Smith S, Rowbotham NJ, Edwards CT. Short‐acting inhaled bronchodilators for cystic fibrosis. Cochrane Database of Systematic Reviews 2022, Issue 6. Art. No.: CD013666. DOI: 10.1002/14651858.CD013666.pub2. Accessed 25 July 2022.

Randomised controlled trials (RCTs) or quasi‐RCTs

Children and adults with CF

Short‐acting inhaled bronchodilators (Terbutaline, Inhaled Bronchodilator Therapy, Fenoterol, Salbutamol, Ipratropium Bromide). For this review 'inhaled' includes the use of pressurised metered dose inhalers (MDIs), with or without a spacer, dry powder devices and nebulisers.

Clinical outcomes and safety. CF Pulmonary Exacerbation, Quality of Life, FEV1, CF Quality of Life, CF Questionnaire-Revised

11 trials from the systematic search, with 191 participants meeting inclusion criteria; three of these trials had three treatment arms. Eight trials compared short‐acting inhaled beta‐2 agonists to placebo and four trials compared short‐acting inhaled muscarinic antagonists to placebo. Three trials compared short‐acting inhaled beta‐2 agonists to short‐acting inhaled muscarinic antagonists. All were cross‐over trials with only small numbers of participants. Short‐acting inhaled beta‐2 agonists versus placebo. All eight trials (six single‐dose trials and two longer‐term trials) reporting on this comparison reported on forced expiratory volume in 1 second (FEV1), either as per cent predicted (% predicted) or L. Authors were able to combine the data from two trials in a meta‐analysis which showed a greater per cent change from baseline in FEV1 L after beta‐2 agonists compared to placebo (mean difference (MD) 6.95%, 95% confidence interval (CI) 1.88 to 12.02; 2 trials, 82 participants). Only one of the longer‐term trials reported on exacerbations, as measured by hospitalisations and courses of antibiotics. Only the second longer‐term trial presented results for participant‐reported outcomes. Three trials narratively reported adverse events, and these were all mild. Three single‐dose trials and the two longer trials reported on forced vital capacity (FVC), and five trials reported on peak expiratory flow, i.e. forced expiratory flow between 25% and 75% (FEF25-75). One trial reported on airway clearance in terms of sputum weight. We judged the certainty of evidence for each of these outcomes to be very low, meaning we are very uncertain about the effect of short‐acting inhaled beta‐2 agonists on any of the outcomes assessed. Short‐acting inhaled muscarinic antagonists versus placebo: All four trials reporting on this comparison looked at the effects of ipratropium bromide, but in different doses and via different delivery methods. One trial reported FEV1 % predicted; three trials measured this in L. Two trials reported adverse events, but these were few and mild. One trial reported FVC and three trials reported FEF25-75. None of the trials reported on quality of life, exacerbations or airway clearance. The certainty of evidence for each of these outcomes was very low, meaning we are very uncertain about the effect of short‐acting inhaled muscarinic antagonists on any of the outcomes we assessed. Short‐acting inhaled beta‐2 agonists versus short‐acting inhaled muscarinic antagonists. None of the three single‐dose trials reporting on this comparison provided data we could analyse. The original papers from three trials report that both treatments lead to an improvement in FEV1 L. Only one trial reported on adverse events; but none were experienced by any participant. No trial reported on any of our other outcomes. The certainty of evidencewas very low, meaning we are very uncertain about the effect of short‐acting inhaled beta‐2 agonists compared to short‐acting inhaled muscarinic antagonists on any of the outcomes we assessed.

All included trials in this review are small and of a cross‐over design. Most trials looked at very short‐term effects of inhaled bronchodilators, and therefore did not measure longer‐term outcomes. The certainty of evidence across all outcomes was very low, and therefore we have been unable to describe any effects with certainty.