bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric oxide metabolites in induced sputum: a marker of airway inflammation in asthmatic subjects
Authors: Jang  , Choi  , Lee  , Seo  , Yang  , Park  , Lee  , Lee  , Park  , Park  
Published: March 2003

Background and objectiveThe role of nitric oxide (NO) needs to be further clarified in allergic inflammation. This study was designed to investigate the relationships between NO metabolites and eosinophil count, eosinophil cationic protein (ECP), interleukin (IL)‐5 in induced sputum from asthmatics.MethodsHypertonic saline‐induced sputum was obtained in 25 asthmatic subjects, among which 13 patients were examined before and after anti‐asthmatic medications including steroid preparations. Ten normal subjects were enrolled as controls. Fresh expectorated sputum separated from saliva was treated with equal volume of dithiothreitol 0.1%, cytospined for cell count, and the supernatant was collected for biochemical assay. NO metabolites were assayed by using modified Griess reaction. ECP was measured by fluoroimmunoassay, and detected IL‐5 by a sandwich ELISA.ResultsAsthmatic subjects, compared with controls, had significantly higher concentration of NO metabolites (1035.4 ± 125.3 vs 557.2 ± 101.5 μmol/L, P < 0.01), higher percentage of eosinophils (25.6 ± 4.6 vs 1.7 ± 0.2%, P < 0.01), and higher levels of ECP (1117.8 ± 213.9 vs 154.6 ± 47.4 μg/L, P < 0.01) in the induced sputum. IL‐5 was detected more frequently in asthmatic subjects than in control subjects (11/25 [44%] vs 1/10 [10%], P < 0.05). According to asthma severity, moderate to severe asthmatic subjects (n = 18) had higher level of NO metabolites (1143.8 ± 156.3 vs 575.5 ± 89.5 μmol/L, P < 0.01), higher levels of ECP and IL‐5 (P < 0.01, respectively) in the induced sputum than in those of mild asthmatic subjects (n = 7). NO metabolites, the percentage of eosinophils, the levels of ECP, and IL‐5 were reduced following treatment with anti‐asthmatic drugs (P < 0.01, respectively). There were significant positive correlations between NO metabolites and percentage of eosinophils or ECP (r = 0.34, P < 0.05; r = 0.28, P < 0.05). Negative correlations were noted between FEV1, FEV1/FVC and proportion of eosinophils, ECP, or IL‐5 levels.ConclusionThese findings confirmed that the level of NO metabolites was increased in the tracheobronchial secretion of asthmatic subjects and was paralleled with severity of asthma. Measurement of NO metabolites in induced sputum may be used for monitoring the degree of airway inflammation in asthmatics.
Elevated levels of soluble TNF receptors in bronchoalveolar lavage fluid in extrinsic allergic alveolitis
Authors: Dai  , Guzman  , Bauer  , Costabel  
Published: March 2003

BackgroundSoluble TNF receptors (sTNFR1 and sTNFR2) are inhibitors of TNF and can block TNF bioactivity. TNF plays an important role in the development of extrinsic allergic alveolitis (EAA).ObjectiveTo evaluate whether sTNFR1 and sTNFR2 are locally increased in EAA.MethodsWe measured sTNFR1 and sTNFR2 in bronchoalveolar lavage fluid (BALF) and serum from nine EAA patients and 11 control subjects using an ELISA method.ResultsBALF sTNFR1 and sTNFR2 levels were 0.24 ± 0.04 ng/mL and 0.59 ± 0.16 ng/mL in EAA patients, and thus significantly elevated in comparison with the controls (0.13 ± 0.02 ng/mL and 0.08 ± 0.04 ng/mL, both P < 0.05). Serum sTNFR levels were not significantly different between the two groups. Both sTNFR1 and sTNFR2 concentrations in BALF correlated significantly with the lymphocyte percentage of BALF (r = 0.57 and 0.81, respectively).ConclusionThe two alveolar sTNFRs, particularly sTNFR2, may be involved in the pathogenesis of EAA as counter‐regulators of TNF.
Serum eosinophilic cationic protein and blood eosinophil counts for the prediction of the presence of airways inflammation in children with wheezing
Authors: Shields  , Brown  , Stevenson  , Fitch  , Schock  , Turner  , Taylor  , Ennis  
Published: March 2003

BackgroundSerum eosinophilic cationic protein (ECP) concentrations may be useful noninvasive markers of airways inflammation in atopic asthma. However, the usefulness of serum ECP measurement for the prediction of airways inflammation in children with a history of wheezing is unknown.ObjectiveTo determine the test accuracy of serum ECP and blood eosinophil percentage as noninvasive markers of eosinophilic airways inflammation.MethodsBronchoalveolar lavage (BAL) fluid and peripheral blood samples for eosinophil percentages and serum ECP were obtained from children undergoing elective surgery and who gave a history of wheezing in the previous year. Sensitivity, specificity and likelihood ratios (LH) and the area under the curve (AUC) for the receiver operator characteristic (ROC) curve were calculated for each blood marker for the prediction of airways inflammation defined by a BAL eosinophil percentage > 0.86. Data were analysed on the basis of how recently symptoms had occurred.ResultsSeventy‐seven children (median age 6.75 years) were studied. An AUC of 0.75 (log serum ECP concentration) and 0.76 (log blood eosinophil percentage) was obtained for predicting airways inflammation. A serum ECP > 13 μg/L yielded a LH of 4.4, whereas using a cutoff blood eosinophils > 4% yielded a LH of 1.9, for the prediction of elevated eosinophils in BAL. Serum ECP and eosinophil percentages in BAL and blood were lowest (not statistically significant) when last symptoms had occurred more than 12 weeks previously.ConclusionsSerum ECP and blood eosinophil percentages are useful markers for predicting eosinophilic airways inflammation in wheezing children.
Grass pollen immunotherapy decreases the number of mast cells in the skin
Authors: Durham  , Varney  , Gaga  , Jacobson  , Varga  , Frew  , Kay  
Published: March 2003

BackgroundAllergen injection immunotherapy is effective for summer hay fever and reduces cutaneous sensitivity to grass pollen.ObjectiveWe have addressed whether this effect of immunotherapy may be due to a decrease in mast cell numbers in the skin.MethodsTotal mast cells and mast cell subtypes in the dermis were measured by dual immunocytochemistry in 40 adult patients who had received either ‘active’ grass pollen immunotherapy or placebo injections for 9 months in a double‐blind clinical trial.ResultsClinical improvement in hay fever was accompanied by a greater than 10‐fold reduction in the immediate cutaneous response to grass pollen (P = 0.0002) and a sevenfold decrease in mast cell numbers in the skin (P = 0.0001). The number of mast cells after immunotherapy correlated with the clinical response in terms of seasonal symptoms (r = 0.61, P = 0.001) and rescue medication use (r = 0.75, P = 0.0001). Specific double immunostaining showed that the majority of mast cells (greater than 60%) were tryptase/chymase‐positive (MCTC) and the remainder tryptase‐only (MCT) cells. Following immunotherapy both subtypes were equally reduced.ConclusionOne mechanism by which immunotherapy may act is to reduce mast cell numbers with a consequent reduction in immediate allergic sensitivity.
Intracellular expression and serum levels of eosinophil peroxidase (EPO) and eosinophil cationic protein in asthmatic children
Authors: Krug  , Napp  , Enander  , Eklund  , Rieger  , Schauer  
Published: March 2003

BackgroundEosinophils are involved in the chronic inflammatory response in asthma and their basic proteins are thought to play a major pathophysiological role in this process. While serum levels of basic proteins have been used to monitor the ongoing allergic disease, little is known about the intracellular expression of these proteins in clinical situations.ObjectiveThe aim of the study was to determine the intracellular expression of eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) in asthmatic children and control subjects and relate it to serum levels of both proteins,lung function tests and immunoglobulin (Ig)E levels.MethodsSerum ECP and EPO concentrations were determined by immunoassays in 13 asthmatic children (mean age: 9 ± 1 years, mean FEV1: 92 ± 10% predicted, geometric mean PC20 histamine 0.5 mg/mL) and 10 age‐matched, healthy control subjects. A flow cytometric single cell assay was employed to detect intracellular ECP and EPO in peripheral blood eosinophils.ResultsWhile serum concentrations of both ECP (asthma: median 15.0 μg/L [range 3.6–57.7] vs control: 5.9 μg/L [2.7–9.1]; P = 0.02) and EPO (22.9 μg/L [5.2–82.5] vs 7.2 μg/L [2.5–12.7]; P = 0.008) were significantly elevated in asthmatics, the intracellular expression of ECP and EPO (measured as mean fluorescence intensity) was decreased (EG1: 55.3 [17.7–120.8] vs 100.3 [46.5–264.4]; P = 0.01; EG2: 80.2 [24.1–135.3] vs 133.7 [32.1–244.9]; P = 0.04 and EPO: 49.7 [23.1–155.8] vs 94.9 [28.8–115.2]; P = 0.03). In asthmatics there was a significant correlation of FEV1 with intracellular ECP and of bronchial hyperresponsiveness with serum EPO and ECP. Furthermore, total IgE levels were positively correlated with serum EPO only.ConclusionWe conclude that in asthmatics the intracellular content of ECP and EPO in peripheral eosinophils is reduced possibly due to degranulation. Epitope masking in activated eosinophils or a shift to early bone marrow‐derived progenitors with less granule proteins are further possible explanations.
Increased carbon monoxide in exhaled air of patients with seasonal allergic rhinitis
Authors: Monma  , Yamaya  , Sekizawa  , Ikeda  , Suzuki  , Kikuchi  , Takasaka  , Sasaki  
Published: March 2003

BackgroundCarbon monoxide (CO) can be detected in exhaled air and is increased in asthmatic patients. However, it is uncertain whether exhaled CO is increased in patients with allergic rhinitis.Objective and methodsTo study whether exhaled CO is increased in patients with allergic rhinitis, exhaled CO concentrations were measured on a CO monitor by vital capacity manoeuvre in 86 patients with seasonal allergic rhinitis during and out of the cedar pollen season.ResultsDuring the season, exhaled CO concentrations were 3.6 ± 0.3 p.p.m. and decreased to 1.2 ± 0.1 p.p.m. out of the season. The values of exhaled CO out of the season were similar to those in age‐matched non‐smoking healthy control subjects (1.2 ± 0.1 p.p.m.). Exhaled CO concentrations were significantly higher in patients with symptoms than in those without symptoms (P < 0.01). Exhaled CO concentrations in patients did not differ significantly among oral and nasal exhalation, and oral exhalation with an expiratory resistance (P > 0.20).ConclusionThese findings suggest that allergic rhinitis increases the concentration of CO in exhaled air and increases in exhaled CO may be derived from lower airways.
Substrate preference profiles of proteases released by allergenic pollens
Authors: Widmer  , Hayes  , Whittaker  , Kumar  
Published: March 2003

BackgroundPollens are important triggers for allergic asthma and seasonal rhinitis. We have recently reported that proteases released by major allergenic pollens can injure airway epithelial cells in vitro. Disruption of epithelial integrity by proteases released following deposition of pollens on mucosal surfaces could promote sensitization and induce inflammation.ObjectiveTo compare protease activities released by allergenic pollens of various genera.MethodsWe used a rapid microassay which quantifies cleavage of dipeptide ester substrates to characterize the substrate preference profiles of serine proteases in diffusates of the pollens of perennial ryegrass (Lolium perenne), Kentucky blue grass (Poa pratensis), Bermuda grass (Cynodon dactylon), Western ragweed (Ambrosia spp.), white birch (Betula spp.) and Sydney golden wattle (Acacia longifolia).ResultsComparison of the profiles revealed notable differences as well as similarities between serine protease activities released by these pollens. Diffusates of Kentucky blue grass pollen exhibited very high substrate preference for arginine and lysine. For other pollens, cleavage of the cysteine substrate was usually the most rapid and was associated with marked preference for leucine and methionine. There was considerable variation between these pollens in the rates of cleavage of the histidine substrate. In addition, we observed high rates of cleavage of arginine and lysine substrates by Acacia pollen diffusate.ConclusionAt least two dominant patterns of substrate preference are identifiable in the mixtures of proteases released by hydrated pollens. Purification of the proteases responsible for these patterns of activity will facilitate investigation of their role in airway epithelial injury and allergic disease.
Reduced risk of hay fever and asthma among children of farmers
Authors: Von Ehrenstein  , Von Mutius  , Illi  , Baumann  , Böhm  , Von Kries  
Published: March 2003

BackgroundThe prevalence of atopic diseases is on the rise. Traditional lifestyles may be associated with a reduced risk of atopy.ObjectivesTo test the hypothesis that children living on a farm have lower prevalences of atopic diseases. To identify differences in living conditions between farmers and other families which are associated with the development of atopic conditions.DesignCross‐sectional survey among children entering school (aged 5–7 years). A written questionnaire including the ISAAC core questions and asking for exposures on a farm and elsewhere was administered to the parents. Setting: School health entry examination in two Bavarian districts with extensive farming activity. Subjects: 10 163 children.Main outcome measuresThe prevalence of doctor's diagnoses and symptoms of hay fever, asthma and eczema as assessed by parental report.ResultsFarmers' children had lower prevalences of hay fever (adjusted odds ratio = 0.52, 95% CI 0.28–0.99), asthma (0.65, 0.39–1.09), and wheeze (0.55, 0.36–0.86) than their peers not living in an agricultural environment. The reduction in risk was stronger for children whose families were running the farm on a full‐time basis as compared with families with part‐time farming activity. Among farmers' children increasing exposure to livestock was related to a decreasing prevalence of atopic diseases (aOR = 0.41, 95% CI 0.23–0.74).ConclusionsFactors related to environmental influences on a farm such as increased exposure to bacterial compounds in stables where livestock is kept prevent the development of allergic disorders in children.
Quantitative structural and biochemical analyses of tight junction dynamics following exposure of epithelial cells to house dust mite allergen Der p 1
Authors: Wan  , Winton  , Soeller  , Gruenert  , Thompson  , Cannell  , Stewart  , Garrod  , Robinson  
Published: March 2003

BackgroundHouse dust mite allergen Der p 1 is a cysteine peptidase. Previously, we have suggested that the proteolytic activity of this allergen may contribute to asthma by damaging the barrier formed by the airways epithelium.ObjectiveThe present study applied novel techniques to compare changes in permeability with quantitative events in tight junctions (TJs) and desmosomes (DMs) of epithelial cells exposed to Der p 1.MethodsConfluent monolayers of Madin‐Darby canine kidney (MDCK) and 16HBE14o‐human bronchial epithelial cells were used as experimental models. Permeability was estimated from mannitol clearance. Digital imaging with quantification of TJs and DMs was achieved by fluorescent antibody staining and 2‐photon molecular excitation microscopy (2PMEM). Biochemical changes in TJs were studied by immunoblotting, radiolabelling and immunoprecipitation.ResultsDer p 1 caused a time‐dependent breakage of TJs and reduction in their content of the protein ZO‐1. Reduction in ZO‐1 immunofluorescence at TJs occurred with a small increase in the amount of diffuse, cytoplasmic immunoreactive ZO‐1 staining. Morpho‐logical changes in TJs occurred in synchrony with increases in epithelial permeability. DM puncta increased both in size and intensity of staining. Immunoblotting demonstrated that the disruption of TJ morphology was associated with cleavage of ZO‐1 and occludin. Cells recovered from allergen exposure by de novo synthesis of occludin.ConclusionDer p 1 could contribute to sensitization and allergic responses by degrading the function of the airway epithelial barrier.
Warfarin treatment of chronic idiopathic urticaria and angio‐oedema
Authors: Parslew  , Pryce  , Ashworth  , Friedmann  
Published: March 2003

BackgroundChronic idiopathic urticaria is a disabling condition that does not always respond to antihistamine drugs and other agents are sometimes needed to control disease activity. Warfarin has demonstrated efficacy in single unblinded case studies [ 1] but has been dismissed by others [
2].ObjectiveWe investigated the effect of warfarin treatment in eight patients with chronic idiopathic urticaria unresponsive to antihistamines in an open study. Six of the eight patients responded to treatment and three had a dramatic response. These three were included in a double‐blind placebo‐controlled trial of warfarin therapy to confirm significant benefit from treatment.MethodsThe three warfarin responders had their stable warfarin dose encapsulated and placebo capsules were provided. A double‐blind placebo‐controlled crossover trial was performed on each patient. Visual analogue scores recorded disease activity.ResultsComparison of visual analogue scores showed a significant benefit while on warfarin with a reduction in pruritus and angio‐oedema.ConclusionThis is the first double‐blind placebo‐controlled study to show a response of chronic idiopathic urticaria to warfarin. The mechanisms of action are unclear and require further study.
Macrophage migration inhibitory factor (MIF) in bronchial asthma
Authors: Yamaguchi  , Nishihira  , Shimizu  , Takahashi  , Kitashiro  , Hizawa  , Kamishima  , Kawakami  
Published: March 2003

BackgroundMacrophage migration inhibitory factor (MIF) is a pro‐inflammatory cytokine favouring the secretion of TNFα and IL‐8 and counteracts anti‐inflammatory effects of corticosteroids. Airways inflammation is a central feature of bronchial asthma and is characterized by the accumulation of eosinophils.ObjectiveThe aim of this study was to investigate whether MIF is related to asthma symptoms and eosinophil accumulation in the airways.MethodsSerum MIF levels were measured by an enzyme‐linked immunosorbent assay in 44 healthy subjects and 44 asthmatics. Levels of MIF in induced sputum were measured in 10 healthy subjects and 15 asthmatics. Levels of eosinophil cationic protein (ECP) in induced sputum were measured by a radioimmunosorbent assay. Fluorescence double immunostaining was conducted to examine cellular source and localization of MIF.ResultsSerum MIF levels were significantly increased in asthmatic patients compared with age and sex‐matched control subjects. Symptomatic patients had a higher MIF level than asymptomatic patients. Induced sputum obtained from asthmatics contained higher levels of MIF than those from control subjects. MIF levels in induced sputum were correlated with ECP levels in induced sputum. MIF was colocalized with eosinophil peroxidase staining in the cytoplasm of sputum cells.ConclusionIncreased MIF levels are associated with asthma symptoms and one of the cellular sources of MIF in the airways are eosinophils.
Comparative molecular modelling identifies a common putative IgE epitope on cysteine protease allergens of diverse sources
Authors: Furmonaviciene  , Sewell  , Shakib  
Published: March 2003

BackgroundPrevious approaches for studying common allergenic epitopes have mainly focused on sequence comparisons, which unfortunately yield little or no information on the shape of the epitope which is the most important determinant of cross‐reactivity.ObjectivesThe aim of this study was to investigate the structural basis for cross‐reactivity between a previously identified immunodominant epitope of the house dust mite allergen Der p 1 (Leu147‐Gln160) and the corresponding epitopes on other allergens that are either taxonomically closely related (i.e. cysteine proteases of other mite species) or representing evolutionary conserved structures (i.e. plant, human and parasite cysteine proteases).MethodsWe carried out comparative molecular modelling on a range of cysteine proteases, including those of other mite species (Der f 1 and Eur m 1), human (cathepsins B, K, L, S and O), plants (papain, chymopapain and actinidin) and parasites (cruzain, cathepsin l‐like Leishmania protease, Entamoeba ACP1 protease and Schistosoma Q26534, Q11003 and cathepsin L proteases).ResultsOur study shows that all the cysteine proteases investigated here display an epitope corresponding to that previously identified on Der p 1, but with varying shapes and degree of accessibility. It appears that the core of the epitope on these homologous cysteine proteases consists of a centrally located conserved Tyr residue flanked on either sides by accessible amino acids.ConclusionTherefore, these cysteine proteases seem to use similar accessible structures, which may form the basis for the rational design of generic epitope‐directed treatment strategies for controlling allergic diseases.
IgE receptor‐mediated release of nerve growth factor by mast cells
Authors: Xiang Z. , Nilsson G. 
Published: March 2003

BackgroundIt has previously been demonstrated that the level of nerve growth factor (NGF) is increased in serum from humans with allergic diseases and asthma.AimA question raised by these observations is whether NGF could be released from degranulating mast cells during an allergic reaction. The aim of this study was to investigate if NGF is released from mast cells after activation through cross‐linkage of the high‐affinity IgE receptor.MethodsMouse and human in vitro cultured mast cells were activated by IgE and specific antigen, stem cell factor or lipopolysaccharide. Release of NGF was measured by ELISA and mRNA expression was detected by RT PCR.ResultsWe found that mast cells not only express NGF transcripts, but also release NGF polypeptide in response to IgE and specific antigen. Activation of mouse mast cells for 30 min induced significant release of NGF (32.9 ± 1.3 pg/2 × 106 cells) compared to spontaneous release (13.9 ± 2.7 pg/2 × 106 cells) (P < 0.01). Similarly, activation of human cultured mast cells also resulted in a significant increase of NGF release (733 ± 310 pg/3 × 105 cells) compared to spontaneous release (9.2 ± 4.0 pg/3 × 105 cells). Two other mast cell secretogogues studied, stem cell factor and lipopolysaccharide, were not able to induce release of NGF.ConclusionThis study provides evidence that NGF could be specifically released by stimuli causing an allergic reaction, and mast cells can thereby be the source of NGF in IgE‐mediated allergic diseases. Our findings add further support for a close correlation between NGF and mast cells that could be of importance for the allergic inflammation.