The effect of the timing regimens on FEV1 was minor. Although some between-group comparisons were of borderline statistical significance, Smad activation the mean differences and their 95% CIs were all well below 150 mL (the a priori smallest worthwhile effect), and equated to ≤ 2% of the predicted normal value. Therefore, although these borderline results favoured inhalation of hypertonic saline before airway clearance techniques, any differences between the effects of the timing regimens on FEV1 are probably too

small to be clinically important. However, in the long term, clinically worthwhile differences in lung function from the use of a particular timing regimen could occur – possibly through differences in clearance effects and differences in adherence. This could be investigated in future research. For FVC, the between-group comparisons were again either of borderline

statistical significance or were non-significant. However, selleck inhibitor unlike the narrow confidence intervals seen in the FEV1 data, some of the between-group comparisons for FVC had 95% CIs that did not exclude the possibility of substantial effects. For example, inhaling hypertonic saline before airway clearance techniques might increase the improvement in FVC by as much as 180 mL more than inhaling it during or after the techniques. Therefore, further data could be obtained to make the estimate of the effect on FVC Non-specific serine/threonine protein kinase more precise and then to determine whether it is large enough to be clinically worthwhile. As with FEV1, the effect of long-term

use of a timing regimen on FVC could also be investigated. Perceived efficacy and satisfaction were significantly lower when hypertonic saline was inhaled after airway clearance techniques than with the other timing regimens. Inhalation of hypertonic saline after the techniques may fail to capitalise on effects of hypertonic saline on mucus clearance if techniques to promote expectoration are not undertaken until 4–6 hours later. Although these results were statistically significant, some may not be clinically worthwhile because the 95% CIs contain effects smaller than the a priori smallest worthwhile effect of 10 mm on the 100 mm visual analogue scale. However, the effect of inhaling hypertonic saline before rather than after the techniques increased satisfaction by 20 mm (95% CI 12 to 29), which clearly exceeds the smallest worthwhile effect. The data did not support our hypothesis that inhaling hypertonic saline after airway clearance techniques would reduce tolerability. We expected that inhaling the hypertonic saline after the techniques may have delivered it to a more exposed airway epithelium because the amount of overlying mucus would be minimised. However, this timing regimen did not reduce subjective or objective tolerability.