Study design (if review, criteria of inclusion for studies)
Controlled trials assessing HS compared to placebo or other mucolytic therapy, for any duration or dose regimen in people with CF (any age or disease severity).
List of included studies (17)
Adde 2004; Amin 2010; Ballmann 1998; Cardinale 2003; Chadwick 1997; Dentice 2016; Elkins 2006a; Eng 1996; Laube 2009; Mainz 2015; Riedler 1996; Robinson 1996; Robinson 1997; Robinson 1999; Rosenfeld 2012; Suri 2001; Weller 1980
People of all ages and of both sexes with CF diagnosed clinically or by sweat and genetic testing, including all degrees of disease severity.
Hypertonic saline; Hypertonic saline 3% to 7%
Adverse events; Average number of hospital admissions per participant; Average number of visits; Change in log10 colony forming units (CFU)/g from baseline at final visit; Delivery time (mins); Exercise tolerance - FCS; Exercise tolerance - oxygen saturation; Exercise tolerance - VAS for breathlessness; Improvement in FEV1 >10%; Mean percentage change in FEV1; Mean percentage change in FVC; Mean percentage change in quality of life score; Mucociliary clearance measured as area under the curve; Percentage change in FEV1; Percentage change in FVC; Quality of life, change from baseline; Radiolabelled isotope clearance at 60 mins; Visual analogue scale, feeling of cleared chest
A total of 17 trials (966 participants, aged 4 months to 63 years) were included; 19 trials were excluded, three trials are ongoing and 16 are awaiting classification. We judged 14 of the 17 included trials to have a high risk of bias due to participants ability to discern the taste of the solutions. Hypertonic saline 3% to 7% versus placebo At four weeks, we found very lowâquality evidence from three placeboâcontrolled trials (n = 225) that hypertonic saline (3% to 7%, 10 mL twiceâdaily) increased the mean change from baseline of the forced expiratory volume at one second (FEV 1 ) (% predicted) by 3.44% (95% confidence interval (CI) 0.67 to 6.21), but there was no difference between groups in lung clearance index in one small trial (n = 10). By 48 weeks the effect was slightly smaller in one trial (n = 134), 2.31% (95% CI â2.72 to 7.34) (lowâquality evidence). No deaths occurred in the trials. Two trials reporting data on exacerbations were not combined as the age difference between the participants in the trials was too great . One trial (162 adults) found 0.5 fewer exacerbations requiring antibiotics per person in the hypertonic saline group; the second trial (243 children, average age of two years) found no difference between groups (lowâquality evidence). There was insufficient evidence reported across the trials to determine the rate of different adverse events such as cough, chest tightness, tonsillitis and vomiting (very lowâquality evidence). Four trials (n = 80) found very lowâquality evidence that sputum clearance was better with hypertonic saline. A further trial was performed in adults with an acute exacerbation of lung disease (n = 132). The effects of hypertonic saline on shortâterm lung function, 5.10% higher (14.67% lower to 24.87% higher) and the time to the subsequent exacerbation postâdischarge, hazard ratio 0.86 (95% CI 0.57 to 1.30) are uncertain (lowâquality evidence). No deaths were reported. Cough and wheeze were reported but no serious adverse events (very lowâquality evidence). Hypertonic saline versus mucus mobilising treatments Three trials compared a similar dose of hypertonic saline to recombinant deoxyribonuclease (rhDNase); two (61 participants) provided data for inclusion in the review. There was insufficient evidence from one threeâweek trial (14 participants) to determine the effects of hypertonic saline on FEV 1 % predicted, mean difference (MD) 1.60% (95% CI â7.96 to 11.16) (very lowâquality evidence). In the second trial, rhDNase led to a greater increase in FEV 1 % predicted than hypertonic saline (5 mL twice daily) at 12 weeks in participants with moderate to severe lung disease, MD 8.00% (95% CI 2.00 to 14.00) (lowâquality evidence). One crossâover trial (47 participants) reported 15 exacerbations during treatment with hypertonic saline and 18 exacerbations in the rhDNase group (lowâquality evidence). Increased cough was reported in 13 participants using hypertonic saline and 17 on daily rhDNase in one crossâover trial of 47 people (lowâquality evidence). There was insufficient evidence to assess rates of other adverse events reported. No deaths were reported. One trial (12 participants) compared hypertonic saline to amiloride and one (29 participants) to sodiumâ2âmercaptoethane sulphonate. Neither trial found a difference between treatments in any measures of sputum clearance; additionally the comparison of hypertonic saline and sodiumâ2âmercaptoethane sulphonate reported no differences in courses of antibiotics or adverse events (very lowâquality evidence). One trial (12 participants) compared hypertonic saline to mannitol but did not report lung function at relevant time points for this review; there were no differences in sputum clearance, but mannitol was reported to be more 'irritating' (very lowâquality evidence).
Regular use of nebulised hypertonic saline by adults and children over the age of 12 years with CF results in an improvement in lung function after four weeks (very lowâquality evidence from three trials), but this was not sustained at 48 weeks (lowâquality evidence from one trial). The review did show that nebulised hypertonic saline reduced the frequency of pulmonary exacerbations (although we found insufficient evidence for this outcome in children under six years of age) and may have a small effect on improvement in quality of life in adults. Evidence from one small crossâover trial in children indicates that rhDNase may lead to better lung function at three months; qualifying this we highlight that while the study did demonstrate that the improvement in FEV 1 was greater with daily rHDNase, there were no differences seen in any of the secondary outcomes. Hypertonic saline does appear to be an effective adjunct to physiotherapy during acute exacerbations of lung disease in adults. However, for the outcomes assessed, the quality of the evidence ranged from very low to at best moderate, according to the GRADE criteria.