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The New England Journal of Medicine Jun 2022As asthma symptoms worsen, patients typically rely on short-acting β-agonist (SABA) rescue therapy, but SABAs do not address worsening inflammation, which leaves... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
As asthma symptoms worsen, patients typically rely on short-acting β-agonist (SABA) rescue therapy, but SABAs do not address worsening inflammation, which leaves patients at risk for severe asthma exacerbations. The use of a fixed-dose combination of albuterol and budesonide, as compared with albuterol alone, as rescue medication might reduce the risk of severe asthma exacerbation.
METHODS
We conducted a multinational, phase 3, double-blind, randomized, event-driven trial to evaluate the efficacy and safety of albuterol-budesonide, as compared with albuterol alone, as rescue medication in patients with uncontrolled moderate-to-severe asthma who were receiving inhaled glucocorticoid-containing maintenance therapies, which were continued throughout the trial. Adults and adolescents (≥12 years of age) were randomly assigned in a 1:1:1 ratio to one of three trial groups: a fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide (with each dose consisting of two actuations of 90 μg and 80 μg, respectively [the higher-dose combination group]), a fixed-dose combination of 180 μg of albuterol and 80 μg of budesonide (with each dose consisting of two actuations of 90 μg and 40 μg, respectively [the lower-dose combination group]), or 180 μg of albuterol (with each dose consisting of two actuations of 90 μg [the albuterol-alone group]). Children 4 to 11 years of age were randomly assigned to only the lower-dose combination group or the albuterol-alone group. The primary efficacy end point was the first event of severe asthma exacerbation in a time-to-event analysis, which was performed in the intention-to-treat population.
RESULTS
A total of 3132 patients underwent randomization, among whom 97% were 12 years of age or older. The risk of severe asthma exacerbation was significantly lower, by 26%, in the higher-dose combination group than in the albuterol-alone group (hazard ratio, 0.74; 95% confidence interval [CI], 0.62 to 0.89; P = 0.001). The hazard ratio in the lower-dose combination group, as compared with the albuterol-alone group, was 0.84 (95% CI, 0.71 to 1.00; P = 0.052). The incidence of adverse events was similar in the three trial groups.
CONCLUSIONS
The risk of severe asthma exacerbation was significantly lower with as-needed use of a fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide than with as-needed use of albuterol alone among patients with uncontrolled moderate-to-severe asthma who were receiving a wide range of inhaled glucocorticoid-containing maintenance therapies. (Funded by Avillion; MANDALA ClinicalTrials.gov number, NCT03769090.).
Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Asthma; Budesonide; Child; Child, Preschool; Double-Blind Method; Drug Combinations; Ethanolamines; Formoterol Fumarate; Glucocorticoids; Humans; Maintenance Chemotherapy; Nebulizers and Vaporizers; Symptom Flare Up; Young Adult
PubMed: 35569035
DOI: 10.1056/NEJMoa2203163 -
International Journal of Molecular... Nov 2022Asthma is a common inflammatory disease of the lungs. The prevalence of asthma is increasing worldwide, and the tendency indicates that the number of asthma sufferers... (Review)
Review
Asthma is a common inflammatory disease of the lungs. The prevalence of asthma is increasing worldwide, and the tendency indicates that the number of asthma sufferers will soar in the coming years for several reasons, in particular, the lifestyles we have adopted that expose us to risk factors. Salbutamol is the first selective short-acting β-agonist (SABA) used as an alternative reliever in the treatment of asthma. Its therapeutic effect is based on its potent smooth muscle relaxant properties, which allow the inhibition of bronchial smooth muscle contraction and subsequent bronchodilation. Salbutamol can be administered orally, intravenously (IV), intramuscularly (IM), subcutaneously, or by inhalation. For this reason, the pharmacokinetic (PK) parameters-absorption, distribution, metabolism, and elimination-are highly diverse and, consequently, the efficacy and adverse effects also differ between each formulation. Here, we review the pharmacological profile of different salbutamol formulations, focusing on their efficacy and adverse effects for its original application, asthma.
Topics: Humans; Albuterol; Asthma; Bronchi; Drug-Related Side Effects and Adverse Reactions; Risk Factors
PubMed: 36430683
DOI: 10.3390/ijms232214207 -
Italian Journal of Pediatrics Feb 2023Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children. This document aims to update the consensus document... (Review)
Review
Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children. This document aims to update the consensus document published in 2014 to provide guidance on the current best practices for managing bronchiolitis in infants. The document addresses care in both hospitals and primary care. The diagnosis of bronchiolitis is based on the clinical history and physical examination. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Evidence suggests no benefit with the use of salbutamol, glucocorticosteroids and antibiotics with potential risk of harm. Because of the lack of effective treatment, the reduction of morbidity must rely on preventive measures. De-implementation of non-evidence-based interventions is a major goal, and educational interventions for clinicians should be carried out to promote high-value care of infants with bronchiolitis. Well-prepared implementation strategies to standardize care and improve the quality of care are needed to promote adherence to guidelines and discourage non-evidence-based attitudes. In parallel, parents' education will help reduce patient pressure and contribute to inappropriate prescriptions. Infants with pre-existing risk factors (i.e., prematurity, bronchopulmonary dysplasia, congenital heart diseases, immunodeficiency, neuromuscular diseases, cystic fibrosis, Down syndrome) present a significant risk of severe bronchiolitis and should be carefully assessed. This revised document, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of acute bronchiolitis.
Topics: Infant, Newborn; Child; Infant; Humans; Child, Preschool; Bronchiolitis; Hospitalization; Risk Factors; Albuterol; Respiratory Syncytial Virus Infections
PubMed: 36765418
DOI: 10.1186/s13052-022-01392-6 -
Archivos Argentinos de Pediatria Aug 2021In 1995, the first Guideline on Diagnosis and Treatment for Childhood Asthma was published in Archivos Argentinos de Pediatría. Updates were made in 2007 and 2016....
In 1995, the first Guideline on Diagnosis and Treatment for Childhood Asthma was published in Archivos Argentinos de Pediatría. Updates were made in 2007 and 2016. After 5 years, the new contents are presented. The most relevant modifications, although not the only ones, are observed in therapeutic strategies. In this version, treatment is stratified into "levels" (1 to 5). The current paradigm of change in chronic asthma treatment consists in eradicating the prescription of bronchodilators (salbutamol) on demand. Besides that, the option of intermittent treatment with inhaled corticosteroids plus long-acting bronchodilators (LABA) appears for milder forms (levels 1 and 2) in children > 12 years old. There is still not enough evidence to support these options in<12 years old maintaining the previous recommendations in this group. For more details we suggest reading the full document.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Albuterol; Asthma; Bronchodilator Agents; Child; Humans
PubMed: 34309325
DOI: 10.5546/aap.2021.S123 -
British Journal of Clinical Pharmacology Jul 2022The propellants in metered-dose inhalers (MDIs) are powerful greenhouse gases, which account for approximately 13% of the NHS's carbon footprint related to the delivery... (Review)
Review
The propellants in metered-dose inhalers (MDIs) are powerful greenhouse gases, which account for approximately 13% of the NHS's carbon footprint related to the delivery of care. Most MDI use is in salbutamol relievers in patients with poorly controlled disease. The UK lags behind Europe in this regard, with greater reliance on salbutamol MDI and correspondingly greater greenhouse gas emissions, roughly treble that of our European neighbours. There has been a broad switch towards MDIs in asthma treatment in the UK over the last 20 years to reduce financial costs, such that the treatment for two-thirds of asthma patients in the UK is dominated by salbutamol MDI. Strategies that replace overuse of reliever MDIs with regimes emphasising inhaled corticosteroids have the potential to improve asthma control alongside significant reductions in greenhouse gas emissions. Real-world evidence shows that once-daily long-acting combination dry-powder inhalers (DPIs) can improve compliance and asthma control, and reduce the carbon footprint of care. Similarly, maintenance and reliever therapy (MART), which uses combination reliever and inhaled steroids in one device (usually a DPI), can simplify therapy, improve asthma control and reduce greenhouse gas emissions. Both treatment strategies are popular with patients, most of whom would be willing to change treatment to reduce their carbon footprint. By focussing on patients who are currently using high amounts of salbutamol MDI and prioritising inhaled steroids via DPIs, there are golden opportunities to make asthma care in the UK more effective, safer and greener.
Topics: Administration, Inhalation; Albuterol; Asthma; Dry Powder Inhalers; Environment; Greenhouse Gases; Humans; Metered Dose Inhalers
PubMed: 34719810
DOI: 10.1111/bcp.15135 -
BMJ Open Respiratory Research Dec 2021Uncontrolled asthma is associated with substantial morbidity. While fast-acting bronchodilators provide quick relief from asthma symptoms, their use as rescue fails to... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of as-needed albuterol/budesonide versus albuterol in adults and children aged ≥4 years with moderate-to-severe asthma: rationale and design of the randomised, double-blind, active-controlled MANDALA study.
INTRODUCTION
Uncontrolled asthma is associated with substantial morbidity. While fast-acting bronchodilators provide quick relief from asthma symptoms, their use as rescue fails to address the underlying inflammation. Combining a short-acting beta-agonist, such as albuterol (salbutamol), with an inhaled corticosteroid, such as budesonide, in a single inhaler as rescue therapy could help control both bronchoconstriction and inflammation, and reduce the risk of asthma exacerbations.
METHODS AND ANALYSIS
The Phase 3 MANDALA study was designed to determine the efficacy of albuterol in combination with budesonide (albuterol/budesonide 180/160 µg or 180/80 µg, two actuations of 90/80 µg or 90/40 µg, respectively) versus albuterol (180 µg, two actuations of 90 µg) as rescue therapy in adult, adolescent and paediatric patients with moderate-to-severe asthma. This event-driven study enrolled symptomatic patients (3000 adults/adolescents and 100 children aged 4-11 years) who experienced ≥1 severe asthma exacerbation in the previous year and were receiving maintenance therapy for ≥3 months prior to study entry. The primary efficacy endpoint was time-to-first severe asthma exacerbation.
ETHICS AND DISSEMINATION
The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and Good Clinical Practice and the applicable regulatory requirements.
TRIAL REGISTRATION
NCT03769090.
Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Asthma; Budesonide; Child; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans
PubMed: 34887317
DOI: 10.1136/bmjresp-2021-001077 -
JAMA Nov 2020While intravenous magnesium decreases hospitalizations in refractory pediatric acute asthma, it is variably used because of invasiveness and safety concerns. The benefit... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of Nebulized Magnesium vs Placebo Added to Albuterol on Hospitalization Among Children With Refractory Acute Asthma Treated in the Emergency Department: A Randomized Clinical Trial.
IMPORTANCE
While intravenous magnesium decreases hospitalizations in refractory pediatric acute asthma, it is variably used because of invasiveness and safety concerns. The benefit of nebulized magnesium to prevent hospitalization is unknown.
OBJECTIVE
To evaluate the effectiveness of nebulized magnesium in children with acute asthma remaining in moderate or severe respiratory distress after initial therapy.
DESIGN, SETTING, AND PARTICIPANTS
A randomized double-blind parallel-group clinical trial from September 26, 2011, to November 19, 2019, in 7 tertiary-care pediatric emergency departments in Canada. The participants were otherwise healthy children aged 2 to 17 years with moderate to severe asthma defined by a Pediatric Respiratory Assessment Measure (PRAM) score of 5 or greater (on a 12-point scale) after a 1-hour treatment with an oral corticosteroid and 3 inhaled albuterol and ipratropium treatments. Of 5846 screened patients, 4332 were excluded for criteria, 273 declined participation, 423 otherwise excluded, 818 randomized, and 816 analyzed.
INTERVENTIONS
Participants were randomized to 3 nebulized albuterol treatments with either magnesium sulfate (n = 410) or 5.5% saline placebo (n = 408).
MAIN OUTCOMES AND MEASURES
The primary outcome was hospitalization for asthma within 24 hours. Secondary outcomes included PRAM score; respiratory rate; oxygen saturation at 60, 120, 180, and 240 minutes; blood pressure at 20, 40, 60, 120, 180, and 240 minutes; and albuterol treatments within 240 minutes.
RESULTS
Among 818 randomized patients (median age, 5 years; 63% males), 816 completed the trial (409 received magnesium; 407, placebo). A total of 178 of the 409 children who received magnesium (43.5%) were hospitalized vs 194 of the 407 who received placebo (47.7%) (difference, -4.2%; absolute risk difference 95% [exact] CI, -11% to 2.8%]; P = .26). There were no significant between-group differences in changes from baseline to 240 minutes in PRAM score (difference of changes, 0.14 points [95% CI, -0.23 to 0.50]; P = .46); respiratory rate (0.17 breaths/min [95% CI, -1.32 to 1.67]; P = .82); oxygen saturation (-0.04% [95% CI, -0.53% to 0.46%]; P = .88); systolic blood pressure (0.78 mm Hg [95% CI, -1.48 to 3.03]; P = .50); or mean number of additional albuterol treatments (magnesium: 1.49, placebo: 1.59; risk ratio, 0.94 [95% CI, 0.79 to 1.11]; P = .47). Nausea/vomiting or sore throat/nose occurred in 17 of the 409 children who received magnesium (4%) and 5 of the 407 who received placebo (1%).
CONCLUSIONS AND RELEVANCE
Among children with refractory acute asthma in the emergency department, nebulized magnesium with albuterol, compared with placebo with albuterol, did not significantly decrease the hospitalization rate for asthma within 24 hours. The findings do not support use of nebulized magnesium with albuterol among children with refractory acute asthma.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01429415.
Topics: Acute Disease; Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Albuterol; Asthma; Bronchodilator Agents; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Emergency Service, Hospital; Female; Hospitalization; Humans; Ipratropium; Magnesium; Male; Nebulizers and Vaporizers; Treatment Failure
PubMed: 33231663
DOI: 10.1001/jama.2020.19839 -
PloS One 2021A combination of ipratropium bromide (IB) and salbutamol is commonly used to treat asthma in children and adolescents; however, there has been a lack of consistency in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A combination of ipratropium bromide (IB) and salbutamol is commonly used to treat asthma in children and adolescents; however, there has been a lack of consistency in its usage in clinical practice.
OBJECTIVE
To evaluate the efficacy and safety of IB + salbutamol in the treatment of asthma in children and adolescents.
METHODS
The MEDLINE, Embase, and Cochrane Library as well as other Chinese biomedical databases (including China Biological Medicine Database, Chinese National Knowledge Infrastructure, Chongqing VIP, and Wanfang Chinese language bibliographic database) were systematically searched from the earliest record date to September 2020 for randomized controlled trials in children and adolescents (≤18 years) with asthma who received IB + salbutamol or salbutamol alone. The primary outcomes included hospital admission and adverse events. A random effects model with a 95% confidence interval (CI) was used. Subgroup analysis was performed according to age, severity of asthma, and co-interventions with other asthma controllers. This study was registered with PROSPERO.
RESULTS
Of the 1061 studies that were identified, 55 met the inclusion criteria and involved 6396 participants. IB + salbutamol significantly reduced the risk of hospital admission compared with salbutamol alone (risk ratio [RR] 0.79; 95% CI 0.66-0.95; p = 0.01; I2 = 40%). Subgroup analysis only showed significant difference in the risk of hospital admission in participants with severe asthma exacerbation (RR 0.73; 95% CI 0.60-0.88; p = 0.0009; I2 = 4%) and moderate-to-severe exacerbation (RR 0.69; 95% CI 0.50-0.96; p = 0.03; I2 = 3%). There were no significant differences in the risk of adverse events between IB + salbutamol group and salbutamol alone group (RR 1.77; 95% CI 0.63-4.98).
CONCLUSION
IB + salbutamol may be more effective than salbutamol alone for the treatment of asthma in children and adolescents, especially in those with severe and moderate to severe asthma exacerbation. The very low to high quality of evidence indicated that future well-designed double-blind RCTs with large sample are needed for research on evaluating the effectiveness of IB + salbutamol treatment for asthma in children and adolescents.
Topics: Administration, Inhalation; Adolescent; Albuterol; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Child, Preschool; China; Disease Progression; Drug Therapy, Combination; Female; Humans; Ipratropium; Male
PubMed: 33621253
DOI: 10.1371/journal.pone.0237620 -
JAMA Network Open Jul 2021Despite guidelines recommending administration of intravenous (IV) magnesium sulfate for refractory pediatric asthma, the number of asthma-related hospitalizations has... (Randomized Controlled Trial)
Randomized Controlled Trial
Association Between Intravenous Magnesium Therapy in the Emergency Department and Subsequent Hospitalization Among Pediatric Patients With Refractory Acute Asthma: Secondary Analysis of a Randomized Clinical Trial.
IMPORTANCE
Despite guidelines recommending administration of intravenous (IV) magnesium sulfate for refractory pediatric asthma, the number of asthma-related hospitalizations has remained stable, and IV magnesium therapy is independently associated with hospitalization.
OBJECTIVE
To examine the association between IV magnesium therapy administered in the emergency department (ED) and subsequent hospitalization among pediatric patients with refractory acute asthma after adjustment for patient-level variables.
DESIGN, SETTING, AND PARTICIPANTS
This post hoc secondary analysis of a double-blind randomized clinical trial of children with acute asthma treated from September 26, 2011, to November 19, 2019, at 7 Canadian tertiary care pediatric EDs was conducted between September and November 2020. In the randomized clinical trial, 816 otherwise healthy children aged 2 to 17 years with Pediatric Respiratory Assessment Measure (PRAM) scores of 5 points or higher after initial therapy with systemic corticosteroids and inhaled albuterol with ipratropium bromide were randomly assigned to 3 nebulized treatments of albuterol plus either magnesium sulfate or 5.5% saline placebo.
EXPOSURES
Intravenous magnesium sulfate therapy (40-75 mg/kg).
MAIN OUTCOMES AND MEASURES
The association between IV magnesium therapy in the ED and subsequent hospitalization for asthma was assessed using multivariable logistic regression analysis. Analyses were adjusted for year epoch at enrollment, receipt of IV magnesium, PRAM score after initial therapy and at ED disposition, age, sex, duration of respiratory distress, previous intensive care unit admission for asthma, hospitalizations for asthma within the past year, atopy, and receipt of oral corticosteroids within 48 hours before arrival in the ED, nebulized magnesium, and additional albuterol after inhaled magnesium or placebo, with site as a random effect.
RESULTS
Among the 816 participants, the median age was 5 years (interquartile range, 3-7 years), 517 (63.4%) were boys, and 364 (44.6%) were hospitalized. A total of 215 children (26.3%) received IV magnesium, and 190 (88.4%) of these children were hospitalized compared with 174 of 601 children (29.0%) who did not receive IV magnesium. Multivariable factors associated with hospitalization were IV magnesium receipt from 2011 to 2016 (odds ratio [OR], 22.67; 95% CI, 6.26-82.06; P < .001) and from 2017 to 2019 (OR, 4.19; 95% CI, 1.99-8.86; P < .001), use of additional albuterol (OR, 5.94; 95% CI, 3.52-10.01; P < .001), and increase in PRAM score at disposition (per 1-U increase: OR, 2.24; 95% CI, 1.89-2.65; P < .001). In children with a disposition PRAM score of 3 or lower, receipt of IV magnesium therapy was associated with hospitalization (OR, 8.52; 95% CI, 2.96-24.41; P < .001).
CONCLUSIONS AND RELEVANCE
After adjustment for patient-level characteristics, receipt of IV magnesium therapy after initial asthma treatment in the ED was associated with subsequent hospitalization. This association also existed among children with mild asthma at ED disposition. Evidence of a benefit of IV magnesium regarding hospitalization may clarify its use in the treatment of refractory pediatric asthma.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT01429415.
Topics: Acute Disease; Administration, Inhalation; Administration, Intravenous; Adolescent; Albuterol; Anti-Asthmatic Agents; Asthma; Canada; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Emergency Service, Hospital; Female; Hospitalization; Humans; Magnesium Sulfate; Male; Treatment Outcome
PubMed: 34279646
DOI: 10.1001/jamanetworkopen.2021.17542 -
Pediatric Pulmonology Dec 2020The benefits of metered-dose inhalers with a spacer (MDI+S) have increasingly been recognized as an alternative method of albuterol administration for treating pediatric... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVES
The benefits of metered-dose inhalers with a spacer (MDI+S) have increasingly been recognized as an alternative method of albuterol administration for treating pediatric asthma exacerbations. The aim of this systematic review was to compare the response to albuterol delivered through nebulization (NEB) with albuterol delivered through MDI+S in pediatric patients with asthma exacerbations.
METHODS
We conducted an electronic search in MEDLINE/PubMed, EMBASE, Ovid, and ClinicalTrials. To be included in the review, a study had to a randomized clinical trial comparing albuterol delivered via NEB versus MDI+S; and had to report the rate of hospital admission (primary outcome), or any of the following secondary outcomes: oxygen arterial saturation, heart rate (HR), respiratory rate (RR), the pulmonary index score (PIS), adverse effects, and need for additional treatment.
RESULTS
Fifteen studies (n = 2057) met inclusion criteria. No significant differences were found between the two albuterol delivery methods in terms of hospital admission (relative risk, 0.89; 95% confidence interval [CI], 0.55-1.46; I = 32%; p = .65). There was a significant reduction in the PIS score (mean difference [MD], -0.63; 95% CI, -0.91 to -0.35; I = 0%; p < .00001), and a significantly smaller increase in HR (better; MD -6.47; 95% CI, -11.69 to -1.25; I = 0%; p = .02) when albuterol was delivered through MDI+S than when it was delivered through NEB.
CONCLUSIONS
This review, an update of a previously-published meta-analysis, showed a significant reduction in the PIS and a significantly smaller increase in HR when albuterol was delivered through MDI+S than when it was delivered through NEB.
Topics: Acute Disease; Administration, Inhalation; Albuterol; Asthma; Bronchodilator Agents; Child; Disease Progression; Humans; Nebulizers and Vaporizers; Randomized Controlled Trials as Topic; Respiratory Sounds
PubMed: 32940961
DOI: 10.1002/ppul.25077