胃癌患者血清可溶性白细胞介素－2受体初步研究

应用双抗体夹心ＥＬＩＳＡ法对３０例胃癌患者血清ｓＩＬ－２Ｒ水平进行测定。结果表明，胃癌患者血清ｓＩＬ－２Ｒ水平明显高于正常对照（Ｐ＜０．０１）及慢性良性胃病患者（Ｐ＜０．０５）；Ⅲ－Ⅳ期患者血清ｓＩＬ－２Ｒ水平显著高于Ⅰ－Ⅱ期患者（Ｐ＜０．０５）；低度分化者较中度分化者ｓＩＬ－２Ｒ水平明显升高（Ｐ＜００１）；贲门癌患者ｓＩＬ－２Ｒ水平较胃窦（体）癌者高，但未达到统计学差别（Ｐ＞０．０５）；胃癌根治术后一周血清ｓＩＬ－２Ｒ水平较术前升高（Ｐ＜０．０１），术后二周血清ｓＩＬ－２Ｒ较术前明显降低（Ｐ＜０．０１），与正常人相比无明显差异（Ｐ＞００５）。结果提示血清ｓＩＬ－２Ｒ测定可作为胃癌患者病情判断、观察疗效及估价预后新的生物学指标。     

囊虫病患者 IL-2 及 sIL-2R 测定

应用四甲基偶氮唑盐（ＭＴＴ）法检测了３１例未经治疗的囊虫病患者外周血单个核细胞（ＰＢＭＣ）产生ＩＬ－２水平，同时用ＥＬＩＳＡ双抗体夹心法测定其血清中ｓＩＬ－２Ｒ水平，以３０例健康人作对照。实验结果显示，囊虫病患者ＰＢＭＣ产生ＩＬ－２水平明显低于正常人（Ｐ＜０．０５），而患者血清中ｓＩＬ－２Ｒ水平明显高于正常人（Ｐ＜０．０１）。本实验提示囊虫病患者外周血中低水平的ＩＬ－２及血清中高水平的ｓＩＬ－２Ｒ可能与患者细胞免疫功能低下有关。     

过敏性哮喘患者细胞因子对IgE生成机制的探讨

对３０例过敏性哮喘患者发作期和缓解期及３０例健康成年人的外周血，采用ＥＬＩＳＡ双抗体夹心法，测定血清ＩｇＥ，可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）和白细胞介素－４（ＩＬ－４）水平，生物学方法测定血清ＩＬ－２水平和３Ｈ－ＴｄＲ掺入法定量测定血清ＩＬ－６。结果：过敏性哮喘患者发作期血清ＩｇＥ、ｓＩＬ－２Ｒ、ＩＬ－４和ＩＬ－６水平明显升高，与缓解期和对照组有明显差异（Ｐ＜０．０１），而发作期血清ＩＬ－２水平明显下降，与缓解期和对照组有明显差异（Ｐ＜０．０１），且血清ＩｇＥ分别与ｓＩＬ－２Ｒ和ＩＬ－４水平有明显正相关（Ｐ均＜０．０１），与ＩＬ－２水平有明显负相关（Ｐ＜０．０１）。说明ＩｇＥ合成增加是过敏性哮喘的关键，细胞因子有促进Ｂ细胞合成ＩｇＥ的作用，并且直接参与过敏性哮喘气道炎症的形成。     

SLE患者血清中白细胞介素-2受体和睾酮水平的变化

选择５９例系统性红斑狼疮（ＳＬＥ）患者和２０例正常人,检测白细胞介素－２受体（ｓＩＬ－２Ｒ）和睾酮（Ｔｃ）水平。用疾病活动评分（ＳＬＡＭ）判断疾病活动性,并对ｓＩＬ－２Ｒ和Ｔｃ水平的变化及两者回的相关性进行分析。结果ＳＬＥ患者血清ｓＩＬ－２Ｒ水平显著高于正常人（Ｐ〈０．００１）,Ｔｅ显著低于正常人（Ｐ〈０．００１）,ＳＬＥ活动期ｓＩＬ－２Ｒ水平与ＳＬＡＭ指数显著高于非活动期（Ｐ〈０．０１）,Ｔｅ显     

老年高血压病患者血清可溶性白介素2受体与临床分期相关性的观察

目的探讨老年高血压病患者血清中可溶性白介素－２受体（ｓＩＬ－２Ｒ）的水平，并比较老年高血压病不同临床分期的ｓＩＬ－２Ｒ变化。方法采用双抗体夹心（ＥＬＩＳＡ）法，对４６例老年高血压病人血清ｓＩＬ－２Ｒ的水平，与３０例正常人（ＮＣ）进行检测对比，并对其老年高血压病患者不同临床分期的ｓＩＬ－２Ｒ的水平进行观察。结果老年高血压病患者ｓＩＬ－２Ｒ水平明显高于对照组（Ｐ＜０．０１）；且随临床分期的增加而增高（Ｐ＜０．０１），有明显的正相关性。结论老年高血压病患者体内存在有免疫功能系乱，导致ｓＩＬ－２Ｒ的增高。ｓＩＬ－２Ｒ可作为临床观察老年高血压病的细胞免疫功能及病情判定的有效指标。     

胃癌患者血清可溶性白细胞介素—2受体初步研究

应用双抗体夹心ＥＬＩＳＡ法对３０例胃癌患者血清ＳＩＬ－２Ｒ水平进行测定，结果表明，胃癌患者血清ＳＩＬ－２Ｒ水平明显高于正常对照（Ｐ＜０．０１）及慢性良性胃病患者（Ｐ＜０．０５）；Ⅲ－Ⅳ期患者血清ＳＩＬ－２Ｒ水平显著高于Ｉ－ＩＩ期患者（Ｐ＜０．０５）；低度分化者较中度分化者ＳＩＬ－２Ｒ水平明显升高（Ｐ＜０．０１）；贲门癌患者ＳＩＬ－２Ｒ水平较胃窦（体）癌者高，但未达到统计学差别（Ｐ＞０．０５）；胃癌     

IFN-α对慢性乙型肝炎患者血清IL-2和SIL-2R水平的影响

目的 探讨ＩＦＮ－α对慢性乙型肝炎（乙肝）患者血清ＩＬ－２、ＳＩＬ－２水平的影响。方法 分别采用放射免疫法（ＲＩＡ）和双抗体夹心ＥＬＩＳＡ法检测３０例慢性乙肝患者干扰素治疗前后血清ＩＬ－２、ＳＩＬ－２Ｒ水平，以３０例健康献血员作为对照。结果慢性乙肝患者血清ＩＬ－２和ＳＩＬ－２Ｒ水平明显高于对照组（Ｐ〈０．０５）。干扰素治疗后，应答者４３％，非应答者５７％。应答者ＩＬ－２水平明显高于非就答者（Ｐ〈０     

老年肺部疾病患者血清sIL-2R水平和T淋巴细胞亚群的研究

目的：探讨老年肺疾患者血清可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）浓度和Ｔ细胞亚群的关系。方法采用双抗体夹心ＥＬＩＳＡ法和碱性磷酸酶抗碱性磷酸酶（ＡＰＡＡＰ）法。结果肺疾患各组ｓＩＬ－２Ｒ水平升高均高于对照组（Ｐ〈０．００１）。其中以肺癌组ｓＩＬ－２Ｒ水平升高最显著,与肺良性疾病组比较亦有显著差异（Ｐ〈０．００１）。肺疾患组的ＣＤ４低于对照组（Ｐ〈０．０５）。结论ｓＩＬ－２Ｒ和Ｔ细胞亚群可作为肺疾     

胃癌患者血清可溶性IL—2受体T细胞亚群及NK细胞的临床 …

目的 较全面地观察胃癌虱的细胞免疫功能,为胃癌的预测,诊断,病情估计及免疫治疗提供依据。方法 应用酶联免疫双抗夹心法（ＥＬＩＳＡ）及碱性磷酸酶抗碱性磷酸酶（ＡＰＡＡＰ）桥联酶标法,检测３４例胃癌患者与对照者血清可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）,Ｔ淋巴细胞亚群及自然杀伤（ＮＫ）细胞。结果 胃癌患者ｓＩＬ－２Ｒ水平明显高于对照组,Ⅲ,Ⅳ期高于Ⅰ,Ⅱ期（Ｐ〈０．０１）;ＣＤ４,ＣＤ８,ＣＤ４／Ｃ     

肝硬化和肝细胞癌患者血清IL-2、sIL-2R、IL-6、T细胞亚群的变化及相互关系

目的研究肝硬化和肝细胞癌患者ＩＬ－２、ｓＩＬ－２Ｒ、ＩＬ－６、Ｔ细胞亚群的变化和相互关系。方法分别采用双抗体夹心ＥＬＩＳＡ法、ＡＢＳ－ＥＬＩＳＡ法和红细胞花环实验,对４６例肝炎肝硬化和肝癌进行了ＩＬ－２、ＩＬ－６、ｓＩＬ－２Ｒ和Ｔ细胞亚群的测定,并与６６例健康献血员进行了对照。结果肝炎肝硬化（ＬＣ）、肝细胞癌（ＨＣＣ）患者血清ＩＬ－２、ＣＤ＋４／ＣＤ＋８水平明显低于正常对照（ＮＣ）组（Ｐ＜００１）,而ＩＬ－６、ｓＩＬ－２Ｒ水平明显升高,ＨＣＣ组的平均ＩＬ－６水平高出正常１０倍以上,较肝硬化组明显升高（Ｐ＜００１）。在肝炎肝硬化和肝癌患者均发现ＩＬ－２与ＣＤ＋４／ＣＤ＋８比值、ＩＬ－６与ｓＩＬ－２Ｒ正相关,ＩＬ－６与ＣＤ＋４／ＣＤ＋８比值显著负相关,而与ＩＬ－２无相关关系。结论肝炎肝硬化和肝细胞癌患者存在免疫功能紊乱和低下、淋巴因子网络失衡,这与其病理生理机制有关,也为临床上ＬＣ、ＨＣＣ应用ＩＬ－２治疗提供了理论依据。ＩＬ－６的显著增高有助于ＨＣＣ的早期诊断     

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.     

The ECP/Eo Count Ratio in Children with Asthma

We hypothesized that the serum eosinophil eationic protein (ECP) concentration to peripheral blood eosinophil count ratio (ECP/Eo ratio), reflecting active eosinophils, could better correlate with asthma severity in asthmatic patients, than each of these parameters alone. One hundred twenty children with mild to moderate persistent stable asthma were included into the study. At the first visit, previous asthma medications were withheld and patients were administered β‐2 agonists “as needed.” At the second visit peripheral blood eosinophil count, serum ECP, sIL‐2R, and sICAM‐1 were measured, and spirometry and histamine challenge tests were performed. During the study, patients filled daily diary cards to assess symptoms score. One hundred seventeen patients completed the study. The univariate logistic regression analysis showed that asthma severity is related to PC20H, ECP, ECP/Eo ratio, sIL‐2R, and sICAM‐1. In general, patients with higher level of ECP, ECP/Eo ratio, sIL‐2R, sICAM‐1 and with lower PC20H exhibited the higher risk of moderate asthma. Multivariate regression analysis showed that only PC20H and ECP/Eo ratio were the best predictors of asthma severity; higher PC20H (1 mg/mL change) slightly decrease (OR = 0.656; 95% CI: 0.44–0.99) and higher ECP/Eo ratio (0.1 pg/cell change) increase (OR = 1.84; 95% CI: 1.02–3.34) a risk of moderate asthma. These data show that the ECP/Eo ratio is a better and more useful marker than ECP or peripheral blood eosinophil count separately in assessing asthma in children.     

Reduction in bronchodilation following a deep inhalation is poorly related to airway inflammation in asthma.

In patients with bronchial asthma, forced expiratory flows are differently sensitive to a previous volume history. A reduced ability of a deep inhalation (DI) to dilate obstructed airways has been hypothesized to be a physiological marker for the degree of airway responsiveness and to relate to the presence and magnitude of inflammation in the lung, even in mild stable asthma. However, there are at present doubts as to whether functional changes could be used as a substitute for airway inflammation studies. In order to investigate the interrelations among airway inflammation, bronchial hyperresponsiveness and effects of volume history, 58 consecutive asthmatics with mild to moderate asthma were studied. The effects of DI were assessed as the isovolumic ratio of flows from forced expiratory manoeuvres started from maximal (M) or partial (P) lung inflation. Airway inflammation was assessed by using induced sputum. Sputum was analysed for total and differential cell counts, and levels of eosinophil cationic protein (ECP) which reflects eosinophil activation. Airway responsiveness was assessed as the provocative concentration of histamine which caused a 20% fall in forced expiratory volume in one second (FEV1) from control (PC20). The M/P ratio was significantly related to ECP (r=-0.31, p<0.03) and eosinophils (r=-0.29, p<0.03), FEV1/vital capacity (VC) (r=0.32; p<0.01), clinical score (r=-0.33; p<0.03) and age (r=-0.41; p<0.0001). In a stepwise multiple regression analysis including age, score, baseline lung function, ECP, number of eosinophils and the response to beta2-agonist, age (p<0.037) predicted a small amount of the variance in M/P ratio (r2=0.12). It is concluded that volume history response is substantially independent of both sputum outcomes (inflammatory cell number and eosinophil cationic protein) and bronchial hyperresponsiveness; rather it seems to be associated with anthropometric characteristics. Functional aspects do not provide information on eosinophilic, probably central, airway inflammation.     

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.     

Comparison of exhaled nitric oxide,serum eosinophilic cationic protein,and soluble interleukin-2 receptor in exacerbations of pediatric asthma

The hypotheses tested in this study were that during acute asthma exacerbations (1) exhaled nitric oxide concentrations [eNO] are a more sensitive, noninvasive indicator of asthma disease activity than serum markers of inflammation such as eosinophil cationic protein (ECP) or soluble interleukin 2 receptor (sIL2R), and (2) elevated [eNO] are reduced after treatment with glucocorticoids (GC). Peak eNO levels were measured by chemiluminescence during slow expiration. Seven asthmatic subjects (mean age 11 yrs; mean morning FEV1 65% predicted) receiving inhaled GC, and with no radiographic evidence of acute sinusitis, were studied before and after a course of oral GC. Measurements of [eNO], ECP and sIL2R levels, and FEV1% were obtained before and after a course of GC. Six atopic nonasthmatic subjects (mean age 12 years; mean FEV1 94% predicted) and seven normal subjects (mean age 13 years; mean FEV1 100% predicted) were studied. The mean peak [eNO] level (parts per billion: ppb) for the asthma subjects before treatment (52 ± 5 ppb SEM) was greater than the value for both nonasthmatic atopic and normal subjects (16 ± 2 ppb and 14 ± 2 ppb SEM, respectively; P < 0.0001). There was no significant difference in ECP or sIL2R values between asthmatic subjects and either atopic or normal subjects (P > 0.05). Baseline pre-GC treatment ECP levels in the asthmatic subjects were significantly higher (P < 0.002) than post-GC treatment values. The mean peak [eNO] level in the asthmatic subjects declined after oral GC treatment to 14 ± 1 ppb (P < 0.0002) and was less than 2 ppb different from either control group (P > 0.75). We conclude that [eNO] is a more sensitive marker of asthma disease activity than ECP and sIL2R levels. In addition, [eNO] appears to be a more useful indicator of the beneficial response to GC therapy than these other measurements in pediatric asthma. Pediatr. Pulmonol. 1997; 24:305–311. © 1997 Wiley-Liss, Inc.     

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.     

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。     

Bronchodilator Responses after Methacholine and Adenosine 5'-Monophosphate (AMP) Challenges in Children with Asthma: Their Relationships with Eosinophil Markers

Background. Bronchodilator responsiveness (BDR) and eosinophilic inflammation are characteristic features of asthma. Objective. The aim of this study was to compare the relationships of BDR after methacholine challenge or adenosine 5'-monophosphate (AMP) challenge to blood eosinophil markers in children with asthma. Methods. Methacholine and AMP challenges were performed on 69 children with mild intermittent to moderate persistent asthma. BDR was calculated as the change in forced expiratory volume in 1 second, expressed as percentage change of the value immediately after the each challenge and the value after inhalation of salbutamol. Serum total IgE levels, blood eosinophil counts, and serum eosinophil cationic protein (ECP) levels were determined for each subject. Results. A positive relationship between serum total IgE levels and BDR was found only after the AMP challenge (R(2) = 0.345, p = .001) rather than after the methacholine challenge (R(2) = 0.007, p = .495). Peripheral blood eosinophil counts correlated more significantly with BDR after AMP challenge (R(2) = 0.212, p = .001) than BDR after methacholine challenge (R(2) = 0.002, p = .724). Both BDR after methacholine challenge (R(2) = 0.063, p = .038) and BDR after AMP challenge (R(2) = 0.192, p = .001) were significantly correlated with serum ECP levels. Conclusion. BDR after AMP challenge may be more closely related to eosinophilic inflammation, compared with that after methacholine challenge.     

Clinical evaluation of tulobuterol patch in patients with mild or moderate persistent bronchial asthma-effects of long-term treatment on airway inflammation and hypersensitivity]

The tulobuterol transdermal therapeutic system (TTS) is the world's first commercially available transdermal preparation of tulobuterol, a beta-2 stimulant, that can maintain effective blood tulobuterol levels for 24 hours when applied once daily. In the present study, a total of 36 adult patients with mildly persistent (Step 2) or moderately persistent (Step 3) bronchial asthma 19 who were using inhalational steroids and 17 who were not used tulobuterol TTS for one year and underwent measurement of peak expiratory flow (PEF) once daily. Peripheral eosinophil count, serum eosinophil cationic protein (ECP) level and airway responsiveness (Dmin) were evaluated at 6 months and 1 year after the start of the study. PEF exhibited significant improvements at 6 months and 1 year in patients treated with or without inhalational steroids, while serum ECP was improved significantly only in the patients on inhalational steroids. Patients not using inhalational steroids exhibited no significant exacerbation of Dmin at either 6 months or 1 year: One-year treatment with tulobuterol TTS did not appear to cause tachyphylaxis. The significant improvements in Dmin at 6 months and 1 year in the patients using inhalational steroids suggested that inhalational steroids offer beneficial effects in controlling airway inflammation. Tulobuterol TTS is considered quite beneficial in improving quality of life (QOL) in patients with bronchial asthma because its incidence of adverse effects including palpitations and shivering is significantly lower than those of oral preparations, because of its remarkable improvement of pulmonary function and symptoms of airway obstruction without increasing airway responsiveness even after repeated use, and because it is simple to use and offers excellent clinical efficacy.