Summary of findings 2. Summary of findings ‐ Inhaled mannitol compared with control (non‐respirable mannitol) for cystic fibrosis.

Inhaled mannitol compared with control (non‐respirable mannitol) for CF
Patient or population: adults, children and young people with CF Settings: outpatients Intervention: inhaled mannitol Comparison: non‐respirable mannitol
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Non‐respirable mannitol	Inhaled mannitol
HRQoL ‐ all domains (change from baseline) Scale: age‐appropriate versions of the CFQ‐R questionnaire Follow‐up: 2 weeks	At the end of the study there were no significant differences between mannitol and control for the respiratory, health, physical and vitality domains.		NA	391 1 cross‐over study	⊕⊝⊝⊝ verylow1,2,3
Lung function: FEV1 mL (absolute change from baseline) Follow‐up: 2 weeks	A statistically significant improvement on mannitol compared to control was observed.		NA	391 1 study	⊕⊕⊝⊝ low1,2
Lung function: FEV1 % predicted (change from baseline) Follow‐up: 2 weeks to 8 weeks	One study showed a statistically significant improvement in absolute change from baseline on mannitol compared to control at 2 weeks. The second study showed statistically significant improvement in both absolute and relative change from baseline on mannitol compared to control at 8 weeks.		NA.	1261 2 cross‐over studies	⊕⊕⊝⊝ low1,2
Lung function: FVC mL or % predicted (change from baseline) Follow‐up: 2 weeks to 8 weeks	No statistically significant differences in absolute or relative change from baseline in FVC (mL or % predicted) were found in either study.		NA	1261 2 cross‐over studies	⊕⊕⊝⊝ low1,2
Lung function: FEF25-75 mL/s or % predicted (change from baseline) Follow‐up: 2 weeks to 8 weeks	One study showed a statistically significant improvement in absolute change from baseline in FEF25-75 (mL/S) on mannitol compared to control at 2 weeks. The other study showed statistically significant improvement in both absolute and relative change from baseline in in FEF25-75 (% predicted) on mannitol compared to control at 8 weeks.		NA	1261 2 cross‐over studies	⊕⊕⊝⊝ low1,2
Adverse events relating to treatment Scale: mild, moderate, severe and total Follow‐up: 2 weeks to 8 weeks	The most commonly reported adverse events in both groups in the two studies were cough, haemoptysis, headache, nasopharyngitis and lung infections.		NA	123‐1254 2 cross‐over studies	⊕⊕⊝⊝ low1,2	Frequencies of adverse events according to severity and association to treatment only were reported, a statistical comparison was not made in either study.
*The basis of the assumed risk and the corresponding risk is described in the comments. The study authors adjusted for the cross‐over design of the study via a mixed model of analysis of variance when analysing and presenting results, however the format of the presented data does not allow us to perform analyses in this review. Published results from the study paper are presented 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; NA: not applicable.
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. In one of the studies it was stated that 39 participants were randomised, unclear how many were evaluated for each outcome. In the other study, the study may have been underpowered and imputation of missing data may have introduced bias (evidence downgraded due to risk of bias of incomplete outcome data).

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.

4. One of the studies, adverse event data available for 38 and 36 participants in the mannitol and control groups respectively.