Combination Of Ipratropium Research Articles

Therapy pattern of bronchodilators in chronic obstructive pulmonary disease (COPD) patients with acute exacerbations

Background: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a worsening condition of acute respiratory symptoms caused by microbial infection, increased air pollution, and fatigue. Objective: This study determines the pattern of bronchodilators in patients with acute exacerbations of COPD. Method: This study was observational, using the health medical records of patients with COPD at the Universitas Airlangga Hospital, Surabaya. It was conducted between January-December 2019 on male patients who received bronchodilator therapy until discharge and were from age 40 and older. Result: A total of 48 patients met the inclusion criteria. The most commonly used bronchodilator therapy for inpatients was the combination of ipratropium bromide/salbutamol sulfate 0.5 mg/2.5 mg through inhalation in 63.64%. The most frequently used bronchodilator for discharge was salbutamol sulfate 2-4 mg orally in 87.50%. Conclusion: Therapy for acute exacerbation of COPD using a combination of ipratropium bromide/salbutamol sulfate as a preventive therapy is in line with the GOLD guidelines.

Comparison of Efficacy of Nebulized Salbutamol with Salbutamol / Ipratropium Combination in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Objectives: To compare the nebulized salbutamol alone with combination of nebulized salbutamol and ipratropium for acute exacerbation of chronic obstructive pulmonary disease in terms of mean length of stay. Study Design: Quasi-experimental study Place and Duration of Study: Department of Medicine, Military Hospital, Rawalpindi Pakistan. Study was carried out over a period of six months from May to Nov 2017. Methodology: A total of 300 patients of chronic obstructive pulmonary disease (150 in each group) were recruited in the study. Group A received nebulized salbutamol (5mg) alone and Group B received a combination of nebulized salbutamol (5mg) and ipratropium bromide (0.5mg). Results: Mean age of the patients was 66.4±6.4 years and 65.7±6.8 years in Group-A and B, respectively. In Group-A, there were 136(90.7%) and in Group-B 134(89.3%) were males while 14(9.3%) and 16(10.7%) were females in Group-A and B, respectively. Mean duration of disease in Group-A was 5.2±2.4 years and in group-B 6.0±1.6 years. Comparison of mean length of stay (days) revealed in hospital between nebulized Salbutamol alone 5.0±0.5 days with combination of nebulized Salbutamol and Ipratropium 4.3±0.6 days with p-value <0.001. Conclusion: In conclusion, the routine addition of nebulized ipratropium bromide to salbutamol appears to be of benefit in the treatment of acute exacerbations of chronic obstructive pulmonary disease and in terms of mean length of hospital stay.

Comparison of efficacy between levosalbutamol and levosalbutamol-ipratropum nebulization in mild to moderate childhood asthma

Background: The objective of the study was to compare the efficacy between levosalbutamol and ipratropium combination over levosalbutamol nebulisation in reversing airflow obstruction and improve oxygenation, evaluated using the pulmonary asthma score, SaO2, and PEFR in mild and moderate asthma.Methods: A prospective, randomized, study was performed in RMMCH pediatric emergency department. Children between 6 and 12 years of age who presented with mild to moderate asthma exacerberations were enrolled in the study. They were randomly allocated into two different groups: one nebulised with levosalbutamol alone and another with addition of ipratropium bromide to levosalbutamol. Baseline Peak expiratory flow rate and Final absolute values or change from baseline 60-120 minutes after the inhalation are measured. Patients were evaluated using the pulmonary score.Results: After treatment there is improvement in the mean pulmonary asthma scores and PEFR percentage in A+B group than A group, but it is not statistically significant (p value >0.05). There is statistically significant improvement in pulmonary asthma score and PEFR in each of the groups after nebulisation and pulmonary asthma score has a sensitivity of 66.7% and 65.6% in diagnosing severity of asthma in relation to PEFR.

Efficacy and safety of eco-friendly inhalers: focus on combination ipratropium bromide and albuterol in chronic obstructive pulmonary disease

BackgroundChronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and its treatment is critical to improve quality of life, reduce symptoms, and diminish the frequency of COPD exacerbations. Due to the harmful environmental effects of pressurized metered-dose inhalers (pMDIs) containing chlorofluorocarbons (CFCs), newer systems for delivering respiratory medications have been developed.MethodsA search of the literature in the PubMed database was undertaken using the keywords “COPD,” “albuterol,” “ipratropium bromide,” and “Respimat® Soft Mist Inhaler™”; pertinent references within the identified citations were included. The environmental effect of CFC-pMDIs, the invention of the Respimat® Soft Mist Inhaler™ (SMI) (Boehringer Ingelheim, Ingelheim, Germany), and its use to deliver the combination of albuterol and ipratropium bromide for the treatment of COPD were reviewed.ResultsThe adverse environmental effects of CFC-pMDIs stimulated the invention of novel delivery systems including the Respimat SMI. This review presents its development, internal mechanism, and use to deliver the combination of albuterol and ipratropium bromide.ConclusionCFC-pMDIs contributed to the depletion of the ozone layer and the surge in disorders caused by harmful ultraviolet B radiation. The banning of CFCs spurred the development of novel delivery systems for respiratory medications. The Respimat SMI is an innovative device that produces a vapor of inhalable droplets with reduced velocity and prolonged aerosol duration that enhance deposition within the lower airway and is associated with improved patient satisfaction. Clinical trials have demonstrated that the Respimat SMI can achieve effects equivalent to pMDIs but with lower medication doses. The long-term safety and efficacy remain to be determined. The Respimat SMI delivery device is a novel, efficient, and well-received system for the delivery of aerosolized albuterol and ipratropium bromide to patients with COPD; however, the presence of longer-acting, less frequently dosed respiratory medications provide patients and providers with other therapeutic options.

BRONCHODILATATOR RESPONSIVENESS IN COPD

PURPOSE: Combination bronchodilatator therapy for chronic obstructive pulmonary disease (COPD) is available widely throughout the world. The subjects of reversibility to bronchodilatators in COPD has proven to be controversal.The aim of this stady was to determine the acute effect of salbutamol (S), Ipratropium bromide ( IB ), fixed combination Ipratropium bromide + Fenoterol (Berodual), Salbutamol and Ipratropium bromid (S,IB) by nebuliser on lung function in COPD patients.

Anticholinergic drugs for wheeze in children under the age of two years

Wheeze in infancy and early childhood is common and appears to be increasing though the magnitude of any increase is unclear. Most wheezing episodes in infancy are precipitated by respiratory viral infections. Treatment of very young children with wheeze remains controversial. Anti-cholinergics are often prescribed but practice varies widely and the efficacy of this form of therapy remains the subject for debate. Wheeze in infancy and early childhood is common and appears to be increasing. Most wheezing episodes in infancy are a result of viral infection. Bronchodilator medications such as beta2-agonists and anti-cholinergic agents are often used to relieve symptoms, but patterns of use vary. The objective of this review was to assess the effects of anti-cholinergic therapy in the treatment of wheezing infants. This is a second update of this review. We searched the Cochrane Airways Group Specialised Register of trials and the reference lists of articles. We contacted researchers in the field and industry sources. Searches were current as of June 2004. Randomised trials that compared anti-cholinergic therapy with placebo or beta2-agonists in wheezing children under two years of age. Children with acute bronchiolitis and chronic lung disease were excluded. Eligibility for inclusion and quality of trials were assessed independently by two reviewers. Six trials involving 321 infants in three different settings were included. Compared with beta2-agonist alone, the combination of ipratropium bromide and beta2-agonist was associated with a reduced need for additional treatment, but no difference was seen in treatment response, respiratory rate or oxygen saturation improvement in the emergency department. There was no significant difference in length of hospital stay between ipratropium bromide and placebo; or between ipratropium bromide and beta2-agonist combined compared with beta2-agonist alone. However, combined ipratropium bromide and beta2-agonist compared to placebo showed significantly improved clinical scores at 24 hours. Parents preferred ipratropium bromide over nebulised water or placebo for relief of their children's symptoms at home. A further updated search conducted in June 2004 did not yield any new studies. There is not enough evidence to support the uncritical use of anti-cholinergic therapy for wheezing infants, although parents using it at home were able to identify benefits.

Aging does not affect beta-agonist responsiveness after methacholine-induced bronchoconstriction.

To assess the response to an inhaled beta-agonist alone or in combination with an anticholinergic agent after methacholine-induced bronchoconstriction in four age groups. Retrospective analysis. Pulmonary function laboratory in a university-affiliated hospital. Seven hundred sixty-four consecutive subjects with a 20% reduction or more in forced expiratory volume during the first second (FEV1) of exhalation from total lung capacity after inhaling 189 or fewer cumulative units of methacholine were included in the analysis. The first 382 subjects received three inhalations of metaproterenol (total of 1.95 mg), and the other 382 subjects received three inhalations of albuterol and ipratropium combination (total of 309 microg of albuterol and 54 microg of ipratropium) after methacholine-induced bronchoconstriction. The response to bronchodilators was assessed as the postbronchodilator percentage change in FEV1 and the percentage of subjects recovering to 90% or better of baseline FEV1 after the use of bronchodilator. The percentage change in FEV1 postbronchodilator in the elderly was similar to that of the younger subjects. The percentage of subjects who recovered to 90% or better of their baseline FEV1 postbronchodilator was also similar in the elderly and younger age groups. Response to metaproterenol was similar to that of the albuterol/ipratropium combination in all age groups (all P>.05). Aging does not affect bronchodilator response to beta-agonist after methacholine-induced bronchoconstriction. The responsiveness to beta-agonist alone is similar to the responsiveness to the combination of beta-agonist and anticholinergic agent in all age groups.

Airway Reactivity Is a Determinant of Bronchodilator Responsiveness After Methacholine‐induced Bronchoconstriction

Airway hyperresponsiveness (AHR) is one of the characteristics of asthma and a risk factor for persistent airflow limitation. Poor response to bronchodilator may be a cause of persistent airflow limitation. Multiple factors may determine bronchodilator responsiveness, including airway reactivity to nonspecific bronchoconstrictive agents. If patients with AHR have poor bronchodilator responsiveness, then it could be a potential mechanism for asthma and persistent airflow limitation in these patients. The objective of this study is to assess the relationship between airway reactivity to methacholine and responsiveness to beta‐agonist and beta‐agonist/anticholinergic combination in a large subject population. A retrospective data analysis was undertaken of 764 consecutive subjects with ≥ 20% reduction in forced expiratory volume during the first second of exhalation from total lung capacity (FEV1) after ≤ 189 cumulative units of methacholine. The first 382 subjects received 3 inhalations of metaproterenol and the second 382 subjects received 3 inhalations of albuterol and ipratropium combination after ≥ 20% reduction in FEV1. Bronchodilator responsiveness was measured as the percent increase in FEV1 after the treatment. Airway reactivity was assessed as the log10 of methacholine dose response slope. In a simple linear regression model, airway reactivity was significantly related to bronchodilator responsiveness. The coefficient of determination (r2) was 0.15 for the whole groups; 0.14 for metaproterenol group and 0.18 for albuterol/ipratropium combination group (all p < 0.0001). The regression coefficient (β) was 14.0 for the whole group; 14.8 and 13.2, respectively, for the two bronchodilator groups. Airway reactivity to methacholine is a determinant of airway responsiveness to both beta‐agonist and beta‐agonist/anticholinergic combination. Subjects with higher airway reactivity have higher bronchodilator responsiveness.

Use of a Mucus Clearance Device Enhances the Bronchodilator Response in Patients With Stable COPD

To determine whether the use of a mucus clearance device (MCD) [Flutter; Axcan Scandipharm; Birmingham, AL] could improve the bronchodilator response to inhaled ipratropium and salbutamol delivered by a metered-dose inhaler in patients with stable, severe COPD. Twenty-three patients with severe COPD were studied. Mean +/- SD age was 71.7 +/- 6.3 years. Mean FEV(1) was 0.74 +/- 0.28 L or 34.5 +/- 12.7% predicted. Patients were tested in random order on 2 subsequent days after using an MCD or a sham MCD. A bronchodilator (four puffs; each puff delivering 20 microg of ipratropium bromide and 120 microg of salbutamol sulfate) was administered by metered-dose inhaler with a holding chamber after use of the MCD or sham MCD. Spirometry was performed before and after use of the MCD or sham MCD, and at 30 min, 60 min, and 120 min after the bronchodilator. Six-minute walk distance was tested between 30 min and 60 min; oxygen saturation, pulse, and a dyspnea score were recorded before and after walking. Immediately after use of the MCD, but not the sham MCD, there was a statistically significant (p < 0.05) improvement in FEV(1) and FVC (11 +/- 24% vs 1 +/- 7% and 18 +/- 33% vs 6 +/- 18%, respectively). Whether patients were pretreated with the MCD or sham MCD, there was a significant improvement in FEV(1) and FVC compared to baseline with combined bronchodilator therapy. At 120 min, the change in FEV(1) after treatment with the MCD was greater than with the sham MCD (186 +/- 110 mL vs 130 +/- 120 mL; p < 0.05). When comparing the MCD to the sham MCD, 6-min walk distance was greater (174 +/- 92 m vs 162 +/- 86 m; p < 0.05), with less dyspnea before and at the end of walking. Patients with severe COPD may demonstrate a significant bronchodilator response to combined ipratropium and salbutamol delivered by metered-dose inhaler. This response may be enhanced and additional functional improvement obtained with the prior use of a bronchial MCD.

Anticholinergic drugs for wheeze in children under the age of two years.

Wheeze in infancy and early childhood is common and appears to be increasing though the magnitude of any increase is unclear. Most wheezing episodes in infancy are precipitated by respiratory viral infections. Treatment of very young children with wheeze remains controversial. Anti-cholinergics are often prescribed but practice varies widely and the efficacy of this form of therapy remains the subject for debate. Wheeze in infancy and early childhood is common and appears to be increasing. Most wheezing episodes in infancy are a result of viral infection. Bronchodilator medications such as beta2-agonists and anti-cholinergic agents are often used to relieve symptoms, but patterns of use vary. The objective of this review was to assess the effects of anti-cholinergic therapy in the treatment of wheezing infants. We searched the Cochrane Airways Group trials register and the reference lists of articles. We contacted researchers in the field and industry sources. Randomised trials that compared anti-cholinergic therapy with placebo or beta2-agonists in wheezing children under two years of age. Children with acute bronchiolitis and chronic lung disease were excluded. Eligibility for inclusion and quality of trials were assessed independently by two reviewers. Six trials involving 321 infants in three different settings were included. Compared with beta2-agonist alone, the combination of ipratropium bromide and beta2-agonist was associated with a reduced need for additional treatment, but no difference was seen in treatment response, respiratory rate or oxygen saturation improvement in the emergency department. There was no significant difference in length of hospital stay between ipratropium bromide and placebo; or between ipratropium bromide and beta2-agonist combined compared with beta2-agonist alone. However, combined ipratropium bromide and beta2-agonist compared to placebo showed significantly improved clinical scores at 24 hours. Parents preferred ipratropium bromide over nebulised water or placebo for relief of their children's symptoms at home. There is not enough evidence to support the uncritical use of anti-cholinergic therapy for wheezing infants, although parents using it at home were able to identify benefits.

Formoterol Monotherapy Compared with Combined Ipratropium Bromide plus Fenoterol in the Treatment of Chronic Obstructive Pulmonary Disease

Objectives To compare the efficacy and tolerability of formoterol (12 or 24μg twice daily) alone with combined ipratropium bromide and fenoterol in the treatment of chronic obstructive pulmonary disease (COPD).

Pharmacoeconomic Evaluation of COPD

The clinical outcomes and health-care costs of a cohort of 413 patients with COPD are reported. This study was a retrospective pharmacoeconomic analysis. University teaching hospital and affiliated clinics. COPD patients with an FEV(1) < 65% of predicted and an FEV(1)/FVC ratio < 70% were eligible to be included in this analysis. Health-care resource utilization and costs were identified through chart review and were stratified according to the severity of COPD using the American Thoracic Society stages I, II, and III. The pharmacoeconomic analysis was a cost-of-illness evaluation that included the acquisition costs of initially prescribed pulmonary drugs, acquisition cost of pulmonary drugs added during the follow-up period, oxygen therapy, laboratory and diagnostic test costs, clinic visit costs, and emergency department and hospital costs. Total treatment cost was highly correlated with disease severity, with stage I COPD having the lowest cost ($1,681 per patient per year), stage III COPD having the highest cost ($10, 812 per patient per year), and stage II COPD having a cost intermediate to stage I and stage III ($5,037 per patient per year). With the exception of add-on drug acquisition cost, all cost variables were the highest in stage III COPD, the lowest in stage I COPD, and intermediate in stage II COPD. Hospitalization was the most important cost variable for all three stages of COPD severity. When stratified by both disease severity and initial bronchodilator drug selection, ipratropium alone in stage I COPD patients and the combination of ipratropium plus a ss-agonist (with or without steroid therapy) in stage II and stage III COPD patients had the lowest total costs. Reasons for the lower total cost of the ipratropium and ipratropium plus ss-agonist treatment groups included lower add-on drug costs, fewer diagnostic and laboratory tests, and a lower utilization rate for clinic visits, emergency department visits, and hospitalizations. Our study demonstrates a strong correlation between disease severity and total treatment cost in COPD. In addition, the type of bronchodilator therapy impacts total cost in COPD. In stage I COPD, ipratropium alone had the lowest total cost, while in stage II and stage III COPD, a combination of ipratropium plus a ss-agonist had the lowest total cost. These data support the concept that adherence to published treatment guidelines will result in lower health-care costs due to COPD.

The Role of Ipratropium Bromide in the Emergency Management of Acute Asthma Exacerbation: A Metaanalysis of Randomized Clinical Trials

Study objective: This study was conducted to determine whether the addition of inhaled ipratropium to inhaled β-agonist therapy is effective in the treatment of adults with acute asthma exacerbation. Methods: Published reports of randomized, controlled trials assessing the use of ipratropium and β-agonists in asthma were identified by a search of the MEDLINE, EMBASE, CINAHL, Biological Abstracts on CD, the Cochrane Library, and Current Contents databases. Bibliographies from identified studies and from review articles were manually searched. Published and unpublished reports in English, French, and Italian were identified and assessed for inclusion in the metaanalysis. Randomized, double-blind, placebo-controlled trials were selected in which ipratropium was used as adjunctive therapy to β-agonists in adult patients with acute asthma exacerbation presenting to a hospital emergency department or similar acute care setting. Data were extracted independently by 2 reviewers. For eligible trials, the mean percent change in peak expiratory flow rate (PEFR), or forced expiratory volume in one second (FEV 1 ), and their SDs were assessed in the ipratropium-treated and control groups. The effect of ipratropium on hospitalization rates and adverse effects were also analyzed. Results: Data from 10 studies, reporting on a total of 1,377 patients with asthma, were pooled using a weighted average method. Compared with placebo, the use of ipratropium was associated with a pooled 7.3% improvement in FEV 1 (95% confidence interval [CI] 3.8% to 10.9%), corresponding to an absolute improvement in FEV 1 in the ipratropium/ β-agonist group, which was 100 mL (95% CI 50 to 149 mL) above that seen for the group that received β-agonist without ipratropium. Similarly, the pooled estimate of treatment effect in trials that reported data as PEFR was 22.1% (95% CI 11.0% to 33.2%), corresponding to an absolute peak expiratory flow improvement of 32 L/min (95% CI 16 to 47 L/min) in favor of the ipratropium/ β-agonist combination group. When these data were combined using effect size as a common measure, the use of ipratropium was associated with a summary effect size of .38 (95% CI .27 to .48). Effect sizes were negatively correlated with baseline mean expiratory flows, suggesting that studies enrolling patients with more severe airflow obstruction showed greater absolute benefits of combination bronchodilator therapy. For the 3 trials reporting hospital admission data (n=1,031), patients receiving ipratropium had a relative risk of hospitalization of .73 (95% CI .53 to .99). The use of ipratropium was not associated with any severe adverse effects when used in conjunction with β 2 -agonists. Conclusion: There is a modest statistical improvement in airflow obstruction when ipratropium is used as an adjunctive treatment to β 2 -agonists for the treatment of acute asthma exacerbation. Although the clinical significance of this improvement in airflow obstruction remains unclear, it would seem reasonable to recommend the use of combination ipratropium/ β-agonist therapy in acute adult asthmatic exacerbations, since the addition of ipratropium seemed to provide physiologic evidence of benefit without risk of adverse effects.[Stoodley RG, Aaron SD, Dales RE: The role of ipratropium bromide in the emergency management of acute asthma exacerbation: A metaanalysis of randomized clinical trials. Ann Emerg Med July 1999;34:8-18.]

Superiority of Ipratropium Plus Albuterol Over Albuterol Alone in the Emergency Department Management of Adult Asthma: A Randomized Clinical Trial

Study objective: The use of nebulized ipratropium in combination with β-agonists for the treatment of acute asthma in adults is controversial. We wished to test the hypothesis that combined aerosol treatment results in a greater rate of airflow improvement and a lower proportion of hospital admission in adults with acute asthma. Methods: In a randomized, double-blind, placebo-controlled trial, 55 adult asthmatic patients with peak expiratory flow rate (PEFR) less than 200 L/min were randomly assigned to nebulization treatment with albuterol alone (2.5 mg initial dose followed by 2 more doses at 20-minute intervals), or the same albuterol regimen plus ipratropium (.5 mg combined with the initial dose of albuterol only). Patients were recruited from an emergency department at an urban academic medical center. The primary endpoints were changes in PEFR and in percent predicted PEFR over time (ie, treatment by time effect). PEFRs were assessed at baseline and at 20-minute intervals for a 1-hour period. The proportion of admissions in the two groups were examined as secondary endpoints. Results: The increases in PEFR and percent predicted PEFR over time were both significantly greater in the combined ipratropium plus albuterol treatment group ( P≤.001). In addition, the proportion of admitted patients was less in this group (3/27) than the proportion in the albuterol-only group (10/28). The 95% confidence interval for the absolute difference of 25% in the proportion admitted was 3% to 46%, P=.03. Most of the baseline clinical and historical features in the two groups were similar. Conclusion: These data suggest that ipratropium should be combined with initial albuterol nebulization in the ED treatment of acute asthma in adults, especially those with PEFRs less than 200 L/min. [Lin RY, Pesola GR, Bakalchuk L, Morgan JP, Heyl GT, Freyberg CW, Cataquet D, Westfal RE: Superiority of ipratropium plus albuterol over albuterol alone in the emergency department management of adult asthma: A randomized clinical trial. Ann Emerg Med February 1998;31:208-213.]

Routine Nebulized Ipratropium and Albuterol Together Are Better Than Either Alone in COPD

We compared the long-term safety and efficacy of the combination ipratropium bromide (IB) and albuterol sulfate (ALB) inhalation solution with that of each separate component using three-times-daily administration. Using a parallel design, we randomized patients to receive 3.0 mg ALB, 0.5 mg IB, or the combination by small-volume nebulizer (SVN) for 85 days. Subjects were allowed to use up to two extra doses of study medication daily for control of symptoms on an as-needed basis. The main efficacy evaluation was the acute pulmonary function response to an aerosol of the maintenance study medication over the course of the investigation. Physician global evaluation, subject quality of life assessments, COPD symptom scores, and twice-daily peak expiratory flow rate (PEFR) were also assessed over the study period. Twenty-five centers participated in the investigation. We studied 652 patients with moderate to severe COPD. Over the course of the study, the acute spirometric response and evening PEFR values with the SVN combination of IB plus ALB were statistically significantly better compared to ALB or IB alone. The quality of life scores, physician global evaluations, symptom scores, and morning PEFR scores were unchanged over the duration of the study in all treatment groups. There was no significant difference in adverse events in the three treatment groups. In patients with COPD, maintenance SVN therapy with IB and ALB provides better bronchodilation than either therapy alone without increasing side effects.

In Chronic Obstructive Pulmonary Disease, a Combination of Ipratropium and Albuterol Is More Effective Than Either Agent Alone

Combination bronchodilator therapy for chronic obstructive pulmonary disease (COPD) is widely available throughout the world except in North America. Previous studies have yielded conflicting results regarding the advantages of combining anticholinergic therapy with sympathomimetic therapy in COPD. The authors report the results of a 12-week prospective, double-blind, parallel-group evaluation of the use of the following: albuterol, a ±-adrenergic agent; ipratropium, an anticholinergic agent; or a combination of the two, administered by metered-dose inhaler to patients with moderately severe stable COPD. Following baseline studies, 534 patients were given one of the 3 bronchodilator preparations to be used at home 4 times daily, in addition to oral theophylline and corticosteroids as required. The doses of the latter two drugs were kept stable. Subjects were tested on days 1, 29, 57, and 85. Analysis of 1-s forced expiratory volume (FEV1) curves on those test days indicated that the combination was superior to either single agent alone in peak effect, in the effect during the first 4 hours after dosing, and in the total area under the curve of the FEV1 response. The mean peak percent increases in FEV1 over baseline on the 4 test days were 31% to 33% for the combination, 24% to 25% for ipratropium, and 24% to 27% for albuterol. The differences between the combination and its components were statistically significant on all test days. The AUC0–4 means for the combination were 21% to 44% greater than the ipratropium means, and 30% to 46% greater than the albuterol means. Similar changes were noted in the forced vital capacity curves. Symptom scores did not change over time and did not differ among the treatment groups. The authors conclude that the combination of ipratropium and albuterol, when given by metered-dose inhaler to patients with COPD, is more effective than either of the two agents alone. The advantage of the combination is apparent primarily during the first 4 hours after administration. The availability of combination therapy by metered-dose inhaler should help to improve patient compliance.

In Chronic Obstructive Pulmonary Disease, a Combination of Ipratropium and Albuterol Is More Effective Than Either Agent Alone: An 85-Day Multicenter Trial

Combination bronchodilator therapy for chronic obstructive pulmonary disease (COPD) is available widely throughout the world except in North America. Previous studies have yielded conflicting results regarding the advantages of combining anticholinergic therapy with sympathomimetic therapy in COPD. We report the results of a 12-week prospective, double-blind, parallel-group evaluation of the use of the following: albuterol, a beta-adrenergic agent; ipratropium, an anticholinergic agent; or a combination of the two, administered by metered-dose inhaler to patients with moderately severe stable COPD. Following baseline studies, 534 patients were given one of the three test bronchodilator preparations to be used at home four times daily in addition to oral theophylline and corticosteroids as required. The doses of the latter two drugs were kept stable. Subjects were tested on days 1, 29, 57, and 85. Analysis of 1-s forced expiratory volume (FEV1) curves on those test days indicated that the combination was superior to either single agent alone in peak effect, in the effect during the first 4 h after dosing, and in the total area under the curve of the FEV1 response. The mean peak percent increases in FEV1 over baseline on the four test days were 31 to 33 percent for the combination, 24 to 25 percent for ipratropium, and 24 to 27 percent for albuterol. The differences between the combination and its components were statistically significant on all test days. The AUC0-4 means for the combination were 21 to 44 percent greater than the ipratropium means and 30 to 46 percent greater than the albuterol means. Similar changes were noted in the forced vital capacity curves. Symptom scores did not change over time and did not differ among the treatment groups. We conclude that the combination of ipratropium and albuterol, when given by metered-dose inhaler to patients with COPD, is more effective than either of the two agents alone. The advantage of the combination is apparent primarily during the first 4 h after administration. The availability of combination therapy by metered-dose inhaler should help to improve patient compliance.

Response to nebulizaed ipratropium bromide and terbutaline in acute severe asthma

Outpatient studies on asthmatics have shown that inhaled anti-cholinergic agents decrease in efficacy as FEV1 falls. To determine whether there are changes in response to inhaled anti-cholinergics during acute bronchoconstriction we have examined the effects of nebulized ipratropium and terbutaline in nine hospitalized patients recovering from acute severe asthma. At 6 a.m. each day throughout the admission, baseline PEFR was recorded. Ipratropium bromide, 1 mg, was nebulized and PEFR measured again 1 h later. Following this, terbutaline, 5 mg, was nebulized with further measurement of PEFR 15 min after nebulization. Results were analysed by paired t-tests. Mean baseline PEFR rose from 157 l m-1 on patients worst day to 300 l m-1 on their best day (P less than 0.01). Ipratropium improved mean PEFR by 55 l m-1 and 42 l m-1 on patients worst and best days respectively (P less than 0.01). Subsequent terbutaline improved mean PEFR on patients worst day by 23 l m-1 (P less than 0.01) but only by a non-significant 4 l m-1 on their best day (P = 0.09). Hence, ipratropium produced 96% of total bronchodilatation when baseline was highest, but achieved only 71% of total response when baseline was lowest, a highly significant change in response (P less than 0.01). We conclude that in acute severe asthma as baseline PEFR rises response to inhaled ipratropium improves, compared with total response to combined ipratropium followed by terbutaline.

The Effect of Nebulized Bronchodilator Therapy on Intraocular Pressures in Patients with Glaucoma

A controlled double-blind crossover study of ocular complications associated with nebulized ipratropium bromide and salbutamol therapy for respiratory distress was undertaken in 46 chronic bronchitis patients. There was no significant rise in intraocular pressure or change in anterior chamber angle in patients with open-angle glaucoma, narrow-angle glaucoma or control subjects following treatment with either drug. However, when the two drugs were used in combination, intraocular pressure rose in patients with narrow-angle glaucoma but not in patients with open-angle glaucoma or in control subjects. Transient angle closure was seen in five of these patients. Intraocular pressures did not rise when swimming goggles were used to protect the eyes or when antiglaucoma treatment was continued. Nebulized bronchodilator therapy is safe in nonglaucomatous patients and those with open-angle glaucoma. Ocular complications can follow combined ipratropium bromide and salbutamol nebulization in patients with narrow-angle glaucoma, but can be prevented by using the drugs separately, protecting the eyes and ensuring continued antiglaucoma measures.

Exercise-Induced Asthma (EIA): Its Prevention with the Combined Use of Ipratropium Bromide and Fenoterol

Until now very few studies have been performed on the prevention of exercise-induced asthma (EIA) in children with ipratropium bromide + fenoterol. This is why we decided to study 30 children aged between 6 and 15 years, whose EIA was confirmed by a test including a 6-min free race on day 1 of the study. The criterion was a decrease of more than 20% of the basal values of forced expiratory volume in 1 s (FEV1) or FMF. Children whose FEV1 or FMF baseline values were under 60% of those expected according to Polgard tables were excluded. Three tests were performed, the first to determine EIA, the second was performed 72 h later after inhalation of placebo. 72 h after day 2 the patients returned in order to repeat the test, but this time, aerosol therapy with the combination ipratropium + fenoterol was applied prior to the race. The dosage of the combination was 1 puff of aerosol per 10 kg body weight, up to a maximum of 4 puffs. Each puff of the combination contains 0.02 mg of ipratropium bromide and 0.05 mg fenoterol. Functional assessment of children was carried out by means of forced spirometry. There were no significant differences between the placebo group and the group which received no medication, but there was a significant difference between the treated group and the other two, not only in the FEV1 and FMF values but also in forced vital capacity TEST.(ABSTRACT TRUNCATED AT 250 WORDS)