Inhaled corticosteroids for cystic fibrosis (Cochrane Review)

A substantive amendment to this systematic review was last made on 19 October 1999. Cochrane reviews are regularly checked and updated if necessary.

Background: Maintenance of optimal lung function is an important therapeutic goal in cystic fibrosis as it is lung damage that, in the long term, is responsible for most premature death among affected people. Inhaled corticosteroids are being increasingly used to treat children and adults with cystic fibrosis. The rationale for their use is that they have the potential to reduce lung damage arising from inflammation. However chronic use of inhaled steroids may also have adverse effects. It is thus important to establish the current level of evidence about the potential benefits and harms of this practice.

Objectives: The objective of this review is to assess the effectiveness of regular use of inhaled corticosteroids when compared to no inhaled corticosteroids, in the management of patients with cystic fibrosis.

Search strategy: Trials were ascertained from the Cochrane Cystic Fibrosis and Genetic Disorders Specialised Register of Controlled Trials which includes published and unpublished trials identified through electronic databases such as Medline and Embase as well as those identified from handsearching of journals and conference proceedings. Pharmaceutical companies manufacturing inhaled corticosteroids were also contacted to identify any trials of inhaled corticosteroids in cystic fibrosis.Date of the most recent search of the Group's specialised register: February 2000.

Selection criteria: All trials, both published and unpublished, in which inhaled corticosteroids were compared to either placebo or standard treatment in patients with cystic fibrosis. Trials employing random treatment allocation and those using quasi-random allocation methods such as alternate allocation to treatment and control group were included.

Data collection and analysis: The following outcomes were assessed: objective measures of lung function, respiratory exacerbations, use of intravenous antibiotics, hospital admissions, nutritional status, symptoms, quality of life, survival and frequency of adverse effects. Methodological quality of trials was assessed independently using established criteria by two reviewers, who also extracted relevant data independently using standard proformas. Differences were resolved by discussion.

Main results: Nine trials were identified reporting the use of inhaled steroids in 266 subjects aged between seven and 45 years with cystic fibrosis. Methodological quality was difficult to assess from published information, specifically with respect to concealment of allocation and method used to generate random sequence. Trials were heterogeneous with respect to inclusion criteria, specifically age, severity of pulmonary involvement, clinical diagnosis of asthma and pulmonary colonisation with Pseudomonas aeruginosa. Trials also differed in type and duration of treatment. Beclomethasone was given for periods of between four and 22 weeks in four trials, budesonide for six weeks and six months respectively in two, and fluticasone for periods of between six weeks and two years in the remaining three. Measures of the volume of air breathed out on a forcible expiration (forced expiratory volumes) were reported in most trials but these data could not be combined for this review partly because reports differed in the way data were summarised and partly because some data were not included in published reports. Outcomes of potentially greater relevance to affected individuals such as nutritional status or quality of life were not reported in any trial. Survival was not reported in any trial, but this may reflect the fact that maximum duration of follow up was too short to allow this outcome to be meaningfully assessed. Adverse effects were systematically documented in only two trials. Although one trial was halted prematurely because a proportion of all those taking part had acquired chronic lung infections with Pseudomonas aeruginosa, no conclusions can be reached from this one small trial as to whether this risk is increased as a consequence of taking inhaled corticosteroids.

Reviewers' conclusions: Current evidence from randomised trials is insufficient to establish whether there is a beneficial or harmful effect of inhaled corticosteroids when used in subjects with cystic fibrosis. Further data are being sought from trialists for a future update of this review as it may be possible to calculate a pooled estimate of effects on certain objective measures of lung function. Future updates of this review based on existing trials are unlikely to be conclusive as treatment periods in existing trials tend to be short, information from medium and long term follow up is lacking, and not all relevant outcomes have been measured. Further trials are needed to determine whether inhaled steroids are effective and whether they are associated with any adverse effects. As the practice of prescribing inhaled steroids in cystic fibrosis is already widespread in Europe and may be increasing in North America, these may need to be trials designed to show whether withdrawing rather than starting treatment with inhaled corticosteroids is beneficial or detrimental. While data from this review do not allow precise estimates of sample size, large multicentre trials are likely to be needed to have sufficient power to identify potential benefits and harms with confidence. Important questions to be addressed in such trials include the impact of treatment on respiratory function and symptoms, nutritional status, concomitant therapy and quality of life, the prevalence of important adverse effects, and whether certain sub-groups are likely to benefit.

Citation: Dezateux C, Walters S, Balfour-Lynn I. Inhaled corticosteroids for cystic fibrosis (Cochrane Review). In: The Cochrane Library, Issue 3, 2003. Oxford: Update Software.

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This is an abstract of a regularly updated, systematic review prepared and maintained by the Cochrane Collaboration. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).

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