Nebulised hypertonic saline for cystic fibrosis.

Transcription

1 Revista: Cochrane Database Syst Rev. 2003;(1):CD Nebulised hypertonic saline for cystic fibrosis. Autor: Wark PA, McDonald V. Source: Department of Respiratory Medicine, John Hunter Hospital, Locked Bag No. 1, Hunter Regional Mail Centre, Newcastle, NSW 2310, Australia, PMID: PMID: PMID:

2 2 Cochrane Database Syst Rev. 2000;(2):CD Nebulised hypertonic saline for cystic fibrosis. Wark PA, McDonald V. Source Department of Respiratory Medicine, John Hunter Hospital, Locked Bag No. 1, Hunter Regional Mail Centre, Newcastle, NSW 2310, Australia, Update in Cochrane Database Syst Rev. 2003;(1):CD Abstract BACKGROUND: The lung disease in cystic fibrosis is characterised by impaired mucociliary clearance, recurrent bronchial infection and airway inflammation. Hypertonic saline has been shown to enhance mucociliary clearance in-vitro and this may act to lessen the destructive inflammatory process in the airways. OBJECTIVES: To determine if nebulised hypertonic saline treatment improved lung function, exercise tolerance, quality of life and decreased the incidence of exacerbations of respiratory infections in patients with cystic fibrosis. SEARCH STRATEGY: Studies were identified from the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register. Titles and abstracts were reviewed to identify all controlled trials. Review articles and bibliographies identified from this process were surveyed for additional citations & RCTs. Identification of unpublished work was obtained from abstract books from the three major Cystic Fibrosis conferences (International Cystic Fibrosis Conference, The European Cystic Fibrosis Conference and the North American Cystic Fibrosis Conference). Trial authors were contacted for additional information when only abstracts were available to review. Date of the most recent search of the Group's specialised register: November SELECTION CRITERIA: All controlled trials that assessed the effect of hypertonic saline compared to placebo or other mucolytic therapy, for any duration or dose regimen in subjects with cystic fibrosis of any age or severity were reviewed. Studies in languages other than English were included. DATA COLLECTION AND ANALYSIS: All identified trials were independently reviewed by both reviewers & all data collected. Trial quality was scored by the Cochrane assessment of allocation concealment & the Jadad scale of methodological quality. MAIN RESULTS: Twelve controlled trials of hypertonic saline were identified. Seven trials met the inclusion criteria; these involved 143 subjects with an age range of 6 to 46 years. Of these, six were

3 3 published studies and one in abstract form. The durations of the trials were limited to immediate effects on mucociliary clearance to a maximum of three weeks. In two studies, involving thirty five subjects, a score for the feeling of cleared chest was made using visual analogue scales. This analysis showed a weighted mean difference of (95% confidence Interval -1.6, -0.34), favouring hypertonic saline over isotonic saline. In two trials with 22 subjects hypertonic saline improved mucociliary clearance as measured by isotope clearance from the lungs in 90 minutes demonstrating a weighted mean difference of (95% confidence Interval -18.6, -4.0), and as area under the clearance time curve; weighted mean difference of -212 (95%CI -272, -152), also favouring hypertonic saline over isotonic saline. Lung function as measured by improvement in FEV1 was observed in one study of 27 subjects. The percentage increase in FEV1 at two weeks increased by a mean 15.0% with hypertonic saline and 2.8% with isotonic saline (p=0.004). Adverse events were adequately described in only one trial and none were serious. REVIEWER'S CONCLUSIONS: Nebulised hypertonic saline improves mucociliary clearance immediately after administration which may have a longer term beneficial effect in cystic fibrosis. The maximum time data were recorded for was only three weeks. Most of the patients had mild to moderate lung disease and the effect on severe lung disease remains unclear. Further studies of hypertonic saline should be carried out to determine the effect on pulmonary function tests, quality of life, frequency of exacerbations of respiratory disease and efficacy comparisons with nebulised deoxyribonuclease, with larger numbers and for longer duration. At this stage there is insufficient evidence to support the use of hypertonic saline in routine treatment for patients with cystic fibrosis. PMID:

4 4 Revista: Cochrane Database Syst Rev. 2005;(3):CD Nebulised hypertonic saline for cystic fibrosis. Autor: Wark PA, McDonald V. Source: Department of Respiratory Medicine, John Hunter Hospital, Locked Bag No. 1, Hunter Regional Mail Centre, Newcastle, NSW 2310, Australia, PMID:

5 5 Cochrane Database Syst Rev. 2003;(1):CD Nebulised hypertonic saline for cystic fibrosis. Wark PA, McDonald V. Source Level D, Centre Block, University Medicine, Southampton General Hospital, Southampton, UK, SO16 6YD. Update in Cochrane Database Syst Rev. 2005;(3):CD Abstract BACKGROUND: The lung disease in cystic fibrosis is characterised by impaired mucociliary clearance. Hypertonic saline (HS) has been shown to enhance mucociliary clearance in-vitro and this may act to lessen the destructive inflammatory process in the airways. OBJECTIVES: To investigate the effects of treatment with nebulised hypertonic saline on people with CF compared to placebo and or other treatments that enhance mucociliary clearance. SEARCH STRATEGY: 'We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Date of the most recent search of the Group's register: October SELECTION CRITERIA: All controlled trials (any language) assessing the effect of hypertonic saline compared to placebo or other mucolytic therapy, for any duration or dose regimen in people with cystic fibrosis of any age or severity. DATA COLLECTION AND ANALYSIS: All identified trials were independently reviewed by both reviewers & all data collected. Trial quality was assessed along with allocation concealment. MAIN RESULTS: Fourteen controlled trials were identified. Nine trials met the inclusion criteria; these involved 235 participants with an age range of 6 to 46 years. Two short-term trials of immediate effect on mucociliary clearance demonstrated that HS increased isotope clearance compared to control. Lung function as measured by improvement in Forced Expiratory Volume at one second (FEV1 l/min) was observed in four trials. When 3% to 7% saline was used in a volume of 10mls twice a day, in comparison to placebo, HS led to a significant increase in FEV1, WMD (95%CI 4.30 to 20.10). In comparison to deoxyribonuclease (DNase) two trials used a similar concentration and volume of HS. Over

6 6 a three week period the groups showed a similar increase in FEV1, WMD (95%CI to 7.96). However after 12 weeks treatment in participants with moderate to severe lung disease compared to DNase, HS 5mls twice a day showed less benefit to FEV1, WMD (95%CI to -3.54). No serious adverse events were noted. REVIEWER'S CONCLUSIONS: Nebulised hypertonic saline improves mucociliary clearance in short term clinical trials and appears to increase lung function compared to control. In comparison to DNase it may be less effective at improving lung function, after three months. At this stage there is insufficient evidence to support the use of hypertonic saline as routine treatment for people with cystic fibrosis. Update of Cochrane Database Syst Rev. 2000;(2):CD PMID:

7 7 Revista: Cochrane Database Syst Rev. 2009;(2):CD Nebulised hypertonic saline for cystic fibrosis. Autor: Wark PA, McDonald V. Source: Department of Respiratory Medicine, John Hunter Hospital, Locked Bag No. 1, Hunter Regional Mail Centre, Newcastle, NSW 2310, Australia, PMID:

8 8 Cochrane Database Syst Rev Jul 20;(3):CD Nebulised hypertonic saline for cystic fibrosis. Wark PA, McDonald V, Jones AP. Source Respiratory Medicine HMRI, Level 3 John Hunter Hospital, Locked Bag 1 HRMC, Newcastle, New South Wales, Australia, NSW peter.wark@hnehealth.nsw.gov.au Update in Cochrane Database Syst Rev. 2009;(2):CD Abstract BACKGROUND: Lung disease in cystic fibrosis is characterised by impaired mucociliary clearance. Hypertonic saline has been shown to enhance mucociliary clearance in vitro and this may act to lessen the destructive inflammatory process in the airways. OBJECTIVES: To investigate the effects of treatment with nebulised hypertonic saline on people with cystic fibrosis compared to placebo and or other treatments that enhance mucociliary clearance. SEARCH STRATEGY: 'We searched the Cochrane Cystic Fibrosis 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 of the Trials Register: September SELECTION CRITERIA: All controlled trials assessing the effect of hypertonic saline compared to placebo or other mucolytic therapy, for any duration or dose regimen in people with cystic fibrosis of any age or severity. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed all identified trials and all data collected. Trial quality was assessed along with allocation concealment. MAIN RESULTS: Fourteen controlled trials were identified. Nine trials met the inclusion criteria involving 235 participants with an age range of 6 years to 46 years. Two short-term trials of immediate effect on mucociliary clearance demonstrated that hypertonic saline increased isotope clearance compared to control. Lung function, measured by improvement in forced expiratory volume at one second (FEV1 litre per minute), was observed in four trials. When 3% to 7% saline was used in a volume of 10 ml twice-a-day, in comparison to placebo, hypertonic saline led to a significant increase in FEV1, weighted mean difference (95%CI 4.28 to 20.10). Two further trials compared a similar concentration and volume of

9 9 hypertonic saline to recombinant deoxyribonuclease. Over a three-week period one trial showed a non-significant difference, mean difference 1.60 (95% CI to 11.16). However, in a further trial, after 12 weeks treatment in participants with moderate to severe lung disease, recombinant deoxyribonuclease led to a greater increase in FEV1 than hypertonic saline (5 ml twice-daily), mean difference 8.00 (95%CI 2.00 to 14.00). No serious adverse events were noted. AUTHORS' CONCLUSIONS: Nebulised hypertonic saline improves mucociliary clearance in short-term clinical trials and appears to increase lung function compared to control. In comparison to recombinant deoxyribonuclease it may be less effective at improving lung function after three months. Currently there is insufficient evidence to support the use of hypertonic saline as routine treatment for people with cystic fibrosis. Update of Cochrane Database Syst Rev. 2003;(1):CD PMID: