Inhaled corticosteroids for cystic fibrosis

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.

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.

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Cochrane Cystic Fibrosis and Genetic Disorders Specialised Register of Controlled Trials which includes published and unpublished trials identified through electronic databases such as Medline and Embase as well as those identified from handsearching of journals and conference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: November 1999.

All trials, both published and unpublished, in which inhaled corticosteroids were compared to either placebo or standard treatment in patients with cystic fibrosis.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.

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.

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