Hydrofluoroalkane-beclomethasone dipropionate effectively improves airway eosinophilic inflammation including the distal airways of patients with mild to moderate persistent asthma as compared with fluticasone propionate in a randomized open double-cross study.

Background: To evaluate whether hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) controls eosinophilic inflammation, including that in the distal airways, more effectively than fluticasone propionate (FP) Diskus(R). Methods: Fifty patients with well-controlled mild to moderate persistent asthma using FP for more than 6 months were randomly assigned to FP and HFA-BDP groups, and the treatment regimens of the two groups were switched twice between FP and HFA-BDP in a double cross-over manner at 3-month intervals after 2-week washout periods. Evidence of eosinophilic inflammation in blood and induced sputum samples was assessed, together with pulmonary function testing and an Asthma-related Quality of Life Questionnaire (AQLQ) survey after each treatment period. Results: The peripheral blood differential eosinophil count and sputum levels of eosinophil cationic protein (ECP) showed reciprocal changes during the study periods in both groups. The blood differential eosinophil count was significantly lower during the HFA-BDP than during the FP treatment period in both the FP (p = 0.004) and the HFA-BDP (p = 0.020) group. The late-phase induced sputum ECP level was significantly decreased during the HFA-BDP treatment period in both the FP (p = 0.016) and the HFA-BDP group (p = 0.023). The significant elevation of surfactant protein D values in the late-phase sputum observed in both groups indicated that late-phase sputum was obtained mainly from proximal peripheral airways. Both symptom and activity limitation domains of the AQLQ in the HFA-BDP group significantly increased after switching from FP to HFA-BDP. There were no significant changes in pulmonary function indices in either group at any time during the study. Conclusions: HFA-BDP improved residual eosinophilic inflammation in asthmatic airways, including distal airways, more effectively than FP.     

Apoptotic eosinophils in sputum from asthmatic patients correlate negatively with levels of IL-5 and eotaxin

BACKGROUND: Eosinophilic inflammation of the airways is a key characteristic of asthma. A defect in eosinophil apoptosis might contribute to the chronic tissue eosinophilia associated with asthma. OBJECTIVE: Our purpose was to examine whether the occurrence of apoptotic eosinophils in induced sputum from asthmatic patients correlate with interleukin (IL)-5 and eotaxin. METHODS: Thirty stable and 30 exacerbated asthmatic patients were recruited. Twenty healthy subjects were enrolled as a control group. Induced sputum was obtained from asthmatic patients and from control subjects. The number of apoptotic eosinophils in sputum was assessed by flow cytometry. In sputum supernatant, eosinophil cationic protein (ECP) was measured by sensitive radioimmunoassay, and IL-5 and eotaxin by sandwich enzyme linked immunosorbant assay. RESULTS: Levels of eosinophils, apoptotic eosinophils, IL-5, ECP and eotaxin from asthmatic patients were higher than those from healthy subjects. Thirty exacerbated asthmatics showed higher proportions of eosinophils (median 29.3%, range 13.4%-40.9%), more detectable levels of IL-5 (50.44, 32.99-67.01 pg/ml) and eotaxin (644.6, 197.4-937.7 pg/ml) in their sputum than the patients with stable asthma (P<0.05). There were significant inverse correlations between the levels of sputum IL-5 and the proportion of sputum eosinophil apoptosis in patients with exacerbated and stable asthma (r=-0.85 and -0.79, P<0.01 and P<0.05, respectively). Also inverse correlations were found between the levels of eotaxin and the proportion of sputum eosinophil apoptosis in exacerbated (r=-0.85, P<0.01), or stable asthma (r=-0.69, P<0.05). Additional positive correlations between the levels of sputum IL-5 and eotaxin in either exacerbatated (r=0.93, P<0.01) or stable asthma (r=0.82, P<0.05) were observed. CONCLUSIONS: Apoptosis of eosinophils might be suppressed by proinflammatory cytokines and chemokines such as IL-5 and eotaxin leading to their accumulation in the lung. Stimulation of eosinophils in airway with IL-5 and eotaxin may play a crucial role in allergic inflammation.     

Clinical Implication of Protein Levels of IL-5 in Induced Sputum in Asthmatic Patients

To determine whether protein levels of interleukin-5 (IL-5) in induced sputum reflect the degree of eosinophilic inflammation, we evaluated the role of IL-5 on clinical characteristics in stable asthmatic patients. IL-5 level, differential eosinophil count, and level of eosinophil cationic protein (ECP) in induced sputum were all significantly higher for asthmatics than for normal controls. Both eosinophil counts and ECP levels in induced sputum were inversely correlated with the degree of airflow limitation (FEV₁/FVC). In addition, patients with measurable IL-5 in sputum had significantly more eosinophils, higher levels of ECP in sputum, and lower FEV₁ (percent predicted) than did patients with levels of IL-5 beneath the limit of detection. However, we found no significant difference in IL-5 levels between atopic and nonatopic asthmatics. IL-5 level in induced sputum is a good indicator of eosinophilic inflammation in atopic and nonatopic asthmatic patients.     

Effects of pranlukast on chemical mediators in induced sputum on provocation tests in atopic and aspirin-intolerant asthmatic patients.

BACKGROUND: Leukotrienes (LTs) are important in asthma, and LT modifiers modulate antigen-induced asthma. Overproduction of LT by suppression of cyclooxygenase activity is involved in patients with aspirin-intolerant asthma (AIA). METHODS: House dust mite (HDM) inhalation provocation tests were performed in HDM-sensitive asthmatic inpatients without AIA (HDM group; n = 6), and aspirin oral provocation tests were performed in AIA patients (ASA group; n = 7). Tests were repeated using the same regimen after 7 days of treatment with pranlukast, an LT receptor antagonist (LTRA). The effects of pranlukast on changes in sputum LTC(4)-LTD(4), eosinophil cationic protein (ECP), eosinophil count, urinary LTE(4)/creatinine, 11-dehydrothromboxane B(2) (11-dhTXB(2))/creatinine, serum LTC(4)-LTD(4), ECP, and peripheral blood eosinophil count, during immediate asthmatic reaction (IAR) and late asthmatic reaction (LAR) in the HDM group and during IAR in the ASA group for each test, were compared in each group. RESULTS: In the HDM group, IAR and LAR were observed. Sputum LTC(4)-LTD(4) and urinary LTE(4)/creatinine increased significantly both during IAR and LAR. Sputum ECP increased during IAR and further increased during LAR. Eosinophil count in the sputum did not increase during IAR but significantly increased during LAR. Pranlukast suppressed the fall in FEV(1) both during IAR and LAR (73.8% and 51.9%, respectively) and inhibited the increase in sputum eosinophil count during LAR and sputum ECP during IAR and LAR. In the ASA group, aspirin-induced IAR was associated with a fall in urinary 11-dhTXB(2)/creatinine, increased the levels of sputum LTC(4)-LTD(4) and ECP and urinary LTE(4)/creatinine. Pranlukast suppressed IAR and inhibited the increase of the level of sputum ECP, but failed to change aspirin-induced LT production in the sputum and urine. The levels of sputum LTC(4)-LTD(4) and urinary LTE(4)/creatinine in the stable phase in the ASA group were significantly greater than those in the HDM group. CONCLUSION: Our results indicated that HDM-provoked asthma is associated with overproduction of LT with an antigen-antibody reaction, while AIA is associated with overproduction of LT with a shift to the 5-lipoxygenase series of the arachidonate cascade. LTRA may be useful against both types of asthma through inhibition of LT activity and eosinophilic inflammation of the airways.     

Eotaxin level in induced sputum is increased in patients with bronchial asthma and in smokers

BACKGROUND: Airway eosinophilia is one of the hallmarks of asthma. Eotaxin may play an important role in eosinophil recruitment. OBJECTIVES: To examine the relationship between eotaxin levels in the sputum and eosinophilic inflammation. METHODS: The sputum was obtained from 11 non-smokers, 14 smokers and 13 asthmatic patients using a sputum induction method. Eotaxin and interleukin (IL)-5 levels in the sputum were determined by ELISA and immunocytochemical analysis. RESULTS: Asthmatic patients had eosinophilia and smokers showed neutrophilia in their sputum. The eotaxin level in the sputum was significantly higher in smokers (median 412.5, range 91.1-872.2 pg/ml) and asthmatic patients (351.0, 185.0-928.0 pg/ml) compared with non-smokers (123.2, 0-369.0 pg/ml; both p < 0.05). IL-5 was detected in the sputum of 1 non-smoker, none of the smokers and 4 asthmatic patients. The percentage of eotaxin-positive cells was higher in smokers and asthmatic patients than in non-smokers, but the percentage of IL-5-positive cells was significantly higher only in asthmatic patients (p < 0.05). CONCLUSIONS: These findings suggest that the elevated eotaxin level in the sputum does not always accompany the increase in eosinophils, and cooperation with another cytokine such as IL-5 may be required for the recruitment of eosinophils.     

Exhaled nitric oxide and sputum eosinophil markers of inflammation in asthmatic children.

Exhaled nitric oxide and eosinophil sputum markers are considered noninvasive ways in which to evaluate airway inflammation in asthma. The aim of this study was to evaluate the relationships between these methods of evaluation in asthmatic children. In a cross-sectional study of 25 mild-moderate asthmatic children (aged 6-13 yrs, 10 patients on inhaled steroids) exhaled NO was measured along with induced sputum by inhalation of hypertonic saline solution. The sputum was processed for eosinophil count and eosinophil cationic protein (ECP) determination. Serum ECP and lung function (forced expiratory volume in one second (FEV1)) were also measured. A significant correlation was observed between exhaled NO and sputum eosinophils (r = 0.438, p = 0.032) as well as between sputum eosinophils and sputum ECP (r = 0.532, p<0.01). No correlation was observed among exhaled NO and serum ECP, sputum ECP, FEV1, respectively. Furthermore no correlation was observed between sputum eosinophil (%) and serum ECP and between sputum eosinophils and FEV1. There was no correlation among the investigated parameters in children treated with inhaled steroids. In conclusion, exhaled NO and sputum eosinophil counts are concordant in evaluating the degree of airway inflammation in patients with mild-to-moderate asthma. However, the association between these two noninvasive markers becomes less in steroid treated patients.     

不同控制水平的支气管哮喘患者气道炎症与外周气道功能状态的研究

目的 了解不同临床控制水平的支气管哮喘(简称哮喘)患者的气道炎症状况及外周气道功能,观察哮喘患者诱导痰中的炎症指标能否反映外周气道功能的改变.方法 收集在北京朝阳医院就诊的哮喘患者66例,分为控制组(21例)、部分控制组(28例)、未控制组(17例)以及健康对照组(20名).所有受试者第1天进行哮喘控制测试(ACT)评分,行脉冲振荡肺功能检测气道阻力及肺功能基础值、诱导痰细胞计数和分类以及嗜酸粒细胞阳离子蛋白(ECP)浓度测定;第2天测定呼出气一氧化氮浓度(FE_(NO)),若所测得的FEV_1≥70%预测值则行乙酰甲胆碱激发试验,当气道阻力升高至基础阻力2倍或乙酰甲胆碱达到最大浓度时终止试验,3 min后行气道阻力及通气功能检测;然后嘱受试者行5次深吸气后再复测气道阻力及通气功能.比较4组受试者诱导痰细胞计数和分类、诱导痰中ECP浓度、FE_(NO)水平与ACT评分间的相关性;观察激发后以及深吸气后外周气道阻力的变化与ACT评分、诱导痰中嗜酸粒细胞(EOS)计数、痰ECP水平及FE_(NO)间的关系.结果 (1)哮喘患者诱导痰EOS计数、ECP浓度以及FE_(NO)随着控制水平的下降逐渐增高,且诱导痰EOS计数、ECP浓度均与ACT评分呈负相关(r值分别为-0.43和-0.56,均P<0.01).(2)在健康对照组,乙酰甲胆碱激发后中心气道阻力(R_(20))、外周气道阻力(R_5-R_(20))增高程度间比较差异无统计学意义(F=3.472,P>0.05),而在控制组及部分控制组激发试验后外周气道的反应强于中心气道(F值分别为18.09和14.14,均P<0.01),但激发后R_5-R_(20)的变化与ACT评分、诱导痰EOS计数、ECP、FE_(NO)水平间无相关性.(3)深吸气后,健康对照组R_5-R_(20)由(0.13±0.14)kPa·L~(-1)·s~(-1)降至(0.08±0.09)kPa·L~(-1)·s~(-1)(t=2.84,P<0.05),而控制组、部分控制组R_5-R_(20)分别由(0.24±0.15)、(0.31±0.18)kPa·L~(-1)·s~(-1)>增至(0.30±0.16)、(0.39±0.17)kPa·L~(-1)·s~(-1)(t值分别为3.90、4.68,均P<0.01),但相关分析显示,深吸气后R_5-R_(20)的变化与ACT评分、诱导痰EOS计数、ECP、FE_(NO)水平无相关性.结论 即使在控制水平的哮喘患者,仍存在气道嗜酸粒细胞炎症,且该炎症状态随着疾病控制水平的降低而逐渐加重;哮喘患者深吸气所致的外周气道舒张作用消失;检测诱导痰中的炎症指标并不能反映外周气道功能的改变.     

Serum measurement of eosinophil cationic protein in the management of asthma

Asthma is a disease characterized by chronic eosinophilic inflammation of the airways. Serum eosinophil cationic protein (ECP) has been increasingly used as a noninvasive inflammatory marker in asthma. The serum ECP level seems to reflect, although indirectly, the intensity of ongoing eosinophilic inflammation of the airways and respond sensitively to intervention, whereas it is unlikely to be useful for establishing the diagnosis of asthma in an individual patient. Monitoring of serum ECP could be of utility in the long-term follow-up of asthmatic patients. However, further longitudinal studies are required to establish the role of serum ECP measurement in the treatment modulation in asthma.     

支气管哮喘豚鼠模型支气管肺组织血管细胞粘附分子和Eotaxin的表达及调控

目的　研究支气管哮喘 (简称哮喘 )时嗜酸细胞选择性粘附分子———血管细胞粘附分子(VCAM 1)和趋化因子Eotaxin及转录调控因子核因子 (NF) κB、活化蛋白 1(AP 1)在大、小气道及肺组织中的表达 ,探讨嗜酸细胞趋肺的机制。方法　以卵蛋白致敏法制备豚鼠哮喘模型 ,3 6只豚鼠分设 6组 ,每组 6只。对照组 (F组 )、哮喘 1天组 (A组 )、哮喘 4天组 (B组 )、哮喘 14天组 (C组 )、地塞米松注射组 (D组 )、布地奈德吸入组 (E组 )。用免疫组化法分别测定VCAM 1、Eotaxin、NF κB和AP 1在段支气管及细支气管肺泡区的蛋白表达 ,用逆转录 聚合酶链反应 (RT PCR)法测定肺组织匀浆VCAM 1及Eotaxin的mRNA表达 ,电泳迁移实验 (EMSA)测定肺组织匀浆NF κB及AP 1的DNA结合活性。结果各模型组显示 ,与段支气管相似 ,细支气管肺泡区VCAM 1、Eotaxin的蛋白C组分别为 (2 6 3± 3 2、89 0± 8 6)及mRNA相对表达量与F组 (11 2± 3 7、5 0± 4 0 )比较 (P <0 0 1、0 0 0 1) ;NF κB及AP 1的蛋白相对表达量 (C组分别为 179± 7、76± 6) ,与F组 (3 6± 3、2 7± 5 )比较 (P <0 0 1、0 0 0 1) ,且与VCAM 1、Eotaxin呈显著正相关 (r分别 =0 919、0 965　 0 90 4、0 881,P均 <0 0 0 1) ;以上 4项指标在B、C组段支气管及     

The Significance of Sputum ECP Levels in Differential Diagnosis of Asthma in Children

Asthma and chronic bronchitis are diseases that may present similar symptoms. Because eosinophil granulocytes play an important role in the pathogenesis of asthma, the assessment of eosinophilic inflammation may be useful in making a differential diagnosis of these two diseases. This study investigated the serum and sputum eosinophil cationic protein (ECP) levels in children with asthma and chronic bronchitis and compared them with controls. Fifty asthmatic patients being treated for mild or moderately severe asthma at a university hospital were enrolled in the study. Fifteen children with symptoms of cough and sputum production lasting more than 3 months were studied in the chronic bronchitis group and 25 healthy children were included in the control group. Asthmatic patients were divided into subgroups according to the presence or absence of asthmatic exacerbations. Clinical evaluation and determination of ECP concentrations in serum and sputum were performed for each group. In-creased activity of eosinophils was found in patients with asthma as assessed by high serum ECP (mean 21.44 ± 20.33 ug/L) and sputum ECP (mean 129.65 ± 125.01 u.g/L) levels. In patients diagnosed with chronic bronchitis, serum ECP levels were similar to those of the control group (mean serum ECP 11.04 44 10.23 ug/L and 12.07 ± 6.12 ug/L, respectively). More importantly, sputum ECP levels of the chronic bronchitis group were much lower (mean 53.36 ± 55.43 ug/L) than those in patients with asthma (mean 129.65 ± 125.01 ug/L). The serum and sputum ECP levels of the asthmatic patients who were evaluated during an acute exacerbation were also higher than those in the chronic bronchitis group. Sputum ECP levels may be helpful in the differential diagnosis of asthma and chronic bronchitis in children.     

Effects of hydrofluoroalkane and dry powder-formulated corticosteroids on sputum inflammatory markers in asthmatic patients

BACKGROUND

Inhaled corticosteroids are powerful drugs that can suppress airway inflammation in asthmatic patients. Deposition of most of the inhaled corticosteroid occurs mainly in the central airways. However, a new hydrofluoroalkane formulation of beclomethasone dipropionate (HFA-BDP) is preferentially deposited in the distal airways. Inflammatory characteristics of induced sputum have been shown to differ in samples collected early after sputum induction compared with later.

OBJECTIVE

To compare the effects of HFA-BDP and budesonide in a dry powder inhaler (DPI-BUD) on inflammatory cells and inflammatory cytokine expression in early and late induced sputa compared with placebo.

METHODS

Seventeen patients with mild, intermittent bronchial asthma were randomly assigned to two treatment groups: eight patients received HFA-BDP and nine patients received DPI-BUD. Each patient was treated with one of the active treatments and placebo (for four weeks), with a two-week washout interval in between. Inflammatory cells and expression of interleukin (IL)-4 and IL-5 were measured in early and late induced sputa before and after active treatment, as well as before and after placebo treatment using immunocytochemistry and in situ hybridization.

RESULTS

Compared with placebo, eosinophils were significantly reduced in both early and late induced sputa after HFA-BDP treatment (P<0.05), whereas DPI-BUD had a significant effect only on early induced sputum. Both HFA-BDP and DPI-BUD decreased IL-4 expression in early and late induced sputa, but the effect was more prominent with HFA-BDP. IL-5 expression was reduced in both early and late induced sputa after HFA-BDP treatment. DPI-BUD significantly decreased IL-5 expression in early but not in late induced sputum. The number of lymphocytes was not altered by either treatment.

CONCLUSIONS

HFA-BDP reduced eosinophilic inflammation and T helper 2-type cytokine expression in both early and late induced sputa, whereas the effect of DPI-BUD on inflammation was predominantly demonstrated in early induced sputum.     

哮喘和慢性阻塞性肺疾病患者糖皮质激素治疗前后痰液炎性标志物 …

探讨哮喘和慢性阻塞性疾病患者吸入糖皮质激素治疗后痰液中细菌因子和嗜酸细胞阳离子蛋白浓度及糖皮质激素对其影响。方法采用荧光酶联免疫法检测糖皮质激素治疗前后痰液中白细胞介素（ＩＬ）－５、ＩＬ－８、ＥＣＰ浓度及嗜酸细胞和嗜中性粒细胞计数。     

Usefulness of HFA-BDP for adult patients with bronchial asthma: randomized crossover study with fluticasone.

In this randomized crossover study, 22 adult patients with moderate-to-severe persistent bronchial asthma were assigned to one of two groups. Patients in group 1 were administered fluticasone dry powder inhaler (DPI) for 8 weeks followed by a 2-week washout period, then hydrofluoroalkane-beclometasone dipropionate (HFA-BDP) for 8 weeks. After a further 2-week washout, they were again administered fluticasone DPI for 8 weeks. Patients in group 2 were assigned HFA-BDP followed by fluticasone PII and finally HFA-BDP over the same time periods. In both groups, no significant difference was observed in use of beta2-agonists and symptom score between the treatment periods; however, markers of pulmonary function were significantly higher when on HFA-BDP versus fluticasone DPI. Significant increases of morning peak expiratory flow (PEF) (p < 0.01), forced expiratory volume in 1 second (FEV1.0) (p < 0.01), V50 (p < 0.05), and V25 (p < 0.01) were observed at 18 weeks in group 1, whereas there were significant decreases of V50 (p < 0.05) at 18 weeks in group 2. No significant difference was noted in circulating eosinophil count and serum ECP between the 2 treatments; however, ECP in induced sputum and nitric oxide in expired gas were significantly lower (p < 0.05 and < 0.01, respectively) when on HFA-BDP versus fluticasone DPI. HFA-BDP might be delivered to small airways more effectively than fluticasone DPI.     

嗜酸细胞趋化因子在哮喘、慢性支气管炎患者诱导痰中的表达及其与气道炎症的关系

目的　探讨嗜酸细胞趋化因子 (eotaxin)在嗜酸细胞性气道炎症和气流阻塞发生中的作用。方法　收集单纯型慢性支气管炎 (A组 )、慢性喘息性支气管炎 (B组 )、支气管哮喘 (C组 )急性发作期患者各 11例和健康对照者 (D组 ) 7名。用夹心法酶联免疫吸附测定 (ELISA)诱导痰上清液中eotaxin浓度。结果　B组 [(2 3 4± 5 8) % ]、C组 [(2 0 7± 3 1) % ]诱导痰嗜酸细胞占白细胞百分比(EOS/Leu % )分别与A组 [(11 6± 2 6 ) % ]、D组 [(1 2± 0 3) % ]比较 ,差异有显著性 (P均 <0 0 0 1) ;B组eotaxin浓度 [(0 2 90± 0 170 )g/L]与A组 [(0 12 0± 0 0 2 0 )g/L]比较 ,差异有显著性 (P =0 0 0 7) ;B组与D组 [(0 0 30± 0 0 5 0 )g/L]比较 ,差异也有显著性 (P <0 0 0 1) ,C组 [(0 2 40± 0 140 )g/L]与A组比较 ,差异有显著性 (P =0 0 18) ;C组与D组比较差异也有显著性 (P =0 0 0 1) ,但B组EOS/Leu %和eotaxin浓度与C组比较差异均无显著性 (P =0 196、0 490 )。B、C组EOS/Leu %与一秒钟用力呼气容积占预计值百分比 (FEV1占预计值 % )呈负相关 (r分别 =- 0 92 1、- 0 6 6 3,P <0 0 0 1或 0 0 2 6 ) ;C组eotaxin浓度与FEV1占预计值 %呈负相关 (r =- 0 6 43,P =0 0 33)。B、C组eotaxin浓度与E     

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.     

诱导痰炎性标志物检测在判定哮喘严重程度和鉴别诊断中的应用

目的探讨哮喘患者诱导痰中嗜酸性粒细胞(Eos)和嗜酸细胞阳离子蛋白(ECP)与其哮喘严重程度的关系及鉴别诊断价值。方法选择武汉大学人民医院2002-07~2004-06的门诊哮喘患者59例,检测其肺功能并分别采用瑞氏染色及荧光免疫法检测高渗盐水诱导痰中Eos数量和ECP质量浓度。选择同期20例慢性阻塞性肺疾病患者和10名健康人作为对照。结果哮喘患者诱导痰中Eos数量与患者第1秒用力呼气容积/用力肺活量(FEV1%)呈显著负相关(r=-0·65,P<0·01);ECP质量浓度与患者FEV1%呈显著负相关(r=-0·59,P<0·01)。随病情加重哮喘患者诱导痰中Eos数量和ECP质量浓度逐渐升高,且轻度、中度和重度患者之间比较差异有统计学意义(P<0·05)。哮喘患者诱导痰中Eos数量和ECP质量浓度显著高于慢性阻塞性肺疾病组和健康组(P<0·01)。结论诱导痰中Eos和ECP质量浓度可了解哮喘的严重程度,并有助于与慢性阻塞性肺疾病的鉴别。     

Kinetics of allergen-induced airway eosinophilic cytokine production and airway inflammation.

Airway eosinophilia is the hallmark of asthma exacerbation. Coordination of cytokines such as interleukin (IL)-5, eotaxin and regulated on activation, normal T-cell expressed and secreted (RANTES) seem to be necessary for eosinophil extravasation including adhesion, chemotaxis, and activation. The purpose of this study was to characterize both the kinetics of allergen-induced inflammatory cell recruitment to the airways and cytokines selective for eosinophil chemotaxis, activation, or resolution. Eight atopic asthmatic individuals demonstrating a dual response to inhaled allergen completed a diluent-controlled crossover study. The subjects showed significant allergen-induced early and late airway asthmatic responses (p < 0.001), and an increase in the number of sputum eosinophils and metachromatic cells (p < 0.05). The number of eosinophils immunopositive for IL-5, eotaxin, and RANTES increased 7 h after allergen inhalation (p < 0.05), coincident with the peak number of activated eosinophils. Sputum cells immunopositive for IL-10 decreased significantly following allergen challenge (p = 0. 04), and correlated negatively with sputum eosinophils (r = -0.34, p = 0.02). This study shows that allergen-induced increases in sputum eosinophils are associated with the presence of cytokines specific for the activation and chemotaxis of eosinophils, and suggests that cooperation of eosinophilic cytokines may be important for the accumulation and regulation of activated eosinophils at the site of allergic inflammation.     

Airway inflammation and cellular stress in noneosinophilic atopic asthma

STUDY OBJECTIVES: It has been suggested that patients with noneosinophilic asthma (NEA) show increased numbers of sputum neutrophils and a lack of response to therapy with corticosteroids, which are features that are commonly related to COPD. The aim of our study was to test the hypothesis that airway inflammation in NEA patients is different from that seen in patients with eosinophilic asthma (EA) and is similar to COPD. DESIGN: Sputum cellular stress markers and neutrophilic and eosinophilic fluid-phase mediators were analyzed in asthma and COPD patients. NEA patients were identified based on a sputum eosinophil count of < or = 2.2% of the total nonsquamous cell count, and were compared to EA and COPD patients. SETTING: University Hospital of Heraklion, Department of Thoracic Medicine. PATIENTS: A total of 37 atopic asthmatic patients and 25 patients with COPD. MEASUREMENTS: Sputum cell counts, cellular expression of heme oxygenase-1, inducible nitric oxide synthase, and nitrotyrosine, and sputum levels of eosinophilic cationic protein (ECP), myeloperoxidase (MPO), interleukin-8, and granulocyte macrophage colony-stimulating factor. RESULTS: A total of 17 asthmatic patients (46%) belonged to the NEA group and 20 patients (54%) to the EA group. Patients with NEA showed no difference in neutrophil counts, fluid-phase mediators, or cellular stress markers compared to patients with EA. Compared to COPD patients, NEA patients showed the following significant differences: lower total cell counts (p < 0.03); lower neutrophil counts (p < 0.01); lower nitrotyrosine positive cell counts (p < 0.003); lower ECP levels (p < 0.005); lower MPO levels (p < 0.000); higher lymphocyte counts (p < 0.01); and higher macrophage counts (p < 0.03). CONCLUSIONS: Despite low eosinophil counts, airway inflammation in NEA patients may share common features with that in EA patients but is distinct from COPD. Larger studies are needed to investigate further the clinical and inflammatory characteristics of NEA before we are able to categorize asthma patients into those with or without eosinophilic inflammation.