Summary of findings 4. Summary of findings ‐ Inhaled mannitol compared with dornase alfa for cystic fibrosis.

Inhaled mannitol compared with dornase alfa for CF
Patient or population: children and young people with CF Settings: outpatients Intervention: inhaled mannitol Comparison: dornase alfa
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Dornase alfa	Inhaled mannitol
HRQoL ‐ all domains (change from baseline) Scale: age‐appropriate versions of the CFQ‐R questionnaire Follow‐up: up to 3 months	No significant differences were found between treatment groups for any domains of the CFQ‐R.		NA	up to 231 1 cross‐over study	⊕⊝⊝⊝ verylow1,2,3
Lung function: FEV1 mL (percentage change from baseline) Follow‐up: up to 3 months	The mean (SD) absolute change from baseline in the dornase alfa group was 84 (273) mL.	The mean (SD) absolute change from baseline in the mannitol group was ‐1 (279) mL.	MD 2.80% (95% CI: ‐4.80% to 10.40%).	up to 231 1 cross‐over study	⊕⊝⊝⊝ verylow1,2	Only the relative effect of percentage change from baseline could be analysed*.
Lung function: FEV1 % predicted Follow‐up: NA	Outcome not reported.				NA
Lung function: FVC mL (percentage change from baseline) Follow‐up: up to 3 months	The mean (SD) absolute change from baseline in the dornase alfa group was 7 (415) mL.	The mean (SD) absolute change from baseline in the mannitol group was ‐58 (361) mL.	MD 0.14% (95% CI: ‐0.02% to 0.30%).	up to 231 1 cross‐over study	⊕⊝⊝⊝ verylow1,2	Only the relative effect of percentage change from baseline could be analysed*.
Lung function: FEF25-75 mL/s (percentage change from baseline) Follow‐up: up to 3 months	The mean (SD) absolute change from baseline in the dornase alfa group was 173 (310) mL/s.	The mean (SD) absolute change from baseline in the mannitol group was 55 (282) mL/s.	MD ‐0.01% (95% CI: ‐0.23 to 0.21%).	up to 231 1 cross‐over study	⊕⊝⊝⊝ verylow1,2	Only the relative effect of percentage change from baseline could be analysed*.
Adverse events relating to treatment Scale: mild, moderate, severe and total Follow‐up: up to 3 months	CF exacerbation was the most commonly reported adverse event (5% of participants).	Cough and CF exacerbation were the most commonly reported adverse events (22% and 17% of participants respectively).	See comment.	up to 231 1 cross‐over study	⊕⊝⊝⊝ verylow1,2	Frequencies of adverse events according to severity only were reported, a statistical comparison was not made.
*The basis of the assumed risk and the corresponding risk is described in the comments. For lung function outcomes, absolute data was not presented in a format which could be analysed due to the cross‐over design of the study, therefore only analyses of percentage change from baseline were included in this review CF: cystic fibrosis;CFQ‐R: Cystic Fibrosis Questionnaire‐Revised version, CI: confidence interval; FEF25-75: mid‐expiratory flow; FEV1: forced expiratory volume at one second; FVC: forced vital capacity; HRQoL: health‐related quality of life; MD: mean difference; NA: not applicable; SD: standard deviation.
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate.

1. Stated that 28 participants were randomised, unclear how many participants dropped out and how many were evaluated for each outcome (evidence downgraded due to incomplete outcome data). Evidence also downgraded due to imprecision, study is known to be underpowered.

2. Evidence downgraded due to indirectness: the participant population included only those with CF who passed the tolerance test and not all potential participants with CF.

3. Evidence downgraded due to indirectness: the CFQ‐R tool used in the studies was not designed to assess mucolytics. Also, pooling of the age‐appropriate tools may not be valid so results should be interpreted with caution.