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Meta-Analysis
. 2018 Sep 27;9(9):CD001506.
doi: 10.1002/14651858.CD001506.pub4.

Nebulised hypertonic saline for cystic fibrosis

Peter Wark  1 , Vanessa M McDonald
Affiliations
Meta-Analysis

Nebulised hypertonic saline for cystic fibrosis

Peter Wark et al. Cochrane Database Syst Rev. .

Update in

  • Nebulised hypertonic saline for cystic fibrosis.
    Wark P, McDonald VM, Smith S. Wark P, et al. Cochrane Database Syst Rev. 2023 Jun 14;6(6):CD001506. doi: 10.1002/14651858.CD001506.pub5. Cochrane Database Syst Rev. 2023. PMID: 37319354 Free PMC article.

Abstract

Background: Impaired mucociliary clearance characterises lung disease in cystic fibrosis (CF). Hypertonic saline enhances mucociliary clearance and may lessen the destructive inflammatory process in the airways. This is an update of a previously published review.

Objectives: To investigate efficacy and tolerability of treatment with nebulised hypertonic saline on people with CF compared to placebo and or other treatments that enhance mucociliary clearance.

Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also searched ongoing trials databases.Date of most recent searches: 08 August 2018.

Selection criteria: Randomised and quasi-randomised controlled trials assessing hypertonic saline compared to placebo or other mucolytic therapy, for any duration or dose regimen in people with CF (any age or disease severity).

Data collection and analysis: Two authors independently reviewed all identified trials and data, and assessed trial quality. The quality of the evidence was assessed using GRADE.

Main results: 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 placeboAt four weeks, we found very low-quality evidence from three placebo-controlled trials (n = 225) that hypertonic saline (3% to 7%, 10 mL twice-daily) increased the mean change from baseline of the forced expiratory volume at one second (FEV1) (% 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 -2.72 to 7.34) (low-quality 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 (low-quality 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 low-quality evidence). Four trials (n = 80) found very low-quality 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 short-term lung function, 5.10% higher (14.67% lower to 24.87% higher) and the time to the subsequent exacerbation post-discharge, hazard ratio 0.86 (95% CI 0.57 to 1.30) are uncertain (low-quality evidence). No deaths were reported. Cough and wheeze were reported but no serious adverse events (very low-quality 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 three-week trial (14 participants) to determine the effects of hypertonic saline on FEV1 % predicted, mean difference (MD) 1.60% (95% CI -7.96 to 11.16) (very low-quality evidence). In the second trial, rhDNase led to a greater increase in FEV1 % 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) (low-quality evidence). One cross-over trial (47 participants) reported 15 exacerbations during treatment with hypertonic saline and 18 exacerbations in the rhDNase group (low-quality evidence). Increased cough was reported in 13 participants using hypertonic saline and 17 on daily rhDNase in one cross-over trial of 47 people (low-quality 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 sodium-2-mercaptoethane sulphonate. Neither trial found a difference between treatments in any measures of sputum clearance; additionally the comparison of hypertonic saline and sodium-2-mercaptoethane sulphonate reported no differences in courses of antibiotics or adverse events (very low-quality 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 low-quality evidence).

Authors' conclusions: 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 low-quality evidence from three trials), but this was not sustained at 48 weeks (low-quality 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 cross-over 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 FEV1 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.

PubMed Disclaimer

Conflict of interest statement

Peter Wark: I or my institution have received money in support of investigator initiated research, participation in advisory boards or fees for speaking from GSK, Astra Zeneca, Bohringer Ingelheim, Vertex and Menarini; none of which are relevant to this review. I was an investigator and an author on one trial included in the review (Dentice 2016) and a co‐investigator on a further trial, the National Hypertonic Saline in Cystic Fibrosis Study trial (Elkins 2006a).

Vanessa McDonald: I have received honorariums for participation in educational meetings from GSK, AstraZeneca and Menarini and was a co‐investigator in the National Hypertonic Saline in Cystic Fibrosis Study trial (Elkins 2006a).

Figures

1
1
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
Forest plot of comparison: 1 Hypertonic saline 3% to 7% versus isotonic saline, outcome: 1.10 Average number of exacerbations.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Adde 2004 {published data only}
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Amin 2010 {published data only}
    1. Amin. The Effect of Hypertonic Saline on the Lung Clearance Index in Patients With Cystic Fibrosis. NCT00635141 August 2013.
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Cardinale 2003 {published data only}
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Dentice 2016 {published data only}
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Eng 1996 {published data only}
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Laube 2009 {published data only}
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Mainz 2015 {published data only}
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Riedler 1996 {published data only}
    1. Button BM, Riedler J, Eng P, Roberston CF. Inhaled hypertonic saline as an adjunct to chest physiotherapy in cystic fibrosis; the three year clinical experience [abstract]. Pediatric Pulmonology 1996;Suppl 13:306. [CFGD Register: BD69a]
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Robinson 1996 {published data only}
    1. Robinson M, Regnis JA, Bailey DL, King M, Bautovich GJ, Bye PT. Effect of hypertonic saline, amiloride, and cough on mucociliary clearance in patients with cystic fibrosis. American Journal of Respiratory and Critical Care Medicine 1996;153(5):1503‐9. [CFGD Register: BD83; ] - PubMed
Robinson 1997 {published data only}
    1. Robinson M, Hemming A, Regnis J, Wong A, Bailey D, Bautotvich G, et al. Effect of increasing doses of hypertonic saline on mucociliary clearance inpatients with cystic fibrosis. Thorax 1997;52(10):900‐3. [CFGD Register: BD45b] - PMC - PubMed
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Robinson 1999 {published data only}
    1. Robinson M, Daviskas E, Eberl S, Baker J, Anderson SD, Bye PT. Effect of inhaling a dry powder of mannitol on mucociliary clearance in adults with cystic fibrosis [abstract]. Pediatric Pulmonolgy 1998;Suppl 17:280. [CFGD Register: BD84a]
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Rosenfeld 2012 {published data only}
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Suri 2001 {published data only}
    1. Grieve R, Thompson S, Normand C, Suri R, Bush A, Wallis C. A cost‐effectiveness analysis of rhDNase in children with cystic fibrosis. International Journal of Technology Assessment in Health Care 2003;19(1):71‐9. [CFGD Register: BD96h] - PubMed
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    1. Suri R, Grieve R, Normand C, Metcalfe C, Thompson S, Wallis C, et al. Effects of hypertonic saline, alternate day and daily rhDNase on healthcare use, costs and outcomes in children with cystic fibrosis [abstract]. Thorax 2001;56(Suppl 3):iii84. [CFGD Register: BD96f] - PMC - PubMed
    1. Suri R, Marshall LJ, Wallis C, Metcalfe C, Bush A, Shute JK. Effects of recombinant human DNase and hypertonic saline on airway inflammation in children with cystic fibrosis. American Journal of Respiratory and Critical Care Medicine 2002;166(3):352‐5. [CFGD Register: BD96d] - PubMed
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Weller 1980 {published data only}
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References to studies excluded from this review

Brivio 2016 {published data only}
    1. Brivio A, Ceruti C, Gambazza S, Colombo C. Randomized double‐blind monocentric trial on tolerability, acceptability and efficacy of two formulations of inhaled 7% hypertonic saline with and without hyaluronic acid in reducing airways inflammation in patients with cystic fibrosis ‐ preliminary results [abstract]. Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society 2013;12 Suppl 1:S104, Abstract no: 217. [CENTRAL: 999881; CFGD Register: BD208a; CRS: 5500127000000003]
    1. Brivio A, Conese M, Gambazza S, Biffi A, Tirelli AS, Russo M, et al. Pilot Randomized Controlled Trial Evaluating the Effect of Hypertonic Saline With and Without Hyaluronic Acid in Reducing Inflammation in Cystic Fibrosis. Journal of Aerosol Medicine and Pulmonary Drug Delivery 2016 May 15 [Epub ahead of print]. [CENTRAL: 1155400; CFGD Register: BD208b; CRS: 5500135000001523; PUBMED: 27149365] - PubMed
Buonpensiero 2010 {published data only (unpublished sought but not used)}
    1. Buonpensiero P, Gregorio F, Sepe A, Pasqua A, Ferri P, Siano M, et al. Hyaluronic acid improves "pleasantness" and tolerability of nebulized hypertonic saline in a cohort of patients with cystic fibrosis. Advances in Therapy 2010;27(11):870‐8. [CENTRAL: 781252; CFGD Register: BD156c; CRS: 5500100000003514; EMBASE: 2010642492; PUBMED: 20953746] - PubMed
    1. Buonpensiero P, Gregorio F, Sepe A, Pasqua A, Ferri P, Siano M, et al. Hyaluronic acid improves tolerability of hypertonic saline in CF patients [abstract]. Journal of Cystic Fibrosis 2010;9 Suppl 1:S63, Abstract no: 245. [CENTRAL: 775087; CFGD Register: BD156b; CRS: 5500100000003507]
    1. Buonpensiero P, Gregorio F, Sepe A, Pasqua A, Ferri P, Siano M, et al. Inhaled hyaluronic acid improves pleasantness and tolerability of nebulised hypertonic saline in patients with cystic fibrosis [abstract]. Pediatric Pulmonology 2009;44 Suppl 32:243, Abstract no: 93. [CFGD Register: BD156a]
    1. NCT01658449. Comparison of the tolerability of two formulations of hypertonic saline in cystic fibrosis patients. clinicaltrials.gov/ct2/show/NCT01658449 (first posted 07 August 7 2012).
DeCono 2008 {published data only}
    1. Cono N, Schelstraete P, Haerynck F, daele S, Sanders M, Baets F. Hypertonic saline: effect on mucus rheology and spirometry. Journal of Cystic Fibrosis 2008;7(Suppl 2):S24, Abstract 93. [CFGD Register: BD130]
Dentice 2012 {published data only}
    1. ACTRN12611000673943. A randomised trial of the effect of timing of nebulised hypertonic saline in relation to airway clearance physiotherapy, in people with cystic fibrosis lung disease [Randomised trial of the effect of timing of nebulised hypertonic saline in relation to airway clearance physiotherapy, on subjective efficacy, tolerability and overall satisfaction, and lung function parameters in adults with cystic fibrosis lung disease]. apps.who.int/trialsearch/Trial3.aspx?trialid=ACTRN12611000673943 (first received 04 July 2011).
    1. Dentice R, Elkins M, Bye P. Hypertonic saline before vs during vs after physiotherapy techniques for airway clearance in people with cystic fibrosis: A randomised trial [abstract]. Physiotherapy (United Kingdom) 2011;97:eS308‐eS309, Abstract no: RR‐PL‐3136. [CENTRAL: 1089301; CFGD Register: BD160d; CRS: 5500050000000300; EMBASE: 71882596]
    1. Dentice R, Elkins MR, Bye PT. A randomised trial of the effect of timing of hypertonic saline inhalation in relation to airway clearance physiotherapy in adults with cystic fibrosis [abstract]. Pediatric Pulmonology 2010;45 Suppl 33:384, Abstract no: 459. [CFGD Register: BD160a]
    1. Dentice RL, Elkins MR, Bye P. Adults with cystic fibrosis prefer hypertonic saline before or during airway clearance techniques: a randomised crossover trial. Journal of Physiotherapy 2012;58(1):33‐40. [CFGD Register: BD160b] - PubMed
    1. Dentice RL, Elkins MR, Bye PT. Online Supplementary Material ‐ Table 3 : Individual outcome data to "Adults with cystic fibrosis prefer hypertonic saline before or during airway clearance techniques: a randomised crossover trial" [online]. Journal of Physiotherapy 2012;58(1):33‐40 Online. [CFGD Register: BD160c] - PubMed
Donaldson 2006 {published data only}
    1. Donaldson SH, Bennett W, Zeman K, Knowles MR, Boucher RC. Efficacy of amiloride and hypertonic saline in cystic fibrosis [abstract]. Pediatric Pulmonology 2003;Suppl 25:251. [CFGD Register: BD110a]
    1. Donaldson SH, Bennett WD, Zeman KL, Knowles MR, Tarran R, Boucher RC. Mucus clearance and lung function in cystic fibrosis with hypertonic saline. New England Journal of Medicine 2006;354(3):241‐50. [CFGD Register: BD110b] - PubMed
    1. Donaldson SH, Bennett WD, Zeman KL, Knowles MR, Tarran R, Boucher RC. Online supplement to 'Mucus clearance and lung function in cystic fibrosis with hypertonic saline'. New England Journal of Medicine 2006;354(3):241‐50 Online. [CFGD Register: BD110c] - PubMed
    1. NCT00274391. Efficacy of amiloride and hypertonic saline in cystic fibrosis [Efficacy of amiloride and hypertonic saline in cystic fibrosis]. clinicaltrials.gov/ct2/show/NCT00274391 (first posted 10 January 2006).
Elkins 2006b {published data only}
    1. ACTRN12606000053527. Pilot trial of the tolerability of hypertonic saline when delivered by a high‐output nebuliser twice or four times daily to people with cystic fibrosis [Pilot trial of the tolerability of hypertonic saline when delivered by a high‐output nebuliser twice or four times daily to people with cystic fibrosis]. apps.who.int/trialsearch/Trial3.aspx?trialid=ACTRN12606000053527 (first received 07 February 2006).
    1. Elkins MR, Tingpej P, Moriarty CP, Yozghatlian V, Rose BR, Harbour C, et al. Tolerability of hypertonic saline when delivered rapidly via the Eflow® rapid nebulizer in subjects with cystic fibrosis [abstract]. Pediatric Pulmonlogy 2006;41 (Suppl 29):292. [CFGD Register: BD124]
EUCTR2007‐002707‐40‐BE {unpublished data only}
    1. EUCTR2007‐002707‐40‐BE. The effect of inhalation with hypertonic saline (7%) on lung function and sputum rheology in cystic fibrosis patients. www.clinicaltrialsregister.eu/ctr‐search/search?query=2007‐002707‐40 (first received 28 June 2007).
Genkova 1998 {published data only}
    1. Genkova N, Bosheva M, Ivancheva D. Inhaled hypertonic saline solution in cystic fibrosis [abstract]. Proceedings of the 22nd European Cystic Fibrosis Conference; 1998 June 13‐19; Berlin. 1998.
Grasemann 2013 {published and unpublished data}
    1. Grasemann H, Tullis E, Ratjen F. A randomized controlled trial of inhaled L‐arginine in patients with cystic fibrosis. Journal of Cystic Fibrosis 2013;12(5):468‐74. - PubMed
    1. NCT00405665. The short term safety and efficacy of inhaled L‐arginine in patients with cystic fibrosis [Pilot Study of the Short Term Safety and Efficacy of Inhaled L‐arginine in Patients With Cystic Fibrosis]. clinicaltrials.gov/ct2/show/NCT00405665 (first posted 30 November 2006).
IRCT20180307038994N1 {published data only}
    1. IRCT20180307038994N1. Comparison of the nebulized mannitol with nebulized hypertonic saline on pulmonary function in patients with cystic fibrosis. apps.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20180307038994N1 (first received 15 April 2018).
King 1997 {published data only}
    1. King M, Dasgupta B, Tomkiewicz RP, Brown NE. Rheology of cystic fibrosis sputum after in vitro treatment with hypertonic saline alone and in combination with recombinant human deoxyribonuclease. American Journal of Respiratory and Critical Care Medicine 1997;156(1):173‐7. - PubMed
Kobylyansky 2000 {published data only}
    1. Kobylyansky VI, Gembitskaya TE. Study of the mucociliary and cough clearance in patients with mucoviscidosis and evaluation of hypertonic sodium chorlide solution influence on them [abstract]. European Respiratory Journal 2000;16(Suppl 31):121S. [CFGD Register: BD111; ]
NCT01094704 {published data only}
    1. NCT01094704. Durability of hypertonic saline for enhancing mucociliary clearance in cystic fibrosis. clinicaltrials.gov/show/NCT01094704 (first posted 29 March 2010).
O'Neill 2017 {published data only}
    1. NCT01753869. Timing of hypertonic saline inhalation relative to airways clearance in cystic fibrosis [Timing of hypertonic saline inhalation relative to airways clearance in cystic fibrosis]. clinicaltrials.gov/ct2/show/NCT01753869 (first posted 20 December 2012).
    1. O'Neill K, Moran F, Tunney MM, Elborn JS, Bradbury I, Downey DG, et al. Timing of hypertonic saline and airway clearance techniques in adults with cystic fibrosis during pulmonary exacerbation: pilot data from a randomised crossover study. BMJ Open Respiratory Research 2017;4(1):e000168. [DOI: 10.1136/bmjresp-2016-000168] - DOI - PMC - PubMed
    1. O’Neill K, Moran F, Bradbury I, Downey DG, Rendall J, Tunney MM, et al. Exploring the timing of hypertonic saline (HTS) and airways clearance techniques (ACT) in cystic fibrosis (CF): a cross over study. Thorax 2016;71(Suppl 3):A134‐5.
Ros 2012 {published data only}
    1. Ros M, Casciaro R, Lucca F, Alatri F, Salonini E, Favilli F, et al. Tolerability and acceptability in patients with cystic fibrosis (CF) of two formulations of 7% hypertonic saline: a prospective multicenter clinical study [abstract]. Pediatric Pulmonology 2012;47(S35):364, Abstract no: 390. [CFGD Register: BD181a; ]
    1. Ros M, Casciaro R, Lucca F, Troiani P, Salonini E, Favilli F, et al. Hyaluronic acid improves the tolerability of hypertonic saline in the chronic treatment of cystic fibrosis patients: a multicenter, randomized, controlled clinical trial. Journal of Aerosol Medicine and Pulmonary Drug Delivery 2014;27(2):133‐7. [CFGD Register: BD181b] - PubMed
San Miguel 2016 {published data only}
    1. Herrero Cortina B, San Miguel Pagola M, Cebria i Ranzo MA, Gomez Romero M, Diaz Gutierrez F, Reychler G. Short‐term effects of hypertonic saline nebulization combined with oscillatory positive expiratory pressure in cystic fibrosis:randomised crossover trial. Journal of Cystic fibrosis 2016;15 Suppl 1:S33. [Abstract no.: WS21.3; CFGD Register: BD229a] - PubMed
    1. NCT02303808. Positive expiratory pressure during inhalation of hypertonic saline in patients with cystic fibrosis [Effect of introducing a positive expiratory pressure device during inhalation of hypertonic saline in patients with cystic fibrosis: a randomized crossover trial]. clinicaltrials.gov/ct2/show/NCT02303808 (first received 01 December 2014).
    1. San Miguel Pagola M, Herrero Cortina B, Cebria i Iranzo MA, Gomez Romero M, Diaz Gutierrez F, Reychler G. Hypertonic saline nebulization combined with oscillatory positive expiratory pressure accelerate sputum clearance in cystic fibrosis: A randomised crossover trial. European Respiratory Journal 2016;48(Suppl 60):PA1369. [CFGD Register: BD229b] - PubMed
Van Ginderdeuren 2008 {published and unpublished data}
    1. Ginderdeuren F, Verbanck S, Cauwelaert K, Vanlaethem S, Schuermans D, Vincken W, et al. Chest physiotherapy in cystic fibrosis: short‐term effects of autogenic drainage preceded by wet inhalation of saline versus autogenic drainage preceded by intrapulmonary percussive ventilation with saline. Respiration 2008;76(2):175‐80. [CFGD Register: BD178] - PubMed
Van Ginderdeuren 2011 {published data only}
    1. Ginderdeuren F, Vanlaethem S, Eyns H, Schutter I, Dewachter E, Malfroot A. Influence of inhaled hypertonic saline (NaCl 6%) before or during autogenic drainage on sputum weight, oxygen saturation, heart frequency and dyspnea in cystic fibrosis patients [abstract]. Journal of Cystic Fibrosis 2011;10(Suppl 1):S62. [CFGD Register: BD164]
Vanlaethem 2008 {published data only}
    1. Vanlaethem S, Ginderdeuren F, Eyns H, Malfroot A. Influence of inhaled hypertonic saline combined with airway clearance on SpO2, heart rate, dyspnoea and wet sputum weight in hospitalised CF patients [abstract]. Journal of Cystic Fibrosis 2008;7(Suppl 2):S71. [CENTRAL: 643104; CFGD Register: BD129; CRS: 5500100000003217]

References to studies awaiting assessment

Amin 2016 {published data only}
    1. Amin R, Stanojevic S, Kane M, Webster H, Ratjen F. A randomized controlled trial to evaluate the lung clearance index as an outcome measure for early phase studies in patients with cystic fibrosis. Respiratory Medicine 2016;112:59‐64. [CFGD Register: BD228; CRS: 5500135000001524; PUBMED: 26856191] - PubMed
Balinotti 2015 {published data only}
    1. Balinotti J, Rodriguez V, Zaragoza S, Lubovich S, Kofman C, Garcia Bournissen F. Effect of early intervention with inhaled hypertonic saline on lung function in infants and toddlers with cystic fibrosis diagnosed by neonatal screening [abstract]. American Journal of Respiratory and Critical Care Medicine 2015;191(Meeting Abstracts):A3342. [CENTRAL: 1127230; CFGD Register: BD227b; CRS: 5500050000000303]
    1. Teper A, Balinotti J, Rodriguez V, Zaragoza S Lubovich S, Kofman C, Garcia Bournissen F. Effect of early intervention with inhaled hypertonic saline on lung function in infants and toddlers with cystic fibrosis (CF) diagnosed by neonatal screening [abstract]. Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society 2015;14 Suppl 1:S49, Abstract no: ePS04.8. [CFGD Register: BD227a; CRS: 5500135000001305]
Brown 2010 {published data only}
    1. Brown AW, Laube BL, Zeman K, Lechtzin N, Sharpless G, Wu J, et al. Durability of hypertonic saline for enhancing mucociliary clearance in cystic fibrosis [abstract]. Pediatric Pulmonology 2010;45 Suppl 33:303, Abstract no: 237. [CFGD Register: BD173; ]
Corcoran 2017 {published data only}
    1. Corcoran TE, Godovchik JE, Donn KH, Busick DR, Goralski J, Locke LW, et al. Overnight delivery of hypertonic saline by nasal cannula aerosol for cystic fibrosis. Pediatric Pulmonology 2017;52(9):1142‐9. [CFGD Register: BD207; CTG: NCT02141191] - PMC - PubMed
Donaldson 2013 {published data only}
    1. Donaldson SH, Samulski D, LaFave C, Wu J, Zeman K, Salazar C, et al. Sustained effect of hypertonic saline on mucociliary clearance in CF children with mild lung disease. Pediatric Pulmonology 2013;48 Suppl 36:280. [Abstract no.: 210; CENTRAL: 999885; CFGD Register: BD206; CRS: 5500127000000007]
    1. NCT01031706. Effect of hypertonic saline on mucus clearance in children ages 5‐12 with cystic fibrosis [Sustained impact of hypertonic saline on mucociliary clearance in young children with cystic fibrosis]. clinicaltrials.gov/ct2/show/study/NCT01031706 (first received 15 December 2009).
Dwyer 2013 {unpublished data only}
    1. ACTRN12610000754044. Trial of different concentrations of nebulised saline for cystic fibrosis saline at lower tonicity in cystic fibrosis (SALTI‐CF) trial [The effect of nebulised 0.9% vs 3% vs 6% saline on lung function and quality of life in people with cystic fibrosis]. apps.who.int/trialsearch/Trial3.aspx?trialid=ACTRN12610000754044 (first received 13 September 2010).
    1. Dwyer T, Elkins M, Dentice R, Forbes S, MacArthur M, Cooper P, et al. Saline at a lower tonicity in cystic fibrosis (SALTI‐CF) trial ‐ a randomised controlled trial comparing 0.9% v 3% v 6% nebulised saline. Journal of Cystic Fibrosis 2013;12 Suppl 1:S19. [Abstract no.: WS9.5; CFGD Register: BD186]
Hofmann 1997 {published data only}
    1. Hofmann T, Senier I, Ziersch A, Geidel C, Regnis J, Lindemann H. Additive effects of amiloride and hypertonic saline on respiratory ion transport in cystic fibrosis [abstract]. Proceedings of the 21st European Cystic Fibrosis Conference; 1997; Davos. 1997:119. [CFGD Register: BD75]
NCT00928135 {unpublished data only}
    1. NCT00928135. Aerosolized hypertonic xylitol versus hypertonic saline in cystic fibrosis (CF) subjects [Randomized controlled study of aerosolized hypertonic xylitol versus hypertonic saline in hospitalized patients with exacerbation of cystic fibrosis]. clinicaltrials.gov/ct2/show/NCT00928135 (first received 25 June 2009).
NCT01355796 {unpublished data only}
    1. NCT01355796. Inhaled xylitol versus saline in stable subjects with cystic fibrosis [Randomized cross over study of inhaled hypertonic xylitol versus hypertonic saline in stable subjects with cystic fibrosis]. clinicaltrials.gov/ct2/show/NCT01355796 (first posted 18 May 2011).
NCT01377792 {published data only}
    1. NCT01377792. Study of long‐term treatment with hypertonic saline in patients with cystic fibrosis [Phase 4 study of the efficacy of long‐term treatment with hypertonic saline on pulmonary exacerbations in patients with cystic fibrosis]. clinicaltrials.gov/ct2/show/NCT01377792 (first received 21 June 2011).
NCT01619657 {unpublished data only}
    1. NCT01619657. Preventive inhalation of hypertonic saline in infants with cystic fibrosis (PRESIS). clinicaltrials.gov/ct2/show/NCT01619657 (first received 14 June 2012).
NCT02378467 {published data only}
    1. NCT02378467. Saline hypertonic in preschoolers (SHIP) [Saline hypertonic in preschoolers]. clinicaltrials.gov/ct2/show/NCT02378467 (first received 04 March 2015).
NCT03391414 {published data only}
    1. NCT03391414. Effects of inhaled bicarbonate on airway pH in cystic fibrosis. clinicaltrials.gov/show/NCT03391414 (first received 05 January 2018).
Nenna 2017 {published data only}
    1. ISRCTN13412080. Effects of inhaled hypertonic saline in children with cystic fibrosis [Effects of inhaled hypertonic (7%) saline on lung function test in preschool children with cystic fibrosis: a crossover, randomized clinical trial]. apps.who.int/trialsearch/Trial3.aspx?trialid=ISRCTN13412080 (first received 06 July 2016).
    1. Nenna R, Midulla F, Lambiase C, Castro G, Zicari AM, Indinnimeo L, et al. Effects of inhaled hypertonic (7%) saline on lung function test in preschool children with cystic fibrosis: results of a crossover, randomized clinical trial. Italian Journal of Pediatrics 2017;43(1):60. [CFGD Register: BD238; DOI: 10.1186/s13052-017-0376-6] - DOI - PMC - PubMed
Palacio 2014 {published data only}
    1. Palacio S, Giugno H, Diaz Casaux A, Lucero B, Smith S, Giorgetti M, et al. Inhaled 7% hypertonic saline treatment in preschool children with cystic fibrosis [abstract]. Journal of Cystic Fibrosis 2014;13 Suppl 2:S7, Abstract no: WS3.5. [CENTRAL: 1000053; CFGD Register: BD205; CRS: 5500131000000003]
PRESIS 2018 {published data only}
    1. Stahl M, Graeber SY, Sommerburg O, Ricklefs I, Diekmann G, Dopfer C, et al. Randomized double blind controlled pilot study on safety and efficacy of hypertonic saline as preventive inhalation therapy in infants with CF (PRESIS). Atemwegs‐ und Lungenkrankheiten. Conference: 40th annual joint meeting of the society for pediatric pneumology. Austria 2018;44(2):60‐1. [CFGD Register: BD249b]
    1. Stahl M, Ricklefs I, Dopfer C, Barth S, Schlegtendal A, Graeber SY, et al. Randomised, double‐blind, controlled pilot study on safety and efficacy of hypertonic saline as preventive inhalation therapy in infants with CF (PRESIS). Journal of Cystic Fibrosis 2018;17(Suppl 3):S25‐6. [CFGD Register: BD249a]

References to ongoing studies

NCT02276898 {unpublished data only}
    1. NCT02276898. A randomized‐controlled trial of inhaled hypertonic saline (7%) to evaluate the lung clearance index [A randomized‐controlled trial of inhaled hypertonic saline (7%) to evaluate the lung clearance index as a short‐term pharmacodynamic biomarker in patients with cystic fibrosis]. clinicaltrials.gov/ct2/show/NCT02276898 (first received 28 October 2014).
NCT02343445 {unpublished data only}
    1. NCT02343445. Clearing lungs with ENAC inhibition in cystic fibrosis (CLEAN‐CF) [A randomized, double‐blind, placebo‐controlled, parallel‐group study to evaluate the safety and efficacy of P‐1037 solution for inhalation in patients with cystic fibrosis (CF)]. clinicaltrials.gov/ct2/show/NCT02343445 (first received 22 January 2015).
NCT02950883 {unpublished data only}
    1. ACTRN12615001067561. Saline hypertonic in preschoolers with cystic fibrosis and lung structure as measured by computed tomography (CT) [A Phase 3 randomised, double‐blind, controlled trial of inhaled 7% hypertonic saline versus 0.9% isotonic saline for 48 weeks on lung structure in patients with cystic fibrosis at 3‐6 years of age, in parallel with the North American SHIP clinical trial, as measured by computed tomography (CT)]. apps.who.int/trialsearch/Trial3.aspx?trialid=ACTRN12615001067561 (first received 13 October 2015).
    1. NCT02950883. Saline hypertonic in preschoolers + CT (SHIP‐CT) [Saline hypertonic in preschoolers with cystic fibrosis and lung structure as measured by computed tomography (CT)]. clinicaltrials.gov/ct2/show/NCT02950883 (first received 01 November 2016).

Additional references

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References to other published versions of this review

Wark 1999
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