Mark Elkins, Ruth Dentice

Inhalation of hypertonic saline improves sputum rheology, accelerates mucociliary clearance and improves clinical outcomes of people with cystic fibrosis. To determine whether the timing of hypertonic saline inhalation (in relation to airway clearance techniques or in relation to time of day) has an impact on its clinical efficacy in people with cystic fibrosis. We identified relevant randomised and quasi-randomised controlled trials from the Cochrane Cystic Fibrosis Trials Register, the Physiotherapy Evidence Database (PEDro), and international cystic fibrosis conference proceedings.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register: 19 December 2016. Any trial of hypertonic saline in people with cystic fibrosis where timing of inhalation was the randomised element in the study protocol with either: inhalation up to six hours before airway clearance techniques compared to inhalation during airway clearance techniques compared to inhalation up to six hours after airway clearance techniques; or morning compared to evening inhalation with any definition provided by the author. Both authors independently assessed the trials identified by the search for potential inclusion in the review. The searches identified 97 trial reports which represented 46 studies, of which two studies (providing data on 63 participants) met our inclusion criteria. Both studies used a cross-over design. Both studies had low risk of all types of bias except the participants and the therapists who applied the treatments were not blinded. Intervention periods ranged from one treatment to three treatments in one day. The effects of the various regimens on lung function were non-significant. Satisfaction was rated significantly lower on a 100-mm scale when hypertonic saline was inhaled after the airway clearance techniques: mean differences 20.38 mm (95% confidence interval 12.10 to 28.66) compared to before airway clearance techniques and 14.80 mm (95% confidence interval 5.70 to 23.90) compared to during the techniques. Perceived effectiveness showed similar significant results. Other outcomes were unaffected by the timing regimen used. No trials compared morning versus evening inhalation of hypertonic saline. People with cystic fibrosis could be encouraged to inhale hypertonic saline before or during airway clearance techniques to maximise perceived efficacy and satisfaction, even though these timing regimens may not have any better effect on lung function than inhalation after airway clearance techniques. Given the long-term efficacy of hypertonic saline has only been established for twice-daily inhalations, clinicians should advise patients to inhale hypertonic saline twice daily. However, if only one dose per day is tolerated, the time of day at which it is inhaled could be based on convenience or tolerability until evidence comparing these regimens is available.