Bronchodilator efficacy of the fixed combination of ipratropium and albuterol compared to albuterol alone in moderate-to-severe persistent asthma (original) (raw)
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American Journal of Respiratory and Critical Care Medicine, 2000
We designed a larger, double-blind, randomized, prospective trial to test our hypothesis that patients with acute asthma given combination high dose therapy with ipratropium bromide (IB) and  2agonists will have greater improvement in pulmonary function and fewer hospital admissions than those given  2-agonists alone. One hundred eighty patients (mean age Ϯ SD, 34.3 Ϯ 10.5 yr) who presented to an emergency department (ED) for treatment of an exacerbation of asthma (baseline FEV 1 Ͻ 50% of predicted) were assigned in a randomized, double-blind fashion to receive albuterol and placebo (n ϭ 92) or albuterol and IB (n ϭ 88). Both drugs were administered through a metered-dose inhaler and spacer at 10-min intervals for 3 h (24 puffs or 2,880 g of albuterol and 504 g of IB each hour). Primary outcome measures were improvement in pulmonary function (FEV 1 or peak expiratory flow [PEF]), and hospital admission rates. In both groups, pulmonary function improved significantly over baseline values (p Ͻ 0.01). Subjects who received IB had an overall 20.5% (95% CI: 2.6 to 38.4%) (p ϭ 0.02) greater improvement in PEF and a 48.1% (95% CI: 19.8 to 76.4%) (p ϭ 0.001) greater improvement in FEV 1 from the control group. At the end of protocol (3 h), 39% (n ϭ 36) of patients in the control group and 20% (n ϭ 18) in the IB group were admitted (p ϭ 0.01). The use of high doses of IB reduced the risk of hospital admission 49% (relative risk ϭ 0.51, 95% CI: 0.31 to 0.83). Five (95% CI: 3 to 17) patients would need to be treated with high doses of IB to prevent a single admission. Kaplan-Meierestimated curves of the proportion of patients who reached the discharge threshold during the 3 h of treatment, showed a significant difference in favor of the IB group (log-rank test ϭ 0.005). A subgroup analysis showed that patients most likely to benefit from the addition of high doses of IB were those with more severe obstruction (FEV 1 р 30% of predicted) and long duration of symptoms before the ED presentation (у 24 h). On the contrary, previous use of inhaled  2-agonists did not modify the admission rate and the pulmonary function response to IB. In conclusion, our data support a substantial therapeutic benefit from the addition of IB to albuterol administered in high doses through MDI plus spacer, particularly in patients with FEV 1 less than 30%, and with long duration of symptoms before the ED presentation (у 24 h).
The role of ipratropium bromide as adjunct therapy to p-agonists in acute asthma is uncertain. We therefore decided to compare the use of 3 mg of salbutamol sulfate alone vs 3 mg salbutamol sulfate with 0.5 mg ipratropium bromide in patients with acute asthma. Patients presenting with acute asthma and an FEVX less than 70% predicted were randomized to a single combination treatment vs salbutamol alone. All patients received supplemental oxygen and methylpred-nisolone, 125 mg, IV. Baseline measurements were repeated at 45 and 90 min and these included spirometry, oximetry, and vital signs. A total of 952 patients were screened of whom 342 patients were deemed eligible and were randomized in two groups of 171 patients. The mean (SE) age was 30 years (0.9) vs 29 years (0.7), women, 103 (60.2%) vs 110 (64%), 81 (47.4%) never-smoked vs 83 (48.5%), and duration of asthma in years 16.0 (0.8) vs 16.6 (0.8) were no different in the combination vs salbutamol alone group, respectively. Likewise, there was no significant differ¬ ence in asthma therapy received in the 24 h prior to presentation; most notably, 151 (88.3%) vs 153 (89.5%) received inhaled p-agonists in that period. Baseline FEVj was 1.62 L (0.05 L) vs 1.53 L (0.03 L), and median time to treatment being received was no different between both groups. Both treatment arms improved significantly. The increase in FEVX in the combination group was 0.61 L (0.04 L) and in the salbutamol alone group was 0.52 L (0.04 L) at 90 min. There was a trend toward greater bronchodilatation in the combination group, but this did not reach statistical significance. Fewer hospitalizations, 5.9% vs 11.2%, occurred in the combination group, but this did not reach statistical significance. In conclusion, this large multicenter study failed to show a significantly better response to a combination of salbutamol and ipratropium bromide vs salbutamol alone. (CHEST 1997; 111:311-15)
Combination bronchodilator therapy in asthma
Journal of Allergy and Clinical Immunology, 1982
This study has compared the short-term bronchodilator effects of inhaled anticholinergic (ipratropium bromide) and sympathomimetic (fenoterol) agents alone and in combination in 18 asthmatic patients. The study was of double-blind, placebo-controlled, crossover design. The combination of 60 hg ipratropium bromide and 200 pg offenoterol had a greater bronchodilator effect than lower dose combinations or either drug alone. Small but significant gains may be made with combination inhaled bronchodilator therapy. (J ALLERGY CLIN IMMUNOL 69:60, 1982.)
The Journal of pediatrics, 1995
The objective of this trial was to determine the efficacy of frequent nebulized ipratropium added to high-dose albuterol therapy in children with severe asthma. One hundred twenty children (5 to 17 years) of age) with severe acute asthma (forced expiratory volume in 1 second (FEV1), < 50% of the predicted value) were enrolled into a randomized double-blind three-arm placebo-controlled trial comparing three groups: group 1, three doses of nebulized ipratropium bromide within 60 minutes (250 micrograms/dose); group 2, one dose of ipratropium; group 3, no ipratropium. All patients were also treated with three doses of nebulized albuterol within 60 minutes (0.15 mg/kg per dose). Pulmonary function and clinical measures were assessed every 20 minutes for up to 120 minutes. The groups were comparable at baseline. At 120 minutes, the mean percentage of predicted FEV1 improved from 33.4% to 56.7% in group 1, from 34.2% to 52.3% in group 2, and from 35.4% to 48.4% in group 3 (p = 0.0001)....
Journal of Pediatrics, 2001
nary ammonium derivative of atropine that is poorly absorbed from mucosal surfaces. Laboratory pulmonary function tests demonstrate enhanced bronchodilation from β-agonists when given in combination with IB. 1 Evidence from clinical trials, however, does not uniformly support the routine addition of inhaled anticholinergic therapy to β-agonists for the management of acute asthma. In the emergency department setting, some randomized placebo-controlled trials demonstrate modest benefits from combined IB-β agonist therapy for at least a subset of patients. 6,7 Although anticholinergic agents are often used in the hospital treatment of patients with status asthmaticus, their efficacy in this setting remains uncertain. We conducted a randomized, double-blind, placebo-controlled trial to examine the effect on hospital length of stay, asthma carepath progression, requirement for additional therapy, and side effects resulting from the addition of repeated doses of nebulized IB with standardized β-agonist and systemic corticosteroid therapy for hospitalized children with acute asthma.
Meta-analysis of the effects of ipratropium bromide in adults with acute asthma: The reply
The American Journal of Medicine, 2000
To determine whether inhaled ipratropium bromide provides additional benefits to adults with acute asthma, who are being treated with beta-agonists in an emergency department. Searching MEDLINE was searched from 1978 to April 1999 using the following MeSH terms: 'N-isopropylatropine' or 'ipratropium bromide', and 'adult', 'acute asthma' or status asthmaticus'. Searches of Current Contents, the Science Citation Index, and review articles were also performed. Studies were limited to those published in the English language. Details of additional published and unpublished studies were obtained by contacting experts (pulmonologists and emergency physicians) and the manufacturer of ipratropium bromide (Boehringer Ingelheim), and by searching the Medical Editors Trial Amnesty. Study selection Study designs of evaluations included in the review Randomised, double-blind controlled trials (RCTs) were eligible for inclusion. Specific interventions included in the review Studies comparing the addition of inhaled ipratropium bromide to treatment with beta-agonists in an emergency department were eligible. The dosing regimes of ipratropium were: once only; twice every 45 minutes to 2 hours; or continuously. The dosing regimes of the beta-agonists were: for fenoterol, once or twice every 30 minutes; and for salbutamol, once or twice every 45 minutes to 2 hours, thrice every 20 minutes, or continuously. The cointerventions included corticosteroids. Participants included in the review Adults (older than 16 years) with acute exacerbations of asthma were eligible. The mean age of the participants ranged from 30 to 50 years, and 36% were men. The mean baseline asthma severity ranged from 34% to greater than 40% for forced expiratory volume in 1 second (FEV1), and from less than 30% to less than 45% for peak expiratory flow (PF). Outcomes assessed in the review The inclusion criteria for the outcomes were not defined. All studies measured pulmonary function as a continuous variable in terms of FEV1 and PF, and reported them as percentages of the predicted values. The admission rates and adverse events were also assessed. How were decisions on the relevance of primary studies made? Two authors independently examined the search and reviewed each identified study according to the inclusion criteria. Any disagreements were resolved by consensus. Assessment of study quality Validity was assessed and scored using the following criteria: randomisation method, scored 1 (not specified) to 2 (specified); demographic characteristics of the sample provided, scored from 0 (none) to 2 (detailed; inclusion and exclusion criteria specified, scored from 0 (none) to 2 (detailed); asthma definition, scored from 0 (no definition) to 2 (American Thoracic Society criteria used);
Combined Ipratropium and 2-Adrenergic Receptor Agonist in Acute Asthma
Journal of the American Board of Family Medicine, 2000
This munth we continue the new feature-STEPped Care: An Evidence-BtlSedApproach to Drug Therapy. These articles are designed to provide concise answers to the drug therapy questions that family physicians encounter in their daily practice. The format of the feature will follow the mnemunic STEP: safety (an analysis of adverse effects that patients and providers care about), tolerability (pooled drop-out rates from large clinical trials), effectiveness (how well the drugs work and in what patient population[sJ), and price (costs of drug, but also cost effectiveness of therapy). I Hence, the name STEPped Care. Since the informatics pioneers at McMtlSter University introduced evidence-btlSed medicine, 2 Slawson and colleague!,4 have brought it to mainstream family medicine education and practice. This feature is designed to further the mission of searching for the truth in medical practice. Authors will provide information in a structured format that allows the readers to get to the meat of a therapeutic issue in a way that can help physicians (and patients) make informed decisions. The articles will discourage the use of disetlSe-oriented evidence (DOE) to make treatment decisions. Examples of DOEs include blood pressure lowering, decretlSes in hemoglobin Ale> and so on. We will include studies that are POEMs-patientoriented evidence that matters (myocardial infarctions, pain, strokes, mortality, etc)-with the goal of offering our patients the most practical, appropriate, and scientifically substantiated therapies. Number needed to treat to observe benefit in a single patient will also be included tIS a way of defining advantages in terms that are relatively easy to understand. 5,6 At times this effort will be frustrating. Even tIS vtlSt tIS the biomedical literature is, it does not always support what clinicians do. We will avoid making conclusions that are not Asthma is a chronic inflammatory disease of the lungs that afflicts an estimated 13.7 million people
Active Albuterol or Placebo, Sham Acupuncture, or No Intervention in Asthma
New England Journal of Medicine, 2011
BACKGROUND-In prospective experimental studies in patients with asthma, it is difficult to determine whether responses to placebo differ from the natural course of physiological changes that occur without any intervention. We compared the effects of a bronchodilator, two placebo interventions, and no intervention on outcomes in patients with asthma.
Chest, 1996
Inhaled f-agonists are the treatment of choice for patients with acute asthma presenting to the Emergency Department (ED).' The choice of nebulized medication in most EDs has been nebulized albuterol. Even though the package insert for albuterol recommends only 2.5 mg administered 3 to 4 times per day, common practice in the acute setting is to give the medication more frequently and in higher doses. Current recommendations are to give three nebulization treatments of albuterol, 2.5 mg (0.5 mL in 2 to 3 mL of saline solution) within the first 1 to 1.5 h.' Theoretically, the more frequent the administration of inhaled treatment, the earlier the delivery of medication to progressively distal regions of the tracheobronchial tree, ie, as bronchoconstriction is alleviated proximally, more medication is delivered distally. When the med