A Cochrane review included 4 studies with a total of 302 subjects. Time range was 29 days to 12 months. There were no differences in either the number of respiratory exacerbations or the number of participants with an exacerbation between cystic fibrosis transmembrane conductance regulator (CFTR) gene transfer replacement therapy or placebo groups at any time point. Most respiratory function tests (FEV1, FEV1%,FVC) showed no difference between treatment and placebo groups, but the smallest study (n=16) reported forced vital capacity (litres) increased more in the placebo group at up to 24 hours. The more recent study (n=140) demonstrated a small improvement in FVC at 2 and 3 months and again at 11 and 12 months with gene replacement therapy compared with placebo.
Alton measured ion transport in the lower airways and demonstrated significant changes toward normal values in the participants who received gene transfer agents (P < 0.0001), weighted mean difference 6.86 (95% CI of 3.77 to 9.95). In these participants there was also evidence of increased salt transport in cells obtained by brushing the lower airway. These outcomes, whilst important, are not of direct clinical relevance.Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment) and by imprecise results ( few patients and wide confidence intervals).