Inhaled corticosteroids for cystic fibrosis
File(s)Balfour-Lynn_et_al-2016-.sup-2.pdf (601.57 KB)
Published version
Author(s)
Balfour-Lynn, Ian M
Welch, Karen
Type
Journal Article
Abstract
Background
Reduction of lung inflammation is one of the goals of cystic fibrosis therapy. Inhaled corticosteroids are often used to treat children and adults with cystic fibrosis. The rationale for this is their potential to reduce lung damage arising from inflammation, as well as their effect on symptomatic wheezing. It is important to establish the current level of evidence for the risks and benefits of inhaled corticosteroids, especially in the light of their known adverse effects on growth. This is an update of a previously published review.
Objectives
To assess the effectiveness of taking regular inhaled corticosteroids, compared to not taking them, in children and adults with cystic fibrosis.
Search methods
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We requested information from pharmaceutical companies manufacturing inhaled corticosteroids and authors of identified trials.
Date of most recent search of the Group's Trials Register: 15 August 2016.
Selection criteria
Randomised or quasi-randomised trials, published and unpublished, comparing inhaled corticosteroids to placebo or standard treatment in individuals with cystic fibrosis.
Data collection and analysis
Two independent authors assessed methodological quality and risk of bias in trials using established criteria and extracted data using standard pro formas.
Main results
The searches identified 34 citations, of which 26 (representing 13 trials) were eligible for inclusion. These 13 trials reported the use of inhaled corticosteroids in 506 people with cystic fibrosis aged between six and 55 years. One was a withdrawal trial in individuals who were already taking inhaled corticosteroids. Methodological quality and risk of bias were difficult to assess from published information. Many of the risk of bias judgements were unclear due to a lack of available information. Only two trials specified how participants were randomised and less than half of the included trials gave details on how allocation was concealed. Trials were generally judged to have a low risk of bias from blinding, except for two which were open label or did not use a placebo. There were some concerns that a number of trials had not been published in peer-reviewed journals, but the risk of bias from this was unclear. Inclusion criteria varied between trials, as did type and duration of treatment and timing of outcome assessments. Objective measures of airway function were reported in most trials but were often incomplete. Significant benefit has not been conclusively demonstrated. Four trials systematically documented adverse effects and growth was significantly affected in one study using high doses.
Authors' conclusions
Evidence from these trials is insufficient to establish whether inhaled corticosteroids are beneficial in cystic fibrosis, but withdrawal in those already taking them has been shown to be safe. There is some evidence they may cause harm in terms of growth. It has not been established whether long-term use is beneficial in reducing lung inflammation, which should improve survival, but it is unlikely this will be proven conclusively in a randomised controlled trial.
Reduction of lung inflammation is one of the goals of cystic fibrosis therapy. Inhaled corticosteroids are often used to treat children and adults with cystic fibrosis. The rationale for this is their potential to reduce lung damage arising from inflammation, as well as their effect on symptomatic wheezing. It is important to establish the current level of evidence for the risks and benefits of inhaled corticosteroids, especially in the light of their known adverse effects on growth. This is an update of a previously published review.
Objectives
To assess the effectiveness of taking regular inhaled corticosteroids, compared to not taking them, in children and adults with cystic fibrosis.
Search methods
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We requested information from pharmaceutical companies manufacturing inhaled corticosteroids and authors of identified trials.
Date of most recent search of the Group's Trials Register: 15 August 2016.
Selection criteria
Randomised or quasi-randomised trials, published and unpublished, comparing inhaled corticosteroids to placebo or standard treatment in individuals with cystic fibrosis.
Data collection and analysis
Two independent authors assessed methodological quality and risk of bias in trials using established criteria and extracted data using standard pro formas.
Main results
The searches identified 34 citations, of which 26 (representing 13 trials) were eligible for inclusion. These 13 trials reported the use of inhaled corticosteroids in 506 people with cystic fibrosis aged between six and 55 years. One was a withdrawal trial in individuals who were already taking inhaled corticosteroids. Methodological quality and risk of bias were difficult to assess from published information. Many of the risk of bias judgements were unclear due to a lack of available information. Only two trials specified how participants were randomised and less than half of the included trials gave details on how allocation was concealed. Trials were generally judged to have a low risk of bias from blinding, except for two which were open label or did not use a placebo. There were some concerns that a number of trials had not been published in peer-reviewed journals, but the risk of bias from this was unclear. Inclusion criteria varied between trials, as did type and duration of treatment and timing of outcome assessments. Objective measures of airway function were reported in most trials but were often incomplete. Significant benefit has not been conclusively demonstrated. Four trials systematically documented adverse effects and growth was significantly affected in one study using high doses.
Authors' conclusions
Evidence from these trials is insufficient to establish whether inhaled corticosteroids are beneficial in cystic fibrosis, but withdrawal in those already taking them has been shown to be safe. There is some evidence they may cause harm in terms of growth. It has not been established whether long-term use is beneficial in reducing lung inflammation, which should improve survival, but it is unlikely this will be proven conclusively in a randomised controlled trial.
Date Issued
2016-08-23
Date Acceptance
2016-08-23
Citation
Cochrane Database of Systematic Reviews, 2016, 2016 (8)
ISSN
1469-493X
Publisher
Cochrane Collaboration
Journal / Book Title
Cochrane Database of Systematic Reviews
Volume
2016
Issue
8
Copyright Statement
Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
Administration, Inhalation
Anti-Inflammatory Agents [administration & dosage; adverse effects]
Cystic Fibrosis [drug therapy]
Glucocorticoids [administration & dosage; adverse effects]
Randomized Controlled Trials as Topic
Adolescent
Adult
Child
Humans
Middle Aged
Young Adult
SYMPTOMATIC ADRENAL INSUFFICIENCY
FLUTICASONE PROPIONATE
AIRWAY INFLAMMATION
LUNG-FUNCTION
BRONCHIAL HYPERRESPONSIVENESS
SUPPRESSION SECONDARY
ASTHMATIC-CHILDREN
CONTROLLED-TRIAL
DISEASE
BUDESONIDE
Publication Status
Published
Article Number
CD001915