bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diethanolamine‐induced occupational asthma, a case report
Authors: Piipari  , Tuppurainen  , Tuomi  , MÄntylÄ  , Henriks‐Eckerman  , Keskinen  , Nordman  
Published: March 2003

BackgroundAmino alcohols are low molecular weight chemicals used widely in industrial processes, often as minor constituents. They have been found to cause allergic contact dermatitis. Marked exposure through airways is uncommon in other than occupational settings where chemicals containing amino alcohols may be heated or vaporized, liberating free amino alcohols into the ambient air. A few cases of asthma and allergic rhinitis have been reported, but the amounts inducing the airway reactions have not been defined.ObjectiveTo further characterize ethanolamine‐induced asthma and define the concentration inducing the asthmatic reaction, a case of diethanolamine‐induced occupational asthma in a patient handling diethanolamine containing cutting fluid is reported.MethodsSuspicion of work related asthma was raised by symptoms and peak expiratory flow monitorings at work and at home. Specific bronchial provocation tests with the cutting fluid containing DEA and with DEA aerosol at two different concentration below the American Conference of Governmental Industrial Hygienists threshold limit value of DEA (2.0 mg/m3) were done.ResultsDEA caused asthmatic airway obstruction at two different concentrations below the ACGIH TLV. A slight dose–response relationship was observed. Specific IgE‐antibodies against DEA could not be found.ConclusionsDEA is able to induce occupational asthma by a sensitization mechanism, the exact pathophysiological mechanism of which is not known.
Identification of HLA‐DR and ‐DQ alleles conferring susceptibility to pollen allergy and pollen associated food allergy
Authors: Boehncke  , Loeliger  , Kuehnl  , Kalbacher  , BÖhm  , Gall  
Published: March 2003

BackgroundAllergenic crossreactivity of pollen and foods due to the antigeneic similarity of oligopeptides is a well established clinical phenomenon.ObjectiveTo determine the immunopathological relevance of antigen presentation, we analysed the HLA class‐II genotype of patients with either pollen allergy or pollen associated food allergy.MethodsOne hundred and twenty patients with pollen allergy and 80 patients with pollen associated food allergy were evaluated by skin‐ prick tests, RAST, and HLA class‐II genotyping. The control population comprised 4251 healthy blood and bone marrow donors.ResultsMonovalent pollen allergy was observed in 57% (n = 68) of patients with pollinosis (57x grass pollen, 11x birch pollen), but only in 15% (n = 12) of patients with food allergy (9x grass pollen, 3x birch pollen). Hazelnut (71%), almond (65%), walnut (44%) and apple (41%) were the most common food allergens and frequently associated with birch pollen allergy. Grass pollen allergy was associated with an increased frequency of HLA‐DQB1*0301 (RR = 2.3; EF = 0.4; P = 0.0016) when compared with the control population. HLA‐DRB1*08 confered a sixfold higher risk for peanut allergy (EF = 0.3; P = 0.0013) and ‐DRB1*12 a 13‐fold higher risk for carrot allergy (EF = 0.3; P < 0.000001). The differences on allele frequencies detected among patients with food allergies diminished or turned statistically insignificant when their genotypes were directly compared to those of patients with the corresponding pollen allergies. This was found in the case of birch pollen associated hazel nut allergy for the extended haplotype HLA‐DRB1*01, ‐DQA1*0101, ‐DQB1*0501 as well as in grass pollen associated peanut allergy for HLA‐DRB1*08 (from RR = 6, P = 0.0013 to insignificant) and in birch pollen associated carrot allergy for HLA‐DRB1*12 (from RR = 13, P < 0.000001 to insignificant).ConclusionWe were able to identify HLA class‐II alleles associated with some allergies thus indicating that these alleles might confer susceptibility to the respective allergens. Similarities at the level of the HLA class‐II genotype parallel the empirical finding of distinct cross‐reactivity patterns thus complementing investigations of IgE specificities. Our observations provide evidence for the major importance of antigen presentation on the manifestation of distinct crossreactivity patterns.
Inhaled procaterol inhibits histamine‐induced airflow obstruction and microvascular leakage in guinea‐pig airways with allergic inflammation
Authors: Mirza  , Tokuyama  , Arakawa  , Kato  , Mochizuki  , Morikawa  
Published: March 2003

Backgroundβ2‐adrenoceptor agonists (β2‐agonists) are shown to inhibit airway microvascular leakage in experimental animals. This effect may change in animals with chronic airway inflammation.ObjectiveWe examined whether inhaled β2‐agonists inhibit microvascular leakage in guinea‐pig airways with chronic allergic inflammation.MethodsThree weeks after the sensitization with ovalbumin (OA; 6 mg/mL), each guinea‐pig was challenged with inhaled OA once a day for 1 or 3 weeks. Control animals without sensitization with OA also inhaled vehicle for OA (saline) for 3 weeks. One day after the last challenge, different doses of inhaled procaterol (1, 3 or 10 μg/mL) or vehicle was given to animals for 10 min after an anaesthesia. Fifteen minutes after the end of inhalation, the animals were given i.v. Evans blue dye (EB dye; 20 mg/kg), a marker of microvascular leakage, and then i.v. histamine (3 or 30 μg/kg) or vehicle. Lung resistance, a parameter of airflow obstruction, was measured for 6 min and the lungs were removed to calculate the amount of extravasated EB dye into the airways.ResultsA significant increase in eosinophil infiltration into the airways was seen in sensitized and challenged animals compared with control animals without sensitization. Among animals receiving antigenic exposure for either 0 (control), 1 or 3 weeks, 10 μg/mL procaterol significantly inhibited 30 μg/kg histamine‐induced increase in EB dye extravasation to a similar degree (ranged from 28.7 to 69.8% inhibition) as well as that in lung resistance (more than 90% inhibition in all groups). The minimal dose of procaterol to inhibit 3 μg/kg histamine‐induced microvascular leakage was not different between non‐sensitized control animals and those sensitized and challenged for 3 weeks at all airway levels.ConclusionInhaled β2‐adrenoceptor agonists may be also potent in attenuating microvascular leakage even in the airways with chronic allergic inflammation.
Inhibitory effect of NPC‐17731 on BK‐induced and antigen‐induced airway reactions in guinea‐pigs
Authors: Ikemura  , Sasaki  , Ohmori  
Published: March 2003

BackgroundBradykinin (BK) has been suggested to act as a mediator in the airways in inflammatory conditions, such as asthma through the activation of B2‐receptors. NPC‐17731 (D‐Arg0[Hyp3, D‐HypE(trans‐propyl)7, Oic8]BK) has potent antagonistic activity against B2‐receptors without agonistic activity.ObjectiveWe have evaluated the inhibitory effect of NPC‐17731 against BK in guinea‐pig airways. In addition, we have investigated the effects of NPC‐17731 on antigen‐induced airway responses.MethodsBronchoconstriction was assessed as an increase in lung resistance (RL) and a decrease in dynamic compliance (Cdyn). Airway plasma leakage was assessed by extravasation of intravenously injected Evans blue dye. To estimate the effect of drugs on antigen‐induced reactions, guinea‐pigs were actively sensitized by exposure to aerosol ovalbumin (OA) twice and challenged by OA inhalation. Acute bronchoconstriction was measured for 15 min. Airway vascular leakage was measured at 10 min after the challenge. Assessment of airway hyperresponsiveness against acetylcholine and bronchoalveolar lavage were conducted at 18–24 h after the antigen‐challenge.ResultsNPC‐17731 (0.3–30 μg/kg, iv) inhibited intravenously applied BK‐induced bronchoconstriction in a dose‐dependent manner. The 50% inhibitory doses (ID50) were 1.3 μg/kg for RL and 2.8 μg/kg for Cdyn. NPC‐17731 (1–10 μg/kg, iv) inhibited BK‐induced microvascular leakage in a dose‐dependent manner (ID50 = 4.2 μg/kg). In addition, 10 μg/kg of NPC‐17731 abolished the inhaled BK‐induced bronchoconstriction. In the sensitized animals, 100 μg/kg NPC‐17731 significantly reduced the airway microvascular leakage and the decrease in Cdyn induced by ovalbumin exposure (P < 0.05), but did not influence the increase in RL. NPC‐17731 (100 μg/kg) inhibited the antigen‐induced airway hyperresponsiveness and the increase in eosinophils in BAL fluids.ConclusionThese results indicate that NPC‐17731 is a potent BK antagonist in vivo and that BK may partially contribute to the antigen‐induced airway responses in guinea‐pigs.
Mite antigen‐induced IL‐4 and IL‐13 production by basophils derived from atopic asthma patients
Authors: Shimizu  , Shichijo  , Hiramatsu  , Takeuchi  , Nagai  , Takagi  
Published: March 2003

BackgroundThere is increasing evidence for the role of basophils in the pathogenesis of atopic diseases such as bronchial asthma, atopic dermatitis and atopic rhinitis. Recently, it has been reported that basophils derived from healthy donors produce the immunoregulatory cytokines interleukin (IL)‐4 and IL‐13 after cross‐linking of cell surface IgE. In addition to well‐known inflammatory mediators, such as histamine and leukotriene C4, these cytokines produced by basophils are also considered to be associated with atopic diseases.ObjectiveOur first objective was to determine whether or not mite‐sensitive atopic asthmatic basophils produce IL‐4 and IL‐13 in response to mite antigens. Our second objective was to investigate the relationship between antigen‐specific or nonspecific IgE in the serum and the production of these cytokines in order to determine the association of basophil‐derived cytokines with the pathogenesis of atopic asthma. Our final objective was to study how production of these cytokines could be regulated by some anti‐asthma drugs.MethodsBasophils were purified from peripheral venous blood of 67 atopic asthma patients with elevated RAST for the house dust mite. Cells were stimulated with mite antigens for 6 hours and then IL‐4 and IL‐13 levels in the supernatants were measured by enzyme‐linked immunosorbent assay (ELISA).ResultsMite‐sensitive asthmatic basophils produced IL‐4 and IL‐13 when stimulated with mite antigens. Mite‐induced IL‐4 production peaked at 6 hours after the stimulation, whereas IL‐13 production continued up to 24 hours. The higher the concentration of mite‐specific IgE but not total IgE released in the serum, the more IL‐4 and IL‐13 were produced by basophils in response to mite antigens. The production of these cytokines was significantly suppressed by the anti‐asthma drugs theophylline (IL‐4, p < 0.001, n = 6; IL‐13, p < 0.001, n = 10) and dexamethasone (IL‐4, p < 0.001, n = 15; IL‐13, p < 0.001, n = 10).ConclusionMite‐antigen‐induced IL‐4 and IL‐13 production by basophils derived from mite‐sensitive asthma patients was associated with the concentration of mite‐specific IgE and may play an important role in the pathogenesis of atopic asthma. The inhibitory effect of dexamethasone and theophylline on allergic inflammation may be due to the inhibition of IL‐4 and IL‐13 production not only by T cells but also by basophils.
CD11b and L‐selectin expression on eosinophils and neutrophils in blood and induced sputum of patients with asthma compared with normal subjects
Authors: IN 'T Veen  , Grootendorst  , Bel  , Smits  , Van Der Keur  , Sterk  , Hiemstra  
Published: March 2003

BackgroundPatients with asthma show altered surface expression of the adhesion molecules CD11b and L‐selectin on airway granulocytes compared with blood granulocytes.ObjectiveTo investigate whether this modulation is related to disease activity or due to transendothelial migration, we compared the CD11b and L‐selectin expression on blood and induced sputum eosinophils and neutrophils between patients with asthma and normal subjects.MethodsEleven normal subjects (21–43 years), nine patients (21–34 years) with mild atopic asthma and 10 patients (20–47 years) with moderate to severe atopic asthma on regular treatment with inhaled steroids underwent sputum induction by inhalation of nebulized hypertonic saline (4.5%). CD11b and L‐selectin expression on granulocytes from blood and DTT‐homogenized sputum were analysed by flow cytometry. Eosinophils could be discriminated from neutrophils by using depolarized light scatter. Disease activity was assessed by baseline FEV1 and airway responsiveness to histamine (PC20).ResultsSputum eosinophils showed higher expression of CD11b (P < 0.001) and lower expression of L‐selectin (P < 0.001) compared with peripheral blood eosinophils. CD11b and L‐selectin expression on eosinophils from blood or sputum did not differ between the three groups. Similar results were obtained for neutrophils. The PC20 in the patients with moderate‐to‐severe asthma was related to CD11b expression on blood (R = − 0.92, P = 0.001) and sputum eosinophils (R = 0.75, P = 0.02).ConclusionsFlow cytometry of induced sputum granulocytes from asthmatic as well as normal subjects is feasible. We conclude that the modulated expression of CD11b and L‐selectin on airway granulocytes is not specific for asthmatic airway inflammation, but is probably the result of tissue migration per sé. This implies that CD11b and L‐selectin expression on granulocytes in induced sputum cannot be used as marker of disease activity.
Identification and partial characterization of multiple major allergens in peanut proteins
Authors: DE Jong  , Van Zijverden  , Spanhaak  , Koppelman  , Pellegrom  , Penninks  
Published: March 2003

BackgroundPeanuts are a major cause of food allergies both in children as in adults which can induce an anaphylactic shock. The identification and characterization of peanut allergens could lead to more insight into the mechanism and contribute to the improvement of diagnostic tests and treatment for peanut allergy.ObjectiveIn the present study, the peanut protein‐specific immunoglobulin concentrations as well as their recognition of the various peanut proteins or protein subunits was determined in the plasma of peanut‐allergic (PA) and non‐allergic (NA) individuals. Moreover, two peanut allergens were characterized in more detail to confirm them as the earlier described Ara h1 and Ara h2.MethodsThe presence of Ig‐binding sites in peanut proteins was studied by immunoblotting assays whereas the concentrations of peanut‐specific Ig was determined by ELISA.ResultsPeanut proteins were found to contain multiple binding sites for immunoglobulins. Of these proteins, six were recognized by peanut‐specific IgE present in more than 50% of the plasma samples of the PA group. Their molecular weights were ≈44, 40, 33, 21, 20 and 18 kDa. The last three protein bands were recognized by peanut‐specific IgE present in more than 70% of the PA plasma samples and were thought to contain Ara h2. This allergen as well as another protein that was thought to be Ara h1, which was not recognized by the majority of the patients' IgE‐containing plasma samples, were isolated and the N terminal amino acid sequence was determined. Peanut protein‐specific IgA, IgM, IgG and IgG‐subclasses showed a more diverse recognition pattern of peanut protein in the PA group compared to the NA group. No differences were found in the plasma concentrations of peanut protein‐specific immunoglobulins of the various classes between the PA and NA group.ConclusionsFrom the present study, we conclude that peanuts contain multiple allergens, of which six can be described as major allergens, Ara h2 included. In our population Ara h1 is not a major allergen. The recognition of peanut proteins by immunoglobulins is more diverse in PA individuals compared with NA individuals which, however, is not substantiated in the concentrations of peanut‐specific immunoglobulins in plasma, other than IgE.
Anti‐betalactoglobulin IgG antibodies bind to a specific profile of epitopes when patients are allergic to cow's milk proteins
Authors: Duchateau  , Michils  , Lambert  , Gossart  , Casimir  
Published: March 2003

BackgroundWe demonstrated recently that mite‐allergic patients differed from healthy controls in the specificity of their IgG antibodies towards mite antigens.ObjectiveThe present study investigates whether these discriminatory IgG responses could be associated with the expression and the evolution of clinical manifestations in allergy to cow's milk proteins.MethodsAntibody specificity was evaluated by comparing IgG‐binding to native bovine beta‐lactoglobulin (nBLG) and its products of pepsin hydrolysis (dBLG) using a solid‐phase enzyme‐linked immunosorbent assay (ELISA). Antibody specificity was further investigated in competitive ELISA using streptavidin‐biotin technology with purified IgG fractions from selected subjects and specific mouse monoclonals raised against BLG.ResultsIgG antibodies from CM‐intolerant or allergic sera (n = 222) showed a higher degree of binding to nBLG than to dBLG, while control sera showed similar levels to both nBLG and dBLG (n = 99 children/65 adults). Sera from symptomatic patients, wether or not they contained IgE antibodies, demonstrated group‐segregating capacities to compete with pooled purified IgG from each clinical class, and with selected murine anti‐nBLG monoclonal antibodies for binding to n‐ and dBLG. Furthermore, this inhibitory capacity shifted dramatically in a small subset (n = 14) of children as they developed CM‐tolerance.ConclusionThe IgG responses to BLG of CM‐intolerant or allergic patients are very different from those of healthy controls, being characterized not only by increased titres but also similar patterns of modified specificity, including a marked preference for conformational epitopes.Cross‐competition experiments confirmed that the restricted specificity was clinically associated, appearing as an immunological signature, which allowed almost complete discrimination between patient groups. This phenomenon is a particularly promising diagnostic feature in this category of young patients where conventional tests usually only document the status of sensitization.
Home dampness and respiratory health status in European children
Authors: Andriessen  , Brunekreef  , Roemer  
Published: March 2003

BackgroundLiving in a damp home has been associated with impaired respiratory health in previous studies, but objective data on lung function variability and atopy have been lacking from most studies.ObjectivesData collected in the winter of 1993–1994 in the framework of the PEACE study (Pollution Effects on Asthmatic Children in Europe) were used to study the association between home dampness and Peak Flow (PEF) variability, frequency of respiratory symptoms and relief medication use during the period of observation.MethodsChildren were selected with a screening questionnaire on the basis of positive answers to questions on symptoms of asthma and chronic cough. Children were instructed to perform PEF measurements with Miniwright PEF meters twice daily over a period of 2 months. Parents kept diaries on respiratory symptoms and medication use of their children. Data on demographic and housing characteristics were derived from a parent‐administered questionnaire. As indicators for home dampness reported moisture stains and moulds were used. Children were tested for atopy with skin‐prick tests. Data from 1614 children from 13 centres in 10 different countries were available for analysis. Linear regression models and prevalence rate ratios were used to investigate the association between home dampness and PEF variability and the period prevalence of cough, phlegm, lower and upper respiratory symptoms and bronchodilator use.ResultsIn atopic children, PEF variability was positively related to self‐reported moulds but not to moisture stains. The period prevalence of cough and upper respiratory symptoms was significantly higher in children living in houses with reported moulds, compared with ‘dry’ homes.ConclusionsThese results show that self‐reported moulds in homes are associated with objective as well as subjective markers of airway lability in European children with chronic respiratory symptoms.
Comparison between the in vitro cytokine production of mononuclear cells of young asthmatics with and without immunotherapy (IT)
Authors: Van Bever  , Vereecke  , Bridts  , De Clerck  , Stevens  
Published: March 2003

BackgroundThe underlying mechanisms of immunotherapy (IT) are still unknown but may be related to modifications of cytokine production of T lymphocytes.ObjectiveIn this study we determined the in vitro allergen‐induced production of IL‐2, IL‐4, IL‐5, IL‐12 and IFNγ of peripheral blood mononuclear cells (PBMC) of eight young asthmatics, aged 15 ± 2 years, receiving IT (IT group) and of eight comparable asthmatics, aged 13 ± 3.5 years, who never received IT (non‐IT group).MethodsAll patients suffered from perennial asthma and were allergic to house dust mite (HDM). They were selected if they showed a positive stimulation index (SI) of PBMC after in vitro incubation with HDM (i.e. SI > 2). Cells were incubated with and without HDM (10 μg/mL) during 24 h, 48 h and 7 days. Cytokines were determined in the supernatant at the three time points and are expressed as median values in pg/mL.ResultsIn the IT group the secretion of IL‐2 was lower compared with the non‐IT group after 7 days incubation of PBMC with HDM (0 vs 33.2, P = 0.008). In both groups maximal secretion of IL‐2 was observed after 48 h. In the non‐IT group a high value of IL‐2 persisted after 7 days, whereas in the IT group a significant decline of IL‐2 occurred after 7 days. Although IL‐4 secretion was low in all subjects, more patients of the non‐IT group showed detectable IL‐4 in the HDM cultures after 24 h and 48 h, although the difference was not statistically significant (P = 0.08 and P = 0.28, respectively). Furthermore, IL‐4 secretion was lower in the HDM cultures after 24 h in the IT group (1.75 vs 4.1, P = 0.011) and 48 h (2.2 vs 4.1, P = 0.035). IL‐5 secretion was lower in the HDM cultures after 24 h (12.4 vs 47.6, P = 0.035) and 48 h (26.8 vs 135, P = 0.046) in the IT group than in the non‐IT group. After 7 days of incubation with HDM there was no difference between the groups. There was no difference between both groups in secretion of IFNγ and IL‐12.ConclusionsThese results show a difference in vitro cytokine secretion of PBMC of asthmatics receiving IT compared with asthmatics who never received IT. PBMC of patients receiving IT secrete less IL‐2 and IL‐5 after in vitro incubation with HDM and show a tendency to secrete less IL‐4. The efficacy of IT may be attributed to a modified cytokine secretion of PBMC.