一氧化氮对急性肝功能衰竭大鼠脏器影响的实验研究

１．资料与方祛：选用雄性Ｗｉｓｔａｒ大鼠（湖南医科大学实验动物中心提供）５０只,体重２５０～３５０ｇ,随机分为５组：假手术（ＳＯ）组、急性肝功能衰竭（ＡＬＦ）组、左旋精氨酸（Ｌ－Ａｒｇ）组、左旋甲基精氨酸甲酯（Ｌ－ＮＡＭＥ）组及Ｌ－Ａｒｇ＋Ｌ－ＮＡＭＥ组,每组１０只。切除大鼠肝左叶和中叶,右叶和尾状叶热缺血ｌｈ建立ＡＬＦ模型,Ｌ－Ａｒｇ组、Ｌ－ＮＡＭＥ组手术前后３０ｍｉｎ经尾静脉注入用生理盐水稀释的Ｌ－Ａｒｇ或Ｌ－ＮＡＭＥ;Ｌ－Ａｒｇ＋Ｌ－ＮＡＭＥ组手术前３０ｍｉｎ经尾静脉注入Ｌ－Ａｒｇ,间隔３…     

硝酸甘油对哮喘患者一氧化氮内皮素的影响及机制

目的　了解哮喘患者肺泡巨噬细胞（ＡＭ） 、支气管上皮细胞（ＢＥＣ） 源性一氧化氮（ＮＯ）、内皮素（ＥＴ）的分泌状态及硝酸甘油（ＮＴＧ）对哮喘患者ＡＭ、ＢＥＣ产生ＮＯ、ＥＴ的影响及机制。方法　分离纯化了１５ 例轻、中度哮喘发作期患者、７ 名健康受试者ＡＭ、ＢＥＣ,并分为哮喘未干预组、哮喘ＮＴＧ干预组和健康对照组,用放射免疫法和镀铜镉还原法分别测定ＡＭ、ＢＥＣ培养４８ 小时上清液中ＥＴ、ＮＯ·２／ＮＯ·３ 浓度,用原位杂交的方法检测ＡＭ、ＢＥＣｉＮＯＳｍＲＮＡ、ＥＴｍＲＮＡ 的表达。结果　（１） 健康受试者ＡＭ、ＢＥＣ分泌少量ＮＯ和ＥＴ及少量ｉＮＯＳｍＲＮＡ 、ＥＴｍＲＮＡ表达;（２）哮喘患者ＡＭ、ＢＥＣ源性ＮＯ、ＥＴ水平及ＡＭ、ＢＥＣｉＮＯＳｍＲＮＡ、ＥＴｍＲＮＡ表达与各组比较差异有显著性（ Ｐ均＜ ０－０５）;（３）ＮＴＧ 促进哮喘患者ＡＭ、ＢＥＣ源性ＮＯ产生（ Ｐ均＜０－０５）,明显抑制ＥＴ产生和ＥＴｍＲＮＡ 的表达,与对照组比较差异均无显著性（ Ｐ均＞ ０－０５） ,ＮＴＧ同时抑制哮喘患者ＡＭ、ＢＥＣｉＮＯＳｍＲＮＡ的表达,与健康对照组、哮喘未干预组比较差异有显著性（Ｐ均＜０－０５） ;（４） 除哮喘ＮＴＧ     

一氧化氮、内皮素对冠脉血流动力学及内皮依赖性舒张功能影响的实验研究

在开胸麻醉犬心脏模型上分三组观察了冠状动脉（冠脉）内灌注内皮素（ＥＴ）、Ｎ－单甲基左旋精氨酸（Ｌ－ＮＭＭＡ）＋ＥＴ、Ｌ－ＮＭＭＡ前后各自不同的血流动力学和内皮依赖性舒张功能的改变．结果发现：灌注Ｌ－ＮＭＭＡ后，ＥＴ使静息冠脉血流量明显下降，主动脉压明显升高，冠脉储备明显下降，左室收缩压明显下降，左室舒张末压明显升高，乙酰胆碱不再使冠脉血流量增加（Ｐ＜０．０１），心电图ＳＴ段压低．提示内源性一氧化氮形成受抑制后，ＥＴ的血管收缩作用明显增加，并引起心肌舒缩功能和心电活动的改变．     

L－精氨酸逆转一氧化氮抑制后的犬冠脉血流动力学改变和内皮素－1含量升高

观察了犬冠脉内灌注Ｎ－单甲基左旋精氨酸（Ｌ－ＮＭＭＡ）后再灌注Ｌ－精氨酸（Ｌ－Ａｒｇ）和单独灌注Ｌ－ＮＭＭＡ前后冠脉血流动力学、冠脉血流储备以及冠脉对不同浓度的乙酰胆碱（Ａｃｈ）反应的变化，同时用放免法测定冠脉前降支（ＬＡＤ）伴行静脉血中内皮素－１（ＥＴ－１）含量。结果发现，Ｌ－Ａｒｇ完全逆转了灌注Ｌ－ＮＭＭＡ引起的血流动力学改变，使心率回升，下降的基础冠脉流量（ＣＢＦ），从２０±８ｍｌ／ｍｉｎ回升至２８±７ｍｌ／ｍｉｎ，Ｐ＜０．０５），降低的冠脉储备恢复，从５１±１０ｍｌ／ｍｉｎ升至９４±１５ｍｌ／ｍｉｎ，Ｐ〈０．０１），ＥＴ－１的含量不再升高，从１５．５±３．０ｎｇ／Ｌ下降至５．０±２．０ｎｇ／Ｌ，Ｐ〈０．０１），Ａｃｈ介导的ＣＢＦ增加不再受到抑制（Ｐ〈０．０１）。结果提示提供外源性Ｌ－Ａｒｇ可增加一氧化氮（ＮＯ）的产生，使由于ＮＯ抑制而产生的血流动力学改变和ＥＴ－１升高发生逆转。     

L－精氨酸逆转一氧化氮抑制后的犬冠脉血流动力学改变和内皮素－1含量升高

观察了犬冠脉内灌注Ｎ－单甲基左旋精氨酸（Ｌ－ＮＭＭＡ）后再灌注Ｌ－精氨酸（Ｌ－Ａｒｇ）和单独灌注Ｌ－ＮＭＭＡ前后冠脉血流动力学、冠脉血流储备以及冠脉对不同浓度的乙酰胆碱（Ａｃｈ）反应的变化，同时用放免法测定冠脉前降支（ＬＡＤ）伴行静脉血中内皮素－１（ＥＴ－１）含量。结果发现，Ｌ－Ａｒｇ完全逆转了灌注Ｌ－ＮＭＭＡ引起的血流动力学改变，使心率回升，下降的基础冠脉流量（ＣＢＦ），从２０±８ｍｌ／ｍｉｎ回升至２８±７ｍｌ／ｍｉｎ，Ｐ＜０．０５)，降低的冠脉储备恢复，从５１±１０ｍｌ／ｍｉｎ升至９４±１５ｍｌ／ｍｉｎ，Ｐ〈０．０１)，ＥＴ－１的含量不再升高，从１５．５±３．０ｎｇ／Ｌ下降至５．０±２．０ｎｇ／Ｌ，Ｐ〈０．０１)，Ａｃｈ介导的ＣＢＦ增加不再受到抑制（Ｐ〈０．０１）。结果提示提供外源性Ｌ－Ａｒｇ可增加一氧化氮（ＮＯ）的产生，使由于ＮＯ抑制而产生的血流动力学改变和ＥＴ－１升高发生逆转。     

犬实验性围手术期心肌缺血的冠状动脉内皮功能障碍

杂种犬１５只均分为３组：Ⅰ组：对照组；Ⅱ组：心肌梗死（ＭＩ）模型组，在结扎左前降支２ｗ后取心脏组织；Ⅲ组：ＭＩ＋胃大部切除组，ＭＩ后２ｗ行胃大部分切除术，测定手术前和手术后的血流动力学、血浆内皮素（ＥＴ）及一氧化氮（ＮＯ）。同时，用原位杂交的方法观察３组心脏冠状动脉内皮一氧化氮合酶（ＮＯＳ）ｍＲＮＡ表达水平。结果在Ⅲ组，手术引起ＬＶ＋ｄｐ／ｄｔｍａｘ、ＣＩ及ＮＯ下降，同时致ＬＶＥＤＰ、ＰＣＷＰ、左室舒张压力下降时间常数、总外周阻力以及血ＥＴ升高；ＭＩ后ＮＯＳｍＲＮＡ表达下降，手术使内皮ＮＯＳｍＲＮＡ表达更加减少。提示ＭＩ后行胃大部切除术是研究围手术期心肌缺血较好的动物模型，能致左室舒缩功能障碍；ＭＩ和手术均致冠状内皮的ＮＯＳｍＲＮＡ表达下降     

哮喘豚鼠肺组织中嗜酸细胞凋亡与白细胞介素5mRNA表达？…

目的 探讨哮喘时嗜酸细胞（ＥＯＳ）凋亡与肺组织白细胞介素５（ＩＬ－５）ｍＲＮＡ表达的关系。方法 将豚鼠随机分为对照组（正常组７只）、哮喘组（８只）、地塞米松组（８只），应用脱氧核糖核酸末端转移酶介导的缺口末端标记（ＴＵＮＥＬ）技术和原位杂交方法，检测支气管肺泡灌洗液（ＢＡＬＦ）中不同密度ＥＯＳ凋亡百分比和肺组织ＩＬ－５ｍＲＮＡ的表达。结果 （１）正常对照组ＢＡＬＦ中低密度ＥＯＳ、正常密度ＥＯＳ凋是     

一氧化氮在哮喘发病机制中的作用

目的通过观察一氧化氮合成酶（ＮＯＳ）抑制剂亚硝基左旋精胺酸甲酯（Ｌ－ＮＡＭＥ）对豚鼠离体气管张力收缩的影响及采用组织化学方法观察ＮＯＳ在豚鼠哮喘模型肺中的分布，了解一氧化氮（ＮＯ）在哮喘发病机制中的作用。方法用Ｌ－ＮＡＭＥ孵育豚鼠离体气管段后，观察对组织胺量效曲线的影响并与对照组比较；另用还原型辅酶ＮＡＤＰＨ－ｄ对豚鼠哮喘模型肺组织行组织化学染色。结果豚鼠离体气管段经Ｌ－ＮＡＭＥ孵育后，组胺诱发的张力曲线明显左移，其最大反应张力是对照组的１７０％（Ｐ＜０．０１）。ＮＡＤＰＨ组化染色可见哮喘模型组肺泡巨噬细胞显著增多，ＮＯＳ染色呈明显阳性反应，对照组肺泡巨噬细胞数极少，且未见ＮＯＳ染色阳性者。结论Ｌ－ＮＡＭＥ使组胺对豚鼠离体气管段收缩张力显著增加，通过增加ＮＯ生成可降低气道对组胺的反应性；哮喘时肺泡巨噬细胞显著增多，且ＮＯＳ染色呈明显阳性。提示在巨噬细胞中的ＮＯＳ作用下产生的ＮＯ在哮喘发病中起重要作用。     

血管利钠肽减弱去甲肾上腺素对心肌生长的刺激作用

本实验目的在于研究血管利钠肽（ Ｖ Ｎ Ｐ）对去甲肾上腺素（ Ｎ Ｅ）促心肌生长作用的影响,并对其机制进行探讨。分离、培养乳鼠心肌细胞,完全随机分为三组:对照组、 Ｎ Ｅ组和 Ｖ Ｎ Ｐ＋ Ｎ Ｅ组。以 Ｍ Ｔ Ｔ法和总蛋白含量测定法观察各组细胞的生长情况。进而采用放射免疫方法研究了 Ｖ Ｎ Ｐ对细胞内ｃ Ｇ Ｍ Ｐ,ｃ Ａ Ｍ Ｐ水平的影响。结果发现: Ｎ Ｅ（１０－ ７ ｍ ｏｌ／ Ｌ～１０－ ５ ｍ ｏｌ／ Ｌ）可以使培养的乳鼠心肌细胞 Ｍ Ｔ Ｔ Ｏ Ｄ值显著升高（ Ｐ＜ ０．０５ ｖｓ 对照组）,并且具有剂量依赖性。 Ｖ Ｎ Ｐ（１０－ ７ ｍ ｏｌ／ Ｌ）可以显著降低 Ｎ Ｅ（１０－ ６ ｍ ｏｌ／ Ｌ） 刺激的心肌细胞 Ｍ Ｔ Ｔ Ｏ Ｄ值和细胞内总蛋白含量（ Ｐ＜０．０５ ｖｓ Ｎ Ｅ组）。对照组和 Ｎ Ｅ组细胞内ｃ Ｇ Ｍ Ｐ,ｃ Ａ Ｍ Ｐ水平无显著差异,而 Ｖ Ｎ Ｐ（１０－ ７ ｍ ｏｌ／ Ｌ）能升高细胞内ｃ Ｇ Ｍ Ｐ水平,降低ｃ Ａ Ｍ Ｐ水平（ Ｐ＜ ０．０５ ｖｓ对照组、 Ｎ Ｅ组）。提示 Ｖ Ｎ Ｐ能减弱 Ｎ Ｅ对心肌生长的刺激作用,其机制可能与ｃ Ｇ Ｍ Ｐ,ｃ Ａ Ｍ Ｐ等信号转导分子有关。     

肠源性内毒素血症在肝硬化发生发展中的作用

目的探讨内毒素在大鼠肝硬化发生发展中的作用。方法采用饮用０．０３％硫代乙酰胺（ＴＡＡ）四个月复制伴有肠源性内毒素血症的肝硬化大鼠模型，观察ＴＡＡ与ＴＡＡ＋内毒素（ＬＰＳ）对肝组织胶原蛋白含量的影响，并测定血浆与肝组织匀浆的肿瘤坏死因子α （ＴＮＦ α）、内皮素（ＥＴ－１）、一氧化氮（ＮＯ）与丙二醛（ＭＤＡ）含量。结果 ＴＡＡ组与ＴＡＡ＋ＬＰＳ组大鼠血浆与肝组织的ＴＮＦ α、 ＥＴ－１、 ＮＯ、 ＭＤＡ与肝组织胶原蛋白含量均明显高于正常对照组。结论内毒素可加剧肝纤维增生并发展为肝硬化。     

气道组胺H2受体与支气管哮喘发病机理关系的临床研究

应用组胺Ｈ２受体（Ｈ２Ｒ）激动剂甲双咪胍治疗缓解期哮喘患者１９例，观察其对气道高反应性（ＢＨＲ）的作用，以进一步探讨Ｈ２Ｒ与哮喘发病机理的关系。研究提示Ｈ２Ｒ激动剂可主要作为抗气道炎症用药，也可作为平喘药的辅助用药，说明Ｈ２Ｒ在哮喘气道炎症反应中具有保护作用。     

尼氟灭酸对支气管哮喘小鼠模型气道高反应性的抑制作用

目的　观察钙激活Cl-通道 (ClCa)阻断剂尼氟灭酸 (NFA)对支气管哮喘 (简称哮喘 )气道高反应性的抑制作用。方法　BALB/c小鼠 4 5只 ,按随机数字表法分为哮喘组 (A组 )、吸入NFA预防组 (B组 )和正常对照组 (C组 ) ,每组 15只。检测各组小鼠气道压力峰值 时间指数 (APTI)的差异 ,并比较各组小鼠支气管肺泡灌洗液 (BALF)中内皮素 1(ET 1)和一氧化氮 (NO)的含量。制备A组、C组小鼠的离体完整上皮气管环 (A1、C1组 )和去上皮气管环 (A2 、C2 组 ) ,观察在梯度浓度乙酰甲胆碱(mACh)的激发下 ,5 0 μmol/LNFA预处理对气管环收缩张力的影响。 结果　A组APTI与B组 (mACh为 2 .0mg/kg时 ,两者分别为 1.6 2± 0 .14和 1.2 1± 0 .0 7)比较 ,差异有显著性 (P <0 .0 1) ;A组BALF中ET 1和NO含量分别为 (10 3± 9)ng/L、(48.5± 3.2 ) μmol/L ,B组分别为 (5 3± 5 )ng/L和 (2 3.7± 2 .5 )μmol/L ,A组与B组比较差异有显著性(P <0 .0 1) ;离体气管环收缩张力实验显示 ,C1组完整上皮气管环的张力峰值比为 1.2 6± 0 .14 ,A1组完整上皮气管环的张力峰值比为 3.79± 0 .4 4 ,C2 组去上皮气管环的张力峰值比为 2 .0 6± 0 .18,A2 组去上皮气管环的张力峰值比为 2 .15± 0 .2 1,A1组与C1组、A1组与A2 组比较差异有显著性 (     

Bronchial hyperresponsiveness and exhaled nitric oxide in patients with cardiac disease

BACKGROUND: Increased concentrations of exhaled nitric oxide (NO) correlate with increased airway inflammation and measurement of exhaled NO is a noninvasive method for the management of bronchial asthma. In various cardiac diseases, bronchial hyperresponsiveness is observed, as is bronchial asthma. However, there have been few studies on the relationship between exhaled NO and bronchial responsiveness in cardiac diseases. OBJECTIVE: The aim of this study was to clarify the association between exhaled NO and bronchial hyperresponsiveness in patients with cardiac disease. METHODS: We measured expired NO and bronchial responsiveness to inhaled methacholine in 19 patients with cardiac diseases and 17 with bronchial asthma. We divided the cardiac disease patients into two groups according to their bronchial responsiveness to inhaled methacholine: BHR(+) group consisted of 12 patients with bronchial hyperresponsiveness and BHR(-) group consisted of 7 patients without bronchial hyperresponsiveness. RESULTS: The concentration of exhaled NO in the asthmatic patients was significantly higher than that in the BHR(+) and BHR(-) groups (142.0 +/- 17.0, 33.6 +/- 6.4 and 42.3 +/- 10.3 ppb, respectively, p < 0.01). There was no significant difference in exhaled NO between BHR(+) and BHR(-) groups. There were also no significant differences in the parameters of bronchial hyperresponsiveness between the cardiac BHR(+) and bronchial asthma groups. These results indicate that bronchial hyperresponsiveness in patients with cardiac diseases is not a consequence of eosinophilic inflammation or of exhaled NO. CONCLUSION: We conclude that bronchial hyperresponsiveness in patients with cardiac diseases can occur independently of NO production.     

Mechanics of the ventilatory system in sedated infants: forced oscillations versus single-breath method

The real--Re(Z)--and imaginary--Im(Z)--parts of the ventilatory system impedance were measured between 6 and 30 Hz in 18 normal infants and in 19 with airway obstruction. The intercept (R0) and slope (S) of the Re(Z)-frequency function, as well as inertance (I) and compliance (C) estimated from Im(Z), were compared with ventilatory system resistance (Rrs) and compliance (Crs) (single-breath method). R0 correlated significantly with Rrs (r = 0.86), although the slope of the regression equation was significantly lower than 1 (P less than 0.01). Negative frequency dependence of Re(Z) was observed in all subjects and a significant correlation was found between S and Rrs (r = -0.80). "Inertance" was negative in 20 subjects and correlated negatively with Rrs (r = -0.61). C correlated with Crs (r = 0.64) and with 1/Rrs (r = 0.85). The ratio of C to Crs (mean +/- SD = 0.168 +/- 0.082) also correlated with 1/Rrs (r = 0.51). The main characteristics of the total impedance/frequency function could be simulated with a model featuring the upper airway wall (Zuaw) in parallel with the ventilatory system (Zrs). It is suggested that the differential change in Zuaw and Zrs with growth accounts for the marked frequency dependence of Re(Z) as well as the inaccurate estimation of both I and C in this population.     

Non-invasive evaluation of lower airway inflammation in hyper-responsive elite cross-country skiers and asthmatics

Asthma-like symptoms and bronchial hyper-responsiveness (BHR) to methacholine are prevalent in competitive cross-country skiers. Whether these symptoms (ski asthma) in these athletes are caused by asthma remains uncertain. Bronchial responsiveness to adenosine 5'-monophosphate (AMP) and nitric oxide (NO) concentration in exhaled air, both indirect markers of asthmatic airway inflammation, were investigated in two non-smoking study populations of skiers and asthmatics. Of 18 skiers with ski asthma, 15 non-steroid and 14 steroid-treated asthmatics, BHR to AMP was present in five (28%), six (40%) and 10 (71%) subjects respectively. Although the groups were not significantly different in responsiveness to methacholine, responsiveness to AMP increased in order of magnitude from ski asthma < non-steroid-treated < steroid-treated asthma. Exhaled NO in 44 (nine with ski asthma) skiers was not significantly different from 82 healthy non-atopic controls [median [interquartile range (IQR)] 6.5 (4.1-9.9) vs. 5.2 (4.2-6.5) ppb]. Exhaled NO in 29 subjects with mild intermittent asthma was three-fold greater [median (IQR) 19.2 (5.1-25.6) ppb, P < 0.01] than in skiers. Exhaled NO was two- and four-fold greater in atopic than non-atopic subjects in the skier (P < 0.001) and asthmatic (P < 0.01) groups, respectively, and was correlated to methacholine responsiveness in atopic asthmatics (n = 22, rho = 0.55, P < 0.01). Exhaled NO was not elevated in ski asthma and may be more useful as a marker of atopic status than inflammation in the lower airway in skiers. Few skiers were hyper-responsive to AMP, indicating that pre-activated mucosal mast cells are not a predominant feature in ski asthma.     

Dexamethasone therapy for bronchopulmonary dysplasia: improved respiratory mechanics without adrenal suppression.

The purpose of the present study was to examine the pattern of changes in respiratory system mechanics induced by dexamethasone (Dex) in infants with bronchopulmonary dysplasia (BPD) and to determine whether dosages that produce these changes induce adrenal suppression. We examined mechanics in seven ventilator-dependent premature infants (age, 33 +/- 4.8 days) with BPD, before and daily during Dex therapy. Dex (0.5 mg/kg/day) was given intravenously for 7 days unless complications necessitated early termination. Respiratory system resistance (Rrs) and compliance (Crs) were measured by the passive expiratory flow-volume technique during the course of dexamethasone therapy or until extubation. Adrenocorticotrophic hormone (ACTH) stimulation tests were done at baseline and following Dex therapy to evaluate adrenal function. Dex therapy caused a 77 +/- 18% increase in Crs (from 0.97 +/- 0.09 SEM mL/cmH2O to 1.6 +/- 0.16 mL/cmH2O; P less than 0.025) and a 33 +/- 5% decrease in Rrs (from 0.20 +/- 0.02 cmH2O/mL/s to 0.14 +/- 0.01 cmH2O/mL/s; P less than 0.01). Concurrently, ventilator rate, mean airway pressure, and FIO2 all decreased significantly (P less than 0.025). Extubation occurred later in infants with the lowest Crs and highest Rrs at baseline. At extubation, all Crs values were greater than 1.33 mL/cmH2O and Rrs values were less than 0.15 cmH2O/mL/s. Systolic blood pressure increased from 61 +/- 6.3 mmHg to 84 +/- 17 mmHg, 72-96 h after the start of Dex (P less than 0.025). There were no episodes of culture-positive sepsis. Neither basal nor ACTH-stimulated levels of cortisol were suppressed as a result of Dex therapy (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Late asthmatic response to Ascaris antigen challenge in dogs treated with metyrapone

We developed an experimental dog preparation that shows a biphasic bronchoconstriction after allergen exposure. After anesthetization, the dogs were intubated with endotracheal tubes and manually ventilated. Respiratory resistance (Rrs) was measured by the forced oscillation method at 3 Hz. Ascaris suum, diluted from 10(-5) to 10(-2) of the extract, was inhaled during tidal breathing for 5 min. One hour before antigen challenge, 10 dogs received 70 mg/kg of metyrapone (cortisol synthesis inhibitor), and 2 h after antigen challenge 35 mg/kg of metyrapone were injected intravenously. In another 10 dogs, metyrapone was not administered. After the maximal increase in Rrs had been assessed (immediate asthmatic response), Rrs increased again 4 to 6 h after antigen challenge in 8 of the 10 dogs treated with metyrapone (late asthmatic response, 443 +/- 282% mean +/- SD of initial Rrs), which was significantly higher than Rrs 6 h after antigen challenge (124 +/- 41%) in dogs without metyrapone (p less than 0.01). In another 5 dogs, ragweed challenge with metyrapone caused no change in Rrs. Bronchoalveolar lavage at the time of the late response revealed a significant correlation between late asthmatic response and neutrophil accumulation (p less than 0.01) in all dogs. We conclude that cortisol depletion augments the occurrence of the late response. The present dog model may be a useful tool for study of the late response in bronchial asthma.     

Evaluation of bronchial hyperresponsiveness by monitoring of transcutaneous oxygen tension and arterial oxygen saturation during methacholine challenge in asthmatic children.

BACKGROUND: Bronchial hyperresponsiveness (BHR) is a key feature of asthma, but the measurement of BHR is hampered by the fact that most tests of airway caliber are difficult to conduct at a young age. Methacholine-induced bronchoconstriction is associated with significant hypoxemia, which can be assessed noninvasively by transcutaneous oxygen pressure (tcPO2) and pulse oximetry. Evaluating BHR by monitoring tcPO2 instead of respiratory resistance (Rrs) has been used over a wide age range in childhood. OBJECTIVE: To investigate whether there is a consistent relationship between changes in arterial oxygen saturation (SaO2) and respiratory resistance (Rrs) similar to the relationship between tcPO2 and Rrs during methacholine challenge in young children and to assess the usefulness of SaO2 as a parameter for the indirect measurement of BHR. METHOD: We performed methacholine inhalation challenge by monitoring SaO2, tcPO2 and Rrs in 37 asthmatic children 5 to 7 years of age. Consecutive doses of methacholine were doubled until a 10% decrease in tcPO2 from the baseline was reached. We recorded the cumulative dose of methacholine (Dmin) at the inflection point of tcPO2 (Dmin-tcPO2), SaO2 (Dmin-SaO2), and Rrs(Dmin-Rrs). RESULTS: The mean value of Dmin-Rrs was 4.27 +/- 2.02 units, the mean value of Dmin-tcPO2 was 4.48 +/- 2.01 units, and the mean value of Dmin-SaO2 was 4.57 +/- 0.20 units. Inhalation of increasing doses of methacholine raised Rrs curvilinearly and depressed tcPO2 and SaO2. There were no significant differences between any of the parameters. There were significant relationships between Dmin-tcPO2 and Dmin-Rrs (r = 0.914, p < 0.001) and between Dmin-SaO2 and Dmin-Rrs (r = 0.905, p < 0.001) and a relationship between Dmin-tcPO2 and Dmin-SaO2 (r = 0.949, p < 0.001). CONCLUSION: We concluded that measurement of SaO2 and/or tcPO2 during methacholine inhalation challenge may be used to assess bronchial hyperresponsiveness. This study showed that both SaO2 and tcPO2 monitoring are safe, useful, and tolerable for use in children who are too young to cooperate with lung function tests.     

双盲对照吸入倍氯以一年对道高反应性与哮喘的防治作用

目的 探讨长期吸入糖皮质激素对哮喘患的治疗作用和无症状的气道高反应性（ＢＨＲ）发生哮喘的预防作用。方法 以随机、双盲对照法比较５９例ＢＨＲ学生，年龄１２－１８岁，吸入倍氯米松粉剂（ＢＤＰ，６００μｇ／ｄ）安慰剂１年对气道反应性及哮喘症关诉作用。结果 试试验１年后哮喘ＢＤＰ组气道高反应性（使ＦＥＶ１较基础值下降２０％的累积吸入组胺量的对数ｌｇＰＤ２０－ＦＥＶ１）显下降（分别为０．３８５±０．４     

Dissociation of symptom scores and bronchial hyperreactivity: study in asthmatic children on long-term treatment with inhaled beclomethasone dipropionate.

The aim of the study was to evaluate the effects of inhaled steroids (IS) on the improvement of clinical asthma symptoms and on the decrease in bronchial hyperreactivity (BHR). Twenty-four children with severe asthma were given 1,000 micrograms beclomethasone dipropionate (BDP) daily and compared with ten asthmatic control children. The study included the evaluation of daily clinical score, of exercise induced asthma, of bronchial obstruction (forced expiratory volume in 1 sec, FEV1), and of BHR at months 0, 1, 2-3, and 4-5 (M0, M1, M2-3, and M4-5). BHR was assessed by standardized inhaled carbachol provocation measuring plethysmographic specific airway resistance (SRaw). The carbachol dose causing a 40% decrease in specific conductance (SGaw) was determined (PD40 SGaw). Clinical scores decreased at M1 (P less than 0.01) and throughout the study. FEV1 increased at M1 (P less than 0.05), M2-3 (P less than 0.01), and M4-5 (P less than 0.05) compared to M0. PD40 SGaw only increased significantly at M1 and M2-3. No individual correlation was found between clinical scores and PD40 SGaw at any testing, or between the decrease of clinical scores and the decrease of BHR. We conclude that bronchoconstrictive challenge tests do not adequately assess the clinical efficacy of IS. In clinical practice non-specific BHR should be preferentially measured for diagnosing atypical forms of asthma.