cell immune responses.ResultsIn this paper, it was demonstrated that dosage of hapten has no effect on the type 1/type 2 T‐cell balance of CHS, whereas epicutaneous administration of hapten through patch application could tilt the type 1/type 2 balance to decrease type 1 and to augment type 2 T‐cell responses. Patch application‐induced modulation is still effective in ever‐sensitized mice and the augmented type 2 T‐cell responses are persistent and increase progressively in strength after repeated immunizations. Moreover, it was demonstrated that the augmented type 2 T‐cell response can downregulate the elicitation of CHS. The major mediating cells of the enhanced type 2 T‐cell responses were determined to be CD4+ T cells (TH2 cells).ConclusionsThese data show that epicutaneous administration of hapten through patch application augments TH2 response which can downregulate the elicitation of murine CHS. This exploration may contribute to the understanding of regulatory mechanisms involved in contact allergy.
Does early exposure to cat or dog protect against later allergy development?
Authors: HESSELMAR  , Åberg  , Åberg  , ERIKSSON  , BJÖRKSTÉN  
Published: March 2003

BackgroundIt is unknown which factors in modern western society that have caused the current increase in prevalence of allergic diseases. Improved hygiene, smaller families, altered exposure to allergens have been suggested.ObjectivesTo assess the relationship between exposure to pets in early life, family size, allergic manifestations and allergic sensitization at 7–9 and 12–13 years of age.MethodsThe prevalence of allergic diseases and various background factors were assessed in 1991 and 1996 by questionnaire studies. In 1991, the study comprised representative samples of children from the Göteborg area on the Swedish west coast (7 years old, n = 1649) and the inland town Kiruna in northern Sweden (7–9 years old, n = 832). In 1992, a validation interview and skin prick test (SPT) were performed in a stratified sub‐sample of 412 children. In 1996, this subgroup was followed up with identical questions about clinical symptoms as in 1991, detailed questions about early pet exposure were added and SPT performed.ResultsChildren exposed to pets during the first year of life had a lower frequency of allergic rhinitis at 7–9 years of age and of asthma at 12–13 years. Children exposed to cat during the first year of life were less often SPT positive to cat at 12–13 years. The results were similar when those children were excluded, whose parents had actively decided against pet keeping during infancy because of allergy in the family. There was a negative correlation between the number of siblings and development of asthma and allergic rhinitis.ConclusionPet exposure during the first year of life and increasing number of siblings were both associated with a lower prevalence of allergic rhinitis and asthma in school children.
A controlled study on the effectiveness of loratadine in combination with flunisolide in the treatment of nonallergic rhinitis with eosinophilia (NARES)
Authors: Purello‐D'Ambrosio  , Isola  , Ricciardi  , Gangemi  , Barresi  , Bagnato  
Published: March 2003

BackgroundNonallergic rhinitis with eosinophilia (NARES), accounting for some 15% of perennial rhinitis, is a nasal disorder whose main features are eosinophil counts in nasal smear higher than 10% and negative IgE tests. The mainstay of treatment is topical corticosteroids.ObjectiveTo evaluate the adjunctive effect of loratadine, a non‐sedating antihistamine with anti‐allergic activity, on nasal symptoms and eosinophil counts in nasal secretions in patients with NARES.MethodsThirty patients with NARES were divided in two groups, half receiving flunisolide two 25 μg puffs per nostril morning and night plus loratadine 10 mg u.i.d. and half the same doses of flunisolide plus placebo, according to a double‐blind fashion, for 3 weeks. The effectiveness of the treatment in the two groups was evaluated by comparing symptom scores and eosinophil counts, and safety was assessed by comparing the adverse effects.ResultsThe loratadine treated group had better results both in nasal symptoms, with a decrease in sneezing (P < 0.000001) and rhinorrhoea (P < 0.006), respectively, corresponding with 73.4% and 66.7% with respect to 46.6% and 26.7% in the control group, and in eosinophil counts which decreased by 20% compared with 14.3% in patients treated with placebo and flunisolide. As to safety, only nasal irritation in two patients, one in each group, was reported.ConclusionLoratadine improves the effectiveness of flunisolide in treatment of NARES with no change in safety, and with no sedation.
Mechanisms of deficient interferon‐γ production in atopic diseases
Authors: JUNG  , MOESSNER  , DIECKHOFF  , HEIDRICH  , NEUMANN  
Published: March 2003

BackgroundThe mechanisms responsible for an imbalanced cytokine response in atopic diseases are still not understood. While impaired interferon‐gamma (IFN‐γ) production may be the result of a pathological T‐cell/antigen‐presenting cell (APC) interaction, evidence was provided that the T cell itself may have an intrinsic defect to produce IFN‐γ.ObjectiveTo clarify whether impaired IFN‐γ production by T cells from patients with atopic dermatitis (AD) represents an intrinsic defect in producing IFN‐γ.MethodsEffector T cells were generated from CD4+ CD45RA+‐naive precursors from patients with AD and healthy control individuals by activation with anti‐CD3+ anti‐CD28 MoAbs. Following restimulation, IFN‐γ production was measured by ELISA and flow cytometry.ResultsIFN‐γ production by atopic T cells was decreased compared with healthy T cells. IL‐12 present at priming or high doses of IL‐2 during the culture period, even in the absence of IL‐12, completely restored IFN‐γ production. Conversion of naive CD45RA+ to CD45R0+ effector cells did not differ between atopic and healthy donors' T cells.ConclusionImpaired IFN‐γ production by T cells from atopic individuals is not the result of an intrinsic, genetically fixed, defect to produce sufficient amounts of IFN‐γ. The data provides evidence that correction of an impaired TH1 response in AD may be successful at the precursor T cell level.
Interleukin‐10 is localized to and released by human lung mast cells
Authors: Ishizuka  , Okayama  , Kobayashi  , Mori  
Published: March 2003

BackgroundMast cells control the local inflammation by producing many kinds of cytokines. Interleukin (IL)‐10 is one of the important cytokine that upregulate or downregulate inflammation.ObjectiveThe aim of this study is to ascertain whether IL‐10 is produced from human lung mast cells by cross‐linkage of high‐affinity Fcε receptors (FcεRI).MethodsMast cells were purified using affinity magnetic selection with mAb YB5.B8 (> 93% pure). Mast cells were precultured with human myeloma IgE (3 μg/mL) for 16 h and then washed, and stimulated with anti‐IgE in the presence or absence of recombinant human stem cell factor (rhSCF). We have studied the production of IL‐10 by using reverse transcription‐PCR, enzyme‐linked immunosorbent assay and immunocytochemistry.ResultsWe found that human lung mast cells were immunocytochemically stained with anti‐IL‐10 mAb after IgE‐dependent stimulation. The activation of mast cells via FcεRI enhanced the intensity of the IL‐10 mRNA signal. Anti‐IgE (1 μg/mL) induced a median IL‐10 release of 301.7 (7.8–1532.4) pg/106 mast cells/24 h. In contrast, mast cells released only a small amount of IL‐10 in the absence of anti‐IgE. This difference was statistically significant (P = 0.02, n = 11).ConclusionOur findings indicate that human lung mast cells are capable of producing IL‐10 in response to IgE‐dependent stimulation.
Regulation of T‐helper cell responses to inhalant allergen during early childhood
Authors: Macaubas  , Sly  , Burton  , Tiller  , Yabuhara  , Holt  , Smallacombe  , Kendall  , Jenmalm  , Holt  
Published: March 2003

BackgroundRecent evidence suggests that preschool children manifest patterns of allergen‐specific skin prick test (SPT) reactivity and in vitro T‐cell cytokine production which are similar to that of either atopic or nonatopic adults. However, published studies on this age group involve small sample sizes and a restricted number of cytokines, usually in response to polyclonal stimuli.ObjectiveTo elucidate the relationship between in vivo and in vitro immune responses to a major inhalant allergen house dust mite (HDM) in preschoolers.MethodsPeripheral blood mononuclear cells (PBMCs) from matched groups of HDM–SPT+ and SPT− 6‐year‐olds (n = 30 and 29, respectively) tested for PBMC responses to HDM, and cytokine production measured at both the protein and mRNA levels. Immunoglobulin (Ig) E and IgG subclass antibody titres were determined in serum. Interrelationships between in vitro and in vivo HDM responses were examined via multivariate analyses.ResultsSPT reactivity to HDM was associated with in vitro production by putative T cells of interleukin (IL) ‐4, IL‐5, IL‐9, IL‐10, IL‐13 and low level IFNγ, and with production in vivo of IgE and (all) IgG subclass antibodies; HDM responses in the SPT− group were restricted mainly to IL‐10 and IFNγ and very low levels of IL‐4; IL‐6 production from non‐T‐cell sources was common. The cytokine most associated with positive SPT responses was IL‐9; SPT weal diameter correlated positively with IL‐4, IL‐5 and IL‐13 and negatively with IL‐10.ConclusionDetailed analysis of cytokine responses in this very young age group have the potential to uncover subtle relationships between in vivo and in vitro allergen reactivity which may be less clear in adults, in whom T‐cell response patterns are modified via chronic stimulation. The present findings which suggest potentially important roles for IL‐9 and IL‐10 in the early phase of allergic disease, may be one such example.
Interleukin‐5 enhances eosinophil adhesion to bronchial epithelial cells
Authors: Sanmugalingham  , De Vries  , Gauntlett  , Symon  , Bradding  , Wardlaw  
Published: March 2003

BackgroundEosinophil–bronchial epithelial cell interactions are thought to be central to the pathogenesis of asthma, both in terms of the epithelium as a source of pro‐inflammatory mediators and as a target for eosinophil‐mediated damage. We have therefore investigated adhesion interactions between these two cell types.ObjectivesTo determine the role of eosinophil and epithelial activation on eosinophil adhesion to bronchial epithelium and to characterize the adhesion receptors mediating eosinophil adhesion.MethodsEosinophils were purified from human peripheral blood by immunomagnetic selection and adhesion to confluent cultures of the airway epithelial cell lines A549 and BEAS‐2B was studied.ResultsStimulation of A549 cells with TNFα, IFNγ or a combination of 50 ng/mL of TNFα, IFNγ and IL‐1 (cytomix) did not effect eosinophil binding despite an increase in ICAM‐1 expression. Similarly stimulation of eosinophils with PAF or IL‐5 had no effect on eosinophil binding to medium‐ or cytokine‐treated A549 cells. In contrast stimulation of BEAS‐2B cells with cytomix caused a significant increase in eosinophil adhesion. This was associated with an increase in expression of ICAM‐1 and induced expression of VCAM‐1. Treatment of eosinophils with Mn2+ and IL‐5 but not eotaxin, RANTES or PAF also significantly enhanced eosinophil adhesion to medium‐treated BEAS‐2B cells. Using blocking mAbs we were able to demonstrate that the increased adhesion resulting from stimulation of eosinophils or BEAS‐2B cells was in both cases mediated by a combination of CD18 and α4 integrins.ConclusionsThis study demonstrates a selective role for IL‐5 in mediating integrin‐dependent eosinophil adhesion to airway epithelium and once again emphasizes the importance of this cytokine in controlling eosinophil activation in diseases such as asthma.