Comparison of Sputum and Serum Eosinophil Cationic Protein (ECP) Levels in Nonatopic Asthma and Chronic Obstructive Pulmonary Disease

The aim of the present study was to investigate whether sputum eosinophil cationic protein (ECP) concentrations could be a useful marker in the differential diagnosis between intrinsic asthma and chronic obstructive pulmonary disease (COPD). For this purpose total blood eosinophil counts were obtained and concentrations of serum and sputum ECP from 10 nonatopic asthmatics with a mild attack and 9 COPD patients with acute exacerbation were measured by radioimmunoassay. Mean serum ECP concentration was 54.3 ± 23.0 g/L in the asthmatic group and 83.3 ± 79.2 g/L in the COPD group (p: n.s.). In the group of asthmatics mean sputum ECP level was 984.5 ± 1245.5 mg/L/g sputum and in the COPD group it was 417.5 ± 363.5 mg/L/g sputum. There was no significant difference in sputum ECP levels between patients with asthma and COPD. We conclude that neither sputum nor serum ECP levels are useful markers in differential diagnosis of asthma attack and acute exacerbation of COPD.     

Inhaled fluticasone propionate is effective as well as oral prednisone in reducing sputum eosinophilia during exacerbations of asthma which do not require hospitalization

The aim of this study was to evaluate whether fluticasone propionate (FP) is effective as well as prednisone (P) in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbations not requiring hospitalization. We measured, in a parallel-group, double-blind double-dummy, randomized study, sputum and blood inflammatory cell counts and soluble mediators in 37 asthmatic subjects during a spontaneous exacerbation of asthma (Visit 1) and after a 2 week (Visit 2) treatment with inhaled FP (1000microg bid) (Group A, n=18) or a reducing course of oral P (Group B, n=19). Asthma exacerbation was accompanied by sputum eosinophilia (eosinophils >2%) in almost all patients (95%). FP improved FEV(1) (from 53.9%+/-16.8 at Visit 1 to 76.4%+/-21.2 at Visit 2, p=0.0001) and reduced the percentage of sputum eosinophils (from 38%[0-78] to 3%[1-31, p=0.0008) as well as oral P (FEV(1): from 51.5%+/-14.4 to 83.6%+/-21.1, p=0.0001; sputum eosinophils: from 52%[1-96] to 11%[0-64], p=0.0003). At Visit 2, sputum eosinophils were significantly lower in Group A than in Group B. P but not FP induced significant decrease in blood and sputum ECP. Oxygen saturation, PEF variability, symptom score and use of rescue medication similarly improved in both groups. We conclude that FP is effective at least as well as P in reducing sputum eosinophilia and in improving airway obstruction due to asthma exacerbation. However, the cost/effectiveness ratio of this option should be further evaluated.     

Induced sputum: time from expectoration to processing.

One of the limitations in the use of induced sputum to measure indices of airway inflammation is the perceived need to process the sample within 2 h. Therefore, the authors investigated whether the processing of induced sputum could be delayed. Induced sputum samples obtained from asthmatic subjects (n=30) were examined. Each sample was stored at 4 degrees C. A portion was selected and processed within 2 h and the remaining expectorate (sputum plus saliva) was refrigerated. Later an equal amount was selected and processed at either 9 (n=15) or 18 (n=15) h. The sputum was examined for cell counts and viability, fluid-phase eosinophil cationic protein (ECP), interleukin-8 (IL-8) and fibrinogen. Repeatability of measurements was assessed by the interclass correlation coefficient (ICC). Measurements obtained at 9 h did not differ from those made at 2 h and the repeatability was excellent (ICC 0.88-0.99). However, by 18 h the median cell viability was reduced from 65.0% to 43.0% and the ICC was generally lower: 0.10 for total cell count, 0.24 for viability, 0.60 for neutrophils, 0.90 for eosinophils, 0.56 for macrophages, 0.76 for ECP, 0.82 for IL-8 and 0.84 for fibrinogen. The results indicate that when induced sputum from subjects with asthma is kept at 4 degrees C, examination of cell counts can be delayed for < or = 9 h and for the fluid-phase indices measured for < or = 18 h. Further investigation of this issue is required for spontaneous sputum, other airway diseases and other inflammatory markers.     

The relationship between airways inflammation and asthma severity

In order to investigate the relationship between airways inflammation and disease severity, and improve the understanding of persistent asthma, 74 asthmatics, with disease severity ranging from intermittent, to mild to moderate and severe persistent (classified according to the Global Initiative for Asthma [GINA] guidelines), and 22 nonatopic control subjects were studied using the method of induced sputum. Sputum was analyzed for total and differential cell counts concentrations of albumin, and levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), and tryptase, inflammatory mediators reflecting eosinophil, neutrophil, and mast cell activation. Asthma severity (assessed by FEV(1), peak expiratory flow [PEF] variability, and daily symptom scores) and methacholine airways responsiveness were related to sputum eosinophilia and ECP. In addition, sputum neutrophilia and MPO levels correlated, albeit weakly, with PEF variability and symptom scores, respectively. Tryptase concentrations were raised in mild to moderate asthmatics. Albumin concentrations were significantly raised across the spectrum of asthma severity and correlated with those of tryptase and ECP. Despite treatment with either high doses of inhaled corticosteroids or oral corticosteroids, prominent eosinophilic inflammation with raised ECP was noted. This study points to persistent, disease severity-related airways inflammation in asthma, involving eosinophils, mast cells, and neutrophils, which is evident despite treatment with corticosteroids.     

NO in exhaled air is correlated with markers of eosinophilic airway inflammation in corticosteroid-dependent childhood asthma.

The relationship between nitric oxide in exhaled air, levels of sputum eosinophils, sputum eosinophil cationic protein (ECP) and urinary eosinophil protein X (EPX) excretion has not yet been investigated in corticosteroid-dependent childhood asthma. Therefore, taking 25 children with stable asthma (mean age 11.2 yrs) treated with inhaled corticosteroids and nine nonatopic healthy control children (mean age 12.8 yrs) the level of exhaled NO was measured by means of a chemiluminescence analyser before and after sputum induction. This was conducted as a slow vital capacity manoeuvre under standardized conditions with a target flow of 70 mL x s(-1) against a resistance of 100 cm H2O x L(-1) x s. Sputum induction was performed by inhalation of hypertonic saline (3, 4, and 5%) in a standardized manner and a single sample of urine was collected. Exhaled NO (p = 0.01), absolute eosinophil cell counts in sputum (p = 0.02), sputum ECP (p = 0.09) and urinary EPX excretion (p = 0.02) were higher in asthmatics compared to control children. Exhaled NO was positively correlated with sputum ECP (r(s) = 0.59, p = 0.002), urinary EPX (r(s) = 0.42, p = 0.03), and sputum eosinophils (r(s) = 0.30, p = 0.15) in the asthmatic children. These correlations appeared to be pronounced after sputum induction, where NO values had decreased (p = 0.01). None of the correlations were observed in the group of nonatopic control subjects. Additionally there were significant correlations between sputum ECP and sputum eosinophils (r(s) = 0.69, p<0.001) as well as between sputum ECP and urinary EPX excretion (r(s) = 0.58, p = 0.003) in the asthmatics. Exhaled NO provides information about the degree of eosinophilic airway inflammation and thus appears to be a useful and easy-to-perform inflammatory marker in corticosteroid-dependent asthma.     

Effects of prednisone on eosinophilic bronchitis in asthma: a systematic review and meta-analysis

OBJECTIVE:

To evaluate the effect size of oral corticosteroid treatment on eosinophilic bronchitis in asthma, through systematic review and meta-analysis.

METHODS:

We systematically reviewed articles in the Medline, Cochrane Controlled Trials Register, EMBASE, and LILACS databases. We selected studies meeting the following criteria: comparing at least two groups or time points (prednisone vs. control, prednisone vs. another drug, or pre- vs. post-treatment with prednisone); and evaluating parameters before and after prednisone use, including values for sputum eosinophils, sputum eosinophil cationic protein (ECP), and sputum IL-5-with or without values for post-bronchodilator FEV₁-with corresponding 95% CIs or with sufficient data for calculation. The independent variables were the use, dose, and duration of prednisone treatment. The outcomes evaluated were sputum eosinophils, IL-5, and ECP, as well as post-bronchodilator FEV₁.

RESULTS:

The pooled analysis of the pre- vs. post-treatment data revealed a significant mean reduction in sputum eosinophils (↓8.18%; 95% CI: 7.69-8.67; p < 0.001), sputum IL-5 (↓83.64 pg/mL; 95% CI: 52.45-114.83; p < 0.001), and sputum ECP (↓267.60 µg/L; 95% CI: 244.57-290.63; p < 0.0001), as well as a significant mean increase in post-bronchodilator FEV₁ (↑8.09%; 95% CI: 5.35-10.83; p < 0.001).

CONCLUSIONS:

In patients with moderate-to-severe eosinophilic bronchitis, treatment with prednisone caused a significant reduction in sputum eosinophil counts, as well as in the sputum levels of IL-5 and ECP. This reduction in the inflammatory response was accompanied by a significant increase in post-bronchodilator FEV₁.     

Immunohistochemically stained activated eosinophils in sputum in patients with asthma

BACKGROUND: Eosinophils play an important role in asthmatic airway inflammation. Monoclonal antibody EG2 has been considered to identify activated eosinophils. OBJECTIVE: The present study was aimed to investigate whether immunohistochemically stained EG2+ eosinophils in sputum reflect the severity of asthma. METHODS: Sputum was obtained in 23 asthmatic patients, of whom 13 patients were examined before and after antiasthma treatment including steroid preparations. We used immunohistochemical staining to detect EG2+ (activation marker) eosinophils and fluoroimmunoassay to detect eosinophil cationic protein (ECP). RESULTS: Moderate to severe asthmatics had a significantly higher proportion of eosinophils and EG2+ eosinophils and higher levels of ECP compared to mild asthmatics (40.9 +/- 5.8 vs. 6.4 +/- 1.2%, 35.5 +/- 5.6 vs. 2.7 +/- 1.0%, 1.470.2 +/- 251.5 vs. 210.6 +/- 52.0 microgram/l, respectively; p < 0.01). Significant increases in proportions of eosinophils, EG2+ eosinophils and ECP in the sputum from patients with exacerbated asthma were evident. The proportions of eosinophils, EG2+ eosinophils, and the levels of ECP were reduced following treatment with antiasthmatic drugs. FEV(1) and FEV(1)/FVC were significantly correlated with EG2+ eosinophils. CONCLUSION: These findings demonstrate that EG2+ eosinophils in sputum are closely related to the clinical status in patients with asthma.     

Pattern of airway inflammation and its determinants in children with acute severe asthma.

The aim of this study was to examine the relationship between sputum cell counts and clinical variables in children with an acute exacerbation of asthma. Sputum was successfully obtained from 37 of 42 children presenting to the Emergency Department with acute asthma, using ultrasonically nebulized normal saline (n = 19) or spontaneous expectoration (n = 18). Sputum portions were selected and dispersed, and total and differential cell counts were performed. Sputum supernatant was assessed for eosinophil cationic protein (ECP), interleukin (IL)-5, and IL-8. The exacerbations were of 3 inflammatory cell patterns: eosinophilic (n = 16 or 43% of total), combined eosinophilic/neutrophilic (E/N; n = 13.3 or 35% of total), or noneosinophilic (n = 8 or 22% of total). IL-5 was highest in eosinophilic exacerbations. Combined E/N exacerbations had increased mast cells (77%) and higher sputum ECP levels than eosinophilic exacerbations: 2,146 ng/mL vs. 666 ng/mL (P = 0.04). The speed of onset of the exacerbation was not related to the inflammatory cell profile. Logistic regression identified maintenance asthma treatment (odds ratio (OR), 5.9; 95% confidence interval (CI), 1.3-26.8) and lung function during the acute episode (OR, 4.0; 95% CI, 1.7-93) as significantly associated with the intensity of sputum eosinophilia. Eosinophils were lowest in children who received maintenance treatment with oral corticosteroids compared to those with no background asthma preventer therapy (P = 0.001). In conclusion, we identified three distinct patterns of airway inflammation in children with acute asthma; they included increased eosinophils, combined eosinophilic-neutrophilic infiltration, and a noneosinophilic pattern. Eosinophil degranulation was greatest with the combined eosinophilic/neutrophilic pattern of airway inflammation. Sputum eosinophils were associated with clinical severity, and background asthma therapy, but not with outcome, nor with speed of onset of exacerbations. These different inflammatory cell profiles imply different etiological agents and may require differing treatment strategies.     

Clinical assessment of asthma severity partially corresponds to sputum eosinophilic airway inflammation

In the aim to evaluate the relationship between sputum eosinophil percentages and eosinophil cationic protein (ECP) concentrations, as markers of airway inflammation, and different Levels of asthma severity, we examined 223 patients consecutively observed in our asthma clinic. Diagnosis of asthma was made according to internationally accepted criteria. Asthma severity was evaluated according to frequency of symptoms, FEV1, peak expiratory flow variability and level of asthma treatment needed to control asthma. Spontaneous or induced sputum was collected. Adequate sputum samples were obtained in 68 untreated subjects and in 117 subjects regularly treated with ICS. A control group of 14 normal subjects was also examined. In untreated subjects, mild intermittent asthmatics showed a lower sputum eosinophil percentage in comparison with other groups of asthma severity, while no difference in ECP levels was detected. In treated subjects, severe asthmatics showed higher levels of sputum eosinophils and ECP in comparison with other groups of asthma severity. Mild persistent and moderate persistent patients did not differ for sputum eosinophils or ECP in both untreated and treated subjects. Controls were significantly different from all groups of untreated and treated asthmatics. In conclusion, the assessment of asthma severity according to clinical and functional findings only partially corresponds to the severity of eosinophilic airway inflammation as assessed by induced sputum analysis.     

Failure of montelukast to reduce sputum eosinophilia in high-dose corticosteroid-dependent asthma.

Sputum eosinophilia is a sensitive predictor of benefit from corticosteroid treatment. Montelukast is a cysteinyl leukotriene antagonist, which also reduces sputum and blood eosinophils. The present study examined the possibility that montelukast has an added eosinophil-lowering effect in subjects with asthma who are corticosteroid responsive but relatively corticosteroid resistant. A total of 14 clinically stable adults with asthma requiring minimum treatment with a high-dose inhaled steroid or prednisone, with baseline sputum eosinophilia (> or =5%), were randomised to receive 4 weeks of 10 mg montelukast or placebo daily in a double-blind crossover trial. The primary outcome was the effect of treatment on the percentage of sputum eosinophils. Secondary outcomes were changes in the blood eosinophil count, symptoms, forced expiratory volume in one second, peak expiratory flow and the need for salbutamol. The median (interquartile range, i.e. 75th-25th centile) for sputum eosinophils at baseline was 15.7% (22). The effect of adding montelukast was not significantly different from that of placebo, sputum eosinophils being 9.3% (18.9) after montelukast and 11.3% (22.8) after placebo. No difference was detected on secondary outcomes. No crossover interactions were observed. In conclusion, the addition of montelukast to existing high-dose corticosteroid therapy in subjects with asthma with elevated sputum eosinophils does not provide additional attenuation of airway eosinophilia.     

Markers of airway inflammation and airway hyperresponsiveness in patients with well-controlled asthma.

In steroid-naive asthmatics, airway hyperresponsiveness correlates with noninvasive markers of airway inflammation. Whether this is also true in steroid-treated asthmatics, is unknown. In 31 stable asthmatics (mean age 45.4 yrs, range 22-69; 17 females) taking a median dose of 1,000 microg inhaled corticosteroids (ICS) per day (range 100-3,600 microg x day(-1)), airway responsiveness to the "direct" agent histamine and to the "indirect" agent mannitol, lung function (forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF)), exhaled nitric oxide (eNO), and number of inflammatory cells in induced sputum as a percentage of total cell count were measured. Of the 31 subjects, 16 were hyperresponsive to mannitol and 11 to histamine. The dose-response ratio (DRR: % fall in FEV1/cumulative dose) to both challenge tests was correlated (r=0.59, p=0.0004). However, DRR for histamine and DRR for mannitol were not related to basic lung function, eNO, per cent sputum eosinophils and ICS dose. In addition, NO was not related to basic lung function and per cent sputum eosinophils. In clinically well-controlled asthmatics taking inhaled corticosteroids, there is no relationship between markers of airway inflammation (such as exhaled nitric oxide and sputum eosinophils) and airway responsiveness to either direct (histamine) or indirect (mannitol) challenge. Airway hyperresponsiveness in clinically well-controlled asthmatics appears to be independent of eosinophilic airway inflammation.     

Sputum eosinophilia in Churg-Strauss syndrome

Sputum induction (IS) can be used to study airway inflammation in asthmatics and other lung diseases. However, no data are available for patients with Churg-Strauss syndrome (CSS). A study was carried out to evaluate eosinophil counts and eosinophil cationic protein (ECP) levels in induced sputum during the follow-up of three patients with CSS. Induced sputum was carried out in 10 patients with corticosteroid-dependent asthma (used as a control group). Patients with CSS had significantly higher eosinophils percentages and ECP levels in sputum than those with stable corticosteroid-dependent asthma. During the follow-up, patients with CSS presented increased ECP levels sputum and eosinophils in sputum as well as increased blood eosinophils, despite their oral corticosteroid and immunosuppressive treatment. Eosinophil percentage in sputum and the total number of eosinophils in peripheral blood were more predictive of exacerbations of CSS than sputum ECP.     

Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma.

Acute exacerbations of asthma are frequently caused by viral infections, but the inflammatory mechanisms in virus-induced asthma are poorly understood. The aim of the present study was to determine whether viral infection in acute asthma was associated with increased sputum neutrophil degranulation and increased cellular lysis and whether these changes are related to clinical severity. Adults (n=49) presenting to the emergency department with acute asthma were examined for infection by means of sputum direct-fluorescence antigen detection, sputum culture, and sputum polymerase chain reaction for Mycoplasma, Chlamydia and Legionella pneumophila, and all common respiratory viruses. Subjects infected with one of these agents were classed as having an infective exacerbation. Spirometry and sputum induction were performed on presentation and 4-5 weeks later. Thirty-seven subjects (76%) had virus infection and acute asthma. Those with virus infection had increased sputum neutrophils (p<0.05) and increased neutrophil elastase (p<0.05), this was related to increased elevated sputum lactate dehydrogenase (LDH). Subjects with noninfective asthma had an increase in the proportion of sputum eosinophils. Both groups had elevated sputum eosinophil cationic protein (ECP) concentrations. Higher levels of sputum LDH and ECP were associated with a longer hospital stay. Virus infection and acute asthma is associated with neutrophilic inflammation, cell lysis and more severe clinical disease.     

糖皮质激素对哮喘患者CD4T淋巴细胞和嗜酸细胞活化的影响

为研究口服糖皮质激素泼尼松对哮喘患者体内ＣＤ４Ｔ淋巴细胞，嗜酸细胞活化的影响，用酶联免疫法对治疗前后哮喘患者血清白细胞介素－５，嗜酸细胞阳离子帽白浓度进行了检测。结果表明，口服泼泥松治疗１周后，血清ＩＬ－５，ＥＣＰ浓度降低，提示糖皮质激素可能通过抑制ＣＤ４Ｔ淋巴细胞活化，减少细胞因子的释放而对哮喘发挥抗炎作用。     

哮喘患者痰液细胞因子和哮嗜酸细胞阳离子蛋白水平及意义

目的 探讨痰中细胞因子、嗜酸细胞阳离子蛋白（ＥＣＰ）水平与哮喘严重程度的关系。方法 采用酶联免疫法及荧光光免疫法对轻（Ｍ组１０例）中、重度（ＭＳ组１５例）哮喘２痰液白细胞介素（ＩＬ）５、肿瘤坏死因子α（ＴＮＦ－α）、可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）、ＥＣＰ水平进行检测。结果 中、重度哮喘患溶液ＩＬ－５（３５ｎｇ／Ｌ以上）、ＴＮＦ－α（Ｍ组为１４９±５９ｎｇ／Ｌ，ＭＳ组为２６７±１４７ｇ／Ｌ     

Suppression of airway inflammation by theophylline in adult bronchial asthma

BACKGROUND: Chronic continuous airway inflammation caused by eosinophils has been noted to play critical roles in the pathophysiology of bronchial asthma, in addition to reversible obstruction and hypersensitivity of the respiratory tract. Therefore, suppression of chronic airway inflammation has become more important in asthma treatment. Although theophylline has been a conventionally used bronchodilator, it has been recently reported to have concurrent anti-inflammatory effects. OBJECTIVE: Accordingly, we studied the effects of a slow-release theophylline preparation, Theolong, on airway inflammation. METHODS: Administration of Theolong 400 mg/day to 24 patients with mild or moderate asthma and measuring eosinophil cationic protein (ECP), a marker of airway inflammation, and eosinophils in sputum and peripheral blood at 4 and 8 weeks. RESULTS: As a result, sputum ECP, serum ECP and sputum eosinophil count (%) were significantly lowered after 4 and 8 weeks. CONCLUSION: Thus, in the theophylline-administered group, slow-release theophylline, Theolong, was effective in treating asthma, with anti-inflammatory effects on inflammatory cells besides its bronchodilator action.     

Smoking and airway inflammation in patients with mild asthma.

STUDY OBJECTIVES: Cigarette smoking is common in asthmatic patients, and we investigated the impact of cigarette smoking on airway inflammation in asthma. DESIGN: Single-center observational study of airway inflammation in asthmatic and healthy smokers and nonsmokers. SETTING: Asthma research unit in a university hospital. PATIENTS OR PARTICIPANTS: Sixty-seven asthmatic and 30 nonasthmatic subjects classified as smokers or nonsmokers. Asthmatics had chronic, stable asthma and were not receiving inhaled or oral steroids at the time of the study. INTERVENTIONS: We examined induced-sputum cell counts and levels of interleukin (IL)-8 and eosinophilic cationic protein (ECP). Bronchial hyperreactivity was assessed using methacholine challenge. MEASUREMENTS AND RESULTS: Asthmatic smokers had higher total sputum cell counts than nonsmoking asthmatics and both smoking and nonsmoking healthy subjects. Smoking was associated with sputum neutrophilia in both asthmatics and nonasthmatics (median, 47% and 41%, respectively) compared with nonsmokers (median, 23% and 22%, respectively), and sputum IL-8 was increased in smokers compared with nonsmokers, both in subjects with asthma (median, 945 pg/mL vs 660 pg/mL, respectively) and in healthy subjects (median, 1,310 pg/mL vs 561 pg/mL, respectively). Sputum eosinophils and ECP levels were higher in both nonsmoking and smoking asthmatics than in healthy nonsmokers. In smoking asthmatics, lung function (FEV(1) percent predicted) was negatively related to both sputum IL-8 (r = - 0.52) and sputum neutrophil proportion (r = - 0.38), and sputum IL-8 correlated positively with smoking pack-years (r = 0.57) and percent neutrophil count (r = 0.51). CONCLUSIONS: In addition to the eosinophilic airway inflammation observed in patients with asthma, smoking induces neutrophilic airway inflammation; a relationship is apparent between smoking history, airway inflammation, and lung function in smoking asthmatics.     

Effects of Suplatast Tosilate on Airway Inflammation and Airway Hyperresponsiveness

Suplatast tosilate (IPD®) is a Th2 cytokine inhibitor that lowers the titer of the IgE antibody through specific inhibition of the production of IL (interleukin)-4 and IL-5 by T cells and inhibits tissue infiltration by eosinophils. In this clinical trial, suplatast tosilate (300 mg/day) was administered orally for 4 weeks to 25 patients (13 patients with atopic asthma, 12 patients with nonatopic asthma) whose bronchial asthma was staged in step 1 or step 2 according to the Guidelines for Prevention and Management of Bronchial Asthma, 1998. Before and after administration, the parameters of airway inflammation, that is, peripheral blood eosinophils count, serum level of eosinophil cationic protein (ECP), ECP level in induced sputum, airway hyperresponsiveness (D_min), and morning peak expiratory flow (PEF), were measured. The peripheral blood eosinophil count, serum level of ECP, and ECP level in induced sputum decreased significantly. Of these parameters, the ECP level in induced sputum was the most sensitive. Furthermore, suplatast tosilate significantly inhibited D_min. These results were especially significant in patients with atopic asthma. Suplatast tosilate was considered to have inhibited airway eosinophilic inflammation through decreases in peripheral blood eosinophils counts and in ECP levels in induced sputum, which resulted in inhibition of airway hyperresponsiveness.     

Effects of Suplatast Tosilate on Airway Inflammation and Airway Hyperresponsiveness

Suplatast tosilate (IPD®) is a Th2 cytokine inhibitor that lowers the titer of the IgE antibody through specific inhibition of the production of IL (interleukin)-4 and IL-5 by T cells and inhibits tissue infiltration by eosinophils. In this clinical trial, suplatast tosilate (300 mg/day) was administered orally for 4 weeks to 25 patients (13 patients with atopic asthma, 12 patients with nonatopic asthma) whose bronchial asthma was staged in step 1 or step 2 according to the Guidelines for Prevention and Management of Bronchial Asthma, 1998. Before and after administration, the parameters of airway inflammation, that is, peripheral blood eosinophils count, serum level of eosinophil cationic protein (ECP), ECP level in induced sputum, airway hyperresponsiveness (D_min), and morning peak expiratory flow (PEF), were measured. The peripheral blood eosinophil count, serum level of ECP, and ECP level in induced sputum decreased significantly. Of these parameters, the ECP level in induced sputum was the most sensitive. Furthermore, suplatast tosilate significantly inhibited D_min. These results were especially significant in patients with atopic asthma. Suplatast tosilate was considered to have inhibited airway eosinophilic inflammation through decreases in peripheral blood eosinophils counts and in ECP levels in induced sputum, which resulted in inhibition of airway hyperresponsiveness.