嗜酸粒细胞性支气管炎在慢性咳嗽病因分布情况及治疗对策

目的 了解嗜酸粒细胞性支气管炎(EB)的发病率,评价孟鲁司特与吸入激素(布地奈德)治疗EB的疗效与安全性.方法 对慢性咳嗽患者,遵循我国咳嗽指南慢性咳嗽诊断流程进行诊断.确诊EB患者随机分成3组,甲组为孟鲁司特治疗组,乙组为布地奈德治疗组,丙组为孟鲁司特联合布地奈德治疗组,疗程4周.比较其疗效与安全性.结果 慢性咳嗽患者467例,其中56例确诊EB患者(占12％),治疗前三组患者性别、年龄、咳嗽病史、咳嗽症状评分、诱导痰嗜酸粒细胞(Eos)比例及嗜酸粒细胞阳离子蛋白(ECP)、白三烯C4( LTC4)相比较,差异均无统计学意义(P＞0.05),三组治疗后改善咳嗽症状有效率、治疗前后外周血Eos计数差异无统计学意义(P＞0.05),三组治疗后诱导痰Eos分类、ECP、LTC4较治疗前明显降低(P＜0.01),治疗后丙组诱导痰Eos分类、ECP、LTC4较甲组、乙组降低(P＜0.05),三组间不良反应发生率差异无统计学意义(P＞0.05).结论 EB发病率较高,是慢性咳嗽的常见原因.孟鲁司特单独或联合布地奈德能改善EB咳嗽症状及降低气道嗜酸粒细胞性炎症.     

嗜酸粒细胞性支气管炎及其与支气管哮喘的关系

嗜酸粒细胞性支气管炎(EB)是慢性咳嗽的重要原因,临床上表现为慢性刺激性干咳或咳少许黏痰,诱导痰嗜酸粒细胞(Eos)增高,糖皮质激素治疗效果良好,但患者肺通气功能正常,无呼吸道高反应性(AHR),峰流速变异率正常[1]。近年来国内外研     

嗜酸粒细胞性支气管炎患者气道炎症细胞及介质特征的探讨

目的观察嗜酸粒细胞性支气管炎(EB)诱导痰和支气管肺泡灌洗液(BALF)中细胞分类和炎症介质浓度,探讨EB的气道炎症特征。方法对43例EB(EB组)患者行诱导痰检查,将20例咳嗽变异型哮喘(CVA)患者(CVA组)、16例典型支气管哮喘(哮喘组)患者和21名健康人(健康对照组)行对照诱导痰检查,并对部分EB(11例)和CVA患者(10例)行支气管肺泡灌洗(BAL)。观察检测诱导痰、BALF中的细胞分类、嗜酸粒细胞阳离子蛋白(ECP)、白三烯C4(LTC4)和组胺的浓度。结果EB组患者诱导痰中嗜酸粒细胞(EOS)百分比为0.1130±0.1470,CVA组为0.1900±0.1800,哮喘组为0.3860±0.2670,与健康对照组(0.0020±0.0050)比较差异有统计学意义(P均<0.01);哮喘组与CVA组、CVA组与EB组比较差异均有统计学意义(P均<0.05);EB组BALF中EOS为0.011±0.016,CVA组为0.053±0.040,两组比较差异有统计学意义(P<0.05);EB组诱导痰中的ECP浓度为(0.62±0.66)mg/L、CVA组为(1.27±1.74)mg/L,对照组为(0.07±0.10)mg/L,3组间比较差异有统计学意义(P<0.01);CVA组诱导痰中的LTC4浓度为(0.65±0.62)μg/L,EB组为(0.39±0.61)μg/L,对照组为(0.15±0.11)μg/L,3组间比较差异有统计学意义(P分别<0.05、0.01);CVA组BALF中组胺浓度为(3.4±1.4)μg/L,EB组为(1.6±1.5)μg/L,两组比较差异有统计学意义(P<0.05)。结论EB组EOS炎症主要局限于中心气道,部分气道炎性介质水平低于CVA组。上述气道炎性特征可能是EB患者无非特异性气道高反应性的重要机制。     

嗜酸粒细胞性支气管炎

Gibson等 [1] 于1989年报道了7例慢性咳嗽患者,临床上表现为慢性刺激性干咳或咳少许黏痰,诱导痰嗜酸粒细胞增高,糖皮质激素(简称激素)治疗效果良好,但患者肺通气功能正常,尤气道高反应性、峰流速变异率正常,不符合支气管哮喘(简称哮喘)的诊断,因此将其定义为嗜酸粒细胞性支气管炎(eosinophilic bronchitis,EB).     

诱导痰细胞分类在嗜酸细胞性支气管炎诊断和治疗中的应用

目的探索诱导痰细胞分类在嗜酸细胞性支气管炎(EB)诊断和治疗中的作用。 方法回顾性分析我院门诊239例慢性咳嗽患者,依据慢性咳嗽中诊断标准,分为非EB组和EB组,分析两组诱导痰中细胞分类情况;同时给予EB患者进行8周治疗,观察经治疗后诱导痰中各细胞分类的改变情况。 结果239例慢性咳嗽患者中,非EB患者216例,占90.7%,EB患者23例,占9.3%,两组中共有121例(50.6%)患者诱导痰中嗜酸细胞百分比升高;非EB患者组细胞总计数为(4.83±2.61)×10⁶个/g、嗜酸细胞比例为(4.56±10.07)%、中性粒细胞比例为(50.32±26.12)%、淋巴细胞比例为(5.14±7.27)%、单核巨噬细胞比例为(40.30±16.70)%,EB患者组痰中细胞总计数为(5.46±3.07)×10⁶个/g、嗜酸细胞比例为(13.85±1 2.23)、中性粒细胞比例为(46.16±16.89)、淋巴细胞比例为(4.83±2.98)、单核巨噬细胞比例为(35.91±16.35),两组间EB组嗜酸细胞比例有显著的增多(P<0.05),在性别、年龄以及其余细胞成分差异无统计学意义(P>0.05);EB患者组经治疗后,痰中细胞总计数为(4.07±3.89)×10⁶个/g、嗜酸细胞比例为(2.52±3.80)%、中性粒细胞比例为(54.18±17.97)%、淋巴细胞比例为(5.59±4.33)%、单核巨噬细胞比例为(38.32±17.23)%,嗜酸细胞较治疗前有显著减少(P<0.05),其余细胞改变无显著差异(P>0.05)。 结论诱导痰细胞分类检查是诊断EB的重要方法,在其诊断和治疗过程中有着重要的指导作用,可作为EB治疗过程的监测指标。     

嗜酸粒细胞性支气管炎的研究进展

嗜酸粒细胞性支气管炎（eosinophilicbronchitis,EB）是慢性咳嗽的主要病因之一,近年来其发病率呈上升趋势,国内其发病率为17．2％。EB是以慢性咳嗽为主要症状,其特点是肺部影像学、肺功能、气道反应性、PEF日间变异率均正常,而诱导痰嗜酸粒细胞比例增高,糖皮质激素治疗有效。病因尚不清楚,发病机制有待进一步研究。本文对EB的流行病学、病因、病理表现、发病机制、诊断、治疗和预后作一综述。     

糖皮质激素对稳定期COPD患者气道炎症和通气功能的影响

目的探讨糖皮质激素对稳定期慢性阻塞性肺病（COPD）患者气道炎症和通气功能的影响.方法收集稳定期COPD患者30例,均口服强的松0.5mg/（kg＊d）.治疗前后均测肺通气功能、诱导痰细胞学及嗜酸细胞趋化因子（eotaxin）、嗜酸粒细胞阳离子蛋白（ECP）,并据舒张试验第1秒用力呼气量（FEV1）提高率将患者分为A组（FEV1提高率0～7%）和B组（FEV1提高率8%～14%）.结果 A、B两组治疗前嗜酸细胞、eotaxin、ECP差异均有显著性（P＜0.05）;治疗后两组以上指标比较差异无显著性（P＞0.05）;FEV1提高率与嗜酸细胞、eotaxin、ECP呈正相关（r分别为0.687、0.647、0.586,P均＜0.01）.结论糖皮质激素可能通过抑制气道嗜酸粒细胞聚集、趋化,从而减少eotaxin和ECP的分泌释放,减轻气道炎症,改善稳定期COPD患者肺功能.     

慢性咳嗽的临床诊断(附65例报告)

采用Irwin的慢性咳嗽解剖学诊断流程,并补充痰细胞分类检查,对65例慢性咳嗽患者行病因诊断,并针对病因予特异性治疗。结果56例确定病因,其中咳嗽变异性哮喘(CVA)14例,鼻后滴综合征(PNDS)12例,感染后咳嗽(PIC)13例,胃食管反流性咳嗽(GER)8例,药源性咳嗽8例,嗜酸粒细胞性支气管炎(EB)1例。确诊患者予特异性治疗后,50例临床控制,6例部分缓解。认为慢性咳嗽的解剖学诊断流程及诱导痰细胞分类学检查是诊断慢性咳嗽的重要手段。CVA、PNDS、PIC、GER、血管紧张素转换酶抑制剂药源性咳嗽、EB等是慢性咳嗽的主要病因。     

变应原在嗜酸粒细胞性支气管炎患者发病中的作用及机制

嗜酸粒细胞性支气管炎(EB)是引起慢性咳嗽的常见原因,主要以慢性咳嗽、痰液中嗜酸粒细胞(EOS)增多为特征,无肺通气功能的异常[1] 。我们对EB患者进行了变应原皮肤试验,并检查了气道黏膜组织的病理改变;免疫组织化学检测气道黏膜中淋巴细胞亚群CD3 、CD4、CD8,以及髓过氧化物酶(MPO)的阳性细胞,旨在探讨变应原在EB发病中的作用及其机制。对象与方法　(1)EB入选标准参照Gibson等[1] 诊断条件。选择2 0 0 1年1月～2 0 0 2年12月在山东省立医院门诊就医的符合入选标准的2 6例患者(A组) :其中男14例,女12例,平均年龄(40±15 )岁。有慢性…     

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。     

Sputum eosinophilia and bronchial responsiveness in patients with chronic non-productive cough responsive to anti-asthma therapy

OBJECTIVE: We aimed to examine airway inflammation and bronchial responsiveness in patients with chronic non-productive cough responsive to anti-asthma therapy. METHODOLOGY: Bronchial responsiveness to methacholine as well as the number of inflammatory cells and concentration of eosinophil cationic protein (ECP) in induced sputum were measured in 42 patients with chronic non-productive cough of unknown origin. Their response to bronchodilator, antiallergic and inhaled or oral glucocorticoid therapy was subsequently assessed. RESULTS: Complete remission of coughing was attained with anti-asthma therapies in 34 patients (responder group), while eight patients did not respond (non-responder group). Twenty patients in the responder group and three in the non-responder group showed bronchial hyperresponsiveness (BHR). The number of eosinophils and ECP levels in the sputum from responders with BHR were significantly increased when compared with those from non-responders and healthy subjects. These sputum measures were also significantly increased in responders without BHR when compared with healthy subjects. However, there were no significant differences in these inflammatory markers between the responders with and without BHR. The neutrophil numbers in the sputum from non-responders and responders both with and without BHR were also significantly higher than in control subjects, but there were no significant differences. CONCLUSIONS: These findings suggest that patients with chronic non-productive cough responsive to anti-asthma therapy characteristically have eosinophilic airway inflammation, which may play an important role in the development of chronic cough. Furthermore, the evaluation of not only bronchial responsiveness but also airway inflammation by examination of induced sputum may be useful for diagnosis and deciding on therapeutic strategies.     

Eosinophilic bronchitis is an important cause of chronic cough.

Eosinophilic bronchitis presents with chronic cough and sputum eosinophilia, but without the abnormalities of airway function seen in asthma. It is important to know how commonly eosinophilic bronchitis causes cough, since in contrast to cough in patients without sputum eosinophilia, the cough responds to inhaled corticosteroids. We investigated patients referred over a 2-yr period with chronic cough, using a well-established protocol with the addition of induced sputum in selected cases. Eosinophilic bronchitis was diagnosed if patients had no symptoms suggesting variable airflow obstruction, and had normal spirometric values, normal peak expiratory flow variability, no airway hyperresponsiveness (provocative concentration of methacholine producing a 20% decrease in FEV(1) ([PC(20)] > 8 mg/ml), and sputum eosinophilia (> 3%). Ninety-one patients with chronic cough were identified among 856 referrals. The primary diagnosis was eosinophilic bronchitis in 12 patients, rhinitis in 20, asthma in 16, post-viral-infection status in 12, and gastroesophageal reflux in seven. In a further 18 patients a diagnosis was established. The cause of chronic cough remained unexplained in six patients. In all 12 patients with eosinophilic bronchitis, the cough improved after treatment with inhaled budesonide 400 micrograms twice daily, and in eight of these patients who had a follow-up sputum analysis, the eosinophil count decreased significantly, from 16.8% to 1.6%. We conclude that eosinophilic bronchitis is a common cause of chronic cough, and that sputum induction is important in the investigation of cough.     

Airway inflammation, airway responsiveness and cough before and after inhaled budesonide in patients with eosinophilic bronchitis.

Eosinophilic bronchitis is a common cause of chronic cough, characterized by sputum eosinophilia similar to that seen in asthma, but unlike asthma the patients have no objective evidence of variable airflow obstruction or airway hyperresponsiveness. The reason for the different functional associations is unclear. The authors have tested the hypothesis that in eosinophilic bronchitis the inflammation is mainly localized in the upper airway. In an open study the authors measured the lower (provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20)) and upper (PC25 MIF50) airway responsiveness to histamine, lower and upper airway inflammation using induced sputum and nasal lavage, in II patients with eosinophilic bronchitis. The authors assessed changes in these measures and in cough reflex sensitivity to capsaicin and cough severity after 400 microg of inhaled budesonide for 4 weeks. A nasal eosinophilia was present in only three patients with one having upper airway hyperresponsiveness. Following treatment with inhaled corticosteroids the geometric mean sputum eosinophil count decreased from 12.8% to 2.9% (mean difference 4.4-fold, 95% confidence interval (CI) 2.14-10.02), the mean +/- sem cough visual analogue score on a 100 mm scale decreased from 27.2 +/- 6.6 mm to 12.6 +/- 5.7 mm (mean difference 14.6, 95% CI 9.1-20.1) and the cough sensitivity assessed as the capsaicin concentration required to cause two coughs (C2) and five coughs (C5) improved (C2 mean difference 0.75 doubling concentrations, 95% CI 0.36-1.1; C5 mean difference 1.3 doubling concentration, 95% CI 0.6-2.1). There was a significant positive correlation between the fold change in sputum eosinophil count and doubling dose change in C5 after inhaled budesonide (r=0.61). It is concluded that upper airway inflammation is not prominent in eosinophilic bronchitis and that inhaled budesonide improves the sputum eosinophilia, cough severity and sensitivity suggesting a causal link between the inflammation and cough.     

Development of irreversible airflow obstruction in a patient with eosinophilic bronchitis without asthma.

Eosinophilic bronchitis is a recently described condition presenting with chronic cough and sputum eosinophilia without the abnormalities of airway function seen in asthma. The patient, a 48-yr-old male who had never smoked, presented with an isolated chronic cough. He had normal spirometric values, peak flow variability and airway responsiveness, but an induced sputum eosinophil count of 33% (normal <1%). Although his cough improved with inhaled corticosteroids the sputum eosinophilia persisted. Over 2 yrs he developed airflow obstruction, which did not improve following nebulized bronchodilators and a 2-week course of prednisolone 30 mg once daily sufficient to return the sputum eosinophilia to normal (0.5%). It is suggested that the progressive irreversible airflow obstruction was due to persistent structural change to the airway secondary to eosinophilic airway inflammation, and it is further speculated that eosinophilic bronchitis may be a prelude to chronic obstructive pulmonary disease in some patients.     

Eosinophilic airway inflammation as an underlying mechanism of undiagnosed prolonged cough in primary healthcare patients

Prolonged cough is a common problem in patients seen in general practice. Using a simple method of sputum induction and processing of sputum samples, we determined whether eosinophilic airway inflammation could be a cause of undiagnosed prolonged cough. Eighty-two patients who had had cough for more than 1 month were enrolled into the study, in six primary healthcare centres. Patients with known pulmonary disease, including asthma or chronic obstructive pulmonary disease (COPD), or who were known to have another cause of cough, or to have recently suffered from a respiratory infection, were excluded. Fifty-three healthy individuals served as controls. Sputum was induced by inhalation of 3% saline. Inflammatory cells in smears were studied semi-quantitatively. Concentrations of eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), myeloperoxidase (MPO) and human neutrophilic lipocalin (HNL) were determined. Sputum induction proved safe and adequate samples were obtained from 91%. Sputum eosinophilia (eosinophils accounting for more than 5% of all cells in smears) was present in 14 patients with prolonged cough (19%) but in no healthy individual (P=0.001). Five of the 14 individuals (36%) who exhibited sputum eosinophilia appeared to have asthma, while nine of the 14 (64%) did not. Concentrations of ECP and EPO were higher in patients with prolonged cough than in healthy individuals (P=0.02 for ECP; 0.005 for EPO).We conclude that eosinophilic airway inflammation is a fairly common cause of prolonged cough, even in patients not suffering from asthma or COPD, or in whom no other cause of cough is known to be present. Induced sputum samples obtained in health centres can be studied in a central laboratory. Detection of eosinophilic airway inflammation could aid the decision regarding treatment.     

Eosinophilic bronchitis as a cause of chronic cough

Eosinophilic bronchitis is a recently described condition in patients with chronic cough, sputum eosinophilia, normal spirometry and no evidence of bronchial hyperreactivity. The aim of the study was to assess the causes of chronic cough and to identify the prevalence of eosinophilic bronchitis as a cause of chronic cough. Thirty-six patients [mean age 45.4 +/- 14.3 years (range 16-69 years), M/F: 4/32] with an isolated chronic cough lasting for more than 4 weeks were recruited from the outpatient clinic. In all patients, after a full history and physical examination, blood eosinophil count, eosinophilic cationic protein (ECP), serum total and specific IgE levels were measured. Spirometry, methacholine provocation test, skin prick tests, ear, nose and throat examination, induction of sputum and esophageal pH testing were performed. The mean duration of cough was 31.3 +/- 52.3 months. Sputum eosinophilia greater than 3% was present in 12 (33.3%) patients and they were diagnosed as eosinophilic bronchitis. Their induced sputum had a mean eosinophil count of 8.3% and a mean ECP level of 98.5 mg x l(-1), which were higher than the others (P=0.003, both). The diagnosis of the remaining patients were postnasal drip syndrome in eight, gastroesophageal reflux disease in eight, post-infectious cough in two and cough-variant asthma in one patient. In conclusion, eosinophilic bronchitis is an important cause of chronic cough and should be considered in the assessment of patients before regarding them as having idiopathic chronic cough.     

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.     

Bronchite à éosinophiles

Eosinophilic airway inflammation may be encountered in asthma and in non asthmatic eosinophilic bronchitis, which is a recently identified and common cause of chronic cough. Non asthmatic eosinophilic bronchitis may be differentiated from asthma by the absence of airflow limitation and of bronchial hyperreactiveness (potentially reflecting the different localization of mast cells within the airway wall). Diagnosis is based on the confirmation of eosinophilic airway inflammation, usually by induced sputum, in the absence of other causes of chronic cough or of radiological and lung function abnormality. The cough is generally improved by inhaled corticosteroids. The long-term outcome is still not known; non asthmatic eosinophilic bronchitis may lead to the onset of fixed airway obstruction or asthma.     

Airway inflammation in patients with symptoms suggesting asthma but with normal lung function.

The hypothesis that eosinophilic airway inflammation is present in many patients presenting with respiratory symptoms suggestive of asthma but with normal lung function was tested. Thirty-six consecutive patients presenting with these features were studied. Twenty-five asthmatics and 43 healthy volunteers served as control groups. Signs of eosinophilic inflammation in blood and induced sputum were studied. Patients with respiratory symptoms were single-blindly treated with inhaled beclomethasone dipropionate (BDP), 800 microg daily, or placebo for 3 months, and re-examined at 3 months and 1 yr. Patients with respiratory symptoms had higher numbers of blood and sputum eosinophils than healthy persons (p<0.0001), but the degree of eosinophilic inflammation was less pronounced than in asthmatics (p<0.01). Three-month's treatment with BDP significantly reduced total symptom score (p<0.001), cough score (p<0.0001), and the number of blood eosinophils (p<0.01). For cough alone, the improvement was significant compared with placebo (p<0.05). The patients were followed-up for 1 yr, and 17 (55%) still had symptoms but retained normal lung function. Four (13%) patients had developed asthma and another 10 (32%) had become free of symptoms. Using lung function measurements and induced sputum analyses, a group of patients with symptoms suggestive of asthma and signs of eosinophilic airway inflammation but without enough airflow variability to be diagnosed as asthmatics were detected. They seemed to respond favourably to inhaled beclomethasone dipropionate treatment.