Effect of preservative on the efficacy of terbutaline nebuliser solution in atopic asthma.

The efficacy of bronchodilator nebuliser solutions may be influenced by the presence of preservatives. In a double blind, randomised, crossover study the effect of preservatives in determining the airway responses to 5 mg of terbutaline was studied in a group of 21 atopic asthmatic patients. The presence of preservatives affected neither the bronchodilator action of terbutaline nor its protection against bronchoconstriction induced by histamine.     

Relative efficacy of nebulised ipratropium bromide and fenoterol in acute severe asthma

In a double-blind, randomised, controlled clinical trial of 145 patients with acute asthma, the efficacy of nebulised 4-hourly ipratropium bromide plus 4-hourly fenoterol (group I, 50 patients), 2-hourly fenoterol (group II, 50 patients) and 4-hourly fenoterol (group III, 45 patients) was assessed. All patients received an optimal infusion of aminophylline and 81 patients (27 in each group) received hydrocortisone for clinical indications. It was found that cholinergic side-effects in group I were not more common than in group II. Tremor was more common in group II. Assessment of bronchodilator efficacy was confined to the 81 patients whose therapy included hydrocortisone. Peak expiratory flow rate, forced expiratory volume in 1 second, and forced vital capacity were expressed as a percentage of predicted for each individual and the mean values for each group plotted. It was found that the response rate, as assessed by the area under the curve, was significantly more rapid in group I compared with both group II (P less than 0.001) and group III (P less than 0.005). These findings were consistent for all three lung function measurements. However, there was no significant difference in the responses between group II and group III. It is concluded that adding ipratropium bromide to conventional regimens is likely to benefit patients with acute asthma.     

Sodium cromoglycate and ipratropium bromide in exercise-induced asthma.

In thirteen patients with extrinsic asthma the effects of placebo, sodium cromoglycate, ipratropium bromide, and ipratropium bromide plus sodium cromoglycate were studied in a random double-blind fashion to assess their inhibitory action in exercise-induced asthma (EIA). Exercise testing consisted of steady state running on an inclined treadmill for up to eight minutes. In eight of the 13 patients studied the baseline ratio of expiratory flow at 50% vital capacity (VC) breathing helium-oxygen (V50He) to V50air was over 1.20 and they were called responders; the remaining five patients were called non-responders. There was a significantly lower baseline maximum mid-expiratory flow rate (MMEF) in non-responders (P less than 0.02) as compared to responders but no difference in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC). Sodium cromoglycate (P less than 0.02), ipratropium bromide (P less than 0.01), and ipratropium bromide plus spdium cromoglycate (P less than 0.01) all significantly inhibited the percentage fall in FEV1 after exercise in the responders. Ipratropium bromide had no preventive action on non-responders, unlike sodium cromoglycate (P less than 0.05) and ipratropium bromide plus sodium cromoglycate (P less than 0.02). It is postulated that mediator release is an important factor in development of EIA in most extrinsic asthmatics, whereas cholinergic mechanisms are relevant only in those patients in whom the main site of airflow obstruction is in the large central airways.     

Supraventricular tachycardia caused by nebulised ipratropium bromide.

A 71 year old patient developed a supraventricular tachycardia after the administration of nebulised ipratropium bromide.     

Effects of ipratropium bromide and fenoterol aerosols in pulmonary emphysema.

In patients with radiological evidence of pulmonary emphysema the bronchodilator drugs fenoterol and ipratropium bromide produced a considerable increase in vital capacity and reduction in residual volume. The response to fenoterol was virtually complete 15 minutes after administration, but after ipratropium bromide vital capacity was still increasing at 60 minutes. The change in vital capacity was slightly greater with a combination of the two drugs than with either used alone. Changes in FEV1 and peak flow rate were small.     

Comparison of nebulised salbutamol and ipratropium bromide with salbutamol alone in the treatment of chronic obstructive pulmonary disease.

BACKGROUND--Patients admitted with acute exacerbation of chronic obstructive pulmonary disease (COPD) are often prescribed ipratropium bromide in combination with a beta 2 agonist such as salbutamol. Studies have not shown any benefit in adding ipratropium bromide to salbutamol in acute exacerbations of COPD, but these studies have only assessed patients for 60-90 minutes and short term studies may not predict long term clinical response. Combination therapy with the two drugs was compared with salbutamol alone in the treatment of acute exacerbations of COPD during a hospital admission. METHODS--Seventy patients admitted to hospital with an acute exacerbation of COPD were randomly allocated to receive either nebulised salbutamol 5 mg and ipratropium bromide 500 micrograms, or nebulised salbutamol 5 mg alone (all four times a day) on admission. All other treatment was prescribed at the discretion of the attending physician. Length of stay in hospital and spirometric values on days 1, 3, 7, 14, and discharge were assessed. Patients completed a subjective symptom score each day. RESULTS--There was no difference between the two groups in the mean (SD) length of stay (salbutamol 10.5 (4.7) days, salbutamol + ipratropium bromide 11.8 (4.4) days; 95% CI -1.02 to 3.62). There was no difference in spirometric values on days 1, 3, 7, 14, or discharge between the two groups. The subjective improvement was similar with both treatments. CONCLUSIONS--The routine addition of nebulised ipratropium bromide to salbutamol appears to be of no benefit in the treatment of acute exacerbations of COPD.     

Comparison of the effects of inhaled ipratropium bromide and salbutamol on the bronchoconstrictor response to hypocapnic hyperventilation in normal subjects.

A double blind, placebo controlled comparison was made of the effects of nebulised ipratropium bromide (0.05 and 0.5 mg) and salbutamol (0.25 and 2.5 mg) on lung function and the airway response to hyperventilation in eight normal subjects. Both agents at both doses caused similar baseline bronchodilatation, confirming the presence of resting bronchomotor tone. The overall mean increases as percentages of control were 33% in specific airway conductance (sGaw), 10% in maximal flow after expiration of 50% of vital capacity, and 3.7% in FEV1. Hypocapnia (mean end tidal carbon dioxide tension 2.2 kPa) was produced by three minutes of voluntary hyperventilation and resulted in a mean fall in sGaw of 0.49 s-1 kPa-1 (20%). After inhalation of 0.25 mg salbutamol hypocapnic hyperventilation still produced a mean fall in sGaw of 0.55 s-1 kPa-1, whereas salbutamol 2.5 mg reduced this response to 0.15 s-1 kPa-1 (6%). After both doses of ipratropium the decrease in sGaw caused by hyperventilation was similar to the control. This suggests that bronchoconstriction in response to hypocapnic hyperventilation in normal subjects is not mediated via a cholinergic reflex.     

Economic evaluation of Tobramycin nebuliser solution in cystic fibrosis.

Background: The cost effectiveness of inhaled TOBIR tobramycin nebuliser solution (TNS) in CF and chronic pulmonary Pseudomonas aeruginosa infection has been shown in US but not in European studies. Methods: An economic evaluation of TNS was undertaken in children and adults. Lung function and resource utilisation were recorded for 24 months before and during TNS therapy. Interventions were costed. Results: Forty-one patients received TNS; 30 of them matched with a paired control on usual therapy. TNS cases received more inhaled and IV antibiotics in the year before TNS than controls, and were hospitalised more. In the TNS treated group mean days in hospital before and after (change) were 32.0, 24.2 (-7.8); days on IV antibiotics 55.4, 38.9 (-16.4); total cost 22,102 pounds, 28,394 pounds (+ 6292 pounds), composed of cost of TNS 0 pounds, 10,010 pounds (+ 10,010 pounds), cost of hospitalisation 10,897 pounds, 8552 pounds (- 2345 pounds), cost of drugs 11,205 pounds, 9832 pounds (- 1374 pounds). In 19 patients aged < 18 the change in days hospitalised was -10.7 and days on IVs -20.2. Incremental cost was 3830 pounds. Conclusions: TNS was associated with clinically and socially important reductions of hospital attendances and parenteral antibiotics. This would improve patients' quality of life and reduce interference with work and schooling. Its maximal acquisition cost of 10,010 pounds may be reduced by delays in prescribing and dispensing, and was offset by savings of approximately 3500-6200 pounds.     

Comparison of two tobramycin nebuliser solutions: Pharmacokinetic,efficacy and safety profiles of T100 and TNS

BackgroundTobramycin inhalation is an accepted treatment of chronic pseudomonal infection in cystic fibrosis (CF) patients. Twice daily inhalation is efficacious, but time-consuming.MethodsIn this randomized, open-label, multicentre, two-period, crossover study, 58 patients with CF and chronic Pseudomonas aeruginosa (PA) infection received two tobramycin nebuliser solutions: T100/eFlow or TNS/PARI LC PLUS. The primary objective was to demonstrate the equivalence of both treatments with respect to pharmacokinetics (area under the concentration–time curve and maximum concentration in plasma). Secondary endpoints were tobramycin sputum pharmacokinetics, reduction in PA colony forming units, improvement of lung function, incidence of adverse drug reactions and reduction of inhalation times.ResultsTobramycin plasma AUC and C_max were lower after administration of T100 than after TNS. The study failed to demonstrate systemic bioequivalence of the two treatments. After T100 administration, tobramycin sputum AUC and C_max achieved higher values than after TNS. Changes in efficacy parameters from baseline were similar. Safety profiles were not different or unexpected. Inhalation time per inhalation was shorter during treatment with T100.ConclusionThe lower systemic drug burden and the higher local drug deposition together with a comparable efficacy/safety profile and a shorter inhalation time render T100/eFlow an attractive treatment option for CF patients.(www.controlled-trials.com/ISRCTN85410458).     

Dose response of ipratropium bromide assessed by two methods

The dose-response relationships of ipratropium bromide were assessed by two different techniques in two groups of 10 male patients with partially reversible airways obstruction. In a randomised double-blind fashion on four days, 10 patients were given 40 μg, 80 μg, or 120 μg of ipratropium bromide or placebo from identical containers. Baseline FEV₁ and vital capacity were measured and the measurements repeated after 40 minutes, one, two, four, and six hours, and any symptoms were elicited. In the second study, each patient received cumulative doses of 40 μg, 80 μg, and 120 μg. Baseline FEV₁ was obtained and repeated 35 minutes after each dose. The peak increase of the FEV₁ was comparable in both studies. The FEV₁ was slightly greater after 120 μg than after 40 μg. Although this reached statistical significance only in the first study, it was concluded that the cumulative dose-response technique was suitable for determining the peak response. However, this technique was unsuitable for assessing duration of effect, which could be examined only in the first study. After 120 μg of ipratropium bromide, the FEV₁ was significantly greater than after 40 μg at each time interval and it was greater than 80 μg at six hours (p<0·05). No significant side effects were noted in either study. When prolonged effective bronchodilation is sought, a dose of 120 μg of ipratropium bromide may be preferable to the recommended dose of 40 μg.     

Failure of ipratropium bromide to modify the diurnal variation of asthma in asthmatic children.

Thirty one children with asthma were given 40 micrograms of ipratropium bromide and identical placebo by inhalation three times a day in a double blind, randomised crossover study to test the ability of an anticholinergic drug to modify the diurnal variation in airway calibre and bronchial reactivity. Subjects measured peak expiratory flow rate approximately eight hourly, before and after inhaled salbutamol, for four week periods. Paired t tests and cosinor analysis were used to assess the diurnal variation in airway calibre from the peak expiratory flow rate recorded before salbutamol and to assess the diurnal variation in bronchodilator responsiveness from the increase in peak expiratory flow rate after salbutamol. Maintenance treatment with ipratropium bromide 40 micrograms three times daily reduced the provocative dose of histamine which caused a 20% fall in FEV1 (geometric mean PD20 = 0.78 v 0.49 mg/ml, p less than 0.05), despite an eight to 12 hour gap between the last dose of ipratropium and histamine challenge. It did not, however, diminish the diurnal variation in airway calibre (mean amplitude = 12.7 v 10.1) or in bronchodilator responsiveness (mean amplitude = 62.4 v 63.5). There was no improvement in the clinical state of subjects while they were taking ipratropium bromide.     

The effect of aerosol ipratropium bromide and salbutamol on exercise tolerance in chronic bronchitis.

In a double-blind placebo controlled trial in 24 patients fulfilling the MRC criteria for chronic bronchitis, ipratropium bromide 40 microgram and salbutamol 200 microgram produced similar and significant (P less than 0.001) increases in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). A greater increase in FEV1 and FVC was seen when both drugs were used together, but this increase did not differ significantly from that produced by either drug alone. Salbutamol increased 12-minute walking distance significantly (P less than 0.001) by 62 +/- 15 metres, whereas the increase of 43 +/- 15 metres observed after ipratropium was not significant (P less than 0.05). With both drugs in combination 12-minute walking distance increased by 72 +/- 15 metres, but this change was not significantly different from that observed with salbutamol alone. If aerosol bronchodilators in the doses used in this study are to be given with a view to improving exercise tolerance in such patients than salbutamol would appear to be the aerosol of choice.     

Effect of ipratropium bromide on mucociliary clearance and pulmonary function in reversible airways obstruction.

The effects of (a) regular use for one week and (b) a single dose of a synthetic anticholinergic (ipratropium bromide) on lung mucociliary clearance and as a bronchodilator was ascertained in a controlled, double-blind, cross-over study in 12 patients with reversible airways obstruction (mean increase in FEV after isoprenaline: 17% range 10-50%). Two puffs from a metered dose inhaler of either placebo (propellants only) or drug (40 microgram) were administered four times a day for one week (regular use), and mucociliary clearance was measured, by radioaerosol tracer, at the end of each treatment period and after a control period in which no treatment was given. On the mornings of the measurements after the placebo and drug periods one final dose (single dose) of ipratropium (40 microgram) or placebo was given 2.5 hours before the start of the test. There was no statistically significant difference between the three mean mucociliary clearance curves (control, placebo, and drug) for the group; however, there was a significantly greater penetration towards the periphery of the lung of the tracer in the test after drug administration compared with the other two. This increased penetration was attributed to bronchodilatation caused by the drug. Ipratropium bromide does not appear to impair mucociliary clearance, and it acts an effective bronchodilator.     

Assessment of the clinical usefulness of nebulised ipratropium bromide in patients with chronic airflow limitation.

The effect of adding nebulised ipratropium bromide to bronchodilator treatment was studied in 20 patients with severe chronic airflow limitation. Maintenance theophylline with or without a steroid preparation was continued and comparison made between placebo, nebulised salbutamol, and a combination of nebulised salbutamol and ipratropium. Although the mean FEV1 values showed the combination to produce a small but significant increase in peak bronchodilatation over the effect of salbutamol alone, there were eight patients in whom no clinically useful improvement occurred. The remaining 12 patients did obtain clinically useful improvement in the magnitude or the duration of bronchodilatation (or both) as a result of the added ipratropium. The conclusion is that individual patients with chronic airflow limitation responded to the addition of nebulised ipratropium bromide in a variable way. Patients who could obtain additional benefit from ipratropium need to be identified by an appropriate reversibility study before its inclusion in their bronchodilator treatment.     

Effect of four weeks'' high dose ipratropium bromide treatment on lung mucociliary clearance.

In a randomised, double blind crossover study the effect of high dose ipratropium bromide (200 micrograms three times daily given by metered dose inhaler for four weeks) on lung mucociliary clearance and on the wet weight and mean apparent viscosity of sputum was compared with that of placebo. Six smokers, six ex-smokers, and three non-smokers (12 men and three women, median age 60 years) were studied. Eight subjects had chronic obstructive lung disease (median FEV1 46% predicted) and seven had asthma (FEV1 70% predicted). Seven subjects produced sputum regularly, two of whom had asthma. Clearance of secretions was measured by an inhaled radioaerosol technique. The number of coughs and the wet weight, radioactive content, and mean apparent viscosity of sputum produced during the six hour observation period were recorded, as was the mean wet weight of sputum produced during the last two 24 hour periods ending each treatment. Comparison with placebo showed that treatment with high dose ipratropium bromide was associated with a significant increase in the penetration index of inhaled particles, but there was no significant change in alveolar deposition of particles or in tracheobronchial clearance, uncorrected or corrected for sputum expectorated. The wet weight of sputum produced, its radioactive content, and mean apparent viscosity were similar after treatment with ipratropium bromide and placebo. These results show that high dose inhaled treatment with the synthetic anticholinergic bronchodilator ipratropium bromide for four weeks is not associated with detectable modification of the clearance of secretions from the lungs, or of sputum volume or viscosity.     

F-Z液与UW液保存效果的比较研究

目的 比较F-Z液与Uw液在细胞水平的保存效果.方法 1.测定内皮细胞经保存-复温后上清中乳酸脱氢酶(LDH)浓度,比较保存一复温后损伤;2.以MTT法比较保存-复温后的内皮细胞活力.结果 1.保存时间24 h内,UW液组上清中乳酸脱氧酶(LDH)浓度与F-Z液组无明显差别;2.保存时间48 h内,UW液组MTT结果与F-Z液组无明显差别.结论 在细胞水平,于减轻保存-复温后损伤和维持被保存细胞活力两个方面,F-Z液均达到UW液相似的保存效果,因而具进一步开发研究价值.     

Bronchodilator effects of ipratropium bromide and albuterol sulfate among subjects with tetraplegia

Objective: In addition to lung volume restriction, persons with chronic tetraplegia demonstrate obstructive airway physiology evinced by pharmacologically-induced bronchodilation. We previously found independent evidence that anticholinergic agents (ipratropium bromide; IB) and beta-2 adrenergic agonists (albuterol sulfate; AS) were associated with significant bronchodilation in subjects with tetraplegia as determined via spirometry or body plethysmography. Direct comparison of these two classes of agents has received little attention.

Methods: Twelve subjects with chronic tetraplegia completed single dose treatment on alternate days with nebulized IB or AS. Patients underwent pre- and 30-minute post-bronchodilator spirometry, body plethysmography, and impulse oscillation system (IOS) in accordance with established protocols.

Results: Spirometry and specific airway conductance revealed significant bronchodilator responsiveness following both IB and AS. As determined by increases in specific airway conductance post-bronchodilator, IB tended toward greater bronchodilation than AS (71% vs. 47%). IOS revealed a greater reduction in central airway resistance (R20) following IB compared to AS (22% vs. 9%, P?Conclusion: Among subjects with tetraplegia, both IB and AS elicit significant bronchodilation, although the magnitude of the bronchodilator response is greater following IB. This lends support to theory of overriding cholinergic airway tone in tetraplegia. The IOS findings further suggest that the predominant site of action of IB is upon the larger central airways congruent with findings in able-bodied subjects.     

Bronchial responsiveness to hyperventilation in children with asthma: inhibition by ipratropium bromide.

Isocapnic hyperventilation dose response curves were constructed for 11 asthmatic children before and after pretreatment with placebo or ipratropium bromide, 40-1500 micrograms given by inhalation, on three separate days. The response before and after placebo was highly reproducible (within subject coefficient of variation 7.5%, 18%, and 22% for intervals of two hours, within two weeks, and over two weeks). It was independent of baseline lung function. Complete protection against hyperventilation induced asthma was achieved by ipratropium bromide 40 micrograms in six children and by 200 micrograms or more in a further four. The remaining child was unaffected by any dose of ipratropium up to 1500 micrograms. The dose of ipratropium required for protection was better related to the subjects' requirement for regular medication than to their sensitivity to hyperventilation or baseline lung function.     

异丙托溴铵对全麻病人呼吸力学的影响

目的通过麻醉前吸入异丙托溴铵,观察其对气管插管及机械通气时呼吸力学指标的影响。方法49例择期上腹部手术病人随机分为两组,雾化吸入异丙托溴铵0.5 mg的观察组(27例)和雾化吸入生理盐水的对照组(22例),分别于插管后即刻、插管后10、30及60 min监测呼吸力学指标的变化。结果观察组的气道峰压、呼吸功、吸气阻力和呼气阻力与对照组相比明显降低,而观察组肺顺应性明显高于对照组(P<0.05)。随着时间的延长,两组病人的气道峰压、呼吸功、吸气阻力和呼气阻力在不同时间点有不同程度的上升趋势;顺应性在下降到某一数值后则不再随时间而变化(P<0.05)。结论麻醉前雾化吸入异丙托溴铵,可降低机械通气早期气道峰压、呼吸机所做的呼吸功、吸气阻力及呼气阻力,同时改善肺动态顺应性。