IL-5 expression in the sputum of patients with bronchial asthma

Expression of IL-5 mRNA and the content of IL-5 in the sputum of patients with asthma of different severity were studied before and after treatment. The expression of IL-5 mRNA in mild asthma differed from that in severe and moderate asthma before and after treatment. The level of IL-5 before therapy was different in patients with mild and severe disease. In patients with severe asthma the level of IL-5 differed before and after treatment.     

The effect of sputum induction on spirometry parameters in patients with bronchial asthma

Evaluation of differential cell count and biochemical parameters in sputum seems to be a valuable method in asthma studies. The purpose of the paper was to evaluate the effects of sputum induction alone and after fenoterol and salmeterol premedication, on spirometry in asthma patients. The another aim of the study was to observe the correlation between bronchial hyperreactivity and decreases in FEV1 and MEF50 in asthmatics during sputum induction. The studies were carried out on 20 mild to moderate asthma patients (FEV1 baseline 79 +/- 16% of the predicted values) who inhaled an increasing concentration of hypertonic saline (3%, 4% and 5%), using an ultrasonic nebuliser. The forced expiratory volume in one second and MEF50, as the good indicators of bronchial obturation, were evaluated. During the sputum induction significant decreases in FEV1 and MEF50 were observed, which were proportional to the concentration of NaCl. After inhalation of 3% of NaCl the mean of FEV1 was 87.2 +/- 12.7% of the baseline, after 4%--84.3 +/- 16.9% and 5%--77.4 +/- 19.8%. No significant correlation between bronchial hyperreactivity and the induced decreases in FEV1 and MEF50 were found. Fenoterol and salmeterol fully prevented bronchial obturation during sputum induction.     

Differences in response to anti-IgE and to anti-IgG in basophils from patients with bronchial asthma

Peripheral blood basophils of thirty-eight patients with bronchial asthma were examined for their reactivity to anti-IgE and anti-IgG antisera. Basophils of patients with serum IgE levels of more than 1001 i.u./ml reacted strongly to anti-IgE. Basophils of patients with serum IgE levels of less than 100 i.u./ml had a tendency to react more strongly to anti-IgG. An index (basophil ratio) was devised to compare the patient basophil reactivity to anti-IgE and anti-IgG. This basophil ratio was lower (IgE dominant) in the atopic cases which usually exhibited a high serum IgE level. Most cases with low serum IgE exhibited a high basophil ratio (IgG dominant). The basophils of seven intractable patients reacted more strongly to anti-IgG than to anti-IgE regardless of the serum IgE level.     

Cysteinyl-leukotriene levels in sputum differentiate asthma from rhinitis patients with or without bronchial hyperresponsiveness

BACKGROUND: We have previously reported that asthma differs from rhinitis with or without bronchial hyperresponsiveness in the perception and degree of lower airway inflammation. OBJECTIVE: The aim of the present study was to investigate whether sputum levels of inflammatory markers could further distinguish these patient groups. METHODS: Patients with seasonal allergic rhinitis with or without asthma or bronchial hyperresponsiveness to methacholine were investigated. Induced sputum was performed during as well as off season, and analysed for cysteinyl-leukotrienes, hyaluronan, eosinophilic cationic protein (ECP) and other inflammatory markers. RESULTS: Asthmatic patients differentiated from those with rhinitis with or without bronchial hyperresponsiveness in levels of cysteinyl-leukotrienes [geometric mean: 3.3 (lower 95%-upper 95% confidence interval (CI) of geometric mean: 1.9-5.1) vs. 1.4 (0.9-2.2) and 0.7 (0.3-1.6) pg/microg total protein] and hyaluronan [0.30 (0.22-0.43) vs. 0.15 (0.10-0.20) and 0.20 (0.12-0.35) ng/microg total protein] in sputum. The levels of cysteinyl-leukotrienes decreased in sputum from the asthmatic patients, while the levels of hyaluronan remained elevated off-season. Furthermore, elevated levels of ECP were noticed among both the asthmatic and rhinitis patients with hyperresponsiveness compared with controls [0.022 (0.014-0.033) and 0.015 (0.011-0.021) compared with 0.010 (0.007-0.014) ng/microg total protein]. The level of ECP remained elevated off season. CONCLUSION: Cysteinyl-leukotrienes are possibly more related to mast cell-mediated inflammation and remodelling, also indicated by increased levels of hyaluronan during and off season. This inflammation may be partly different from the eosinophil-driven inflammation.     

Fundamental studies on measurement of the eosinophil cationic protein in sputum from patients with bronchial asthma

One of the characteristics of patients with bronchial asthma is activation of eosinophils in the bronchi, which can be evaluated by measuring concentrations of the cationic granule proteins. Sputum seems to be the best material to evaluate the activation of eosinophils in the bronchi because it can be collected easily from the same patient every day even if he (she) has an asthmatic attack. Recently it has become possible to measure the concentration of the eosinophil cationic protein (ECP) thanks to the availability of the ECP RIA kit. However no fundamental studies have been carried out on the handling of sputum samples, and whether only ECP released into sputum is measured. We prepared supernatants of sputum samples according to the method of Gleich and others by adding the same volume of physiological saline, mixing it for one minute by a vortex mixer and centrifuging at 40000 Xg, 4 C, for 30 minutes. We found that the measurement of ECP is not inhibited by materials in sputum supernatants through a dilution test and a recovery test. We also found that the followings did not influence the measurement of ECP; the times of dilution, the duration from collection to handing of sputum, the solution added to sputum, and the gravity of centrifugation. In addition, it was suggested that only ECP released into sputum is measurable from the results of an electron microscopic study and the measurement of ECP after centrifugation following the addition of white blood cells to sputum.     

The influence oc glycocorticoid therapy on sputum ECP concentration in symptomatic patients with bronchial asthma

ECP released from the granules of activated eosinophils is regarded to be a marker of airway inflammation in asthma. The study was performed to compare the usefulness of measuring serum and sputum ECP for monitoring the asthma treatment. 29 subjects with mild to moderate asthma (mean age 41 +/- 17) were admitted in exacerbation (FEV1 55.54 +/- 87.49% N). 10 subjects with grass pollen asymptomatic asthma and 10 healthy subjects were also enrolled in the study. Patients with symptomatic asthma were ordered 30 mg prednisone for 2 weeks and they continued during next 2 weeks inhaled budesonide therapy. The concentrations of ECP (mcg/L) were determined by CAP-system (Pharmacia). The total eosinophil count and serum ECP in all subjects treated orally and next by inhaled GKS didn't differ statistically. The highest sputum ECP concentration was determined in exacerbation of asthma 84.5 +/- 78 mcg/L and statistically were reduced after 2-weeks of prednisone treatment 24.4 +/- 12.1 mcg/L (p = 0.05). In following 2 weeks of budesonide treatment sputum ECP concentration was statistically negligible in relation to previous treatment in spite of increasing tendency (50 +/- 61.3 mcg/L (p = 0.2394). In asymptomatic grass pollen asthma sputum ECP concentration was 19.7 +/- 9.4 mcg/L, higher than in controls 12 +/- 5.8 mcg/L (p = 0.04). There were a significant correlations between total eosinophil count and serum (r = 0.6396) and sputum ECP(r = 0.4683) in exacerbation. CONCLUSIONS: 1. In asthma exacerbation elevated sputum ECP concentration was observed. 2. In consequence of prednisone treatment the sputum ECP concentration was reduced. 3. Sputum ECP measurement is more accurate than serum ECP for monitoring the effectiveness of treatment. 4. Sputum ECP concentration is a sensitive parameter which discriminate asymptomatic patients with asthma from healthy subjects.     

Anti-IgE autoantibody in patients with bronchial asthma

The anti-IgE autoantibody in the IgG class was detected in 95.5% of patients with atopic asthma, and in 72.2% of those with non-atopic asthma, using a newly established solid phase enzyme immunoassay (EIA). The specificity of anti-IgE autoantibody was confirmed by both competitive inhibition and absorption experiments, using human IgG, IgA, IgM, IgD, IgE and rabbit anti-human IgG. Significant correlations were observed between the levels of the anti-IgE autoantibody and the serum IgE. Gel filtration studies indicated that the anti-IgE autoantibody in sera from asthmatic patients was present in the immune complex form with self-IgE, in addition to the monomeric antibody. Furthermore, this anti-IgE autoantibody has the ability to induce the reversed type immediate skin reaction, in asthma free individuals. These observations strongly suggest the putative role of the anti-IgE autoantibody in the modulation of IgE-mediated immune systems and the pathogenesis of bronchial asthma.     

Spontaneous sputum discriminates inflammatory phenotypes in patients with asthma

BackgroundEosinophils in induced sputum are not only a useful biomarker for diagnosing asthma but are also associated with severe asthma. However, little is known about the association between eosinophils in spontaneous sputum and asthma severity.ObjectiveTo investigate whether spontaneous sputum eosinophils are related to severe asthma in adult patients with asthma.MethodsWe conducted a retrospective cross-sectional study on 86 people with asthma whose spontaneous sputa were successfully collected. Patients were classified into 4 phenotypes according to the eosinophil and neutrophil levels in spontaneous sputum. We determined the association between inflammatory phenotypes and severe asthma. Moreover, we also compared asthma severity among the phenotypes classified according to blood eosinophils and spontaneous sputum eosinophils.ResultsAsthma phenotypes were as follows: paucigranulocytic, 30.2%; neutrophilic, 18.6%; eosinophilic, 32.6%; and mixed, 18.6%. People with eosinophilic asthma had the highest blood eosinophils, total immunoglobulin E (IgE), and fractional exhaled nitric oxide among the 4 phenotypes. Significant differences were observed in asthma severity between the phenotypes (P = .019). In particular, 57.2% and 56.2% of patients had severe eosinophilic asthma and mixed asthma, respectively. The logistic regression analysis revealed that spontaneous sputum eosinophilia represented the strongest association with severe asthma among the inflammatory variables. Finally, more patients with severe asthma were included in the phenotype with spontaneous sputum eosinophils greater than 3% and blood eosinophils less than or equal to 300/μL and in the phenotype with spontaneous sputum eosinophils greater than 3% and blood eosinophils greater than 300/μL.ConclusionSpontaneous sputum can provide helpful information on airway inflammatory phenotyping in patients with asthma.     

Nifedipine treatment of patients with bronchial asthma

Nifedipine, 30 mg/day for 4 weeks, was compared to placebo in a double-blind, randomized, crossover study, as an additional drug added to the usual treatment of 14 patients with bronchial asthma. Nifedipine did not significantly change peak expiratory flow rates or subjective symptoms like cough, sputum, wheezing, shortness of breath, or disturbed sleep. Nifedipine did not decrease the number of salbutamol rotacaps inhaled per day. Arterial blood pressure significantly decreased (p less than 0.01) after nifedipine treatment, and side effects (headache and flushing) were not uncommon. In this study, long-term treatment with nifedipine had essentially no effect on subjective symptoms at peak expiratory flow rates.     

Silent gastroesophageal reflux in patients with bronchial asthma

Gastroesophageal reflux (GER) is a common occurrence in patients with asthma. We performed a prospective study to detect GER in patients with asthma using pH monitoring. Twenty consecutive patients (mean age 48 +/- 14 yr, range 23-70; 13 men) with asthma of unexplained etiology were evaluated. Esophageal and gastric pH were studied both while introducing and pulling out pH probe. Upper GI endoscopy was done in all the patients before doing pH monitoring. Esophageal pH was recorded at 25 cm, 30 cm and 35 cm from the incisors. Mean esophageal pH values while introducing pH probe were 2.9 +/- 1.08 (0-5.1), 2.5 +/- 1.2 (0-5) and 1.6 +/- 1.5 (0-4.6) at 25 cm, 30 cm and 35 cm from incisors respectively. The gastric pH was 0.5 +/- 0.4 (0-2). While pulling out pH probe, pH values were 1.5 +/- 1.4 (0-4.7), 2.4 +/- 1.5 (0-5.1) and 2.9 +/- 1.4 (0-5.4) at 35 cm, 30 cm, and 25 cm from incisors respectively. Of 20 patients, 19 had pH of 4 or lower at 25 cm, 30 cm and 35 cm from incisors. The mean pH value was lower at 35 cm than at 30 cm and 25 cm (1.6 +/- 1.5 vs 2.5 +/- 1.2 and 2.9 +/- 1.08, p < 0.04). In conclusion majority of adults with asthma have silent GER as detected on pH monitoring.     

Complement fragments in patients with bronchial asthma]

In this study, we investigated the pharmacological reactions induced by ibudilast to the complement system with the aim of clarifying the functional relation of the complement system to allergic reactions and pathology in patients with bronchial asthma. Complement hemolytic activities (CH50 and ACH50), complement profile, anaphylatoxins (C3a and C5a) and complement fragments (Bb, iC3b and C4d) were measured in 20 patients with bronchial asthma. One of antiasthmatic activities induced by ibudilast was concluded to be brought about though inactivation of the alternative complement pathway working on type III allergic reaction. Ibudilast increased the complement fragment Bb in the patients' plasma with the fairly controlled bronchial asthma. This increase in circulating Bb was suspected to be a result of inactivation of intermediate complement complexes, for example C3b.Bb.P, because the amounts in plasma of C3 and C5 showed no changes, while those of factor, B, P, H and I were decreased by ibudilast administration in patients with fairly controlled bronchial asthma. This antiasthmatic ability of ibudilast was restrained in those patients whose peripheral leukocytopenia was advanced before ibudilast administration, and in those whom ibudilast did not provoke an increase in the plasma level of iC3b, or did not prevent the serum level of C5 from increasing. In those unfairly controlled cases, enough anaphylatoxins, especially C5a might be produced to make the margination of peripheral neutrophils to the lung and increase CR3 on neutrophils binding with iC3b.     

Computer-assisted instructions for patients with bronchial asthma

We produced computer-assisted instruction (CAI) software for bronchial asthma patients (asthma educational system with computer-assisted instruction; ASTCAI) to assist in self-management and avoid asthmatic attacks and death. ASTCAI is a question-and-answer program operating in a multimedia environment, and was evaluated from questionnaires which 33 patients were asked. Thirty-two patients could perform ASTCAI without any assistance. The responses of 31 patients (94%) indicated that they had no difficulty with manipulation, and 29 patients (88%) stated that the program was beneficial to control of their asthma. Elderly patients (over 65) required more time than younger adults. Emergency visits or admissions of at least 1 year after the first CAI trial decreased in eight out of 26 patients, while only two patients deteriorated compared to the previous year. Our results show that CAI is feasible for most patients, and through active self-learning CAI can improve motivation for self-management as well as supplement the physician's instructions.