Predictors of early- and late-phase reactions to bronchial allergen challenge

The influence of inhaled steroids and predictive factors on the response to bronchial allergen challenge (BCA) was evaluated in 80 asthmatics allergic to Dermatophagoides pteronyssinus (Der p). All underwent BCA with Der p and measurement of early (EAR) and late asthmatic reaction (LAR). The cumulative dose of allergen producing 20% fall in FEV1 in the EAR (PD20) was calculated. Bronchial histamine provocation, conjunctival provocation test (CPT), and skin prick test with Der p extract were performed. Specific IgE to Der p in serum (RAST), blood eosinophil (EOS) count, serum eosinophil cationic protein, and eosinophil protein X were measured. Thirty patients (38%) were treated with inhaled steroids. All patients had at least a 20% fall in FEV1 in EAR. Some 42% of nonsteroid- and 33% of steroid-treated patients had LAR with fall in peak flow of at least 20%. For patients not treated with steroid, 35% of variation in PD20 was explained by RAST and histamine reactivity, and 53% of variation of observed PD20 could be predicted. The baseline FEV1, EOS, and EAR explained 28% of variation in LAR, and 28% of variation in observed LAR could be predicted. For patients treated with steroids, 38% of variation in PD20 was explained by EOS and histamine reactivity, and only 18% of variation of observed PD20 could be predicted. For patients treated with steroids, it was impossible to predict LAR. We conclude that to achieve a quantitative estimation of allergen-specific EAR and LAR, BCA cannot be replaced by the tests used in this study. Treatment with inhaled steroids modifies the response to BCA, making quantitative prediction of EAR less accurate and prediction of the magnitude of LAR impossible.     

Total blood eosinophils, serum eosinophil cationic protein and eosinophil protein X in childhood asthma: relation to disease status and therapy

Blood eosinophils, and serum levels of the eosinophil proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured in childhood asthma. Seventeen patients mean age 11.9 years who were symptomatic with asthma, were enrolled in a study examining the eosinophil counts and eosinophil proteins at the onset of study and after treatment in relation to changes in their baseline forced expiratory volume at 1 second (FEV1) and % predicted FEV1. The patients with symptomatic asthma were compared with 17 patients mean age 12.0 years with asymptomatic asthma maintained on daily inhaled steroid and 13 patients, mean age 12.0 years, without asthma but with urticaria who served as non-asthma controls. Patients with symptomatic asthma did not have significantly higher initial eosinophil counts compared with those with asymptomatic asthma (0.43 x 10(9)/l vs 0.26 x 10(9)/l, P = 0.09) but had higher serum ECP levels (28.9 micrograms/l vs 18.5 micrograms/l). Both asthma patient groups had significantly higher serum ECP levels (P < 0.01) than the controls (9.8 micrograms/l). After therapy consisting of increased dose of inhaled steroids and/or oral steroids, patients in the symptomatic asthma group demonstrated a significant rise in FEV1 (1.67 l/sec at Visit 1 vs 2.08 l/sec at Visit 2, P < 0.001). A similar rise was seen for % predicted FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Flow cytometric analysis for the activation of peripheral immunoregulatory cells from patients with bronchial asthma

By use of flow cytometry, we have investigated intracellular activated eosinophil cationic protein (ECP) in eosinophils and mitogen-induced cytokine production of T cells in peripheral blood from children with acute severe asthma. In addition, we measured ECP releasability (serum ECP/lysate ECP) as a maker of activated eosinophils. The monoclonal antibody EG2 (anti-activated ECP/EPX antibody) was used for measuring the amount of intracellular activated ECP. ECP releasability and mean fluorescence intensity (MFI) values of EG2-positive eosinophils increased at the time of asthmatic attack and reduced after treatment with improvement in peak expiratory flow. Furthermore, the frequency of T cells which produced IL-4, IL-5 and IFN-gamma stimulated with phorbol myristate acetate and ionomycin increased and reduced in parallel with MFI of EG2-positive cells. These observations suggest that flow cytometric analysis for intracellular ECP and mitogen-induced cytokine production reflects the activation of T cells in bronchial mucosa, and is useful for monitoring airway inflammation in bronchial asthma.     

Filtration of airborne allergens in various households

The filtration system investigated in this study uses the thermic convection caused by radiators for the adsorption of airborne particles. The effect of this filtration system on the reduction of clinical symptoms of allergic bronchial asthma was tested as well as its capability in retaining airborne allergens, in particular those of the house dust mite Dermatophagoides pteronyssinus (D. pter.), which are responsible for this special kind of asthma. Dust samples were taken before and after the heating season in households of 36 persons with D. pter. caused asthma. Their mite content was investigated using mite flotation and direct microscopy, their guanine content using the Acarex-test. An allergen extract obtained from the filters was tested on its allergen content by RAST-inhibition. It could be observed that compared to the preceding heating season 55% of the volunteers felt an improvement of their asthmatic symptoms. It was possible to extract allergens of D. pteronyssinus, house dust and mould from the filters. All these results show the capability of the filters to adsorb house dust mite (HDM) allergens.     

Diagnosis and rehabilitation strategies for patients with hysterical hemiparesis: a report of four cases

BACKGROUND: Sulphidoleukotrienes (slt) are important mediators in allergic diseases that are synthesized after allergen-specific stimulation. OBJECTIVES: The aim of this study is to determine in vitro slt production after allergen-specific (Dermatophagoides pteronyssinus) stimulus of peripheral blood leucocytes and to observe whether histamine release in whole blood with the same allergen correlates with slt production. We also wanted to evaluate whether a correlation exists between the release of slt and histamine and other diagnostic procedures as well as various clinical situations. METHODS: We studied 62 patients sensitive to Dermatophagoides pteronyssinus (Der p), 30 atopic controls and 12 healthy donors. We determined slt production using the CAST-ELISA technique and histamine release using two concentrations of Der p extract (20 and 2 ng/mL). We also carried out quantification of specific and total IgE levels, skin tests and pulmonary function test on each patient. RESULTS: We observed a significantly increased slt release after in vitro stimulation with Der p. There was a significant difference in the slt release between controls and sensitive patients (P < 0.001) and between atopic controls and sensitive patients (P < 0.001). The data are similar to those obtained with histamine release. We noted a positive correlation (P < 0.001) between slt and histamine release (r = 0.71, at 2 ng/mL and r = 0.83 at 20 ng/mL). We also found a positive (P<0.001), although weak (r=0.4 with at 2ng/mL, and r = 0.34 with P = 0.003 at 20 ng/mL) correlation between slt release and specific IgE levels as well as between slt release and skin-test reactivity (r = 0.49 at 2 ng/mL and r = 0.45 at 20 ng/mL; P < 0.001). No significant correlation between slt release and asthma severity was observed, although a trend toward higher slt production in severe and moderate asthma was detected. We found a significant (P<0.001) but weak (r=-0.3) negative correlation between age and slt release. With respect to sex-related differences, we found significant differences (P < 0.05) in slt release between the sexes with a higher slt release in men than in women. CONCLUSION: We conclude that CAST-ELISA for quantification of slt production is a useful in vitro method for diagnosing sensitization to Der p. There also exists a close correlation between slt release and other parameters of allergic sensitization in vitro as well as in vivo.     

Serum levels of eosinophil cationic protein and eosinophil protein x in pollen atopic patients with stable asthma and its relation with bronchial hyperresponsiveness

Eosinophils are important effector cells in allergic inflammation described in allergic rhinitis (AR) and allergic bronchial asthma (BA). During the pollen season serum levels of eosinophil cationic protein (ECP) and eosinophil X protein/eosinophil-derived neurotoxin (EPX/EDN) are increased in BA. The aim of the present study was to evaluate the serum levels of ECP and EPC in pollen atopic patients with AR and BA during the winter. 92 patients were studied. They were divided into three groups: I 29 patients with AR, II 51 patients with BA and III 12 healthy subjects. Allergic rhinitis and bronchial asthma were diagnosed by routine clinical tests: clinical history, skin tests, total IgE and specific IgE. In addition ECP and EPX were determined in serum. All patients were asymptomatic, stable and without medical treatment. Methacholine challenge test (MCT) was performed in all patients. MCT were positive in 4 patients of group I and 45 patients of group II. ECP levels (ug/l) were: 21 (I), 24 (II) and 7 (III). EPX levels (ug/l) were 35 (I), 45 (II) and 21 (III). Statistical differences (p < 0.01) were observed both in ECP and EPX levels in patients with MCT positive in relation to patients with MCT negative, and in allergic patients (I and II) in comparison with the healthy subjects (III) (p < 0.01). ECP and EPX serum levels are increased in patients with a positive MCT in the winter, out of the pollen season, when patients are asymptomatic, stable and without treatment. This fact suggests that eosinophils play an important role in the pathogenesis of bronchial asthma.     

A pilot study of the effect of mechanical ventilation and heat exchange on house-dust mites and Der p 1 in New Zealand homes

We have examined the effect of reducing relative humidity (RH), with inbuilt mechanical ventilation and heat-exchange (MVHE) units, on house-dust-mite (HDM) counts and allergen levels, in a pilot study of 10 Wellington dwellings. Recent international prevalence studies in adults and children have confirmed a high prevalence of asthma in New Zealand. Sensitivity to HDM is common among the general population, and HDM is the major allergen associated with asthma. Recent studies of allergen levels have confirmed high concentrations of Der p 1 in the domestic environment. While humidity was significantly reduced in those dwellings fitted with ventilation units, no systematic effect on mites or Der p 1 was observed during the study period. When the reductions in humidity were examined in the context of the time spent below the critical equilibrium humidity (CEH), the intervention led to RH values below the CEH for only 39% of the total of 24-h periods for which measurements were made. Reducing RH by means of MVHE in New Zealand domestic dwellings does not lower humidity sufficiently, or long enough, to have any measurable effect on HDM populations.     

Asthma, bronchial hyperreactivity and mediator release in children with birch pollinosis. ECP and EPX levels are not related to bronchial hyperreactivity

BACKGROUND: Symptoms of allergic asthma are triggered by allergen exposure inducing allergic inflammation and hyperreactivity of the bronchi. OBJECTIVES: To investigate the possible relationship between clinical symptoms and signs of asthma, i.e. bronchial variability as measured by peak expiatory flow rate (PEFR), bronchial hyperreactivity (BHR) and mediators of allergic inflammation. METHODS: Twenty-eight children with pollinosis, but no obvious history of asthma, were studied at three occasions, i.e. before, during and after (autumn) the birch pollen season. Twelve children sensitive to birch pollen were considered as the case group. Sixteen children, who were only clinically sensitive to grass pollen, served as controls. Subjective symptoms of asthma were recorded by visual analogue scale, BHR was estimated by methacholine bronchial provocation tests, bronchial variability PEFR and circulating mediators of inflammation, i.e. eosinophil cationic protein, eosinophil protein X, myeloperoxidase and tryptase in serum. RESULTS: Bronchial hyperreactivity and by PEFR was more pronounced after than during the season (P < 0.01), whereas eosinophil mediators and the peak expiratory flow rate increased during the season (P < 0.05). Except for between PEFR variability and BHR in the autumn (r = 0.45; P = 0.014), no correlations were found. However, in the autumn, the majority of children were still hyperreactive in the bronchi and showed PEFR variability but the levels of eosinophil mediators in serum had returned to normal levels. CONCLUSION: Signs and symptoms of asthma did not correlate with serum levels of mediators of allergic inflammation. Bronchial hyperreactivity and PEFR variability persisted after the pollen season when signs of bronchial inflammation had disappeared. We hypothesize that eosinophil mediators and other markers of allergic inflammation disappear after the late-phase reaction, whereas BHR persists. This would explain the lack of correlation between the levels of eosinophil mediators in serum and symptoms of asthma and BHR.     

Current diagnostic and therapeutic management of CNS metastasis in childhood primitive neuroectodermal tumors and ependymomas

The aim of this study was to determine the presence and concentration of immunoreactive eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in human amniotic fluid at term and assess labour-associated changes in their mean concentrations. In addition, ECP and EPX content in term amnion, choriodecidua and placenta obtained before and after labour and delivery was established. Immunoreactive ECP and EPX were identified in all samples of amniotic fluid (n=47) and gestational tissue (n=60) assayed. EPX was quantitatively more abundant than ECP in both amniotic fluid and gestational tissues. In amniotic fluid, ECP and EPX concentrations increased 8-fold (P<0.02) and 1.5-fold (P<0.02), respectively, with labour onset. In gestational tissues, a labour-associated change in tissue content was only identified for ECP in choriodecidua, which increased 1.9-fold with labour and delivery (P<0.01). The labour-associated increase in amniotic fluid concentrations of ECP and EPX demonstrated in this study is consistent with the well-characterized role of these proteins in inflammatory reactions. It remains to be established whether the observed increase in ECP and EPX amniotic fluid concentrations is an epiphenomenon of labour onset or is involved causally in this process.     

Evaluation of the inhaled glucocorticosteroid effects on non specific bronchial reactivity with particular reference to the late inflammatory phase in atopic asthma patients. II. The effect of regular administration of budesonide R on specific and non-specific bronchial reactivity

The purpose of the study was to determine whether regular administration of budesonide R decreases inflammation, specific and non-specific bronchial hyperreactivity in allergic asthma patients. The studies were carried out on 16 patients suffering from mild to moderate allergic asthma, sensitive to D. pteronyssinus allergen. After performance of the specific and non-specific bronchial provocation tests, collection of blood samples for an ECP evaluation, the patients were regularly treated with budesonide R, 2 x 320 micrograms for a period of 8 weeks. At the end of the study the BPTs and blood collection were repeated. BPTs with methacholine and D. pteronyssinus were performed according to Ryan's method. After the allergen challenge, early (EAR) and late asthmatic reaction (LAR) were to be observed. After the therapy non-specific BHR to methacholine expressed as PC20FEV1 and specific BHR to allergen (PD20FEV1D. pteronyssinus) and serum ECP concentrations decreased significantly. Although after the treatment with budesonide R, the patients had to inhale much larger amounts of allergen, in order to induce EAR, the number of LAR did not change significantly. After treatment the LAR appeared about 1 hour later and the decrease in FEV1 was less than previously. We conclude that budesonide R decreases the intensity of the inflammation and BHR.     

Inhibitory effect of pulmonary surfactant proteins A and D on allergen-induced lymphocyte proliferation and histamine release in children with asthma

The role of pulmonary surfactant proteins in the pathogenesis of airway inflammation and the impact on asthma has not been elucidated. This study was designed to examine the effect of surfactant proteins A (SP-A) and D (SP-D) on phytohemagglutinin- (PHA) and mite allergen Dermatophagoides pteronyssinus (Der p)-induced histamine release and the proliferation of peripheral blood mononuclear cells (PBMC) in children with asthma in stable condition (n = 21), asthmatic children during acute attacks (n = 9), and age-matched control subjects (n = 7). The results show that SP-A and SP-D were able to reduce the incorporation of [3H]thymidine into PBMC in a dose-dependent manner. In addition to the intact, native SP-A and SP-D proteins, a recombinant peptide composed of the neck and carbohydrate recognition domain (CRD) of SP-D [SP-D(N/CRD)] was also found to have the same suppressive effect on lymphocyte proliferation. This effect was abolished by the presence of 100 mM mannose (for SP-A) or maltose (for SP-D) in the culture medium, which suggested that the CRD regions of SP-A and SP-D may interact with the carbohydrate structures on the surface molecules of lymphocytes. The inhibitory effects of surfactant proteins on PHA- and Der p-stimulated lymphocyte responses were observed in stable asthmatic children and age-matched control subjects, while only a mild suppression (< 25%) was seen in activated lymphocytes derived from asthmatic children with acute attacks. SP-A and SP-D were also found to inhibit allergen-induced histamine release, in a dose-dependent manner, in the diluted whole blood of asthmatic children. We conclude that both SP-A and SP-D can inhibit histamine release in the early phase of allergen provocation and suppress lymphocyte proliferation in the late phase of bronchial inflammation, the two essential steps in the development of asthmatic symptoms. It appears that SP-A and SP-D may be protective against the pathogenesis of asthma.     

Eosinophil granule proteins activate human heart mast cells

Eosinophilia in humans is often associated with heart disease and cardiac localization of eosinophil granule proteins, and several results suggest that granule proteins mediate endomyocardial damage. Here we investigated the in vitro effects of the four principal eosinophil granule proteins (eosinophil cationic protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin, and eosinophil peroxidase (EPO)) on the activation of effector cells of inflammation (mast cells) isolated from human heart tissue (HHMC). ECP and, to a lesser extent, MBP (0.3-3 microM), but not eosinophil-derived neurotoxin and eosinophil peroxidase stimulated the release of preformed (histamine and tryptase) and the de novo synthesis of vasoactive and proinflammatory mediators (PGD2) from HHMC. Activation of HHMC by ECP and MBP was Ca2+- and temperature-dependent and was abolished by preincubation (15 min, 37 degrees C) with 2-deoxy-D-glucose (10 mM) and antimycin A (1 microM). There was a significant correlation between the maximal percentage of histamine release induced by ECP and anti-IgE from HHMC (rs = 0.73; p < 0.005), by MBP and anti-IgE (rs = 0.79; p < 0.001), and by ECP and MBP (rs = 0.65; p < 0.005). A positive correlation was also found between histamine and tryptase secretion (rs = 0.71; p < 0.001) and between histamine and PGD2 release induced by ECP from HHMC (rs = 0.85; p < 0.001). This is the first demonstration that some eosinophil cationic proteins, namely ECP and MBP, found at the site of heart damage in patients with eosinophilia, act as complete secretagogues on HHMC. This observation indicates another mechanism by which infiltrating eosinophils and their metabolic products cause inflammatory reactions and thus endomyocardial lesions in patients with eosinophilia.     

Prevalence and determinants of house dust mite allergen in East German homes

BACKGROUND: In 1990/91, allergic sensitization to house dust mites (HDM) and other allergens was more prevalent in children from West Germany than from East Germany. OBJECTIVE: To test the hypothesis that low indoor exposure to HDM allergen in East Germany has contributed to this difference. METHODS: HDM allergen concentrations were determined in 634 East German dwellings shortly after the German reunification. RESULTS: HDM group I allergen (Der p 1 + Der f 1) levels in mattresses (median 2.16, geometric mean 2.07, maximum 278.9 microg/g dust) and carpets (median 0.41, geometric mean 0.48, maximum 96.3 microg/g dust) were within the range of levels determined in West Germany in other studies. One particular East German type of dwelling (light concrete buildings) was associated with lower mite allergen exposure, but only a minority of the population lived there. Coal heating, installed in the majority of dwellings before 1989, was associated with higher allergen exposure. Higher relative humidity (RH) was a main risk factor for higher Der p 1 exposure (odds ratio [OR] for exposure to > 0.05 microg/g dust on carpets: 1.4 [95% confidence interval (CI) 1.2-1.8] for + 10% RH) but not for higher Der f 1 exposure. Higher temperature was associated with a lower risk for elevated Der p 1 levels (> 0.05 microg/g dust on carpets): OR 0.6 (95% CI 0.5-0.8) for + 2 degrees C. CONCLUSION: Mite allergen exposure is not lower in East Germany than in West Germany. The data does not support the hypothesis, that low HDM allergen exposure in East Germany is a cause for the lower prevalence of HDM sensitization in East German children.     

Cloning and sequencing of the Dermatophagoides pteronyssinus group III allergen, Der p III

House dust mites are widely recognized as major factors involved in the triggering of allergic diseases such as asthma. It is now apparent that the group III allergens of the Dermatophagoides mite species may play a significant role in a number of house dust mite allergic cases. Natural Der p III was isolated by gel filtration of salt precipitated Dermatophagoides pteronyssinus extract and as reported previously ran as a doublet of Mr 28 and 30 K on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Natural Der fIII was isolated by affinity purification with the 5A12 monoclonal antibody. Amino acid sequence data was generated for both these proteins which was used to construct DNA probes to screen a Dermatophagoides pteronyssinus cDNA library by hybridization and resulted in the isolation of a recombinant Der p III cDNA clone, P3WS1. The 1059 bp cDNA fragment included a 786 bp open reading frame which encodes a pre-pro region of 29 amino acids and a mature protein of 232 amino acids with a calculated Mr 24,985. A search of the BLAST protein database has confirmed that the Der pIII P3WS1 clone is approximately 50% homologous with other trypsin proteins. We have confirmed with both our natural protein sequence and the P3WS1 amino acid sequence data that the group III allergens are trypsin-like proteins.     

Intrathecal administration of p-hydroxymercuribenzoate or phosphoramidon/bestatin-combined induces antinociceptive effects through different opioid mechanisms

BACKGROUND: House dust mite is an important cause of bronchial asthma. Seasonal variation of environmental house dust mite allergen levels and the specific IgE antibody to house dust mite have been reported. OBJECTIVE: We studied the changes in IgG subclass antibodies to house dust mite associated with seasonal variation of house dust mite allergen levels in houses of mite-sensitive asthmatic patients. METHODS: In 14 mite-sensitive asthmatic patients, house dust mite allergen (Der f 1) contents in bedding were measured monthly, and IgG subclass antibodies to house dust mite, Dermatophagoides farinae (D. farinae), were determined by enzyme-linked immunosorbent assay (ELISA) every 3 months from July to December. RESULTS: The concentration of Der f 1 in dust from bedding reached maximum levels in August and September, and significantly decreased in November and December compared with August and September (P < .05). Levels of D. farinae-specific IgG4 antibodies significantly decreased in December compared with September (P < .05) with no statistically significant change between September and June (P > .05). Levels of D. farinae-specific IgG2 antibodies decreased significantly in December compared with June (P < .05). The levels of IgG1 and IgG3 antibodies to D. farinae showed no significant differences during the study period. CONCLUSION: These findings suggest that seasonal changes in natural exposure to house dust mite allergen might lead to concurrent changes in specific IgG4 antibodies to house dust mite in mite-sensitive asthmatic patients and each IgG subclass antibodies to house dust mite might have a different kinetics.     

The effect of theophylline on blood and sputum eosinophils and ECP in patients with bronchial asthma

It was recently reported that theophylline has an anti-inflammatory and bronchodilating effect on bronchial asthma. Accordingly, to examine the anti-inflammatory effect of theophylline on asthma, especially its effect on eosinophil activation, a sustained-release theophylline preparation (Theolong) was administered (daily dose: 400 mg) to 18 patients with mild to moderate bronchial asthma. This was done in order to study the preparation's effects on lung function, blood and sputum eosinophils and ECP four weeks pre- and post-administration. Lung function was determined by spirometry and sputum by induced sputum. Blood and sputum ECP levels were determined using an ECP RIA kit. In lung function, there were no differences in vital capacity (VC) or in forced expiratory volume 1 s (FEV 1.0) pre- and post-administration. There were also no differences in the number of blood and sputum eosinophils, but serum and sputum ECP levels decreased. Theophylline is thus expected to exert an inhibitory effect on eosinophil activation and it is suggested as an effective therapeutic drug for bronchial asthma.     

Induced sputum eosinophil cationic protein (ECP) measurement in asthma and chronic obstructive airway disease (COAD)

BACKGROUND: Induced sputum is a useful way to monitor airway inflammation in asthma, but cell counts are time-consuming and labour intensive. OBJECTIVE: The aim of this study was to evaluate a novel processing method using eosinophil cationic protein (ECP) as a biochemical marker of sputum eosinophil number and activation in subjects with asthma and other airway diseases. METHODS: Sputum was dispersed with dithiothreitol and centrifuged to yield cell free supernatant and a cell pellet. The pellet was treated with a cellular lysis buffer to release cell-associated ECP. ECP was measured in sputum supernatant and in the lysed cell pellet and was compared with sputum eosinophil counts in 31 adults with asthma, chronic obstructive airway disease (COAD), bronchiectasis and healthy controls. The ratio of supernatant to pellet ECP was evaluated as an index of eosinophil degranulation. The effect of sputum processing reagents and storage time on ECP measurement was also evaluated. RESULTS: ECP measured in the cell pellet lysate correlated closely with sputum absolute eosinophil counts across a range of subject groups (r = 0.72, P = 0.004). Sputum eosinophil counts were less well correlated with supernatant ECP levels (r = 0.54, P < 0.05). Incubation with dithiothreitol or lysis buffer did not influence ECP measurement and sputum ECP levels were stable over a 6-9 month period. Sputum supernatant and pellet lysate ECP concentrations were increased in stable asthma, asthma exacerbations and COAD/bronchiectasis (P < 0.05). The ratio of supernatant to pellet ECP was used as an index of eosinophil degranulation and found to be elevated in asthma exacerbations, COAD and bronchiectasis, but not in stable asthma. CONCLUSION: The measurement of ECP in the sputum cell pellet provides a reliable and efficient estimate of sputum eosinophil counts which can potentially be used in clinical trials and epidemiological surveys. The ECP ratio may be a useful marker of eosinophil activation, and was increased in asthma exacerbation and COAD. The increased ECP in COAD reflects a non-selective accumulation of eosinophils in this condition.     

Selective inhibition of hepatic collagen accumulation in experimental liver fibrosis in rats by a new prolyl 4-hydroxylase inhibitor

In order to detect and characterize allergen-specific T cells in the airways of atopic asthmatics, we measured proliferation and cytokine production by bronchoalveolar lavage (BAL) T cells isolated from Dermatophagoides pteronyssinus (Der p)-sensitive asthmatics and nonatopic control subjects, and compared the results with those generated using peripheral blood (PB) T cells. BAL and PB mononuclear cells were collected 24 h after segmental allergen challenge by fibreoptic bronchoscopy and venepuncture, respectively. T cells purified from BAL and PB were stimulated with autologous, irradiated antigen-presenting cells and D. pteronyssinus extract or a control, nonallergen antigen (M. tuberculosis purified protein derivative [PPD]). IL-5 and IFN-gamma concentrations were measured in culture supernatants by ELISA, and T-cell proliferation by 3H-thymidine uptake. D. pteronyssinus-induced proliferation of T cells derived from both BAL and PB was elevated in asthmatics when compared with control subjects (p < 0.05), whereas PPD-induced proliferation was equivalent in both compartments. In the asthmatics, D. pteronyssinus-induced proliferative responses of equivalent numbers of BAL and PB T cells obtained after allergen challenge were statistically equivalent. Nevertheless, BAL T cells stimulated with D. pteronyssinus produced significantly greater amounts of IL-5 than did PB T cells (p < 0.05). Allergen-induced proliferation and IL-5 production by BAL T cells in the asthmatics after segmental allergen challenge correlated with the percentages of eosinophils in the BAL fluid (p < 0.01). Further, BAL T cells from asthmatic patients produced significantly higher amounts of IL-5 than did the same number of cells from nonatopic control subjects (p < 0.05). We conclude that, in D. pteronyssinus-sensitive asthmatics, allergen-specific T cells can be detected in the bronchial lumen after allergen challenge and that allergen-induced proliferation and IL-5 production by these cells correlates with local eosinophil influx. Although bronchial luminal T cells show an equivalent proliferative response to allergen stimulation as compared with PB T cells, they do produce more IL-5, consistent with the hypothesis that local differentiation or priming of these cells within the bronchial mucosal environment results in upregulation of allergen-induced IL-5 secretion.     

Eosinophil markers in seasonal allergic rhinitis. Intranasal fluticasone propionate inhibits local and systemic increases during the pollen season

BACKGROUND: The purpose was to study activation markers of the eosinophil granulocytes in seasonal allergic rhinitis, and the impact of topical steroid therapy thereupon. METHODS: Sixty-three rhinitis patients with monoallergy to grass were examined before and at peak pollen season. Blood eosinophil count, eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO) in serum and nasal lavage fluid were measured. During the season, patients were randomized to treatment with intranasal fluticasone propionate 0.1 mg o.d. (n=26), 0.2 mg o.d. (n=25), or placebo (n=12). Six healthy persons served as controls. RESULTS: During the season, all parameters, except nasal lavage ECP, increased in the placebo group (P<0.001-P<0.05). Significant differences were seen between the steroid groups and the placebo group for all parameters (P<0.001-P<0.05). Higher eosinophil count (P<0.05), serum EPO (P<0.02), and nasal lavage EPO (P<0.05) were found in patients before season than in controls. The following winter, 44 patients returned for repeated measurement. Lower levels of nasal lavage EPO were observed for patients than levels at the beginning of the season (P<0.0001). CONCLUSIONS: Intranasal fluticasone propionate reduced inflammation of the nasal mucosa, demonstrated locally by nasal lavage ECP and EPO, and systemically by blood eosinophils, serum ECP, and serum EPO. EPO seemed more sensitive than ECP as indicator of allergic inflammation. EPO demonstrated some perennial eosinophil activity in hay fever patients, increasing locally during spring.     

High-dose therapy with peripheral blood stem cell (PBSC) support using an innovative mobilization regimen in patients with high-risk primary or chemoresponsive metastatic breast cancers

BACKGROUND: Epidemiologic studies are necessary to determine the prevalence of allergic diseases. This varies widely depending on allergen preparations and patients studied. OBJECTIVE: To investigate the prevalence of atopic disease, skin test reactivity, total and specific IgE to common allergens, and other variables in a sample of students from Málaga, southern Spain. METHODS: Three hundred sixty-five students (age 17.9 +/- 1.18) were interviewed by an allergist. Skin prick tests were performed with Dermatophagoides pteronyssinus, Artemisia vulgaris, Plantago lanceolata, Chenopodium album, Olea europaea, Phleum pratense, Parietaria judaica, Cynodon dactylon, Alternaria tenuis, and cat dander. Total and specific IgE to D. pteronyssinus, Olea, and Parietaria were determined. RESULTS: Of all subjects studied, 19.9% suffered from rhinoconjunctivitis, 4.1% rhinoconjunctivitis plus asthma, 3.1% asthma alone, and 0.8% atopic dermatitis; 46.4% had a positive skin test to at least one allergen (28.2% to D. pteronyssinus, 20.4% to Olea, 13.8% to Phleum); and 43% had total IgE > 100 kU/L and 44.7% a family history of atopy. Allergic symptoms were strongly associated with skin test positivities and family allergic history. Patients with asthma or skin prick test positive had higher total IgE values than others (P < .01). There was a significant correlation between specific IgE values and wheal size in skin test. CONCLUSIONS: Our findings confirm the high prevalence of atopic diseases, and the close relationship of skin tests reactivity (or presence of specific IgE) to allergens with symptoms of asthma and rhinitis. The presence of a family history of allergic diseases influences the development of positive skin tests and atopic illness. Dermatophagoides pteronyssinus and pollen of Olea europaea were found to be the most common allergens.