bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced interferon gamma production by antigen‐stimulated cord blood mononuclear cells is a risk factor of allergic disorders — 6‐year follow‐up study
Authors: Kondo  , Kobayashi  , Shinoda  , Takenaka  , Teramoto  , Kaneko  , Fukao  , Matsui  , Kasahara  , Yokoyama  
Published: March 2003

BackgroundIt is not sufficient to predict ‘high allergic risk newborns’ on the basis of increased IgE concentrations of cord blood alone, because a raised cord blood IgE concentration is specific but not sensitive in the prediction of the development of allergic disorders. Warner et al. have reported that interferon gamma (IFN‐γ) production by allergen‐triggered cord blood cells is a predictor of atopic eczema, based on the 1‐year follow‐up study.ObjectiveWe examined whether IFN‐γ production by antigen‐stimulated cord blood mononuclear cells (CBMCs) is a risk factor of allergic disorders, based on the 6‐year follow‐up study.MethodsThe relationships among cord blood IgE concentrations, IFN‐γ and interleukin‐2 (IL‐2) productions by antigen‐stimulated CBMCs, and the development of allergic disorders in 21 infants for 6 years were investigated.ResultsAtopic dermatitis, atopic dermatitis and allergic rhinitis, or atopic dermatitis and bronchial asthma developed in seven of 21 subjects. The maximal IFN‐γ concentration in culture supernatants of ovalbumin (OA) or bovine serum albumin (BSA) stimulated CBMCs in infants who developed allergic disorders was significantly lower (P < 0.01) than that in infants who did not develop any allergic disorders. In contrast, the maximal IL‐2 concentration in culture supernatants of OA‐ or BSA‐stimulated CBMCs in infants who developed allergic disorders was not lower than in infants who did not develop any allergic disorders. Moreover, the IFN‐γ concentrations were negatively correlated with cord blood IgE concentrations.ConclusionReduced IFN‐γ production by antigen‐stimulated CBMCs is a risk factor of allergic disorders.
Probiotic bacteria down‐regulate the milk‐induced inflammatory response in milk‐hypersensitive subjects but have an immunostimulatory effect in healthy subjects
Authors: Pelto  , Isolauri  , Lilius  , Nuutila  , Salminen  
Published: March 2003

BackgroundProbiotic bacteria can influence immune responses both specifically by stimulating antibody production and nonspecifically by enhancing phagocytosis of pathogens and modifying cytokine production.ObjectiveThe authors hypothesized that probiotic bacteria can alleviate hypersensitivity by influencing phagocytes. The modulation of phagocytes may be different in healthy subjects compared with hypersensitive subjects.Subjects and methodsIn a double‐blind, cross‐over study, challenges with milk in milk‐hypersensitive and healthy adults with or without an intestinal bacterial strain, Lactobacillus GG (ATCC 53103) were performed. The challenge‐induced immunoinflammatory response was recorded by measuring the expression of phagocytosis receptors prior to and after the challenge using flow cytometry.ResultsIn milk‐hypersensitive subjects, milk challenge increased significantly the expression of CR1, FcγRI and FcαR in neutrophils and CR1, CR3 and FcαR in monocytes. Milk with Lactobacillus GG prevented the increase of the receptor expression. In healthy subjects, milk challenge did not influence receptor expression while milk with Lactobacillus GG increased significantly the expression of CR1, CR3, FcγRIII and FcαR in neutrophils.ConclusionProbiotic bacteria appear to modulate the nonspecific immune response differently in healthy and hypersensitive subjects. This is seen as an immunostimulatory effect in healthy subjects, and as a down‐regulation of immunoinflammatory response in milk‐hypersensitive subjects.
Classification of asthma severity: should the international guidelines be changed?
Authors: Sawyer  , Miles  , Lewis  , Fitzharris  , Pearce  , Beasley  
Published: March 2003

BackgroundInternational guidelines recommend that, in addition to symptoms and medication requirements, measurements of forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) are necessary for the objective assessment of asthma severity. The guidelines suggest that parity exists between measurements of FEV1 and PEF when expressed as percentage of predicted normal values, and that asthma severity can be classified as mild, moderate or severe on the basis of FEV1 and PEF measurements of > 80%, 60–80% and < 60% of predicted values, respectively.ObjectiveTo determine the relationship between measurements of FEV1 and PEF when expressed as percentage predicted values.MethodsA total of 1198 paired measurements of FEV1 and PEF were obtained from the medical records of a random sample of 25 adult asthmatic patients attending a hospital‐based chest clinic. Measurements of lung function were expressed as a percentage of predicted normal values, using the European Respiratory Society prediction equations for PEF and FEV1. For the individual paired measurements, the mean differences between PEF and FEV1 percentage predicted were calculated. Measurements of lung function were used to determine asthma severity with < 60%, 60–80%, and > 80% predicted FEV1 and PEF values representing severe, moderate and mild asthma, respectively. The proportion of paired measurements in which differences in classification resulted from the use of FEV1 or PEF percentage predicted values was then calculated.ResultsIn asthma of differing severity, there was considerable variability between measurements of FEV1 and PEF when expressed as percentage predicted values; calculation of the FEV1% predicted resulted in lower values than those of the PEF percentage predicted, with a mean difference of −17.2% (95% CI −16.3%, −18.1%). There was agreement in classification of asthma severity in only 49.9% (598/1198) of paired measurements. Different prediction equations, while variably altering the degree of misclassification, did not correct the basic differences in the assessment of asthma severity dependent on the use of FEV1 or PEF.ConclusionFEV1 and PEF values, expressed as percentage predicted, are not equivalent. Pending further evaluation, the authors suggest that published asthma guidelines should avoid the assumption of parity between these two measurements.
The current cardiac safety situation with antihistamines
Authors: Yap Y.G. , Camm A.J. 
Published: March 2003

Antihistamines (H1‐receptor antagonists) are amongst the most frequently prescribed drugs worldwide for the treatment of allergic conditions. The clinical interest of classical ‘first generation’ antihistamines is currently rather limited by their anticholinergic and sedative properties. The second generation of antihistamines, so‐called non‐sedating antihistamines, are free of these side‐effects. However, since the 1990s, there have been reports that certain non‐sedating antihistamines, mainly terfenadine and astemizole, might be associated with the risk of rare but severe dysrhythmias. These drugs prolong the monophasic action potential and surface electrocardiographic QT interval and may lead to the development of early after‐depolarization and possibly torsades de pointes through an inhibition of potassium channel repolarization. Concomitant administration with drugs that inhibit the hepatic cytochrome P‐450 (imidazole antifungals, macrolide antibiotics) or those that prolong the QT interval by the same or other mechanism (e.g. antiarrhythmics, antipsychotics, tricyclic antidepressants) increases their effect on the cardiac repolarization. The cardiac safety profile of newer non‐sedating antihistamines requires confirmation. Drugs with low or no potential to block the K+ rectification channel (e.g. IKr channels) are likely to possess cardiac safety advantages. Other drug‐related factors such as the physico‐chemical properties of the antihistamines and its metabolic profile may also contribute to the cardiac response. Mizolastine is a new non‐sedating antihistamine with antiallergic properties. It has a good bioavailability and a metabolism via the cytochrome P‐450 oxidation accounting for only 35% of its hepatic clearance. In addition, mizolastine displays low lipophilicity and consequently low cardiac tissue fixation. In clinical studies, mizolastine has not shown any dose‐related increase in QT intervals. Its clinical use has not been associated with ventricular dysrhythmias. Thus, although the post‐marketing experience with mizolastine is still limited, mizolastine offers a safe alternative for the therapeutic management of allergic rhinitis and urticaria. However, more data are still needed on the cardiac safety of this and other non‐sedating antihistamines.
Airway endothelin levels in asthma: influence of endobronchial hypertonic saline challenge
Authors: Makker  , Springall  , Redington  , Ghatei  , Bloom  , Polak  , Howarth  , Holgate  
Published: March 2003

BackgroundThe pathophysiology of exercise‐induced asthma is not well understood. Hypertonicity of the airway lining fluid resulting from loss of water due to hyperventilation is considered to play a role, but the precise mechanism by which hypertonicity can induce bronchoconstriction is unknown. Peptides of the endothelin (ET) family have potent smooth muscle contractile properties, and have been linked to airway narrowing in stable asthma. We postulated that ET release may contribute to the acute bronchoconstrictor response induced by a hypertonic stimulus.MethodsSeven male asthmatic subjects underwent local endobronchial challenge with hypertonic (3.6%) saline and, as a control, isotonic (0.9%) saline aerosols in separate bronchopulmonary segments. Bronchoalveolar lavage (BAL) was performed at both sites during the phase of immediate bronchoconstriction. Concentrations of immunoreactive ET and of the mast cell products, histamine, tryptase and prostaglandin D2, in BAL fluid were measured.ResultsConcentrations of ET in BAL fluid from the hypertonic saline‐challenged sites were significantly lower than those in BAL fluid from sites exposed to isotonic saline (0.19 [0.11–1.24] fmol/mL vs 0.40 [0.20–2.36] fmol/mL, P < 0.05). Concentrations of histamine, tryptase, and prostaglandin D2 did not differ significantly between the two sites.ConclusionsThese findings do not support the hypothesis that ET release within the airway lumen is involved in the bronchoconstrictor response induced by hypertonic saline.
Between‐observer repeatability of sputum differential cell counts. Influence of cell viability and squamous cell contamination
Authors: Ward  , Woltmann  , Wardlaw  , Pavord  
Published: March 2003

BackgroundInduced sputum differential cell counts have been advocated as a method of noninvasively assessing airway inflammation in asthma and other airway diseases. Relatively little is known about the between‐observer repeatability of sputum differential cell counts and the factors that influence it.ObjectiveTo assess the between‐observer variability of induced sputum cell counts.MethodsSputum was induced and processed using standard techniques. Forty‐two slides from 38 patients (31 with asthma, seven normal subjects) were randomly selected. Slides were classified as good (< 20% squamous cells and > 50% viability; n = 24); low viability (< 50% viability; n = 10) and high squamous cell contamination (> 20% squamous cells; n = 8). Two blinded observers counted between 200 and 400 nonsquamous cells and agreement was assessed by the intraclass correlation coefficient (ICC) and the standard deviation of between‐observer differences (
sd).ResultsThe overall ICC were 0.9, 0.89, 0.9 for eosinophils, neutrophils and macrophages and 0.29 and 0.69 for lymphocytes and epithelial cells. Repeatability was greater in slides classified as good compared with slides with low cell viability and particularly excess squamous cell contamination.ConclusionsWe have shown that the overall between‐observer repeatability of the differential eosinophil, neutrophil and macrophage cell counts is good. Low cell viability and particularly excess squamous cell contamination reduce between‐observer repeatability suggesting that techniques that ensure high cell viability and reduce squamous contamination would be an advantage.
Inflammatory mediators in bronchoalveolar lavage samples from children with and without asthma
Authors: Ennis  , Turner  , Schock  , Stevenson  , Brown  , Fitch  , Heaney  , Taylor  , Shields  
Published: March 2003

BackgroundWe investigated whether eosinophils and mast cells, found in the airways of children with wheeze, were activated during relatively asymptomatic periods.MethodsA nonbronchoscopic bronchoalveolar lavage (BAL) procedure was performed on children presenting for an elective surgical procedure. Eosinophil‐derived (eosinophil cationic protein, ECP) and mast cell‐derived (histamine/tryptase) mediator concentrations were measured in the BAL fluid. A detailed history and serum immunoglobulin E were used to classify the children into four groups: atopic with and without asthma, viral‐associated wheeze and normal controls.ResultsThe ECP concentrations in BAL from atopic asthmatic subjects were significantly higher than those measured in BAL from normal controls (P < 0.01), no other groups differed significantly. Histamine concentrations were elevated in both the atopic asthmatic and viral‐associated wheeze groups compared with controls (P < 0.02) and additionally higher concentrations were obtained in atopics with asthma compared with atopics without asthma (P < 0.03). Tryptase concentrations did not differ between groups, although the tryptase and histamine concentrations correlated significantly (r = 0.78, P < 0.0001).ConclusionsElevated histamine concentrations were found in children with wheeze regardless of the aetiology, whereas ECP was only elevated in those asthmatics with atopy. This suggests that even in relatively quiescent periods, there is some on going activation of airway eosinophils in children with atopic asthma.
Molecular characterization of Dau c 1, the Bet v 1 homologous protein from carrot and its cross‐reactivity with Bet v 1 and Api g 1
Authors: HOFFMANN‐SOMMERGRUBER  , O'RIORDAIN  , AHORN  , EBNER  , DA CAMARA MACHADO  , PÜHRINGER  , SCHEINER  , BREITENEDER  
Published: March 2003

BackgroundUp to 70% of patients with birch pollen allergy exhibit the so‐called oral allergy syndrome, an IgE‐mediated food allergy. The most frequent and therefore best characterized pollen–fruit syndrome is apple allergy in patients suffering from tree pollen‐induced pollinosis. The occurrence of adverse reactions to proteins present in vegetables such as celery and carrots in patients suffering from pollen allergy has also been reported. cDNAs for Bet v 1 homologous proteins have been cloned from celery, apple and cherry. Objective    The aim of the study was to identify Bet v 1 homologues from carrot (Daucus carota), to isolate the respective cDNA, to compare the IgE‐binding capacity of the natural protein to the recombinant allergen and determine the cross‐reactivity to Api g 1 and Bet v 1.MethodsMolecular characterization of the carrot allergen was performed using IgE‐immunoblotting, cross‐inhibition assays, N‐terminal sequencing, PCR‐based cDNA cloning and expression of the recombinant protein in Escherichia coli.ResultsA 16‐kDa protein from carrot was identified as a major IgE‐binding component and designated Dau c 1. Sequencing corresponding cDNAs revealed three extremely similar sequences (Dau c 1.1, 1.2 and 1.3) with an open reading frame of 462 bp coding for 154 amino acid residues.ConclusionsPurified recombinant Dau c 1.2 was tested in immunoblots displaying IgE‐binding capacity comparable to its natural counterpart. Cross‐inhibition assays verified the existence of common B‐cell epitopes present on Dau c 1, Api g 1 as well as on Bet v 1.
Serological characterization of allergens in poppy seeds
Authors: Jensen‐Jarolim  , Gerstmayer  , Kraft  , Scheiner  , Ebner  , Ebner  
Published: March 2003

Background and objectivePoppy seeds in food can induce immediate‐type allergic reactions ranging from mild local symptoms to severe anaphylactic reactions. Previous publications showed that poppy seeds cross‐react with other plant‐derived allergens. The IgE‐binding components have not been defined so far.MethodsWe analysed sera from 11 patients with adverse reactions after ingestion of poppy seed‐containing food by IgE‐immunoblotting. Nine of 11 patients showed concomitant IgE binding to allergens of birch, mugwort or grass pollen in RAST‐CAP, and suffered from characteristic seasonal symptoms.ResultsTen of 11 patients showed IgE binding to a 45‐kDa protein, 4/11 to a 34‐kDa, 5/11 to a 17‐kDa, 5/11 to a 14‐kDa, and 3/11 to a 5‐kDa component. Furthermore, individual IgE binding to proteins of 20, 25, 30 and 40 kDa proteins could be observed. Periodate treatment of blots markedly reduced the IgE binding capacity of the 40‐ and 45‐kDa compounds, indicating the existence of IgE epitopes of the carbohydrate type. Inhibition studies indicated the presence of homologues of pollen allergens in extracts from poppy seeds, i.e. Bet v 1 and Bet v 2.ConclusionThe serological analysis showed IgE binding to protein and sugar components of poppy seeds. The 40‐ and 45‐kDa allergens are glycoproteins and contain IgE binding carbohydrate moieties. Moreover, cross‐reacting homologues of pollen allergens including Bet v 1 and profilin were detected in poppy seed extract.
Effect of topical corticosteroids on seasonal increases in epithelial eosinophils and mast cells in allergic rhinitis: a comparison of nasal brush and biopsy methods
Authors: Jacobson  , Juliusson  , Löwhagen  , Balder  , Kay  , Durham  
Published: March 2003

BackgroundNasal brushing and nasal biopsy are well‐tolerated sampling techniques. Seasonal grass pollen‐induced rhinitis is characterized by epithelial mast cell infiltration and seasonal increases in both epithelial and sub‐mucosal eosinophils.ObjectiveTo compare the ability of the nasal brush and nasal biopsy techniques to detect natural seasonal increases in eosinophils and mast cells, and to assess the influence of topical corticosteroid.MethodsNasal brush samples and nasal biopsies were collected from 46 grass pollen‐sensitive seasonal rhinitis patients before the grass pollen season and at the peak of the pollen season following 6 weeks' treatment with either fluticasone propionate aqueous nasal spray (200 μg, twice daily) or placebo nasal spray.ResultsPlacebo patients showed seasonal increases in epithelial eosinophils both with nasal brushing (P < 0.0001) and biopsy (P < 0.001). Epithelial mast cell numbers also increased during the pollen season as detectable by brushing (P < 0.0001) and biopsy (P < 0.03). Changes in cell numbers measured by nasal brushing correlated with those observed with nasal biopsy, both for eosinophils and mast cells (P < 0.05). Sub‐mucosal eosinophils but not mast cells also increased during the pollen season (P < 0.002). Nasal brushing and biopsy revealed that fluticasone treatment inhibited seasonal increases in epithelial eosinophils (P < 0.00001) and epithelial infiltration by mast cells (nasal brushing P < 0.00001 and nasal biopsy P < 0.01). Fluticasone also inhibited seasonal increases in sub‐mucosal eosinophils (P < 0.001) and significantly reduced nasal symptoms (P < 0.001).ConclusionNasal brushing harvests sufficient inflammatory cells from the surface of the nasal mucosa to be used in lieu of nasal biopsies in observation of the effect of drugs on the nasal epithelium.
Detection of inhaled Der p 1
Authors: Poulos  , O'Meara  , Sporik  , Tovey  
Published: March 2003

BackgroundMeasurement of personal exposure to Der p 1 aeroallergen has previously been limited by the low quantity of material collected by sampling systems and the assay sensitivity. This has meant that exposure could only be detected if long sampling periods were used or reservoir dust was artificially disturbed. We have developed a sampling method to sample true personal exposure and combined it with a novel method which is sensitive enough to measure allergen exposure over shorter time frames.ObjectiveTo describe normal domestic exposure to dust mite allergen during a range of activities in houses in Sydney, Australia.MethodsInhaled particles containing mite allergen Der p 1 were collected using a nasal air sampler which impacts particles (> ≈5 μm) onto a protein‐binding membrane coated with a thin, porous, adhesive film. The allergen is bound to the membrane in the immediate vicinity of the particle and detected by immunostaining with monoclonal antibodies specific for Der p 1. In addition, samples were collected using a standard Institute of Occupational Medicine (IOM) personal air sampler and the amount of eluted Der p 1 was assayed by ELISA.ResultsThe median number (range) of inhaled particles containing Der p 1 collected in each 10‐min sampling period was: dust raising 5 (2–10); lying in bed, 0 (0–2); sitting on the bed, 1 (0–2); walking around the bedroom, 0 (0–2). This represented 0–5.1% of all particles captured. The Der p 1 concentration of floor and bed dust was 19.4 and 55.1 μg/g, respectively. The standard IOM personal sampler and ELISA were unable to detect Der p 1 for any of the activities performed.ConclusionsWe were able to count individual allergen‐carrying particles inhaled over short time periods, during different domestic exposure situations. This will offer new insight into several aspects of personal allergen exposure.
Effects of house dust mite avoidance measures on Der p 1 concentrations and clinical condition of mild adult house dust mite‐allergic asthmatic patients, using no inhaled steroids
Authors: Cloosterman  , Schermer  , Bijl‐Hofland  , Van Der Heide  , Brunekreef  , Van Den Elshout  , Van Herwaarden  , Van Schayck  
Published: March 2003

BackgroundExposure to house dust mite (HDM) allergens often results in worsening of asthma. Therefore, avoidance of exposure to HDM allergens is often proposed. Unfortunately, the most effective and feasible avoidance strategy is still not completely assessed. Consequently, we investigated the effects of a combined HDM avoidance strategy on HDM allergen concentrations and clinical condition of allergic, mild asthmatic, patients using no inhaled steroids.MethodsAsthmatic patients, allergic to HDM, using no inhaled corticosteroids, were randomly allocated to an active (n = 76) or a placebo allergen‐avoidance group (n = 81). Avoidance measures consisted of applying Acarosan® (placebo: water) to the living room and bedroom floors, and the use of HDM‐impermeable covers for mattresses and bedding (placebo: cotton covers for mattresses only). Effects on allergen concentrations (Der p 1), FEV1, bronchial hyperresponsiveness, peak flow parameters and asthma symptom scores were studied during 20 weeks and controlled for the allergic status of the patients.ResultsThe active covers reduced Der p 1 concentrations to 9.4% (P = 0.0001), and were always significant lower than in the placebo group (P = 0.0002). Acarosan® resulted in slight but significant decreases (twofold, P = 0.0001), both on living room and bedroom floors, but concentrations were never significantly lower than the placebo group. Although the combined avoidance strategy resulted in a considerable reduction in allergen load in the active group, no differences were seen between the two groups in any of the clinical parameters during the follow‐up period in this group of allergic asthmatics, using no inhaled corticosteroids. Corrections for the allergic status did not alter these results.ConclusionsThe combined avoidance strategy was effective in reducing HDM allergen concentration. This was especially achieved by the allergen‐impermeable covers, while the effects of Acarosan® were only marginal. However, this allergen reduction was not reflected in a convincing improvement in clinical condition in this group of mild allergic asthmatics, using no inhaled steroids. Perhaps, a longer follow‐up period would have resulted in more pronounced effects.