Bronchoconstriction of the asthmatic airway by inhaled and ingested propranolol

Summary Responsiveness to inhaled histamine and DL propranolol hydrochloride was measured in 31 adult asthmatics and compared with bronchoconstriction provoked by acute oral propranolol dosing (max 160 mg).Twelve asthmatics developed 15% reduction in the forced expired volume in 1 s (FEV₁), 2 h after 100 mg oral propranolol; cardiac -adrenoceptor blockade was confirmed by cycle exercise tests in the 19 without airway response. The provocative inhaled dose of each aerosol causing a 20% fall in FEV₁ (PC₂₀) was lower, histamine 0.43 mg·ml^–1, propranolol 3.12 mg·ml^–1, in the 12 with a positive oral test compared with the 19 with a negative test, PC₂₀ histamine 1.65 mg·ml^–1, PC₂₀ propranolol 16.2 mg·ml^–1 (P < 0.001 for both aerosols). A correlation was demonstrated between the PC₂₀ values for asthmatics with a negative oral test (r=0.72, P < 0.001, n=19) but not for the remainder (r=0.14, P > 0.05, n=12).Plasma propranolol concentrations (CL, ng·ml^–1) after the final oral dose did not correlate with the % FEV₁(26.3) (r=-0.28) when an airway response was provoked or with the reduction in exercise tachycardia (25.9%) (r=0.31) when no bronchoconstriction occurred. CL exceeded the limit of detection after the final inhaled propranolol dose (7.5 ng·ml^–1) and was weakly related to the PC₂₀ propranolol value (r=0.53, P=0.01, n=27). The prevalence of a positive oral challenge was low in this group (39%). APC₂₀ propranolol value which was 100% sensitive as a predictor of a positive oral test had low specificity (58%) and a low predictive value (60%).This study has not found that nonspecific bronchial responsiveness to histamine or specific responsiveness to inhaled propranolol can be employed to predict bronchoconstriction in asthmatics following acute oral propranolol dosing.     

Subsensitivity of beta-adrenoceptor responses in asthmatic patients taking regular low dose inhaled salbutamol

Summary Tremor (Tr), chronotropic (HR) and metabolic (K, Glu) responses to cumulative doses of inhaled salbutamol (100 g to 4000 g) were compared in an age and sex matched group of 7 normal (N) and asthmatic (A) subjects.Comparison of regression lines between groups showed differences in HR and K. This was also reflected in attenuation of maximum responses in group A, for HR and K.These results show subsensitivity of chronotropic and hypokalaemic responses in patients with asthma, which may reflect tachyphylaxis from the effects of long term inhaled salbutamol therapy.     

卡介菌多糖核酸治疗慢性支气管炎的疗效评价

为了评价卡介菌多糖核酸对慢性咳嗽咳痰病人的疗效,随机双盲地将慢性咳嗽咳痰病人136例分为卡组72例,对照组64例。两组病人严格按照慢性单纯性支气管炎和慢性喘息性支气管炎的诊断规范再分为2个亚组。在卡组病人中用卡介菌多糖核酸0.5mg/d×36d治疗后和对照组对比,结果显示:①卡组:慢单支组总有效率100％,慢喘支组92.68％;对照组:慢单支组91.67％,慢喘支组75％。②慢单支组:明显显效率卡组明显高于对照组(P=0.0001)。③慢喘支组:卡组中明显显效率和显效率均高于对照组(分别为P=0.0226;P=0.0012)。由此可见,卡介菌多糖核酸是治疗慢单支、慢喘支的有效药物,且疗效好,副作用少。     

γ-干扰素转基因对过敏原导致的小鼠肺嗜酸性粒细胞浸润的抑制作用

目的 :探讨腺病毒介导的小鼠γ 干扰素在小鼠哮喘模型肺上皮细胞内的转基因表达对过敏原所致的嗜酸性粒细胞浸润的作用。方法 :C5 7小鼠经卵蛋白 (ovalbumin ,OVA)腹腔致敏和气道吸入激发建立哮喘模型 ,48h后收获小鼠肺泡灌洗液 (bronchoalveolarlavage ,BAL)和小鼠肺 ;哮喘模型在OVA激发前 48h ,在其气道内给予带有γ 干扰素的复制缺陷腺病毒 (replication deficientadenoviruswithIFN γgene,AdCMVmIFNγ) 5× 10 8空斑形成单位 (pfu) ,同上在OVA激发 48h后收获其肺泡灌洗液和肺。结果 :在卵蛋白所致的哮喘模型中 ,肺组织病理可见支气管周围、血管周围及部分肺泡内明显的嗜酸粒细胞浸润 ,肺泡灌洗液中的嗜酸粒细胞平均占 (75 .13±6 .85 ) % ,而在阴性对照组中则未见嗜酸粒细胞 ;小鼠哮喘模型气道内给予AdCMVmIFNγ后 ,肺内嗜酸粒细胞浸润的程度明显减少 ,肺泡灌洗液中的嗜酸粒细胞占 (9.0 0± 4.5 8) % (P <0 .0 0 1) ,二者均显著低于哮喘模型组。结论 :小鼠的IFN γ经腺病毒介导在小鼠肺上皮细胞内的表达可明显抑制过敏原所致的肺内嗜酸性粒细胞浸润 ,从而为进一步利用细胞因子的体内转基因免疫治疗过敏性哮喘探索了新的治疗途径     

氨茶碱雾化吸入对正常及哮喘豚鼠气道粘膜的影响

目的 观察吸入氨茶碱对正常豚鼠气道粘膜的影响及对豚鼠哮喘的预防作用。方法 ３４只豚鼠随机分为６组：对照组、正常动物氨茶碱吸入组、哮喘组、哮喘豚鼠０．５％氨茶碱吸入组、哮喘豚鼠地塞米松吸入组、哮豚鼠０．５％氨茶碱＋地塞米松吸入组,分别行肺泡灌洗液（ＢＡＬＦ）、血清茶碱浓度及病理学检验。结果 正常动物吸入氨茶碱后气道粘膜上皮纤毛不完整,上皮细胞脱落,表面有炎性渗出,粘膜及粘膜下层炎性细胞浸润明显,肺泡     

温肾宣肺汤合针灸治疗过敏性支气管哮喘30例

目的：探讨温肾宣肺汤结合针灸对过敏性支气管哮喘的治疗作用,并了解其对体内致哮喘因子的调节作用。方法：将５５例患者随机分为２组。治疗组３０例,用温肾宣肺汤结合针灸治疗;对照组２５例,采用必可酮气雾剂吸入加口服博利康尼治疗,观察两种治疗方法的临床疗效、治疗前后肺功能及血中ＩＬ－４（白细胞介素－４）和ＩｇＥ变化情况。结果：治疗组与对照组均有较好的近期临床疗效和改善肺功能作用,两者之间无明显差异（Ｐ〉０．０５）。远期疗效方面,治疗组优于对照组（Ｐ〈０．０５）,治疗组治疗后血中ＩＬ－４和ＩｇＥ比对照组显著降低（Ｐ〈０．０５,Ｐ〈０．０１）。结论：温肾肺汤结合针灸治疗过敏性支气管哮喘疗效确切,且有降低血中ＩＬ－４和ＩｇＥ的作用。     

支气管哮喘患者肺泡巨噬细胞释放内皮素-1的研究

为研究支气管哮喘患者肺泡巨噬细胞（Ａｍ）所释放的内皮素１（ＥＴ１）在哮喘发病中的作用,对发作期哮喘患者２０例,对照组８例,经纤支镜行支气管肺泡灌洗术获得Ａｍ,调整Ａｍ至１×１０６／ｍｌ后分３孔体外培养（１ｍｌ／孔）;生理盐水对照孔、氟美松孔（１μｇ／ｍｌ）、氨茶碱孔（１５μｇ／ｍｌ）,培养６ｈ后取上清液,采用放免法测定ＥＴ１。显示哮喘组血浆ＥＴ１明显高于对照组,并于第１秒用力肺活量（ＦＥＶ１．０）呈显著负相关。哮喘组Ａｍ体外释放ＥＴ１与对照组无显著差异,与ＦＥＶ１．０无相关性。氟美松孔Ａｍ释放ＥＴ１明显低于生理盐水对照孔;氨茶碱孔与生理盐水孔或氟美松孔无差异。提示哮喘Ａｍ所释放ＥＴ１在哮喘发病中意义不大     

地塞米松和环孢菌素A对IL-4、IL-5合成的抑制作用

为研究淋巴细胞在哮喘发病中的作用及地塞米松（Ｄｅｘ）、环孢菌素Ａ（ＣｓＡ）治疗哮喘的机理,用ＥＬＩＳＡ法检测哮喘患者和对照组的外周血单个核细胞（ＰＢＭＣ）在植物血凝素刺激下合成白细胞介素４（ＩＬ－４）、白细胞介素５（ＩＬ－５）水平,以及Ｄｅｘ和ＣｓＡ对哮喘患者的ＰＢＭＣ合成ＩＬ－４、ＩＬ－５的抑制作用。结果表明,哮喘组的ＩＬ－４、ＩＬ－５水平较对照组高（Ｐ＜０．０５）;１０－６ｍｏｌ／Ｌ的Ｄｅｘ和ＣｓＡ均能抑制哮喘组ＰＢＭＣ合成ＩＬ－４、ＩＬ－５,增大药物浓度至２×１０－６、３×１０－６ｍｏｌ／Ｌ时,ＣｓＡ对ＩＬ－５合成的抑制作用逐步增强;Ｄｅｘ对ＩＬ－５合成的抑制作用较ＣｓＡ强（Ｐ＜０．０５）。提示糖皮质激素和ＣｓＡ抑制ＩＬ－４、ＩＬ－５的合成是其治疗哮喘的机理之一。     

止喘雾化液的制备及其质量标准研究

目的：为了优化止喘雾化液的制备工艺,同时建立质量控制标准。方法：采用正交试验法,优选药材浸提分离工艺、增溶剂用量及最适宜ｐＨ值,同时采用ＴＬＣ、ＴＬＣＳ法建立定性定量方法。结果：该雾化液的最佳浸提工艺为药材加１０倍量水浸泡１ｈ,煎煮３次,每次１．５ｈ,配液时加５％吐温－８０,调ｐＨ至６．０～８．０;黄芩甙的含量不低于２０ｍｇ／ｍｌ。结论：止喘雾化液工艺稳定,质量可控     

A cross-sectional study of workers in the chemical industry with occupational exposure to hexamethylenetetramine

Objectives: To assess the health effects of hexamethylenetetramine (HMT) on the airways and the skin of workers in the chemical industry. Methods: A cross-sectional study was performed with 17 employees of a HMT-producing chemical plant and 16 control subjects from the plant. In addition, we examined 4 out of 5 subjects who had left the production for medical reasons during the last 10 years. Anamnestic data, total and specific IgE to four environmental allergens, lung function and bronchial responsiveness to methacholine were assessed by standard procedures. Skin prick tests (SPT) and patch tests were performed with known sensitizing substances and HMT 100 mg/ml and 2% pet and aq. Results: A high number of exposed subjects and controls reported symptoms during the previous year (64.7% vs 68.8%), most of them were not related to work. Work-related symptoms and objective parameters did not show differences between groups. No sensitizations to HMT as assessed by SPT or patch tests were found. Among those who had left the HMT production for medical reasons, 2 former baggers showed sensitizations to HMT by patch tests. These reported eczema during exposure but lost symptoms after removal from exposure. Geometric mean HMT concentrations as assessed by personal sampling were 0.3 [95% confidence intervals (CI) 0.1; 0.9] mg/m³ in shiftleaders and 0.6 (95% CI 0.3; 1.1) mg/m³ in baggers. Conclusion: High exposures to HMT may cause allergic contact dermatitis. There was no evidence of an increased risk for occupational asthma at mean airborne HMT concentrations below 1 mg/m³. Received: 4 February 1999 / Accepted: 10 July 1999