Nebulised hypertonic saline for cystic fibrosis

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 placebo At 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 (FEV 1) (% predicted) 1 Nebulised hypertonic saline for cystic fibrosis (Review)

Real-World Safety of CFTR Modulators in the Treatment of Cystic Fibrosis: A Systematic Review

“…At our site, pre-treatment with a course of oral or IV antibiotics has also been a strategy to optimize lung health and minimize the potential for confounding in the assessment of a patient who does experience significant respiratory AE upon initiation of LUM/IVA. Walayat et al [ 49 ] suggest patients may benefit from discontinuing hypertonic saline and continuing dornase alfa while on LUM/IVA to avoid patients “drowning” in liquefied secretions; although, a justifiable suggestion based on their case report, this may not be the experience of all individuals started on LUM/IVA or alternative CFTR modulators, and the risks versus benefits of discontinuing hypertonic saline (or dornase alfa) must be weighed against demonstrated benefit in pulmonary outcomes [ 132 , 133 , 134 ]. Whether it is safe to stop hypertonic saline or dornase alfa in patients on ELX/TEZ/IVA is currently under investigation [ 135 ], but unlike LUM/IVA, ELX/TEZ/IVA is considered a highly effective CFTR modulator and the study results would not be generalizable.…”

Future Trends in Nebulized Therapies for Pulmonary Disease

“…N-acetylcysteine is the most prescribed mucolytic but clinical administration by nebulization is not well studied. Another mucolytic, hypertonic saline has been shown to attenuate the severity of ALI when nebulized, by reducing inflammatory cytokine production [7,109]. The potential for a more personalized approach to treatment is evident from studies such as the demonstration that a phosphorylation resistant IκBα super-repressor plasmid was nebulized into to an endotoxin-induced lung injury model.…”

“…Adaptable nebulizer technology is ideal for combination in aerosol delivery systems where the objective is to augment lung dose by controlling, and possibly calculating and adapting to, a patient's breathing patterns. The role of nebulizers in treating respiratory disease, and symptoms of disease is the subject of numerous recent reviews, including in acute respiratory distress syndrome (ARDS) [2,3], chronic obstructive pulmonary disorder (COPD) [4,5], cystic fibrosis (CF) [6,7], ventilator-associated pneumonia (VAP) [8,9], dyspnea [10], and acute asthma [11], among others.…”

Efficacy and safety of inhaled dry-powder mannitol in adults with cystic fibrosis: An international, randomized controlled study

“…Furthermore, the mannitol results are similar to those in a Cochrane review of hypertonic saline, with an absolute difference in FEV 1 percent predicted of 3.44% between hypertonic saline and placebo -of course such indirect comparisons should be made with caution. [28] Although as with the current study, the main observation period in these two prior mannitol studies was 26 weeks, they included an open-label 26-week follow-up when all subjects received mannitol 400 mg BID. [ 16 , 17 ] In subjects receiving mannitol 400 mg BID for the full 52 weeks, the FEV 1 improvement from baseline at 26 weeks was maintained over the follow-up period; subjects switched from control to mannitol 400 mg BID at Week 26 had a subsequent improvement in FEV 1 , such that at Week 52 efficacy was similar in the two groups.…”