短程化疗满疗程残存空洞菌阴肺结核患者痰致病力的研究

目的 探讨菌阴肺结核患短程化疗满疗程后,残存空洞内痰的致病力。方法 选初治短程化疗已完成、痰菌阴转残存空洞患的痰接种豚鼠,观察其体重一般情况及局部淋巴结有否肿大,６周后解剖,观察内脏有无结核病并做结核分支杆菌培养及药敏试验,均设有阴性和阳性对照。结果 实验组６３例患痰中有３例（５％）患的痰能使豚鼠的肺、肝、脾出现不同数量的结核结节,结核分支杆菌培养也阳性。结论 短程化疗后残存空洞菌阴肺结核     

Effect of clarithromycin on airway obstruction and inflammatory markers in induced sputum in cystic fibrosis: a pilot study.

To determine whether macrolide antibiotics improve pulmonary function and decrease airway inflammation in cystic fibrosis (CF), we treated 10 patients (females; aged 19-26 years, all colonized with P. aeruginosa, none with atypical Mycobacteria) with 3 weeks of placebo, followed by 6 weeks of clarithromycin (500 mg BID) in a single-blind prospective study. We also determined the safety of sputum induction and the reproducibility of assessing inflammatory markers in induced sputum. Subjects performed spirometry and underwent sputum induction (12-min inhalation of 3% saline) at 3-week intervals. We found that sputum induction was well-tolerated. We also found that the reproducibility was high for neutrophil (PMN) number (R = 0.87, P = 0.009), interleukin (IL)-8 (R = 0.73, P < 0.05, free neutrophil elastase (NE) (R = 0.82, P < 0.05), and myeloperoxidase (MPO) levels (R = 0.86, P < 0.05), but was less so for tumor necrosis factor (TNF)-alpha (R = -0.15, P = 0.7). We found no significant difference in pulmonary function after 6 weeks of treatment with clarithromycin (FEV(1) (% predicted) (mean +/- SEM), 2.2 +/- 0.9 (60 +/- 24%) vs. 2.3 +/- 1 (61 +/- 29%)), and no significant differences in any of the inflammatory indices measured. The median (and range) values before and after treatment for indices of airway inflammation in the induced sputum samples were: for PMNs, 8 (1-326) and 21 (0.2 -175) x 10(6) cells/mL sputum; for IL-8, 156 (24-656) and 202 (16-680) ng/mL; for free NE, 260 (31-1,264) and 237 (49-1,048) microg/mL; for TNF-alpha, 20 (7-128) and 35 (17-87) pg/mL; and for MPO, 169 (13-960) and 195 (14-816) microg/mL. We conclude that clarithromycin is not uniformly effective in improving airway obstruction or in decreasing airway inflammation in patients with CF.     

Characterization of immunoglobulin binding factor in sputum from patients with chronic airway diseases

OBJECTIVE: Immunoglobulin binding factor (IgBF) is known to bind immunoglobulin, to interact with anti-Fc gamma-III antibodies and to be present in the lower respiratory tract of normal healthy subjects. In this study, in order to clarify the role of IgBF in respiratory diseases, we investigated whether IgBF exists in the airway of patients with chronic airway diseases. METHODOLOGY: IgBF was measured in the sputum of 28 normal subjects and 59 patients with chronic airway diseases including 37 cases of chronic bronchitis, 18 bronchiectasis, and four diffuse panbronchiolitis by enzyme-linked immunosorbent assay. RESULTS: Immunoglobulin binding factor concentration in the sputum of patients with chronic airway diseases (purulent sputum, 50.2 +/- 8.2 microg/mL; mucoid sputum, 88.6 +/- 12.8 microg/mL) was higher than that in induced sputum of normal subjects (6.3 +/- 5.5 microg/mL; P < 0.001). Immunoglobulin binding factor level in mucoid sputum was significantly higher than that in purulent sputum (P < 0.05). A significant inverse correlation was shown between the IgBF level and the elastase activity in sputum, and the concentration of IgBF purified from seminal plasma was decreased by treatment with neutrophil elastase, indicating that IgBF might be degraded by elastase. In the gel filtration chromatography of both types of sputum, IgBF was eluted in a region corresponding to a molecular weight of 27 kDa as a single peak. Western blot analysis with a monoclonal antibody to IgBF indicated that IgBF in both types of sputum had a molecular weight of 27 kDa under non-reducing conditions and of 16 kDa under reducing conditions. CONCLUSION: These results demonstrate that a high level of IgBF is present in the respiratory tract of patients with chronic airway diseases and may be related to the pathogenesis of these diseases.     

慢性气道炎症黏液高分泌的分子机制

近年来,在气道黏液高分泌的病理生理机制研究方面取得了明显进展。通过细胞内信号传递,在特定介质下活化转录及转录后程序,促进黏蛋白分泌增加.对气道黏蛋白基因转录及转录后调控的进一步研究,将有助于更好了解慢性气道炎症黏液高分泌信号转导通路,为慢性阻塞性肺部疾病防治提供新的方向。     

Ranitidine therapy in patients with idiopathic gastric acid hypersecretion

One hundred twenty-four patients with idiopathic gastric acid hypersecretion (basal acid output greater than 10.0 meq/hr) were prospectively evaluated and treated with ranitidine twice a day. Fifty-four patients (44%) required standard doses of ranitidine 300 mg/day for adequate treatment, and the other 70 patients (56%) required increased doses of ranitidine (mean 994 mg/day, range 600–3000 mg/day). Mean basal acid outputs for these two groups were 14.0 and 16.6 meq/hr, respectively, which were not significantly different. Nevertheless, there was a significant correlation between basal acid output and daily ranitidine dose required for therapy (r=0.18,P=0.05). The duration of ranitidine therapy consisted of: <1 year (N=46), 1 year (N=16), 2 years (N=19), 3 years (N=22), 4 years (N=15), 5 years (N=6). Only five patients required progressive increases in ranitidine during the time of treatment, which consisted of an average of 0.5 dose adjustments per year. No side effects occurred with any of these high doses of ranitidine. These results indicate that, as in Zollinger-Ellison syndrome, ranitidine is effective therapy for patients with idiopathic gastric acid hypersecretion; however, markedly increased doses as large as 3000 mg/day may be required.     

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     

Effect of a short course of rhDNase on cough and mucociliary clearance in patients with cystic fibrosis

The aim of the study was to measure the effect of a short course of recombinant human deoxyribonuclease I (rhDNase) on ciliary and cough clearance in a group of cystic fibrosis patients, using a radioaerosol and gamma camera technique. Patients were initially randomized to receive either rhDNase (2.5 mg qd) or placebo. Following the measurement of baseline clearance, patients were given a 7-day course of either rhDNase or placebo. The patient then returned on the seventh day for follow-up clearance measurements. This was followed by a 2-week washout period before the whole process was repeated with the alternative inhalation solution. On each of the study days, mucociliary clearance was initially measured for a period of 60 min (IC). This was followed by cough clearance (CC) measurements for 30 min, during which patients were requested to cough a total of 120 times. Post-cough clearance (PCC) was then measured for a further 60 min. Thirteen patients completed the study. Patients' age ranged between 18-38 years, and they had baseline values of FEV(1) of 27-103% of predicted values. Following completion of the course of rhDNase, there was a mean percent increase from baseline of 7.5% for FEV(1) and 5.4% for FVC% (P = 0. 03). There was a small, nonsignificant increase in IC (6.2 +/- 3.6%) on the rhDNase arm compared with the placebo arm (-2.3 +/- 2.9%), P = 0.1. No changes were seen in either CC (1.0 +/- 3.2% [rhDNase] vs. 1.9 +/- 2.4% [placebo], P = 0.9) or PCC (-0.7 +/- 1.5% [rhDNase] vs. 0.9 +/- 1.7% [placebo], P = 0.3). Patients who achieved a 10% or greater improvement in FEV(1) (n = 5) in response to rhDNase did not show any greater change in clearance than nonresponders. In conclusion, we were unable to demonstrate any improvements in either ciliary or cough clearance in response to a short course of rhDNase. The mechanism of action of this drug in vivo remains uncertain.     

Lung surfactant apoprotein (LSP) content of sputum samples from patients with chronic airway diseases

LSP contents of sputum samples from patients with chronic airway diseases were measured by an enzyme-linked immunosorbent assay (ELISA) kit which was designed by Kuroki et al to examine whether a substance identical to lung surfactant contained in alveolar lining layer, is also contained in respiratory tract fluid or not in the ELISA kit. One antibody to LSP was conjugated to peroxidase and another one to LSP was fixed onto a bead. A neo-anionic detergent, Triton X-100 and an anionic detergent, sodium dodecyl sulfate (SDS) were added to extraction medium to separate LSP from lung surfactant, and LSP reaction of sputum sample was maximal when the ratio of Triton X-100 to SDS was in range of 1 to 4. Airway mucous glycoprotein (AMG) purified from sputum sample did not show any LSP reaction. In CsCl density gradient ultracentrifugation of whole sputum, the LSP reaction was detectable only in the top fraction with density of about 1.40 and AMG was located in the fraction with a density of about 1.50. These results indicate that the LSP reaction of sputum sample is not due to false reaction caused by nonspecific binding of viscous AMG to the two antibodies to LSP, but to the existence of LSP. Therefore it was concluded that lung surfactant is contained in respiratory tract fluid. In general, the LSP concentrations in sputum samples were lower in purulent sputa than in mucoid or mucopurulent sputa, and lower in patients with diffuse panbronchiolitis and bronchiectasia than in those with pulmonary emphysema and chronic bronchitis. It was shown that LSP was hydrolyzed by neutrophil leucocyte homogenate. These results suggest that LSP content of sputum is influenced by various factors such as infection and disease in the respiratory tract, and thus is useful to estimate pathological states of chronic airway diseases.     

Chest pain in chronic sputum production: a neglected symptom

One hundred and fifteen patients (80 with bronchiectasis and 35 with mucus hypersecretion alone) who produced sputum on a daily basis were asked if they had suffered chest pain unassociated with an acute exacerbation of their chest symptoms during the last six months. Those with bronchiectasis complained of 28 separate pains of which 18 were considered to be of respiratory origin. Seventeen of these 18 pains were in an area associated with a bronchiectatic lobe(s). Only six chest pains (three considered to be of respiratory origin) were found among the 35 patients with mucus hypersecretion.     

慢性阻塞性肺疾病气道黏液高分泌研究进展

慢性阻塞性肺疾病(COPD)是由慢性气道和肺实质炎症引起的进行性气流受限的阻塞性疾病,气流受限不完全可逆.COPD是全球范围内慢性病发病和死亡的重要原因,而气道黏液高分泌是COPD发病和死亡的重要因素.黏液高分泌导致黏液纤毛清除受损、细菌定植、气道黏液栓形成以及气体交换功能障碍.为了阻止这个恶性循环,必须控制气道慢性炎...     

Inhaled mannitol changes the sputum properties in asthmatics with mucus hypersecretion

BACKGROUND AND OBJECTIVES: Most asthmatics with mucus hypersecretion have difficulty in clearing their secretions so that mucus plugs and airway obstruction are commonly present. Inhaled mannitol facilitates clearance of mucus. This study investigated the changes in the physical properties of sputum in response to mannitol in asthmatics with chronic cough and sputum production. METHOD: Sputum was collected from 12 asthmatics (26-73 year), lifelong non-smokers, at baseline, after eformoterol (24 mug) and after mannitol on each of four visits. Inhaled mannitol doses were: 635 mg (Visit 1), 240 mg (Visit 2), 360 mg (Visit 3) and 360 mg in the presence of montelukast (Visit 4). Eformoterol was inhaled before mannitol on each visit to prevent bronchoconstiction. Sputum measurements included viscosity, elasticity, surface tension, contact angle-glass and percentage solids. RESULTS: There were no significant differences between the sputum properties at baseline and after eformoterol. Mannitol (360 mg) reduced the baseline (mean +/- SEM) elasticity from 29.9 +/- 4.5 to 15.1 +/- 1.4 Pa (P < 0.0001), viscosity from 18.4 +/- 3.2 to 8.1 +/- 1.2 Pa (P < 0.0001) at 1 rad/ s, surface tension from 92.1 +/- 2.2 to 81.9 +/- 2.5 mN/m (P < 0.0001), contact angle-glass from 57.5 +/- 3.2 to 49.6 +/- 2.0 degrees (P < 0.0001), and percentage solids from 6.9 +/- 0.7 to 5.7 +/- 0.4% (P < 0.0001). All doses of mannitol reduced the sputum properties similarly and no property was further reduced by montelukast (P > 0.4). CONCLUSION: Inhaled mannitol reduced the viscoelasticity, surface tension, contact angle and the solids content of sputum in asthmatics with chronic cough and sputum production, consistent with the osmotic effect of mannitol causing water efflux in the airway lumen.     

初治痰菌阳性肺结核疗程结束时空洞或结核球内细菌学分析

目的对初治痰菌阳性肺结核病例短程化疗结束后痰菌阴转，但肺内仍存在结核球或空洞病灶的病例，经皮肺穿刺取材进行细菌学检查，评价短程化疗的疗效。方法2002年1月至2004年5月，选择初治痰菌阳性肺结核83例，患者均经过常规抗结核药物（异烟肼、利福平、乙胺丁醇、吡嗪酰胺）短程化疗，疗程末痰涂片及痰培养均为阴性，但肺部X线表现仍存在空洞或结核球，在疗程结束后1个月内，在CT引导下经皮肺穿刺对空洞壁或空洞内容物或结核球取材，进行细菌学检查，并对检查结果进行分析。结果对活检组织均进行涂片及培养检查，痰菌阴转病例中仅75例（90．4％）获得的组织标本阴性结果，8例（9.6％）获得阳性结果（其中3例为涂片阳性、培养阳性；5例为涂片阴性、培养阳性）。药敏试验结果1例对异烟肼、利福平耐药，其余7例为敏感菌株。24个月的随访结果有6例痰菌阳转。结论初治痰菌阳性空洞、结核球肺结核病例的短程化疗后，组织标本细菌学检查阳性结果的8例病例中在2年内有6例出现痰细菌学复发，提示目前普遍采用的肺结核疗效判断标准（痰菌阴转）值得商榷。     

3-Chlorotyrosine in sputum of COPD patients: relationship with airway inflammation

The airways of patients with chronic obstructive pulmonary disease (COPD) are associated with increased numbers of inflammatory cells, in particular neutrophils and macrophages. Contained within the primary granules of neutrophils is the heme enzyme called myeloperoxidase (MPO) that has been used as a biomarker of neutrophilic inflammation in COPD and other inflammatory diseases. MPO is the only enzyme in the body that produces hypochlorous acid (HOCl), which effectively chlorinates tyrosine residues in proteins. The presence of 3-chlorotyrosine (3Cl-Tyr) in sputum of COPD patients has yet to be established. Spontaneously produced sputum was collected from 14 stable COPD patients, and ultra-centrifuged to prepare sol phase samples for analysis. Sputum 3Cl-Tyr levels were measured using Mass Spectrometry (LC-MSMS). Sputum MPO activity was measured using a standard chromogenic substrate assay. The Spearman rank correlation was used to analyse the data. We report for the first time the measurement of 3Cl-Tyr in sputum from stable COPD patients. The sputum levels of 3Cl-Tyr correlated well with sputum MPO activity (r = 0.88; p < 0.0001). The presence of 3Cl-Tyr in the sputum of stable COPD patients suggests an active process related to MPO that may play a role in the pathophysiology of this disease.     

Lipid and smoker's inclusions in sputum macrophages in patients with airway diseases

We studied the effect of tobacco smoking on macrophage lipid index and macrophage smokers inclusions in induced sputum in 256 patients (143 non-smokers, 81 ex-smokers and 32 current smokers). Lipid index was, using the Oil red O stain, the sum of the lipid staining droplet score (range 0–4) in 100 macrophages. Smokers inclusions were assessed using Wright’s stain and graded as “none”, “few”, “moderate” or “many”. Lipid index was significantly higher in current smokers (112.5, SD 58.5 units) than ex-smokers (29.2, SD 42.8 units) or non-smokers (13.4, SD 121.7). Smokers inclusions were present in all current smokers but only in 2 non-smokers. The mean smoking history of current smokers with few macrophage inclusions was 15.0 (SD 11.2), moderate 21.6 (SD 15.7), and many 30.0 (SD 21.9) pack years. There was a significant difference between the length of time ex-smokers had quit smoking if they had no or few smokers inclusions (mean 17.6 (SD 11.2) years) compared to those with moderate or many smokers inclusions (mean 2.8 (SD 5.8) years) (p = 0.01). Lipid index was significantly correlated with smokers inclusions (r = 0.72, p < 0.01). We conclude that smoker's inclusions within sputum macrophages is a reliable indicator of cigarette smoking and that the sputum lipid index cannot be used as an assessment of oropharyngeal reflux in cigarette smokers.     

慢性阻塞性肺疾病气道黏液高分泌大鼠模型的建立

目的:通过LPS联合烟熏方式建立一种大鼠气道黏液高分泌的慢性阻塞性肺疾病(chronic obstructive pulmonary diseases,COPD)模型。方法:Wistar大鼠36只,随机分为模型组与对照组,每组18只。模型组第1天、第14天气道滴入LPS,2~13d、15~40d烟熏大前门牌香烟每次连续8支,30min/d。分别于第21天、第31天,第41天分期取肺组织(即烟熏第20天、第30天、第40天),AB-PAS染色,黏液染色面积与气道上皮面积的比值反映气道上皮杯状细胞的化生程度。结果:气道上皮黏液染色与上皮面积比值:正常对照组大鼠大气道和中气道上皮第20天、第30天、第40天面积比值差异无统计学意义(P0.05)。模型组第20天、第30天、第40天面积比值,差异均有统计学意义(P0.05)。模型组与正常对照组的面积比值差异均有统计学意义(P0.05)。模型组第20天、第30天、第40天面积比值,差异有统计学意义(P0.05),第30天与第40天,差异无统计学意义(P0.05)。两组大鼠小气道上皮各期均未见到黏液染色。结论:应用复合造模方法在第30天时建立了COPD急性加重期气道黏液高分泌的大鼠模型。     

Lack of effect of hydration on sputum production in chronic bronchitis

Patients with chronic lung disease productive of sputum are generally encouraged to drink a large amount of fluid to facilitate sputum production. This clinical practice has not been tested systematically. Twelve outpatients with chronic obstructive pulmonary disease in clinically stable condition who had daily sputum production were asked in random sequence: 1) to drink one glass of fluid every waking hour after supper and upon waking the next morning (hydration), 2) to drink no fluid after supper and upon waking the next morning (dry), and 3) to drink fluid ad lib (ad lib). Each morning sputum collection was started upon waking and continued for four hours. The differences in volume, elasticity of sputum, respiratory symptoms, and ease of expectoration were not significant. We conclude that moderate hydration and dehydration have no effect on volume expectorated, the elasticity of sputum, respiratory symptoms or forced expiratory volume in one second.     

Effect of the proteolytic enzyme serrapeptase in patients with chronic airway disease

OBJECTIVES: The proteolytic enzyme serrapeptase (SER) is widely used in clinical practice in Japan. We investigated the effect of SER on sputum properties and symptoms in patients with chronic airway diseases. METHODS: This study was an open-labelled trial with a non-treatment control group. Patients were randomly assigned to oral treatment with (n = 15) and without (n = 14) SER 30 mg/day for 4 weeks. Patients collected sputum samples for about 4 h in the morning on the day the trial began and 4 weeks later. We measured the amount of sputum by weighing. Part of each sputum sample was weighed and then completely dried and reweighed. The percentage solid component, viscosity and elasticity of the sputum were measured. Mucociliary transportability index was measured using ciliated bovine trachea ex vivo. Sputum smears were also prepared to count sputum neutrophils. Patients' symptoms were assessed by a questionnaire that used a visual analogue scale. RESULTS: After 4 weeks of SER treatment, sputum weight in the morning, percentage solid component, viscosity and elasticity of sputum, sputum neutrophil count, frequency of coughing and frequency of expectoration significantly decreased. The mean mucociliary transportability index increased from 13.3 +/- 1.8 to 24.4 +/- 2.5 (P = 0.0103). CONCLUSIONS: SER may exert a beneficial effect on mucus clearance by reducing neutrophil numbers and altering the viscoelasticity of sputum in patients with chronic airway diseases.