Nebulised hypertonic saline for cystic fibrosis.
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SUBMITTER: Wark P
PROVIDER: S-EPMC6513595 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAirway oedema (swelling) and mucus plugging are the principal pathological features in infants with acute viral bronchiolitis. Nebulised hypertonic saline solution (≥ 3%) may reduce these pathological changes and decrease airway obstruction. This is an update of a review first published in 2008, and previously updated in 2010 and 2013.ObjectivesTo assess the effects of nebulised hypertonic (≥ 3%) saline solution in infants with acute bronchiolitis.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily, Embase, CINAHL, LILACS, and Web of Science on 11 August 2017. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 8 April 2017.Selection criteriaWe included randomised controlled trials and quasi-randomised controlled trials using nebulised hypertonic saline alone or in conjunction with bronchodilators as an active intervention and nebulised 0.9% saline, or standard treatment as a comparator in children under 24 months with acute bronchiolitis. The primary outcome for inpatient trials was length of hospital stay, and the primary outcome for outpatients or emergency department trials was rate of hospitalisation.Data collection and analysisTwo review authors independently performed study selection, data extraction, and assessment of risk of bias in included studies. We conducted random-effects model meta-analyses using Review Manager 5. We used mean difference (MD), risk ratio (RR), and their 95% confidence intervals (CI) as effect size metrics.Main resultsWe identified 26 new trials in this update, of which 9 await classification due to insufficient data for eligibility assessment, and 17 trials (N = 3105) met the inclusion criteria. We included a total of 28 trials involving 4195 infants with acute bronchiolitis, of whom 2222 infants received hypertonic saline.Hospitalised infants treated with nebulised hypertonic saline had a statistically significant shorter mean length of hospital stay compared to those treated with nebulised 0.9% saline (MD -0.41 days, 95% CI -0.75 to -0.07; P = 0.02, I² = 79%; 17 trials; 1867 infants) (GRADE quality of evidence: low). Infants who received hypertonic saline also had statistically significant lower post-inhalation clinical scores than infants who received 0.9% saline in the first three days of treatment (day 1: MD -0.77, 95% CI -1.18 to -0.36, P < 0.001; day 2: MD -1.28, 95% CI -1.91 to -0.65, P < 0.001; day 3: MD -1.43, 95% CI -1.82 to -1.04, P < 0.001) (GRADE quality of evidence: low).Nebulised hypertonic saline reduced the risk of hospitalisation by 14% compared with nebulised 0.9% saline among infants who were outpatients and those treated in the emergency department (RR 0.86, 95% CI 0.76 to 0.98; P = 0.02, I² = 7%; 8 trials; 1723 infants) (GRADE quality of evidence: moderate).Twenty-four trials presented safety data: 13 trials (1363 infants, 703 treated with hypertonic saline) did not report any adverse events, and 11 trials (2360 infants, 1265 treated with hypertonic saline) reported at least one adverse event, most of which were mild and resolved spontaneously.Authors' conclusionsNebulised hypertonic saline may modestly reduce length of stay among infants hospitalised with acute bronchiolitis and improve clinical severity score. Treatment with nebulised hypertonic saline may also reduce the risk of hospitalisation among outpatients and emergency department patients. However, we assessed the quality of the evidence as low to moderate.
| S-EPMC6485976 | biostudies-literature
Project description:Hypertonic saline inhalation has become a cornerstone in the treatment of cystic fibrosis (CF), but its effect on CF mucus is still not understood. In CF, mucus stagnates in the airways, causing mucus plugging, and forming a substrate for bacterial invasion. Using horizontal Ussing-type chambers to allow easy access to the tissue, we have recently shown that the small intestinal mucus of CF mice is attached to the epithelium and not freely movable as opposed to normal mucus, thus pointing to a similarity between the CF mucus in the ileum and airways. In the same type of system, we investigated how hypertonic saline affects mucus thickness, attachment and penetrability to fluorescent beads the size of bacteria in ileal explants from the cystic fibrosis transmembrane conductance regulator mutant (ΔF508) mouse, in order to characterize how this common therapy affects mucus properties. Hypertonic saline (1.75-5%) detached the mucus from the epithelium, but the mucus remained impenetrable to beads the size of bacteria. This approach might be used to test other mucolytic interventions in CF.
| S-EPMC4303949 | biostudies-literature
Project description:AimInhaled hypertonic saline increases mucociliary clearance, improves pulmonary function, and decreases exacerbations in cystic fibrosis (CF) but contributes to the already significant treatment burden of CF. Overnight delivery of inhaled medications via a specially designed nasal cannula-aerosol device (Trans-nasal Pulmonary Aerosol Delivery [tPAD]) is an alternative approach. Here, we test whether overnight inhalation of hypertonic saline via tPAD improves mucociliary clearance and assess the tolerability of the device.MethodIn this study, 12 CF subjects inhaled 7% hypertonic saline (HS) for 8 h overnight using the tPAD system. Safety and tolerability were assessed and measurements of mucociliary and absorptive clearance (MCC/ABS) were performed after the treatment. Comparisons were made versus sham treatment where the same subjects wore the nasal cannula overnight but did not receive aerosol.ResultsBoth the HS and sham treatments were well-tolerated. Only one subject did not complete the overnight HS treatment. There were no significant differences in MCC associated with HS inhalation at any time point (90 min, 3 h, 6 h) in any lung zone. Changes in FEV1 on both study days were similar. There were no differences in quality of sleep between HS and sham nights as assessed with the modified Leeds Sleep Evaluation Questionnaire (mLSEQ). Sino-Nasal Outcome Test (SNOT-14) questionnaires demonstrated significant increases (worsening) in 2/14 symptom categories with HS.ConclusionsThe most likely cause for the failure to accelerate MCC was under-dosing of HS relative to the active transport of salt from the airways.
| S-EPMC5561478 | biostudies-literature
Project description:Inhaled hypertonic saline (HS) is an effective therapy for muco-obstructive lung diseases. However, the mechanism of action and principles pertinent to HS administration remain unclear.An in vitro system aerosolised HS to epithelial cells at rates comparable to in vivo conditions. Airway surface liquid (ASL) volume and cell height responses were measured by confocal microscopy under normal and hyperconcentrated mucus states.Aerosolised HS produced a rapid increase in ASL height and decrease in cell height. Added ASL volume was quickly reabsorbed following termination of nebulisation, although cell height did not recover within the same time frame. ASL volume responses to repeated HS administrations were blunted, but could be restored by a hypotonic saline bolus interposed between HS administrations. HS-induced ASL hydration was prolonged with hyperconcentrated mucus on the airway surface, with more modest reductions in cell volume.Aerosolised HS produced osmotically induced increases in ASL height that were limited by active sodium absorption and cell volume-induced reductions in cell water permeability. Mucus on airway surfaces prolonged the effect of HS via mucus-dependent osmotic forces, suggesting that the duration of action of HS is increased in patients with hyperconcentrated mucus.
| S-EPMC6000726 | biostudies-literature
Project description:BACKGROUND:Inhaled hypertonic saline (HS) has been shown to increase mucociliary clearance (MCC) and improve clinical outcomes in adults and adolescents with cystic fibrosis (CF). However, in younger children with CF, a large study failed to demonstrate clinical benefits. This discrepancy could reflect pharmacodynamic differences in the MCC response to HS in different populations. We previously demonstrated the absence of a sustained effect of HS on MCC in healthy adults and in this study sought to characterize the durability of the MCC response to HS in adults with CF. METHODS:At two study sites, MCC was measured in CF adults using gamma scintigraphy during three separate visits: at baseline, 15 min, and 4 h after a single dose of HS (7% NaCl, 4 mL). Particle clearance rates at these visits were used to assess the durability of the MCC response to HS. RESULTS:The average 90-minute clearance rate measured 4 h after HS was significantly increased (21.81% ± 12.8) when compared to baseline (13.77% ± 8.7, p = .048) and showed no apparent slowing relative to the rate measured 15 min after HS. While not all subjects responded to HS, the acute response strongly predicted the sustained effect in these subjects (r = 0.896, p < .0001). CONCLUSIONS:These results suggest that, in contrast to healthy adults, a single dose of HS has a prolonged effect on MCC in adults with CF, which lasts at least 4 h. This may explain its clinical efficacy in this population.
| S-EPMC6053331 | biostudies-literature
Project description:BackgroundCystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and recurrent pulmonary exacerbations. Xylitol is a 5-carbon sugar that can lower the airway surface salt concentration and augment innate immunity. We examined the safety and efficacy of aerosolized xylitol use for 2 weeks in subjects hospitalized with a pulmonary exacerbation of CF.MethodsIn a 2-week study, 60 subjects with cystic fibrosis and FEV1 > 30% predicted were enrolled to receive aerosolized 7% hypertonic saline (4 ml) or 15% xylitol (5 ml) twice a day for 14 days. Outcomes assessed included change from baseline in FEV1% predicted, change in sputum microbial density, revised CF quality of life questionnaire including the respiratory symptom score, time to next hospitalization for a pulmonary exacerbation, and frequency of adverse events.Results59 subjects completed the study (one subject in the saline group withdrew before any study product administration). No significant differences were noted between the 2 arms in mean changes in lung function, sputum microbial density for Pseudomonas aeruginosa and Staphylococcus aureus, body weight, quality of life, and frequency of adverse events.ConclusionsAerosolized hypertonic xylitol was well-tolerated among subjects hospitalized for CF pulmonary exacerbation. Future studies examining efficacy for long term use in patients with CF lung disease would be worthwhile. The clinical trial registration number for this study is NCT00928135.
| S-EPMC6980423 | biostudies-literature
Project description:Inhaled hypertonic saline (HTS) treatment is used to improve lung health in patients with cystic fibrosis (CF). The current consensus is that the treatment generates an osmotic gradient that draws water into the airways and increases airway surface liquid (ASL) volume. However, there is evidence that HTS may also stimulate active secretion of ASL by airway epithelia through the activation of sensory neurons. We tested the contribution of the nervous system and airway epithelia on HTS-stimulated ASL height increase in CF and wild-type swine airway. We used synchrotron-based imaging to investigate whether airway neurons and epithelia are involved in HTS treatment-triggered ASL secretion in CFTR-/- and wild-type swine. We showed that blocking parasympathetic and sensory neurons in airway resulted in ~50% reduction of the effect of HTS treatment on ASL volume in vivo. Incubating tracheal preparations with inhibitors of epithelial ion transport across airway decreased secretory responses to HTS treatment. CFTR-/- swine ex-vivo tracheal preparations showed substantially decreased secretory response to HTS treatment after blockage of neuronal activity. Our results indicated that HTS-triggered ASL secretion is partially mediated by the stimulation of airway neurons and the subsequent activation of active epithelia secretion; osmosis accounts for only ~50% of the effect.
| S-EPMC6345831 | biostudies-other
Project description:ObjectivesNebulized hypertonic saline (HTS) has beneficial effects including reducing pulmonary exacerbations in Cystic Fibrosis (CF) patients. Several mechanisms may explain these effects but antimicrobial activity of NaCl remains largely unexplored. We aimed to measure the antimicrobial effect of NaCl on Pseudomonas aeruginosa isolated from the respiratory tract in CF patients.MethodsNaCl minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined for strains characterized for mucoidy, antimicrobial resistance, and ability to form biofilm using 0,9% to 15% NaCl solutions. NaCl effects on biofilm formation, preformed biofilm, and mobility were evaluated. Kinetics of antimicrobial effects was studied.ResultsThe growth of all isolates (n = 85) from 34 patients was inhibited by 6% NaCl solution. A 10% concentration had a bactericidal activity on 90% of the isolates. Mucoid and multidrug resistant (MDR) isolates displayed lower MICs compared to non-mucoid and to non-MDR isolates, respectively. Time-kill kinetics showed that NaCl exhibited a rapid, dose and growth phase dependent bactericidal effect. Three percent or more of NaCl inhibited biofilm formation for 69% of strongly adherent isolates. A dose-dependent decrease of preformed biofilm viability and an inhibitory activity on bacterial motility were observed.ConclusionsNaCl inhibited the growth of all isolates and killed 38% of tested isolates within concentration range currently used in therapeutics. Our results suggest that anti-pseudomonal activity is another mechanism of action of HTS to add to those already established. Clinical trials are needed to compare diverse HTS conditions of use (rhythm, dose and mode of delivery) to obtain efficient and optimized anti-P. aeruginosa effects. More generally, NaCl effect on other opportunistic pathogens as well as on global microbiotae recovered during polymicrobial diseases warrants further investigations.
| S-EPMC3938589 | biostudies-literature
Project description:BackgroundCystic fibrosis (CF) is a life-threatening multiorgan genetic disease, particularly affecting the lungs, where recurrent infections are the main cause of reduced life expectancy. In CF, mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein impair transepithelial electrolyte and water transport, resulting in airway dehydration, and a thickening of the mucus associated with abnormal viscoelastic properties. Our aim was to develop a rheological method to assess the effects of hypertonic saline (NaCl) and NaHCO3 on CF sputum viscoelasticity in vitro, and to identify the critical steps in sample preparation and in the rheological measurements.MethodsSputum samples were mixed with hypertonic salt solutions in vitro in a ratio of either 10:4 or 10:1. Distilled water was applied as a reference treatment. The rheological properties of sputum from CF patients, and the effects of these in vitro treatments, were studied with a rheometer at constant frequency and strain, followed by frequency sweep tests, where storage modulus (G'), loss modulus (G″) and loss factor were determined.ResultsWe identified three distinct categories of sputum: (i) highly elastic (G' > 100,000 Pa), (ii) elastic (100,000 Pa > G' > 1000 Pa), and (iii) viscoelastic (G' < 1000). At the higher additive ratio (10:4), all of the added solutions were found to significantly reduce the gel strength of the sputum, but the most pronounced changes were observed with NaHCO3 (p < 0.001). Samples with high elasticity exhibited the greatest changes while, for less elastic samples, a weakening of the gel structure was observed when they were treated with water or NaHCO3, but not with NaCl. For the viscoelastic samples, the additives did not cause significant changes in the parameters. When the lower additive ratio (10:1) was used, the mean values of the rheological parameters usually decreased, but the changes were not statistically significant.ConclusionBased on the rheological properties of the initial sputum samples, we can predict with some confidence the treatment efficacy of each of the alternative additives. The marked differences between the three categories suggest that it is advisable to evaluate each sample individually using a rheological approach such as that described here.
| S-EPMC8276516 | biostudies-literature
Project description:Inhaled hypertonic saline (HS) is an attractive agent for chronic maintenance therapy in infants and toddlers with cystic fibrosis (CF) because it improves defective mucociliary clearance. Prior to undertaking a clinical trial of HS efficacy in young children with CF, tolerability, adherence, and safety must be established.Three-center, open label evaluation of the short-term tolerability, adherence, and safety of 7% HS administered twice daily for 14 days in children with CF 12-30 months of age. The primary objective was to evaluate the proportion of participants unable to tolerate single and repeated doses of 7% HS according to protocol-defined criteria. Participants inhaled a test dose of HS at the enrollment visit; test dose intolerance was defined as fulfillment of at least one of 4 criteria. Participants who tolerated the test dose inhaled 7% HS twice daily for 14±2 days.Twenty children were enrolled. One was withdrawn due to maternal concern over fussiness with application of the facemask for the test dose. Of the 19 participants administered the test dose, 1 was withdrawn due to test dose intolerance (5%, 95% confidence interval 0, 26%). Eighteen participants completed the study; 1 was intolerant (95% CI 0, 27%) at the final visit due to new wheezes on exam in association with an upper respiratory infection and otitis media. Home symptom diaries demonstrated cough as the main symptom in the hour following inhalation, which decreased in frequency over the study period. Adherence as assessed by daily home diary and returned study drug ampoules was high. Participants reported receiving both treatments on a median of 100% of days; a median of 25 ampoules were used during a median of 13 days.7% HS appears well tolerated for up to 14 days in infants and toddlers with CF, with high adherence. These results provide encouraging short-term tolerability and adherence data for future trials assessing the safety and efficacy of 7% HS in young children with CF.
| S-EPMC3107859 | biostudies-literature