Metered-dose Inhaler Group Research Articles

Respule or metered-dose inhaler for eosinophilic esophagitis treatment? A dose-ranging, randomized clinical trial study on efficacy, safety, and relapse rate

<sec><title>Background</title><p>Eosinophilic esophagitis (EoE) is a chronic allergen/immune-mediated disease known by eosinophil infiltration into the esophagus. Topical steroids are used for its treatment. We investigated the efficacy, side effects, and symptom relapse after discontinuation of two budesonide forms in EoE patients.</p></sec><sec><title>Methods</title><p>In this prospective, dose-ranging, randomized trial, 35 EoE patients under 18 years who received two budesonide forms were assigned to low-dose oral respule (17 patients) and swallowed metered-dose inhaler (MDI) (18 patients) groups. Both groups received low-dose budesonide for eight weeks. Doses were doubled after the first eight weeks if symptom remission was not achieved, but the previous dose was continued for the next eight weeks for the subjects with symptom relief. At the end of week 16, budesonide was discontinued in all patients. The following outcomes were assessed: The primary outcome was symptom relief, assessed by Pediatric EoE Symptom Scores (PEESS®v2.0). Secondary outcomes included safety, side effects, and histological changes, based on repeated endoscopy at weeks 0, 8, 16, and 32.</p></sec><sec><title>Results</title><p>Non-response to low-dose treatment in the first eight weeks was observed in 2 cases (13.3%, 95% CI: 2.6%–35.2%) in the respule group and 7 cases (50.0%, 95% CI: 22.7%–77.3%) in the MDI group, indicating a significant difference between the groups (p = 0.033). In the 16<sup>th</sup> week, the treatment failure rate was 13.3% and 26.6% in the oral respule and swallowed MDI groups, respectively (p = 0.048). The therapeutic response during the 8<sup>th</sup> week was significantly higher in oral respule group than swallowed MDI group (OR = 8.418, p = 0.046).</p></sec><sec><title>Conclusion</title><p>This study indicates that the oral respule formulation of budesonide is more effective than the swallowed MDI in alleviating symptoms of eosinophilic esophagitis (EoE) in children. The oral respule not only resulted in a higher rate of symptom relief but also exhibited a better safety profile, with fewer incidents of oral thrush and adrenal suppression.</p></sec>

Nebulization versus metered-dose inhaler and spacer in bronchodilator responsiveness testing: a retrospective study

Background: The recommended delivery mode for bronchodilators in bronchodilator responsiveness (BDR) testing remains controversial. Objective: To compare the efficacy of salbutamol administration using a nebulizer versus a metered-dose inhaler (MDI) with spacer in BDR testing. Design: A retrospective study. Methods: This study examined the data of patients with chronic obstructive pulmonary disease who completed BDR testing between 1 December 2021 and 30 June 2022, at Xiangya Hospital, Central South University. After administering 400 μg of salbutamol through an MDI with spacer or 2.5 mg using a nebulizer, the changes in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were analyzed in patients with moderate-to-very severe spirometric abnormalities [pre-bronchodilator FEV1 percentage predicted values (FEV1%pred) ⩽59%]. Significant responsiveness was assessed as >12% and >200 mL improvement in FEV1 and/or FVC or >10% increase in FEV1%pred or FVC percentage predicted values (FVC%pred) from pre- to post-bronchodilator administration. Results: Of the enrolled 894 patients, 83.2% were male (median age, 63 years). After propensity score matching, 240 pairs of patients were selected. The increment in FEV1 and increased FEV1 relative to the predicted value (ΔFEV1%pred) were significantly higher in patients <65 years and those with severe spirometric abnormalities in the nebulization group than patients in the MDI group (all p < 0.05). Compared with MDI with spacer, patients who used nebulization had a 30 mL greater increase in ΔFEV1 (95% CI: 0.01–0.05, p = 0.004) and a 1.09% greater increase in ΔFEV1%pred (95% CI: 0.303–1.896, p = 0.007) from baseline. According to the > 12% and >200 mL increase criterion, the significant BDR rate with nebulization was 1.67 times higher than that with an MDI with spacer (OR = 1.67, 95% CI: 1.13–2.47, p = 0.009). Conclusion: Salbutamol delivered using a nebulizer may be preferable to an MDI with spacer in certain circumstances. Nebulization has the potential to increase responsiveness to salbutamol in BDR testing.

Efficacy of inhaled salbutamol therapy through nebulizer versus mdi with spacer in children with acute asthmatic attack and short-term course

Introduction: Asthma is a common chronic disease in childhood and has been subject of studies for at least two decades, due to its increasing prevalence. The symptoms are persistent, recurrent, and entirely related to bronchial hyper-responsiveness to many environmental triggers. Nebulization and metered dose inhaler (MDI) are two available modalities of salbutamol administration in patients with acute asthmatic attack. Aim: The aim of the study was to compare the relative efficacy of nebulizer and MDI with spacer for the administration of salbutamol in the treatment of acute asthmatic attack. Materials and Methods: A randomized, prospective, and interventional study was conducted on 100 children aged 1–12 years with acute asthmatic attack at a tertiary care. The subjects were randomized into two groups for salbutamol administration. Group I was given salbutamol by nebulizer and Group II by MDI with spacer. Demographic data and detailed history was collected. Children were categorized into mild, moderate, and severe grade according to peak expiratory flow rate (PEFR) and pulmonary index (PI) score. Oxygen saturation, PEFR, and PI were monitored at 0, 20, 40, and 60 min of therapy. Other details such as duration of hospital stay and oxygen requirement were also noted. Results: One hundred children with male female ratio of 1.12:1 were included in the study. Highest incidence was seen in age group of 1–3 years (38%). Statistically significant change in PI and PEFR was noted with treatment in both the groups (p<0.05). On comparison between MDI and nebulizer group, no statistically significant difference was found (p>0.05). Conclusion: MDI with spacer is an effective alternative to nebulizer for the administration of salbutamol drug in acute asthmatic attack in pediatric patients.

A Randomized Trial Comparing Metered Dose Inhalers and Breath Actuated Nebulizers

BackgroundDespite little evidence for its effectiveness, the breath-actuated nebulizer (BAN) is the default albuterol delivery method in our pediatric emergency department. ObjectiveWe compared the clinical efficacy of BAN and the metered-dose inhaler (MDI) in treating subjects patients 2 to 17 years of age who presented with mild to moderate asthma exacerbations. MethodsThis is a randomized, nonblinded, noninferiority study conducted at a single pediatric tertiary care emergency department. Subjects presenting with a Pediatric Asthma Score ranging from 5 to 11 received albuterol by BAN or MDI via standard weight-based and symptom severity dosing protocols. Aerosolized ipratropium (via BAN) and intravenous magnesium sulfate were given when clinically indicated. The primary outcome was patient disposition. The noninferiority margin for the primary outcome was an admission rate difference ≤10%. Analyses were adjusted for confounders that were significant at p ≤ 0.10. ResultsWe enrolled 890 subjects between October 2014 and April 2015. BAN and MDI groups were comparable for age, gender, and race but not for pretreatment symptom severity; 51% in the MDI group had a Pediatric Asthma Score of moderate severity (8–11) vs. 63% in the BAN group (p < 0.003). Unadjusted admission rates were 11.9% for MDI and 12.8% for BAN, for an unadjusted risk difference of −0.9% (95% confidence interval −5% to 3%). After adjusting for baseline confounder severity, the risk difference was 2% (95% confidence interval −4% to 7%), which met the criteria for noninferiority. ConclusionsAlbuterol therapy by MDI is noninferior to BAN for the treatment of mild to moderate asthma exacerbations in children 2 to 17 years of age.

Comparison of clinical efficacy of nebulised salbutamol and salbutamol metered dose inhaler in children with mild or moderate exacerbation of bronchial asthma

Background: Bronchial asthma is the commonest chronic disease in industrialized nations. Aerosol therapy has revolutionized the treatment of bronchial asthma in children as in adults. Even though nebulisation is a simple technique, it is expensive and there is a need for power source. The aim of the study was to compare the clinical efficacy of nebulised salbutamol and salbutamol metered dose inhaler (MDI) in children with mild or moderate exacerbation of Bronchial asthma.Methods: This study was a hospital based randomized control study carried out between March 2009 to December 2009 on children attending OP or casualty of Government Medical College, Alappuzha with mild or moderate exacerbation of bronchial asthma.Results: 60 subjects were selected for the study out of which 30 were assigned to salbutamol MDI group and the other 30 to salbutamol nebulisation group. After the administration of drug, all the studied variables showed significant improvement in both groups (p value &lt;0.001). Percentage predicted PEFR increased by about 27% in nebulisation group and 26% in MDI group; however this difference was not statistically significant (P value = 0.99).Conclusions: In this study we concluded that the efficacy of salbutamol in mild or moderate acute exacerbation of asthma was similar when the drug is delivered either by nebuliser or MDI with spacer.

Efficacy and safety of mometasone furoate dry powder inhaler vs fluticasone propionate metered-dose inhaler in asthma subjects previously using fluticasone propionate

To compare the efficacy and safety of mometasone furoate dry powder inhaler (DPI) administered once daily in the evening with fluticasone propionate metered-dose inhaler (MDI) administered twice daily. An 8-week, randomized, open-label, parallel-group study compared mometasone furoate DPI, 400 microg every evening (1 puff daily), with fluticasone propionate MDI, two 125-microg puffs twice daily, in 167 adults and adolescents with moderate persistent asthma previously using fluticasone propionate. The primary efficacy variable was the change in forced expiratory volume in 1 second (FEV1) from baseline to the end point. Variables such as response to therapy and subject satisfaction with the inhaler devices were also analyzed. Improvement in FEV1 was noted at the week 2 visit with both treatments. This improvement was maintained at the 4- and 8-week visits and at the end point for both groups. The mean percent change in FEV1 from baseline to the end point was 4.58% with mometasone furoate DPI and 6.98% with fluticasone propionate MDI (P = .35). At the end point, physicians rated 62% of the mometasone furoate DPI group as "improved" or "much improved" compared with 47% of the fluticasone propionate MDI group (P = .007). A significantly greater proportion of subjects in the mometasone furoate DPI group "liked the inhaler a lot" vs subjects in the fluticasone propionate MDI group (46.8% vs 22.4%; P = .01). Both treatments were well tolerated. Mometasone furoate DPI, 400 microg every evening, provided comparable efficacy as fluticasone propionate MDI, two 125-microg puffs twice daily, in subjects with moderate persistent asthma previously treated with fluticasone propionate.

Comparison of the efficacy and safety of high doses of beclometasone dipropionate suspension for nebulization and beclometasone dipropionate via a metered-dose inhaler in steroid-dependent adults with moderate to severe asthma

Nebulization for the administration of high doses of inhaled corticosteroids can benefit steroid-dependent asthmatics. The objective of this double-blind, double-dummy, multicentre, randomized, prallel-group study was to compare the efficacy and safety of high-dose corticosteroids given by nebulization or metered-dose inhalation in adult patients with asthma. Following a 2-week run-in period, 124 patients, aged 18–70 years, with moderate to severe asthma treated with high-dose inhaled steroids were randomized to one of two treatment groups for 12 weeks: beclometasone dipropionate (BDP) suspension for nebulization 3000–4000 μg day −1 b.i.d. given via a nebulizer ( n=63), or BDP spray 1500–2000 μg day −1 b.i.d. given via a metered-dose inhaler (MDI) plus spacer (BDP MDI) ( n=61). Comparable improvements over baseline, which were statistically significant in most cases, were reported at study end for the two treatment groups in the various efficacy parameters evaluated (pulmonary function tests, clinical symptoms scores, and the use of rescue salbutamol). The primary efficacy endpoint was morning pulmonary expiratory flow rate (PEFR). For the intent-to-treat population, in the BDP nebulization group mean morning PEFR increased statistically significantly from 308.7 ± 107.81 min −1 to 319.2 ± 104.01 min −1, while in the BDP MDI group the increase was from 301.5 ± 94.71 min −1 to 309.3 ± 86.71 min −1. The two treatments were equally well tolerated. A total of 19 patients in each group reported adverse events during the treatment period, and these were generally mild-moderate in severity. In conclusion, the results of this study demonstrate that BDP suspension for nebulization 3000–4000 μg day −1 given via a nebulizer and BDP spray 1500–2000 μg day −1 given van an MDI plus spacer are equally effective, with an acceptable safety and tolerability profile, when used in steroid-dependent adult patients with moderate to severe asthma.

Comparison of the efficacy and safety of beclometasone dipropionate suspension for nebulization and beclometasone dipropionate via a metered-dose inhaler in paediatric patients with moderate to severe exacerbation of asthma

Nebulization simplifies the administration of effective inhaled medications to young asthmatics who experience hand-to-lung co-ordination problems and inspiratory difficulties associated with metered-dose and dry-powder inhalers, respectively. The objective of this double-blind, double-dummy, multicentre, randomized, parallel-group study was to compare the efficacy and safety of corticosteroids given by nebulization or metered-dose inhalation in paediatric patients with exacerbation of asthma. Following a 24-h run-in period, 151 patients, aged 6–16 years, with moderate to severe exacerbation of asthma were randomized to one of two treatment groups for 4 weeks: beclometasone dipropionate (BDP) suspension for nebulization 1600 μg day −1 b.i.d. given via a nebulizer ( n=75), or BDP spray 800 μg day −1 b.i.d. given via a metered-dose inhaler (MDI) plus spacer (BDP MDI) ( n=76). Superimposable and statistically significant improvements over baseline were noted at study end for the two treatment groups in the various efficacy parameters evaluated (pulmonary function tests, asthma symptoms scores, and the use of rescue salbutamol). The primary efficacy endpoint was the morning pulmonary expiratory flow rate (PEFR). In the BDP nebulization group, mean morning PEFR increased statistically significantly from 233·2 ± 86·31 min −1 to 322·0 ± 101·81 min −1, while in the BDP MDI group the increase was from 222·9 ± 87·31 min −1 to 314·9 ± 96·61 min −1. Moreover, an additional 4-week treatment period at half doses, completed by 26 patients, demonstrated that improvements were maintained or further enhanced. The two treatments were equally well tolerated. A total of 25 and 26 patients i nthe BDP nebulization and BDP MDI groups, respectively, reported adverse events during the treatment period, and these were generally mild. In conclusion, the results of this study demonstrate that BDP suspension for nebulization 1600 μg day −1 given via a nebulizer and BDP spray 800 μg day −1 given via an MDI plus spacer are equally effective, with an acceptable safety and tolerability profile, when used in paediatric patients with moderate to severe asthma exacerbation.

The effect of ipratropium bromide on intraocular pressure in patients with chronic obstructive pulmonary disease: an open-label study

Background: After smoking cessation, bronchodilation with anticholinergics and beta 2-agonists is the keystone of pharmacologic therapy for symptomatic chronic obstructive pulmonary disease (COPD). For patients who fail to get relief from a drug delivered via a metered-dose inhaler (MDI) plus spacer, or for acute exacerbations in patients who are unable to use an MDI, a nebulized solution (NS) usually is preferred. Although ipratropium bromide (IB) has a low incidence of adverse events, anticholinergic drugs are known to produce side effects such as urinary retention, constipation, drying of secretions, and precipitation of glaucoma. Objective: In this open-label study, we aimed to assess the acute effects of IB on intraocular pressure (IOP) and tolerability of administration of IB by MDI and NS in patients with COPD and baseline values of IOP that were within normal limits. Methods: Eligible patients were aged >40 years and had a cigarette smoking history of >20 pack-years (ie, packs/d × years of smoking), a clinical history of COPD, and a ratio of forced expiratory volume in 1 second to slow vital capacity (FEV 1/VC) <89% predicted value. After baseline pulmonary function testing (PFT), IOP measurements by Goldmann applanation tonometry were performed. PFT measurements were repeated at 15 and 120 minutes after drug inhalation, and IOP measurements were repeated 120 minutes after drug inhalation. Doses were administered on 3 consecutive mornings: placebo on day 1, MDI IB 40 μg on day 2, and NS IB 250 μg on day 3. Results: Measurements are expressed as mean ± SD. Twenty-one stable patients with COPD (all men; mean age, 60.95 ± 7.90 years; mean smoking history, 47.24 ± 17.62 pack-years) were selected from a university hospital outpatient population. On MDI and NS test days (days 2 and 3), respectively, mean baseline FEV 1 measurements were 1.30 ± 0.62 L (42.74% ± 20.11% predicted value) and 1.23 ± 0.58 L (41.16% ± 18.51% predicted value); mean baseline IOPs for the MDI group were 14.24 ± 2.61 mm Hg and 14.00 ± 2.51 mm Hg (right and left eyes, respectively) and for the NS group were 14.57 ± 2.52 mm Hg and 14.00 ± 2.63 mm Hg (right and left eyes, respectively). Although improvements in forced VC, FEV 1, and maximal mid-expiratory flow rate were significant at 15 and 120 minutes for both delivery methods ( P < 0.01 for both delivery methods at both times), no significant increase in IOP was found. Conclusion: The single-dose administration of MDI and NS formulations of IB at doses producing bronchodilation had no significant effect on IOP in this study population.

吸入指導におけるぜん息用ドライパウダー吸入剤の評価

Under the current concept, asthma is recognized as a chronic inflammatory disorder of the airways and inhaled corticosteroids are the most effective for the treatment of asthma. Dry powder steroids were first introduced to Japan in1998. This study evaluates the dry powder inhaler (DPI) from the perspective of ease of handling and the time required for instruction compared with the metered dose inhaler (MDI). Moreover, the relationship between peak inspiratory flow (PIF) and the number of times required for the complete inhalation of DPI were investigated.One hundred and six adult asthmatic outpatients were entered into this study, including 54 who received DPI with the Diskhaler® and 52 who received MDI with the Volmaticr® spacer. A checklist was prepared for the evaluation of device handling acquirement. More patients in the DPI group performed inhalation correctly than patients in the MDI group (83 vs. 34%). The time required for instruction in the DPI group was shorter than the MDI group (11.37±4.35 vs. 16.14± 3.82 minutes). These results showed that DPI was an easier-to-use device compared with MDI. However, patients with low PIF (< 50L/m) frequently failed to inhale dry powder completely. In addition, PIF and the number of times required for the complete inhalation of DPI were negatively correlated (r= 0.870, p< 0.01). This study showed that sufficient instruction and appropriate selection of the inhaler played an important for asthmatic patients requiring inhaled corticosteroids.

Comparative Efficacy and Safety of Albuterol Sulfate Spiros Inhaler and Albuterol Metered-Dose Inhaler in Asthma

To compare the long-term efficacy and safety of albuterol administration using a Spiros Inhalation System (Dura Pharmaceuticals; San Diego, CA) dry powder inhaler (DPI) and albuterol (Ventolin; Glaxo Wellcome; Research Triangle Park, NC) administration using a metered-dose inhaler (MDI) in patients with asthma. This was a phase III, 12-week, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study of 283 adolescent and adult patients with mild to moderate asthma. The patients were randomized into one of three treatment groups: the Spiros group, who were given 108 microg/actuation of albuterol sulfate equivalent to 90 microg of albuterol base; the MDI group, who were given 90 microg/actuation of albuterol; and the placebo group. Over the length of the study, the Spiros and MDI groups were comparable in all FEV1 parameters. Both active treatment groups were superior to the placebo group for each FEV1 parameter at all visits. With the exception of differences at treatment week 0 for the maximum percent change in the FEV1, the duration of effect, and the area under the curve at baseline, there were no statistically significant differences between the Spiros and MDI groups for any FEV1 parameters. Using a repeated-measures analysis, the FEV1 parameters at week 0 for the Spiros group were not statistically significantly different from the parameters at weeks 4, 8, and 12. The same analysis effect at week 0 for the MDI group was greater for maximum percent change in the FEV1 from baseline (weeks 4, 8, and 12) and duration of effect. Adverse events and changes in clinical laboratory values, vital signs, ECG results, and physical examinations were reported with similar incidence in each of the three treatment groups. Both active treatments were superior to the placebo treatment. The Spiros DPI was well tolerated and was as effective as the albuterol MDI in treating patients with moderate asthma.

Adrenal suppression among asthmatic children receiving chronic therapy with inhaled corticosteroid with and without spacer device.

Inhaled corticosteroids have become a first-line treatment for chronic asthma. It has been shown that inhaled corticosteroids can have a measurable effect on the hypothalamic-pituitary-adrenal axis in asthmatic children. To investigate the prevalence of adrenal suppression among asthmatic children receiving chronic therapy with low to moderate doses (up to 1000 micrograms) of inhaled beclomethasone dipropionate via a metered dose inhaler (MDI) and via MDI attached to a spacer device (MDI-spacer). The study included 39 asthmatic children currently undergoing therapy; 24 received beclomethasone dipropionate by MDI attached to a spacer, and 15 directly by MDI. All the patients had been treated for at least 4 months. Another 21 children were normal controls. The 24-hour urinary free cortisol excretion was measured to evaluate hypothalamic-pituitary-adrenal axis function. Seven of 15 (47%) patients from the MDI group had reduced 24 hour-urinary free cortisol excretion and 2 of 24 (8%) in the MDI-spacer group (P = .006). The mean 24-hour urinary free cortisol excretion of the MDI group was 0.0185 +/- 0.0089 microgram/gram creatinine, and the MDI-spacer and the control groups were, 0.0290 +/- 0.0138 microgram/gram creatinine and 0.0270 +/- 0.0118 microgram/gram creatinine, respectively, (P = 0.37, f = 3.51 ANOVA). Chronic inhalation of low to moderate doses of corticosteroids is associated with adrenal suppression in some asthmatic children. This side effect is more common among patients inhaling directly from the MDI and is less frequent when a large volume spacer is attached to the MDI.

Bricanyl Turbuhaler in the treatment of asthma: a six week multi-centre study carried out in Sweden, the United Kingdom, Denmark, Norway and Finland

Two hundred and fifty eight adult patients with bronchial asthma participated in an open, parallel group study of 8 wks duration. During a 2 wk run-in period the beta 2-agonist terbutaline (0.5 mg q.i.d) was delivered via a pressurized freon aerosol, Bricanyl metered dose inhaler (MDI). During the following 6 wks, one third of the patients continued with MDI and two thirds with the same dose of terbutaline in the form of dry powder, Bricanyl Turbuhaler. There were no statistically significant differences in the increases in peak expiratory flow rate (PEFR) after inhalation between the two treatment groups. The asthma symptom scores decreased in the Turbuhaler group during the study but remained the same in the MDI group. No difference in use of extra trial medication during the day was found. During the night, the difference was statistically significant in favour of Turbuhaler (p less than 0.05). Turbuhaler was well accepted and easy to use. As compared with the MDI used during run-in, 50% of the patients in the Turbuhaler group preferred to use Turbuhaler and 26% MDI, whilst 24% had no preference. In conclusion, Turbuhaler was at least as effective as MDI during the whole Turbuhaler life-span (6 wks).