Ipratropium bromide protects against bronchoconstriction during bronchoscopy

Pulmonary function is reportedly impaired by fiberoptic bronchoscopy. We investigated the effect of two anticholinergic agents, intramuscular atropine and inhaled ipratropium bromide, on bronchoconstriction in 29 patients who were undergoing diagnostic bronchoscopy. The patients were divided into three groups; the first received 0.5 mg of atropine intramuscularly; the second took four puffs of 0.02 mg ipratropium bromide aerosolized by a metered-dose inhaler, and the third inhaled four puffs of a placebo. Fifteen minutes later a standardized topical anesthetic, lidocaine, was administered, and a bronchoscopic examination was performed. Pulmonary function was measured before and 15 minutes after each step. Pulmonary function was not affected by the treatment with anticholinergics or the placebo. In the placebo and the atropine groups, the topical anesthesia produced significant reductions in forced expiratory volume in 1 second (FEV,) and peak expiratory flow rate (PEFR); further reductions in these values were observed after bronchoscopy. In the group treated with ipratropium bromide there were no significant changes in FEV, and PEFR after topical anesthesia. Bronchoscopy induced significant reductions in FEV₁ and PEFR, but the changes were significantly smaller than those seen in the placebo and atropine groups. The results suggest that the deleterious effect of bronchoscopy on pulmonary function is due to topical lidocaine anesthesia and to the bronchoscopic examination itself. Inhaled ipratropium bromide protects against these deleterious effects, whereas intramuscular atropine does not.Offprint request to: H. Aizawa     

内源性硫化氢对吸烟大鼠小气道纤维化的保护作用

目的探讨内源性硫化氢（Hzs）对于吸烟诱导的COPD大鼠模型中小气道纤维化的影响。方法32只健康雄性SD大鼠随机分为正常组、吸烟组、吸烟＋Hzs组和吸烟＋炔丙基甘氨酸（PPG）组,采用被动烟雾吸入法,共吸烟4个月,从第3个月起,每日吸烟前给予大鼠腹腔注射生理盐水、硫氢化钠（NaHS）（14μmol／kg）或PPG（37．5mg／kg）,取肺组织切片进行HE染色和天狼星红染色,观察肺组织病理形态改变,对小气道胶原沉积采用半定量分析,并进行小气道病理评分。Westernblot检测肺组织胱硫醚-γ-裂解酶（CGL）、I型胶原蛋白表达水平。结果与正常组比较,吸烟组小气道病理评分明显升高（P〈0．01）,NaHS干预后较吸烟组评分降低（P〈0．05）。偏振光显微镜下观察天狼星红染色切片,吸烟组和吸烟＋PPG组较正常组小气道周围胶原沉积显著增多（P〈0．01）,吸烟＋H2S组较吸烟组明显减少（P〈0．05）。与正常组相比,吸烟组大鼠肺组织I型胶原蛋白含量明显增多（P〈0．05）,NariS干预后I型胶原蛋白含量较单纯吸烟组明显降低（P〈0．05）。结论内源性H2S参与吸烟诱导的COPD大鼠小气道纤维化的病理生理过程,外源性给予H2S对小气道纤维化具有保护作用。     

间接激发试验诊断运动诱发性支气管痉挛

运动诱发性支气管痉挛（exercise-induced bronchoconstriction,EIB）是由运动诱发的急性短暂的气道缩窄。在运动员中的发病率约3％～13％,诊断EIB需要肺功能下降的客观依据,间接气道激发试验是常用于诊断EIB的肺功能检查,本文就一些国际上认可的间接气道激发试验的方法及判断标准做一综述。     

Comparison of formoterol, salbutamol and salmeterol in methacholine-induced severe bronchoconstriction.

The onset of the bronchodilating effect of formoterol (12 microg by Turbuhaler) was compared with that of salbutamol (50 microg by Turbuhaler), salmeterol (50 microg by Diskhaler) and placebo in methacholine-induced severe bronchoconstriction. Seventeen subjects with mild-to-moderate asthma completed this randomized, double blind, cross-over, double-dummy study. On four study days, baseline forced expiratory volume in one second (FEV1) was recorded and the subjects were challenged with methacholine until FEV1 fell by at least 30%. Immediately thereafter, the study drugs were inhaled and lung function was assessed for 60 min. The geometric mean time for FEV1 to return to 85% of baseline was 7.2 min with formoterol, 6.5 min with salbutamol, 14.1 min with salmeterol and 34.7 min with placebo (p=0.0001, overall ANOVA). The difference between formoterol and salmeterol was statistically significant (p=0.01); there was no difference between formoterol and salbutamol (p=0.69). In conclusion, formoterol reversed methacholine-induced severe bronchoconstriction as rapidly as salbutamol and more rapidly than salmeterol. Classifying beta2-agonists as "fast"- and "slow"- acting may be supplemental to "short"- and "long"-acting.     

Separation of cough and reflex bronchoconstriction by inhaled local anaesthetics

Cough and airway constriction are common features of respiratory diseases. Both can be caused by stimulation of airway nerves. We have studied the effects of airway anaesthesia on these reflexes, stimulated by inhaled capsaicin, in order to determine whether they are controlled by the same sensory nerves. Ten volunteers had capsaicin cough dose responses performed before and at 10 min after inhaling placebo (ascorbic acid in saline), and the topical anaesthetics lignocaine 40 mg, and dyclonine 8 and 4 mg. The effect of the drugs on respiratory resistance (Rrs), measured using a forced oscillation technique, was measured both before and after the inhalation of a dose of capsaicin which caused less than two coughs. Lignocaine (40 mg) and dyclonine (8 mg) caused significant reports of oral anaesthesia but only lignocaine reduced the cough response to inhaled capsaicin, increasing the log dose of capsaicin causing three or more coughs by 162%. None of the treatments altered basal Rrs or its increase after inhaled capsaicin. Thus, the cough and reflex bronchoconstriction caused by inhaled capsaicin have different sensitivities to inhaled local anaesthesia, suggesting that the effect may be mediated by different sensory pathways.     

Inhibition of mast cell PGD2 release protects against mannitol-induced airway narrowing.

Mannitol inhalation increases urinary excretion of 9alpha,11beta-prostaglandin F2 (a metabolite of prostaglandin D2 and marker of mast cell activation) and leukotriene E4. The present study tested the hypothesis that beta2-adrenoreceptor agonists and disodium cromoglycate (SCG) protect against mannitol-induced bronchoconstriction by inhibition of mast cell mediator release. Fourteen asthmatic subjects inhaled mannitol (mean dose 252+/-213 mg) in order to induce a fall in forced expiratory volume in one second (FEV1) of > or = 25%. The same dose was given 15 min after inhalation of formoterol fumarate (24 microg), SCG (40 mg) or placebo. Pre- and post-challenge urine samples were analysed by enzyme immunoassay for 9alpha,11beta-prostaglandin F2 and leukotriene E4. The maximum fall in FEV1 of 32+/-10% on placebo was reduced by 95% following formoterol and 63% following SCG. Following placebo, there was an increase in median urinary 9alpha,11beta-prostaglandin F2 concentration from 61 to 92 ng.mmol creatinine(-1), but no significant increase in 9alpha,11beta-prostaglandin F2 concentration in the presence of either formoterol (69 versus 67 ng.mmol creatinine(-1)) or SCG (66 versus 60 ng.mmol creatinine(-1)). The increase in urinary leukotriene E4 following placebo (from 19 to 31 ng.mmol creatinine(-1)) was unaffected by the drugs. These results support the hypothesis that the drug effect on airway response to mannitol is due to inhibition of mast cell prostaglandin D2 release.     

Therapeutic equivalence of three metered-dose inhalers containing salbutamol (Albuterol) in protecting against methacholine-induced bronchoconstriction in children with asthma.

Many pharmaceutical companies sell salbutamol in metered-dose inhalers (MDI) for the treatment of asthma. However, the therapeutic equivalence of the more recently released generic products has not been compared with the original patented product in children. Twenty children with mild to moderate asthma, presently asymptomatic and with normal lung function, were randomly allocated to receive 200 microg of inhaled salbutamol (Albuterol) from three MDIs prepared by different manufacturers: the original Glaxo product and two generic products. The three drug formulations and placebo were given 10 min before a methacholine challenge test to determine the degree of protection provided against methacholine-induced bronchoconstriction (MIB) by each salbutamol aerosol. Tests were performed on 4 consecutive days. Doubling concentrations of methacholine were inhaled until the forced expired volume in 1 sec (FEV(1)) decreased by 20% from its baseline value. Compared to placebo, all patients increased significantly the provocation concentration that decreased FEV(1) by 20% (PC(20)) by more than one doubling concentration after inhaling each of the three salbutamol aerosols. The effectiveness was not significantly different between medications (P = 0.8). There was a small but significant difference among MDIs in aerosol particle size and total and fine-particle dose released per actuation. However, no relation was found between aerosol particle size or released dose and the protective effect. This study shows that the three tested brands of salbutamol MDI protected asthmatic children equally from MIB. When prescribing these salbutamol MDIs to prevent symptoms triggered by nonspecific stimuli in asthmatic children, the selection may be based on cost-benefit criteria.     

Comparison of efficacy of salbutamol and sodium cromoglycate in the prevention of ticarcillin-induced bronchoconstriction

Nebulized ticarcillin can cause bronchoconstriction in children with cystic fibrosis (CF). We assessed whether pretreatment with salbutamol or sodium cromoglycate (SCG) would prevent this side-effect using a randomized, double-blind, placebo-controlled design. Fifteen children with CF received pretreatments of saline, SCG, or salbutamol, in random order, one on each day. Baseline lung function was measured before and after pretreatment, and after ticarcillin nebulization. On the control day (saline pretreatment), ticarcillin caused a reduction in forced expiratory volume in one second (FEV₁), which was maximal 10 minutes after receiving the aerosol and persisted for 120 minutes. The mean maximal fall in FEV₁, was 9%. Pretreatment with salbutamol abolished the fall in FEV, seen with ticarcillin at all time points. Pretreatment with SCG diminished the maximal fall in FEV₁, at 10 minutes (mean, 4%) and resulted in the FEV, returning to baseline within 120 minutes. These data suggest that pretreatment with salbutamol is more effective in preventing ticarcillin-induced bronchoconstriction in the doses used in routine clinical practice, than it is with SCG. Pediatr Pulmonol. 1993; 16:311–315. © 1993 Wiley-Liss, Inc.     

Transient airway cooling modulates dry-air-induced and hypertonic aerosol-induced bronchoconstriction.

Airflow-induced bronchoconstriction (AIB) may be initiated in asthmatic patients by inhaling dry air during eucapnic hyperventilation or exercise. Hypertonic aerosol-induced bronchoconstriction (HIB) also occurs in these patients, but it differs from AIB by exhibiting a faster time course. Although AIB and HIB probably increase airway fluid osmolality, only AIB is associated with airway cooling. In light of the similarities between our canine model and human AIB, we examined peripheral airway responses to dry air and hypertonic aerosol challenge. Specifically, we studied the magnitude and time course of these responses in an in situ, isolated, perfused lobe in which airway temperature was independently controlled. At body temperature, HIB peaked immediately after challenge, whereas transient airway cooling during aerosol challenge delayed HIB. In contrast, airway cooling attenuated AIB but did not alter its time course. Hypocapnia- and histamine-induced responses were not affected by airway cooling, suggesting that smooth muscle function was not impaired. To the extent that the mechanisms producing AIB in dogs and in humans are similar, our results suggest that (1) changes in airway fluid osmolality initiate AIB, (2) AIB = HIB + Cooling, and (3) exercise-induced asthma results from an imbalance between an excitatory pathway stimulated by airway drying and an inhibitory pathway initiated by airway cooling.     

Plasma concentrations of lidocaine during inhalation anaesthesia for fiberoptic bronchoscopy.

The plasma concentration of lidocaine and its metabolite, mono-ethyl-glycine-xylidine, was measured furing fiberoptic bronchoscopy (FB) using an ultrasonic nebulizer to achieve topical anaesthesia. Most patients received additional anaesthesia of the laryngeal region and the tracheobronchial tree during the procedure. The achieved plasma concentrations showed that a substantial amount of lidocaine was absorbed, but toxic plasma levels were not reached. Lidocaine plasma concentration above the therapeutic range for treating cardiac diseases was observed in one patient. The use of an ultrasonic nebulizer with lidocaine before FB seems to give sufficient local anaesthesia and to be a safe method.     

Effect of single inhalation of a salbutamol,ipratropium bromide and beclomethasone on mucociliary clearance in patients with chronic obstructive airway disease

BACKGROUND: Chronic obstructive airway disease (COAD) is associated with hyperplasia and hypertrophy of the mucus producing glands. The beneficial effect of inhaled drug may be due to improved mucociliary function. The present study was done to evaluate the effect of salbutamol, ipratropium bromide and beclomethasone dipropionate inhalation on mucociliary clearance in patients with COAD. METHODS: Ten patients of COAD were taken up, two patients however did not complete the study. Salbutamol, ipratropium bromide, beclomethasone dipropionate and placebo inhalation were given randomly to each patient on four separate days. Radioaerosol inhalation lung cine-scintigraphy after inhalation of the different drugs was followed up to two hours and than after 24 hours. RESULTS: There was no significant visually noticeable increased mucociliary clearance on any of the days. Two patients showed definite steep slope in the time activity curves with salbutamol as compared to other drugs or placebo. All the quantitative indices analysed at the end of one hour and two hours for the three drugs were comparable to placebo. CONCLUSIONS: A single dose of inhaled salbutamol, ipratropium bromide and beclomethasone dipropionate has no appreciable effect on mucociliary clearance in patients with COAD.     

Effect of salbutamol on dry air- and acetylcholine-induced bronchoconstriction in the canine lung periphery.

We examined the effect of salbutamol on dry airflow-induced bronchoconstriction (AIB) and acetylcholine-induced bronchoconstriction (Ach-IB) in the canine lung periphery using a wedged bronchoscope technique. Collateral system resistance (Rcs) and airway wall temperature (Taw) were monitored in a peripheral lung segment before, during and after airflow challenge. Rcs before and after aerosolized acetylcholine was recorded in a contralateral lung segment. Intravenous salbutamol (2.5 micrograms.kg-1) significantly attenuated the peak fall in Taw during airflow challenge and the peak rise in Rcs following challenge. Intravenous salbutamol attenuated Ach-IB to a similar degree. Significant systemic effects were recorded following i.v. salbutamol. In contrast, aerosolized salbutamol (50 micrograms) minimally decreased the fall in Taw during airflow challenge, while virtually eliminating AIB. The same dose of aerosolized salbutamol only partially attenuated Ach-IB. Aerosolized salbutamol did not affect mean arterial pressure or heart rate. Intravenous salbutamol may in part inhibit AIB by increasing pulmonary blood flow, secondary to its systemic circulatory effects, and decrease heat and water loss during airflow challenge. In contrast, aerosolized salbutamol abolished AIB, while only minimally effecting airway cooling. These data suggest that AIB is a result of mediator release and/or smooth muscle contraction.     

A comparison of the onset of action of salbutamol and formoterol in reversing methacholine-induced bronchoconstriction

This single-centre, randomized, double-blind, double-dummy four-way cross-over study in 24 moderately severe asthmatic patients compared the speed of onset of recommended doses of salbutamol (200 micrograms) and formoterol (12 micrograms) delivered by metered-dose inhaler in reversing the bronchoconstriction induced by a cumulative dose of methacholine to produce a 20% decrease (PD20) in forced expiratory volume in 1 s (FEV1). Specific airway conductance (SGAW) and airway resistance (RAW) were measured in baseline condition, immediately after challenge and 0.5, 1.5, 3, 5, 10, 15, 30, 60 min and every hour up to 4 h after inhalation of the trial drug. FEV1 was measured in baseline condition, after challenge and 15, 30 and 60 min and then every 30 min up to 4 h after inhalation of the study drug. The primary efficacy parameter was the change in SGAW. Salbutamol produced a two-fold increase in SGAW within 4 min and a maximum increase after 79.3 min. Formoterol produced a two-fold increase in SGAW after 5 min and a maximum increase after 119.6 min. Changes in SGAW were slightly, but consistently, higher during the first 2 h after inhalation of salbutamol, both in absolute values and as a percentage of the maximum response. Differences were significant at 10, 15 and 30 min time points. There was no significant difference between the maximum values of SGAW after the two drugs. Changes in RAW and FEV1 reflected the differences in SGAW. It was concluded that in methacholine-induced bronchoconstriction both formoterol and salbutamol have a very fast onset of action, achieving prechallenge values of SGAW within 3 min, salbutamol being slightly faster than formoterol.     

Physiologic effects and serum lidocaine concentrations after inhalation of lidocaine from a compressed gas-powered jet nebulizer

The physiologic effects, efficacy, and serum lidocaine concentrations were determined in 10 normal volunteers who inhaled nebulized lidocaine from a compressed gas-powered jet nebulizer. Physiologic variables and serial venous serum lidocaine concentrations were measured during and after lidocaine inhalation. All 10 subjects experienced loss of the gag reflex, which returned to normal at 32 +/- 5.9 min (mean +/- 1 SD), with a range of 20 to 40 min. There were no significant changes in systolic or diastolic blood pressures or heart rates. There were no significant changes from baseline in any of the measured spirometric variables (FVC, FEV1, peak expiratory flow rate, peak inspiratory flow rate). The peak mean serum lidocaine concentration measured at 20 min after beginning lidocaine inhalation was 0.52 microgram/ml, and the highest single value measured was 1.05 micrograms/ml. We conclude that inhalation of lidocaine from a compressed gas-powered jet nebulizer can produce safe and effective oropharyngeal anesthesia with minimal drug absorption.     

Adrenomedullin inhibits ovalbumin-induced bronchoconstriction and airway microvascular leakage in guinea-pigs.

Human adrenomedullin is a potent vasodilator with bronchodilation properties. The effects of adrenomedullin on antigen-induced bronchoconstriction and airway microvascular leakage in guinea-pigs was investigated. The portion of the adrenomedullin molecule possessing these pulmonary active profiles was also examined, using two truncated adrenomedullin molecules: adrenomedullin (1-25) and adrenomedullin (22-52). Four weeks after sensitization with ovalbumin (0.1 mg x k(-1)), the guinea-pigs were anaesthetized and mechanically ventilated. Respiratory resistance, dynamic compliance and arterial blood pressure were monitored. Airway microvascular leakage was evaluated by extravasation of 20 mg x kg(-1) Evans blue into airway interstitial tissue. In order to enhance the pulmonary effects of adrenomedullin, the active production of endogenous nitric oxide was inhibited by coadministration of a nitric oxide synthase inhibitor, L-N(G)-nitroarginine methethyl ester (10 mg x kg(-1)). Intravenous pretreatment with adrenomedullin (10, 30 and 100 microg x mL(-1)) dose-dependently inhibited ovalbumin-induced bronchoconstriction and airway microvascular leakage in all airway segments. Inhaled adrenomedullin (100 microg.mL(-1), 1 min) also significantly inhibited pulmonary changes induced by ovalbumin inhalation (3 mg x mL (-1) , 3 min). These pulmonary profiles of adrenomedullin were enhanced by inhibiting the active production of endogenous nitric oxide. In conclusion, adrenomedullin has inhibitory effects on antigen-induced microvascular leakage and bronchoconstriction in guinea-pigs. These beneficial effects strongly related to its unique ring structure and N-terminal segment, making it a potential anti-asthma.     

静脉麻醉与雾化吸入麻醉在无痛纤支镜检查中的应用对比

目的探讨静脉麻醉与雾化吸入麻醉在无痛纤支镜检查中的应用价值。方法选取2005年1月～2010年3月间行纤支镜检查的本院住院病人100例为研究对象。随机分为观察组50例和对照组50例。观察组行静脉麻醉无痛纤支镜检查,对照组性雾化吸入纤支镜检查。结果观察组患者麻醉效果、麻醉情况和术中生命体征监测结果与对照组比较,均有显著性差异(P<0.05)。结论静脉麻醉在无痛纤支镜检查中是一项安全、高效、不良反应少的术前麻醉方式。