Intermittent Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists for Asthma

Project Summary Title and Description

Title
Intermittent Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists for Asthma
Description
Objective. To assess efficacy of intermittent inhaled corticosteroid (ICS) therapy in different populations (0 to 4 years old with recurrent wheezing, 5 years and older with persistent asthma, with or without long-acting beta agonist [LABA]), and to assess efficacy of added long-acting muscarinic antagonist (LAMA) in patients 12 years and older with uncontrolled, persistent asthma. Data sources. MEDLINE®, Embase®, Cochrane Central, and Cochrane Database of Systematic Reviews bibliographic databases from earliest date through March 23, 2017; hand searches of references of relevant studies; www.clinicaltrials.gov and the International Controlled Trials Registry Platform. Review methods. Two investigators screened abstracts of identified references for eligibility and subsequently reviewed full-text files. We abstracted data, performed meta-analyses when appropriate, assessed the risk of bias of each individual study, and graded the strength of evidence for each comparison and outcome. Outcomes for which data were extracted included exacerbations, mortality, asthma control composite scores, spirometry, asthma-specific quality of life, and rescue medication use. Results. We included 56 unique studies (54 randomized controlled trials, 2 observational studies) in this review. Compared to rescue short-acting beta-agonist (SABA) use, adding intermittent ICS reduces the risk of exacerbation requiring oral steroids and improves caregiver quality of life in children less than 5 years old with recurrent wheezing in the setting of a respiratory tract infection (RTI). In patients 12 years and older with persistent asthma, differences in intermittent ICS versus controller use of ICS were not detected, although few studies provided evidence, leading to primarily low strength of evidence ratings. Using ICS and LABA as both a controller and quick relief therapy reduced the risk of exacerbations and improved symptom control in patients 12 years and older compared to ICS controller (with or without LABA). Data in patients 4 to 11 years old suggest lower risk of exacerbations with ICS and LABA controller and quick relief use, but with a lower strength of evidence than in the older population. In patients 12 years and older with uncontrolled, persistent asthma, LAMA versus placebo as add-on to ICS reduces the risk of exacerbations requiring systemic corticosteroids and improves lung function measure through spirometry. Current evidence does not suggest that a difference exists in the efficacy of LAMA versus LABA as add-on to ICS. Triple therapy of ICS, LAMA, and LABA improves lung function measured through spirometry, although the risk of exacerbation was not different versus ICS and LABA. Conclusions. Intermittent ICS added to SABA during an RTI provides benefit to patients less than 5 years of age with recurrent wheezing. In patients 12 years and older with persistent asthma, differences in intermittent ICS versus controller use of ICS were not detected, although few studies provided evidence for this question. In patients 12 years and older with persistent asthma, using ICS and LABA as both a controller and quick relief therapy may be more effective at preventing exacerbations than ICS controller (with or without LABA). LAMA is effective in the management of uncontrolled, persistent asthma in patients 12 years of age and older, and current evidence does not suggest a difference between LAMA and LABA as add-on to ICS.
Attribution
N/A
Authors of Report
N/A
Methodology description
Data sources. MEDLINE®, Embase®, Cochrane Central, and Cochrane Database of Systematic Reviews bibliographic databases from earliest date through March 23, 2017; hand searches of references of relevant studies; www.clinicaltrials.gov and the International Controlled Trials Registry Platform. Review methods. Two investigators screened abstracts of identified references for eligibility and subsequently reviewed full-text files. We abstracted data, performed meta-analyses when appropriate, assessed the risk of bias of each individual study, and graded the strength of evidence for each comparison and outcome. Outcomes for which data were extracted included exacerbations, mortality, asthma control composite scores, spirometry, asthma-specific quality of life, and rescue medication use.
PROSPERO
CRD42016047985
DOI
10.26300/0tvg-3a21
Notes
Final report weblink: https://effectivehealthcare.ahrq.gov/topics/asthma-pharmacologic-treatment/research-2017 Final report PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29741837 Data of this project was entered retrospectively by uploading data to the project from other software and file format such as Excel or Word.
Funding Source
AHRQ

Key Questions

1. What is the comparative effectiveness of intermittent ICS compared to no treatment, pharmacologic, or nonpharmacologic therapy in children 0 to 4 years old with recurrent wheezing?
2. What is the comparative effectiveness of intermittent ICS compared to ICS controller therapy in patients 5 years of age and older with persistent asthma?
3. What is the comparative effectiveness of ICS with LABA used as both controller and quick relief therapy compared to ICS with or without LABA used as controller therapy in patients 5 years of age and older with persistent asthma?
4. What is the comparative effectiveness of LAMA as add-on to ICS controller therapy compared to placebo or increased ICS dose in patients 12 years of age and older with uncontrolled, persistent asthma?
5. What is the comparative effectiveness of LAMA compared to other controller therapy as add-on to ICS in patients 12 years of age and older with uncontrolled, persistent asthma?
6. What is the comparative effectiveness of LAMA as add-on to ICS plus LABA compared to ICS plus LABA as controller therapy in patients 12 years of age and older with uncontrolled, persistent asthma?

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing.2008
Preemptive use of high-dose fluticasone for virus-induced wheezing in young children.2009
Intermittent treatment with high dose nebulized beclomethasone for recurrent wheezing in infants due to upper respiratory tract infection.2002
Regular vs prn nebulized treatment in wheeze preschool children.2009
Prophylactic intermittent treatment with inhaled corticosteroids of asthma exacerbations due to airway infections in toddlers.1999
Daily or intermittent budesonide in preschool children with recurrent wheezing.2011
Daily versus as-needed corticosteroids for mild persistent asthma.2005
Comparison of physician-, biomarker-, and symptom-based strategies for adjustment of inhaled corticosteroid therapy in adults with asthma: the BASALT randomized controlled trial.2012
Poor adherence to self-medication instructions in children with asthma and their parents.2004
Doubling the dose of budesonide versus maintenance treatment in asthma exacerbations.2004
Low-dose budesonide with the addition of an increased dose during exacerbations is effective in long-term asthma control. On behalf of the Italian Study Group.2000
Markers of Differential Response to Inhaled Corticosteroid Treatment Among Children with Mild Persistent Asthma.-- Not Found --
Doubling the dose of inhaled corticosteroid to prevent asthma exacerbations: randomised controlled trial.2004
Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial.2011
Quadrupling the dose of inhaled corticosteroid to prevent asthma exacerbations: a randomized, double-blind, placebo-controlled, parallel-group clinical trial.2009
Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma.2007
Daily versus as-needed inhaled corticosteroid for mild persistent asthma (The Helsinki early intervention childhood asthma study).2008
Randomised comparison of guided self management and traditional treatment of asthma over one year.1996
Effect of β2-adrenergic receptor gene (ADRB2) 3' untranslated region polymorphisms on inhaled corticosteroid/long-acting β2-adrenergic agonist response.
Budesonide/formoterol maintenance and reliever therapy via Turbuhaler versus fixed-dose budesonide/formoterol plus terbutaline in patients with asthma: phase III study results.2013
Overall asthma control achieved with budesonide/formoterol maintenance and reliever therapy for patients on different treatment steps.2011
Overall asthma control: the relationship between current control and future risk.2010
Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma.2006
Budesonide/formoterol for maintenance and relief in uncontrolled asthma vs. high-dose salmeterol/fluticasone.2007
The effect of budesonide/formoterol maintenance and reliever therapy on the risk of severe asthma exacerbations following episodes of high reliever use: an exploratory analysis of two randomised, controlled studies with comparisons to standard therapy.2012
Comparison of the effects of budesonide/formoterol maintenance and reliever therapy with fluticasone/salmeterol fixed-dose treatment on airway inflammation and small airway impairment in patients who need to step-up from inhaled corticosteroid monotherapy.2014
Budesonide/formoterol maintenance and reliever therapy versus free-combination therapy for asthma: a real-life study.2013
Treatment comparison of budesonide/formoterol with salmeterol/fluticasone propionate in adults aged > or =16 years with asthma: post hoc analysis of a randomized, double-blind study.2010
Effect of budesonide/formoterol maintenance and reliever therapy on asthma exacerbations.2007
A comparison of budesonide/formoterol maintenance and reliever therapy vs. conventional best practice in asthma management.2009
Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma.2005
Beclometasone-formoterol as maintenance and reliever treatment in patients with asthma: a double-blind, randomised controlled trial.
The use of β2-agonist therapy before hospital attendance for severe asthma exacerbations: a post-hoc analysis.2015
Efficacy and safety of maintenance and reliever combination budesonide-formoterol inhaler in patients with asthma at risk of severe exacerbations: a randomised controlled trial.2013
Predictors of severe exacerbations, poor asthma control, and β-agonist overuse for patients with asthma.-- Not Found --
Airway inflammation in patients with asthma with high-fixed or low-fixed plus as-needed budesonide/formoterol.
Combination budesonide/formoterol inhaler as maintenance and reliever therapy in Māori with asthma.
A comparison of budesonide/formoterol maintenance and reliever therapy versus conventional best practice in asthma management in Spain.
Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study.
Budesonide/formoterol in a single inhaler for maintenance and relief in mild-to-moderate asthma: a randomized, double-blind trial.
Airway inflammation in patients with asthma with high-fixed or low-fixed plus as-needed budesonide/formoterol.2009
Combination budesonide/formoterol inhaler as maintenance and reliever therapy in Māori with asthma.2014
A comparison of budesonide/formoterol maintenance and reliever therapy versus conventional best practice in asthma management in Spain.2011
Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study.2006
Budesonide/formoterol in a single inhaler for maintenance and relief in mild-to-moderate asthma: a randomized, double-blind trial.2006
Budesonide/formoterol maintenance and reliever therapy in primary care asthma management: effects on bronchial hyperresponsiveness and asthma control.2012
Efficacy and safety of budesonide/formoterol single inhaler therapy versus a higher dose of budesonide in moderate to severe asthma.2004
Budesonide/formoterol maintenance and reliever therapy: impact on airway inflammation in asthma.2008
Budesonide/formoterol maintenance and reliever therapy versus conventional best standard treatment in asthma in an attempted 'real life' setting.2011
Poor adherence with inhaled corticosteroids for asthma: can using a single inhaler containing budesonide and formoterol help?2008
A real-life cost-effectiveness evaluation of budesonide/formoterol maintenance and reliever therapy in asthma.2008
Budesonide/formoterol maintenance and reliever therapy in moderate-to-severe asthma: effects on eosinophilic airway inflammation.-- Not Found --
Budesonide/formoterol maintenance and reliever therapy: an effective asthma treatment option?2005
Budesonide/formoterol maintenance and reliever therapy in Asian patients (aged ≥16 years) with asthma: a sub-analysis of the COSMOS study.2012
Budesonide/formoterol maintenance and reliever therapy in Chinese patients with asthma.2012
Budesonide/formoterol combination therapy as both maintenance and reliever medication in moderate-to-severe asthma: a real-life effectiveness study of Malaysian patients.2008
Maintenance plus reliever budesonide/formoterol compared with a higher maintenance dose of budesonide/formoterol plus formoterol as reliever in asthma: an efficacy and cost-effectiveness study.2006
Effect of smoking status on the efficacy of the SMART regimen in high risk asthma.2016
Comparison of early effects of budesonide/formoterol maintenance and reliever therapy with fluticasone furoate/vilanterol for asthma patients requiring step-up from inhaled corticosteroid monotherapy.2016
Tiotropium improves lung function, exacerbation rate, and asthma control, independent of baseline characteristics including age, degree of airway obstruction, and allergic status.2016
Pulmonary function assessment in mild to moderate persistent asthma patients receiving montelukast, doxofylline, and tiotropium with budesonide: a randomized controlled study.2014
Assessment of montelukast, doxofylline, and tiotropium with budesonide for the treatment of asthma: which is the best among the second-line treatment? A randomized trial.2015
Anticholinergic vs Long-Acting β-Agonist in Combination With Inhaled Corticosteroids in Black Adults With Asthma: The BELT Randomized Clinical Trial.2015
Assessment of various second-line medications in addition to inhaled corticosteroid in asthma patients: a randomized controlled trial.2014
Tiotropium in asthma poorly controlled with standard combination therapy.2012
Assessment of second-line treatments for patients with uncontrolled moderate asthma.2015
A randomised controlled trial of tiotropium in adolescents with severe symptomatic asthma.2017
Tiotropium bromide step-up therapy for adults with uncontrolled asthma.2010
Tiotropium is noninferior to salmeterol in maintaining improved lung function in B16-Arg/Arg patients with asthma.2011
Hippocampal synaptic transmission: regulation of the NMDA receptor-mediated component.1989
The effect of fluticasone furoate/umeclidinium in adult patients with asthma: a randomized, dose-ranging study.2015
Long-Term Once-Daily Tiotropium Respimat® Is Well Tolerated and Maintains Efficacy over 52 Weeks in Patients with Symptomatic Asthma in Japan: A Randomised, Placebo-Controlled Study.
The Effect of Tiotropium in Symptomatic Asthma Despite Low- to Medium-Dose Inhaled Corticosteroids: A Randomized Controlled Trial.-- Not Found --
Tiotropium add-on therapy in adolescents with moderate asthma: A 1-year randomized controlled trial.2016

Downloadable Data Content

Files
  • XLSX Project Data