Peter Wark1, Vanessa M McDonald. 1. Respiratory Medicine HMRI, Level 3 John Hunter Hospital, Locked Bag 1 HRMC, Newcastle, New South Wales, Australia, NSW 2310. peter.wark@hnehealth.nsw.gov.au
Abstract
BACKGROUND: Impaired mucociliary clearance characterises lung disease in cystic fibrosis (CF). Hypertonic saline (HS) enhances mucociliary clearance in vitro and may lessen the destructive inflammatory process in the airways. OBJECTIVES: To investigate the effects of nebulised HS in CF compared to placebo or other treatments for mucociliary clearance. SEARCH STRATEGY: We searched the Cochrane CF and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 31 July 2008. SELECTION CRITERIA: 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). DATA COLLECTION AND ANALYSIS: Two authors independently reviewed all identified trials and data; and assessed trial quality. MAIN RESULTS: Twelve trials (442 participants, aged 6 to 46 years) were included; five excluded and two await classification.In two placebo-controlled trials, HS (3% to 7%, 10 ml twice-a-day) significantly increased forced expiratory volume at one second (FEV1) at four weeks, mean difference (MD) 4.15 (95% CI 1.14 to 7.16); but not significantly after 48 weeks, MD 2.31 (95% CI -2.72 to 7.34). Two trials compared a similar dose of HS to recombinant deoxyribonuclease (RhDNAse). One three-week trial showed a non-significant difference, MD 1.60 (95% CI -7.96 to 11.16). However, in the second trial, after 12 weeks, RhDNAse led to a greater increase in FEV1 than HS (5 ml twice-daily), in participants with moderate to severe lung disease, MD 8.00 (95% CI 2.00 to 14.00).One 48-week placebo-controlled trial showed significant improvements in frequency of antibiotic use and quality of life; also that HS did not increase the concentration of Pseudomonas aeruginosa or Staphylococcus aureus. AUTHORS' CONCLUSIONS: Treatment with 7% HS for 48 weeks showed a small improvement in FEV1 at four weeks; however, this was not sustained at 48 weeks (primary outcome measure of the only long-term trial). Unlike RhDNAse, HS can't, in the long term, be said to improve lung function. However, it did improve quality of life and reduce pulmonary exacerbations. Delivered following a bronchodilator, HS appears inexpensive and safe with no increased infection risk.We believe there is sufficient evidence to recommend using HS in CF; qualifying this we highlight that the only long-term trial failed to demonstrate a significant difference in its primary outcome (lung function) with improvements only in secondary outcomes.
BACKGROUND: Impaired mucociliary clearance characterises lung disease in cystic fibrosis (CF). Hypertonic saline (HS) enhances mucociliary clearance in vitro and may lessen the destructive inflammatory process in the airways. OBJECTIVES: To investigate the effects of nebulised HS in CF compared to placebo or other treatments for mucociliary clearance. SEARCH STRATEGY: We searched the Cochrane CF and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 31 July 2008. SELECTION CRITERIA: 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). DATA COLLECTION AND ANALYSIS: Two authors independently reviewed all identified trials and data; and assessed trial quality. MAIN RESULTS: Twelve trials (442 participants, aged 6 to 46 years) were included; five excluded and two await classification.In two placebo-controlled trials, HS (3% to 7%, 10 ml twice-a-day) significantly increased forced expiratory volume at one second (FEV1) at four weeks, mean difference (MD) 4.15 (95% CI 1.14 to 7.16); but not significantly after 48 weeks, MD 2.31 (95% CI -2.72 to 7.34). Two trials compared a similar dose of HS to recombinant deoxyribonuclease (RhDNAse). One three-week trial showed a non-significant difference, MD 1.60 (95% CI -7.96 to 11.16). However, in the second trial, after 12 weeks, RhDNAse led to a greater increase in FEV1 than HS (5 ml twice-daily), in participants with moderate to severe lung disease, MD 8.00 (95% CI 2.00 to 14.00).One 48-week placebo-controlled trial showed significant improvements in frequency of antibiotic use and quality of life; also that HS did not increase the concentration of Pseudomonas aeruginosa or Staphylococcus aureus. AUTHORS' CONCLUSIONS: Treatment with 7% HS for 48 weeks showed a small improvement in FEV1 at four weeks; however, this was not sustained at 48 weeks (primary outcome measure of the only long-term trial). Unlike RhDNAse, HS can't, in the long term, be said to improve lung function. However, it did improve quality of life and reduce pulmonary exacerbations. Delivered following a bronchodilator, HS appears inexpensive and safe with no increased infection risk.We believe there is sufficient evidence to recommend using HS in CF; qualifying this we highlight that the only long-term trial failed to demonstrate a significant difference in its primary outcome (lung function) with improvements only in secondary outcomes.
Authors: Antonio Artigas; Marta Camprubí-Rimblas; Neus Tantinyà; Josep Bringué; Raquel Guillamat-Prats; Michael A Matthay Journal: Ann Transl Med Date: 2017-07