The effect of tiotropium on the pulmonary diffusing capacity

To our knowledge, there is no data on the effect of tiotropium on pulmonary gas exchange in healthy subjects. The aim of this study was to assess the effects of tiotropium on pulmonary diffusing capacity. Twenty-one healthy volunteers were enrolled for a prospective, randomized, double-blind, placebo-controlled study. Spirometric measurements, including pulmonary-diffusing capacity, were obtained before and after inhalation of drug or placebo. There was a significant decrease in forced vital capacity (FVC) and, consequently, an increase in the forced expiratory volume in one second (FEV1) to FVC ratio after placebo inhalation (p < 0.05), but no changes were found for percent-predicted FVC, FEV1, percent-predicted FEV1, percent-predicted forced expiratory flow (FEF25%-75%), percent-predicted peak expiratory flow (PEF), diffusing capacity of the lung for carbon monoxide (DLCO), single-breath alveolar volume (VA) and DLCO/VA ratio when compared with the baseline. Tiotropium inhalation caused a significant increase in FVC, percent-predicted FEV1, FEV1/FVC and percent-predicted FEF25%-75%, although the decrease in DLCO was insignificant (12.4 +/- 0.9 to 11.4 +/- 0.9). In conclusion, tiotropium does not change the pulmonary-diffusing capacity in healthy volunteers.     

The study of in vitro-in vivo correlation: pharmacokinetics and pharmacodynamics of albuterol dry powder inhalers

The pharmacokinetics and pharmacodynamics of albuterol were studied following inhalation of three different in-house dry powder formulations in healthy volunteers and in asthmatics. Albuterol in plasma was measured using liquid chromatography-mass spectrometry (LC-MS). The plasma concentration time profiles were fitted to a two-compartment model with first-order kinetics. Oral absorption of swallowed albuterol was eliminated by oral dosing of 560 mg activated charcoal 1 h prior to albuterol aerosol administration. The peak concentration was reached within 15-20 min. Mean peak concentrations in healthy volunteers (six males and six females) were 1.74 +/- 0.34, 2.01 +/- 0.35, and 2.59 +/- 0.27 ng/mL following inhalation of formulations with fine particle doses (FPDs) of 100, 120, and 160 microg of albuterol, respectively. The corresponding peak plasma concentrations of 1.23 +/- 0.29, 1.37 +/- 0.13, and 1.53 +/- 0.11 ng/mL were obtained when asthmatics (six males and six females) were dosed with the same three formulations. The FPD of each formulation correlated well with the area under the curve of plasma concentration-time (AUC(0-8)) profile. Plasma potassium did not show any significant change over a period of 8 h. The forced vital capacity (FVC), the force expiratory volume in 1 s (FEV(1)), and mid expiratory flow (FEF(25-75)) did not correlate with FPD for the three different formulations.     

Inhaled dopamine induces bronchodilatation in patients with bronchial asthma.

OBJECTIVE: To determine the probable bronchodilating effect of dopamine administered by inhalation route in patients with crisis of bronchial asthma and the effect of dopamine on bronchial motor tone. DESIGN AND METHOD: We have studied eighteen (18) patients with crisis of bronchial asthma, ten (10) subjects with bronchial hyperreactivity and ten (10) healthy subjects. Patients with other pulmonary or cardiac disease were excluded. All received by inhalation placebo (0.9% saline solution), dopamine at 0.5 microg/kg/min (controlled by heart rate and arterial pressure with a dynamap), and placebo. Respiratory parameters: forced vital capacity (FVC), forced expiratory volume at the first second (FEV1), forced maximal expiratory flow (FEFmax) and forced expiratory flow at the 50% of vital capacity (FEF50) were measured in each protocol period. Student's paired t test, Wilcoxon and Mann Whitney analysis were performed. RESULTS: After dopamine inhalation, there was an increase of FVC by 23% (p<0.001); an increase of FEV1 by 39% (p<0.0001); an increase of FEF50 by 33% (p<0.001) and an increase of FEFmax by 31% (p<0.001). There were no respiratory parameter changes in both, subjects with bronchial hyperreactivity and normal after dopamine inhalation. CONCLUSIONS: Inhaled dopamine induces bronchodilatation in patients with crisis of bronchial asthma. Inhaled dopamine neither alters basal bronchial tone in healthy subjects nor in subjects with bronchial hyperreactivity.     

Clinical and functional responses to salbutamol inhaled via different devices in asthmatic patients with induced bronchoconstriction

AIMS: This study aimed at evaluating changes in airway patency, lung volumes and perception of breathing discomfort intensity following salbutamol administration via the Diskus dry-powder inhaler (DPI) or a pressurized metered-dose inhaler with the Volumatic valved holding chamber (pMDI + Volumatic) in asthmatic patients with methacholine-induced bronchoconstriction. METHODS: On six different study days, 18 patients inhaled methacholine until forced expiratory volume in 1 s (FEV(1)) decreased by approximately 35% of baseline. Following placebo, 200 and 400 microg of salbutamol through the pMDI + Volumatic or the Diskus, changes in FEV(1), volume-adjusted mean forced expiratory flow from 25 to 75% of the forced vital capacity (isoFEF(25-75)), lung volumes and breathing discomfort intensity, assessed by visual analogue scale (VAS) score, were repeatedly measured over a 60-min observation period. RESULTS: Induced bronchoconstriction was accompanied by obvious reductions in lung volumes and increases in VAS score. After salbutamol administration, FEV(1) and VAS score changes were similar in all experimental conditions. However, following 400 microg salbutamol via pMDI + Volumatic, isoFEF(25-75) values increased up to 4.48 l s(-1) (95% confidence interval 4.06, 4.90), a significantly (P < 0.01) higher value than those attained in all other experimental conditions. Independently of the salbutamol dose, lung volumes rose to significantly (P < 0.01) higher levels in pMDI + Volumatic than in Diskus trials. The low salbutamol dose via the pMDI + Volumatic and the high dose via the DPI increased isoFEF(25-75) and lung volumes to similar extents. CONCLUSIONS: Salbutamol via the pMDI + Volumatic provides greater isoFEF(25-75) and lung volume increases in asthmatic patients with induced bronchoconstriction; salbutamol-induced changes in VAS scores poorly reflect those in small airway patency. The lack of differences in FEV(1) increases observed after 200 and 400 microg salbutamol may reflect attainment of the flat portion of the dose-response curve using either device.     

Comparison of the dose response to levalbuterol with and without pretreatment with S-albuterol after methacholine-induced bronchoconstriction

STUDY OBJECTIVE: To determine the effect of S-albuterol on the dose response to levalbuterol in patients with moderate bronchoconstriction induced by a methacholine challenge. DESIGN: Prospective, randomized, double-blind, placebo-controlled, crossover study. SETTING: University-affiliated clinical trial center. PATIENTS: Twenty-two adults with mild, stable asthma. INTERVENTION: At the screening visit, patients were switched from their beta2-agonist to ipratropium bromide for use as an as-needed rescue therapy. At the baseline visit 2-6 days later, the provocative concentration of methacholine to induce a 30% decrease in forced expiratory volume in 1 second (FEV(1) PC(30)) was determined, followed by a nebulized racemic albuterol dose-response study with three doses of albuterol, to familiarize patients with the procedures. At visits 2 and 3, patients were randomly assigned to receive nebulized normal saline placebo or S-albuterol 5 mg before the methacholine challenge and were administered three escalating doses of levalbuterol after the challenge. MEASUREMENTS AND MAIN RESULTS: Area under the curve for FEV(1) over 40 minutes (AUC(0-40)) after administration of levalbuterol was the primary outcome, with slope of FEV(1) as the secondary outcome. In addition, the fraction of exhaled nitric oxide (FeNO) was measured before and after the challenges. In the 17 patients who met criteria for completion, no deleterious effect for S-albuterol was found for FEV(1) PC(30), AUC(0-40) FEV(1), or the FEV(1) slope(0-40). However, S-albuterol reduced the provocative concentration of methacholine to induce a 20% decrease in FEV(1) (PC(20) 0.52 +/- 2.06 vs 0.39 +/- 1.58 mg/ml, placebo vs S-albuterol, p=0.044) but did not affect FeNO. CONCLUSION: A single high dose of S-albuterol did not alter the bronchodilator response to levalbuterol. The effect on bronchial responsiveness requires further study.     

Effect of inhaled heparin on water-induced bronchoconstriction in allergic asthmatics

OBJECTIVE: The aim of this study was to investigate the effect of inhaled heparin on bronchoconstriction induced by ultrasonically nebulised distilled water (UNDW) in allergic asthmatics. METHODS: Eight atopic asthmatics, hyperresponsive to UNDW, were selected for this randomised, placebo-controlled, crossover double-blind study. On two consecutive days, these subjects underwent a UNDW challenge 45 min after inhaling aerosolised heparin (1000 U/kg) or placebo. RESULTS: Neither heparin nor placebo had a significant effect on base-line forced expiratory volume in 1 s (FEV1), but heparin significantly attenuated UNDW-induced bronchoconstriction, as shown by its efficacy in preventing the decreases in FEV1 produced by all doses of water (in comparison with placebo: P < 0.05 after 2 ml water; P < 0.01 after 4, 8 and 16 ml water). CONCLUSION: Inhaled heparin is able to exert a protective effect against the bronchoconstrictive response to UNDW in allergic asthmatics, and this action is likely due to inhibition of mast cell degranulation.     

An in vivo model of beta-adrenoceptor desensitization

Chronic use of beta2-agonists and increased production of inflammatory mediators during the late allergic reaction after antigen challenge results in the desensitization of beta-adrenoceptors in the airways and the accompanying rise in nonspecific airway hyperresponsiveness. In this study, we established an in vivo model of beta2-adrenoceptor desensitization in guinea pig airways by administration of IL-1beta intratracheally or chronic albuterol by inhalation. In the establishment of beta-adrenoceptor desensitization in response to both beta-agonist or inflammatory mediator, baseline pulmonary function responses were established to methacholine and isoproterenol-induced relaxation of methacholine bronchoconstriction. This was followed by the administration of IL-1beta (500 IU/d intratracheally for 2 days) or chronic albuterol (0.1 g/L by aerosol for 1 min three times a day for 10 days). After administration, the methacholine and isoproterenol-methacholine response was once again evaluated. Intratracheal administration of IL-1beta or chronic administration of albuterol significantly decreased (p < 0.05) the protective effect of isoproterenol on methacholine-induced bronchoconstriction, eliciting beta-adrenoceptor desensitization in vivo. The in vivo model will be very useful in monitoring the effect of other potential drugs on beta-adrenoceptor function in the airways.     

Plasma concentrations of fluticasone propionate and budesonide following inhalation: effect of induced bronchoconstriction

AIMS: To determine whether and to what extent bronchoconstriction affects plasma concentrations of fluticasone and budesonide following inhalation. METHODS: Twenty people with mild asthma inhaled 1000 microg fluticasone (Accuhaler) plus 800 microg budesonide (Turbohaler) on two visits. On one occasion, prior to drug inhalation, FEV(1) was decreased by at least 25% using inhaled methacholine. Plasma drug concentrations were measured for each drug over 5 h and area under the plasma concentration-time curve (AUC(0,5 h)) compared between visits. RESULTS: The mean difference in FEV(1) prior to drug inhalation on the 2 days was 33%. AUC(0,5 h) values for fluticasone and budesonide were lower by a median of 60% (IQR 36-75) and 29% (IQR 2-44), respectively, when administered following bronchoconstriction; the reduction was greater for fluticasone than for budesonide, P = 0.007. CONCLUSIONS: The lower plasma concentrations of fluticasone and, to a lesser extent, budesonide seen when the drugs were inhaled following induced bronchoconstriction, is likely to reflect variations that will occur with fluctuations in airway caliber in asthma.     

A comparison of lung function methods for assessing dose-response effects of salbutamol

Pulmonary function methods which are able to detect small pharmacological effects may be useful for assessing the full dose-response curve of bronchodilatators. We compared the ability of impulse oscillometry (R5, R20, X5, RF), plethysmography (sGaw) and spirometry [forced expiratory volume in 1 s (FEV(1)), maximal mid expiratory flow rate (MMEF)] to measure the dose-response effects of salbutamol in 12 healthy subjects, 12 mild asthmatics (mean FEV(1) 96% predicted) and 12 moderate asthmatics (mean FEV(1) 63% predicted). The techniques were performed twice to assess variability. Then salbutamol 10, 20, 100, 200 and 800 microg was administered. The sensitivity of the methods were compared by determining the lowest dose that caused changes greater than variability. In healthy subjects significant changes (p < or = 0.05) were observed only in FEV(1) (4.1%) and MMEF (14.6%) at 100 microg and sGaw (25.6%) and R20 (8.3%) at 200 microg. In mild asthmatics significant changes were observed in sGaw (15.9%) at 10 microg, X5 (23%), RF (20.3%) and MMEF (15.7%) at 20 microg, R5 (13.9%) and R20 (9.4%) at 100 microg and FEV(1) (7.1%) at 200 microg. All measurements except R20 demonstrated significant changes at 10 micro g in moderate asthmatics. The most sensitive test for assessing bronchodilatation is different in healthy subjects and asthmatics, and varies with severity of airflow obstruction.     

大环内酯类抗生素联用吸入类固醇治疗哮喘的临床研究

目的通过与小剂量茶碱联用吸入类固醇比较,观察罗红霉素联用吸入类固醇治疗支气管哮喘的疗效。方法选择40例中、重度哮喘患者并随机分为两组:20例患者为罗红霉素联用布地奈德干粉吸入剂组(简称A组),另20例患者为小剂量茶碱联用布地奈德干粉吸入剂组(简称B组)。观察指标为1s用力呼气量(FEV1)、晨晚最大呼气流速(PEFR)及其变异率等。结果第1～12周治疗期间,两组治疗后FEV1均明显高于治疗前,治疗第8周时B组FEV1明显高于A组,但第12周时两组差异无统计学意义,治疗12周时两组平均晨晚PEFR及其变异率差异无统计学意义,两组副作用相似。结论罗红霉素联用吸入类固醇能安全有效地控制哮喘,其治疗12周时疗效与小剂量茶碱联用吸入小剂量类固醇相似。     

Effect of an inhaled histamine H3-receptor agonist on airway responses to sodium metabisulphite in asthma.

Histamine H3-receptor agonists inhibit excitatory neuro-transmission in human and guinea-pig airways. Since neural bronchoconstriction may be important in asthma we have studied the effect of a specific H3-receptor agonist R-alpha-methylhistamine (alpha MeHA) on bronchoconstriction induced by the inhaled irritant sodium metabisulphite (MBS) in six mild asthmatic subjects in a randomised double-blind crossover study. Subjects received either alpha MeHA, 10 mg (as a chloride salt) or matched placebo (P) and were then challenged with doubling concentrations of MBS (0.3-80 mg ml-1) nebulised from a dosimeter at 5 min intervals with measurement of specific airway conductance (sGaw) and FEV1 at 2 and 4 min respectively after each inhalation. There was no effect of alpha MeHA on baseline airway calibre and the log concentrations of MBS required to lower sGaw by 50% (log PC50) and FEV1 by 20% (log PC20) were not significantly different after alpha MeHA when compared with placebo, suggesting that selective stimulation of airway H3-receptors does not inhibit MBS-induced bronchoconstriction.     

Effects of a PAF-antagonist (BN 52063) on bronchoconstriction and platelet activation during exercise induced asthma.

1. The effects of a specific PAF acether antagonist (BN 52063) on the response to isocapnic hyperventilation with dry cold air (ISH study) and exercise (EIA study) were assessed in a single dose and short term treatment study in 10 patients with exercise induced asthma. 2. ISH challenge was performed twice within 1 h after administration of either placebo, 240 mg BN 52063 p.o. or inhalation of 2.4 mg BN 52063. Hyperventilation increased Raw from 0.30 +/- 0.02 to 0.89 kPa s l-1 (P less than 0.001) after the first challenge and from 0.28 +/- 0.04 to 0.84 +/- 0.06 kPa s l-1 (P less than 0.001) after the second challenge. Oral pretreatment with BN 52063 did not result in a reduction of bronchoconstriction during both challenges. A significant increase of Raw was noted immediately after inhalation of BN 52063. An inhibition of PAF induced platelet aggregation (by a factor of 2) occurred after oral administration of BN 52063 after both ISH challenges (P less than 0.05). No significant inhibition of PAF induced platelet aggregation was seen after inhalation of BN 52063. At concentrations up to 30 microM in vitro, BN 52063 inhibited PAF induced platelet aggregation in a dose dependent manner. The IC50 of BN 52063 against the aggregating effect of 1 microM PAF was 7.0 +/- 2.1 microM. 3. In the EIA study the patients were challenged on the third day of treatment with either placebo or 240 mg BN 52063 p.o. or 5 mg BN 52063 by inhalation. Peak expiratory flow rates (PEFR) fell by 155 +/- 37 1 min-1 after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

吸入糖皮质激素对慢性阻塞性肺病急性加重期患者诱导痰中炎性标志物及肺功能的影响

目的探讨诱导痰中可溶性细胞间黏附分子-1(SICAM-1)、白细胞介素-8(IL-8)在慢性阻塞性肺病(COPD)发病机制中的作用和吸入糖皮质激素对COPD的影响。方法将70例患者随机分为一般组(35例)、激素组(35例),并以同期健康体检者为对照组(20例),分别于入院后第1天及治疗2周后行肺功能测定FEV1.0占预计值百分数(FEV1.0pre),应用ELISA法分别检测诱导痰上清液中IL-8和SICAM-1的水平。结果一般组和激素组治疗前后诱导痰液IL-8和SICAM-1水平均高于对照组(均P<0.01),FEV1.0pre低于对照组(P<0.01),治疗缓解后诱导痰液IL-8和SICAM-1水平低于治疗前(均P<0.01),FEV1.0pre有明显改善(P<0.01)。一般组和激素组治疗前诱导痰液IL-8和SICAM-1以及FEV1.0pre差异无统计学意义(P>0.05),治疗后激素组FEV1.0pre改善好于一般组(P<0.01),治疗后IL-8水平激素组低于一般组(P<0.05),SICAM-1水平两组治疗后比较差异无统计学意义(P>0.05)。结论IL-8和SICAM-1参与了COPD的炎症过程,COPD急性加重期患者短期吸入糖皮质激素能抑制IL-8的表达,不能抑制SICAM-1的表达,但可明显改善患者的气流受限状况。     

Large Porous Particles for Sustained Protection from Carbachol-Induced Bronchoconstriction in Guinea Pigs

Purpose. To determine whether a new formulated albuterol aerosol could sustain inhibition to bronchoconstriction for approximately one day in guinea pigs challenged with carbachol. Methods. Large and porous particles, comprising a combination of endogenous or PDA-approved excipients and albuterol sulfate, were prepared by spray drying using a NIRO portable spray drier. The anesthetized animals inhaled 5 mg of large porous or small nonporous particles by forced ventilation via cannulae inserted in the lumen of their exposed tracheae. At regular intervals over a period of 36 hours after drug delivery, airway resistance was determined in response to carbachol challenge dose. Results. Whereas inhalation of small nonporous albuterol particles protected from the carbachol-induced bronchoconstriction for up to 5 hours, inhalation of large porous albuterol particles produced a significant inhibition of carbachol-induced bronchoconstriction for at least 16 hours. Conclusions. The absence of substantial side effects, verified over a period of 24 hours by evaluating cardio-respiratory parameters as well as pulmonary inflammation, supports the utility of large porous albuterol particles for sustained therapies in asthma and other types of lung disease.Dr. Ben-Jebria is also affiliated with     

Evaluation of levalbuterol metered dose inhaler in pediatric patients with asthma: a double-blind, randomized, placebo- and active-controlled trial

OBJECTIVE: To evaluate the efficacy and safety of levalbuterol metered dose inhaler (MDI) in children aged 4-11 years (n = 173). RESEARCH DESIGN AND METHODS: Multicenter, randomized, double-blind 28-day study of QID levalbuterol 90 microg, racemic albuterol 180 mug, and placebo (2:1:1 ratio). Serial spirometry was performed on Days 0, 14, and 28. The primary endpoint was the double-blind average peak percent (%) change in FEV(1) from visit pre-dose; the primary comparison was with placebo. Secondary endpoints included the area under the FEV(1) percent change from pre-dose curve and peak % predicted FEV(1). Safety endpoints included adverse events, laboratory tests, rescue medication use, and electrocardiograms. RESULTS: Levalbuterol significantly improved the least square mean peak percent change in FEV(1) compared with placebo (levalbuterol 25.6% +/- 1.3% [p < 0.001]; racemic albuterol 21.8% +/- 1.8% [p = ns]; placebo 16.8% +/- 1.9%). Results for levalbuterol were similar for the other spirometry endpoints (p < 0.05 vs. placebo). No levalbuterol-treated patients had a peak percent change in FEV(1) < 10% (compared with 15.8% of racemic albuterol-treated patients and 30.3% of placebo-treated patients). The incidence of adverse events was 43.4% for levalbuterol, 56.4% for racemic albuterol, and 51.4% for placebo. The rate of discontinuation was 1.3% for levalbuterol, 2.6% for racemic albuterol, and 8.6% for placebo. The rate of asthma attacks (10.5%, 12.8%, 14.3%, respectively) was similar among treatments. Levalbuterol and racemic albuterol both reduced rescue medication use (p < 0.01 vs. placebo) and produced changes in ventricular heart rate and QT(c-F) that were similar to placebo. CONCLUSIONS: In this study, levalbuterol administered via MDI significantly improved airway function in comparison with placebo in asthmatic children aged 4-11 years with a safety profile that was similar to placebo.     

Long-term effect of the beta2-receptor agonist procaterol on daily life performance and exercise capacity in patients with stable chronic obstructive pulmonary disease. Clinical study with special reference to health-related quality of life and activities of daily living

The present study was undertaken to evaluate the long-term effect of procaterol hydrochloride (CAS 62929-91-3, Meptin), a third generation beta2-receptor agonist on lung function, exercise capacity, health-related quality of life (HRQOL) and activities of daily living (ALDs) in patients with stable chronic obstructive pulmonary disease (COPD). Twenty patients were randomly assigned to the procaterol group or to the control group, who received oxitropium bromide (CAS 30286-75-0), an anticholinergic agent. Procaterol was inhaled three times a day at a dose of 20 pg, while oxitropium was inhaled three times a day at a dose of 200 microg. The subjects were evaluated based on spirometry, exercise capacity, the Borg Scale, HRQOL, and ADLs before and after 12, 24 and 52 weeks of therapy. The values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), functional residual capacity (FRC), residual volume (RV), maximal inspiratory pressure (PImax), and maximal expiratory pressure (PEmax) were significantly improved at 12, 24 and 52 weeks compared with baseline values in the procaterol group (p < 0.05, p < 0.01), while these values did not differ from baseline values at any point in the oxitropium group (p > 0.05). Additionally, 6-min walking distances and Borg Scale values showed significant improvement at 12, 24 and 52 weeks compared with baseline values in the procaterol group (p < 0.05, p < 0.01), but did not significantly differ from baseline values in the oxitropium group at any point (p > 0.05). Likewise, the scores for dyspnea, fatigue, emotional function, mastery, total scores and ADLs were significantly higher at 12, 24 and 52 weeks compared with the baseline values in the procaterol group (p < 0.05, p < 0.01), but did not differ at any point in the oxitropium group (p > 0.05). These results suggest the effectiveness of long-term regular bronchodilator therapy with the beta2-receptor agonist procaterol in patients with stable COPD.     

噻托溴铵联合沙美特罗／氟替卡松治疗稳定期C组慢性阻塞性肺疾病的疗效评价

目的 探讨噻托溴铵联合沙美特罗/氟替卡松对稳定期C组慢性阻塞性肺疾病（COPD）患者临床症状及肺功能的改善作用.方法 60例稳定期C组COPD患者随机分为治疗组30例,给予噻托溴铵吸入剂（18 μg,吸入,1次/d）联合沙美特罗/丙酸氟替卡松吸人剂（50μg/500μg,吸入,2次/d）治疗;对照组30例,给予按需吸入异丙托溴铵或沙丁胺醇气雾剂.治疗前、后8周运动耐量的变化及治疗前、治疗后8周后肺功能变化.结果 治疗8周后两组6 min步行距离（6MWD）值均较治疗前明显增加,而治疗组中各项指标改善显著优于对照组（P＜0.05）.治疗8周后两组FVC、FEV1,和FEV1％pred值均较治疗前明显增加（P＜0.05）,治疗组指标改善显著优于对照组（P＜0.05）.结论 噻托溴铵与沙美特罗/氟替卡松联合吸入治疗稳定期C组COPD患者,优于异丙托溴铵或沙丁胺醇按需吸入治疗.     

雾化吸入戊乙奎醚对慢性阻塞性肺疾病病人的治疗效果

目的评价戊乙奎醚雾化吸入对慢性阻塞性肺疾病(COPD)病人的疗效和安全性。方法40例COPD病人,男性24例,女性16例,随机分为2组,治疗组20例,对照组20例。治疗组雾化吸入戊乙奎醚0.5 mg加入生理盐水10 mL,每日2次,每次吸入20 min;对照组用同样方法吸入等量生理盐水,疗程均为3 d。分别测定2组病人用药前后第1秒用力呼气量(FEV_1)、不同时间最大呼气流量(PEF),同时观察用药前后呼吸频率、心率、平均动脉压、动脉血气的变化。结果治疗组用药后30 min,FEV_1开始升高,差异有显著意义(P<0.05),用药后d 3 FEV_1升高(0.39±s 0.28)L(P<0.01);PEF在用药30 min后升高(P<0.01),d 3达最高值,比用药前增加(37±21)L·min~(-1),而对照组基本没有变化,2组比较治疗组明显高于对照组(P<0.01)。呼吸频率在用药60 min后明显改善(P<0.01),与对照组比较在d 3最为明显(P<0.01)。心率减慢出现在用药后120 min(P<0.05):动脉血气在用药后d 3 PaO_2上升(19±11)mmHg(P<0.01),PaCO_2下降(6±4)mmHg,怛与对照组比较无显著差异(P>0.05)。结论雾化吸入戍乙奎醚能改善COPD病人的肺功能.并有较好的安全性。     

Bradykinin-induced bronchoconstriction: inhibition by nedocromil sodium and sodium cromoglycate.

1. The effects of inhaled nedocromil sodium and sodium cromoglycate on bradykinin-induced bronchoconstriction have been studied in a double-blind, placebo controlled study, in eight mild asthmatic subjects. 2. The subjects attended on four occasions. Fifteen minutes after drug pre-treatment a bradykinin challenge was performed. Increasing concentrations were inhaled until a greater than 40% fall in expiratory flow at 30% of vital capacity from a partial flow volume manoeuvre (V p30) was demonstrated. 3. Inhaled bradykinin (0.06-8.0 mg ml-1) caused dose-related bronchoconstriction with the geometric mean cumulative dose causing a 40% fall in V p30 (PD40) of 0.035 (95% CI: 0.02-0.07) mumol, after placebo inhalation, which was similar to that measured before the trial (0.04: 0.02-0.09 mumol). 4. Both nedocromil sodium (4 mg) and sodium cromoglycate (10 mg) gave significant protection (P less than 0.05) against bradykinin-induced bronchoconstriction (PD40 0.37: 0.19-0.72 mumol after nedocromil sodium and 0.22: 0.11-0.49 after sodium cromoglycate). 5. Since bradykinin-induced bronchoconstriction is probably neurally mediated we conclude that both nedocromil sodium and sodium cromoglycate have an action on neural pathways which may be useful in the control of asthma symptoms.     

Reversal of histamine-induced bronchoconstriction by the H1-receptor antagonist levocabastine: a potential model for efficacy in anaphylaxis.

1. The rate of onset and magnitude of the effect of levocabastine, a potent H1-receptor antagonist, in reversing histamine-induced bronchoconstriction were determined in a double-blind cross-over trial against saline placebo. Histamine was administered by nebuliser so that forced expiratory volume in 1 second (FEV1) was reduced to 80-75% of baseline FEV1 in 10 men with mildly or moderately responsive airways and the effects of intravenous injection of saline or saline + 200 micrograms levocabastine were studied. 2. The maximum rate of recovery of FEV1 was 7[2-10]% min-1 (median [range]) in the first 5 min after levocabastine injection, but only 4[1-7]% min-1 after saline alone (P less than 0.05). 3. The median area under the recovery curve of FEV1 from 0 to 30 min after injection was 405 [228-498]% basal FEV1 X min after levocabastine and 301[98-502]% basal FEV1 X min after saline alone (P less than 0.002). 4. FEV1 returned to 90% of baseline within 30 min in all subjects after levocabastine, but not after saline alone (P less than 0.002). 5. Histamine-induced bronchoconstriction was relieved more quickly by levocabastine than saline alone. This model may have application to the study of drugs used in the treatment of anaphylaxis.