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Meta-Analysis
. 2014 May 12;2014(5):CD002996.
doi: 10.1002/14651858.CD002996.pub3.

Inhaled hyperosmolar agents for bronchiectasis

Anna Hart  1 , Karnam Sugumar, Stephen J Milan, Stephen J Fowler, Iain Crossingham
Affiliations
Meta-Analysis

Inhaled hyperosmolar agents for bronchiectasis

Anna Hart et al. Cochrane Database Syst Rev. .

Abstract

Background: Mucus retention in the lungs is a prominent feature of bronchiectasis. The stagnant mucus becomes chronically colonised with bacteria, which elicit a host neutrophilic response. This fails to eliminate the bacteria, and the large concentration of host-derived protease may contribute to the airway damage. The sensation of retained mucus is itself a cause of suffering, and the failure to maintain airway sterility probably contributes to the frequent respiratory infections experienced by many patients.Hypertonic saline inhalation is known to accelerate tracheobronchial clearance in many conditions, probably by inducing a liquid flux into the airway surface, which alters mucus rheology in a way favourable to mucociliary clearance. Inhaled dry powder mannitol has a similar effect. Such agents are an attractive approach to the problem of mucostasis, and deserve further clinical evaluation.

Objectives: To determine whether inhaled hyperosmolar substances are effective in the treatment of bronchiectasis.

Search methods: We searched the Cochrane Airways Group Specialised Register, trials registries, and the reference lists of included studies and review articles. Searches are current up to April 2014.

Selection criteria: Any randomised controlled trial (RCT) using hyperosmolar inhalation in patients with bronchiectasis not caused by cystic fibrosis.

Data collection and analysis: Two review authors assessed studies for suitability. We used standard methods recommended by The Cochrane Collaboration.

Main results: Eleven studies met the inclusion criteria of the review (1021 participants).Five studies on 833 participants compared inhaled mannitol with placebo but poor outcome reporting meant we could pool very little data and most outcomes were reported by only one study. One 12-month trial on 461 participants provided results for exacerbations and demonstrated an advantage for mannitol in terms of time to first exacerbation (median time to exacerbation 165 versus 124 days for mannitol and placebo respectively (hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.63 to 0.96, P = 0.022) and number of days on antibiotics for bronchiectasis exacerbations was significantly better with mannitol (risk ratio (RR) 0.76, 95%CI 0.58 to 1.00, P = 0.0496). However, exacerbation rate per year was not significantly different between mannitol and placebo (RR 0.92 95% CI 0.78 to 1.08). The quality of this evidence was rated as moderate. There was also an indication, from only three trials, again based on moderate quality evidence, that mannitol improves health-related quality of life (mean difference (MD) -2.05; 95% CI -3.69 to -0.40). An analysis of adverse events data, also based on moderate quality evidence, revealed no difference between mannitol and placebo (OR 0.96; 95% CI 0.61 to 1.51). Two additional small trials on 25 participants compared mannitol versus no treatment and the data from these studies were inconclusive.Four studies (combined N = 113) compared hypertonic saline versus isotonic saline. On most outcomes there were conflicting results and the opportunities for the statistical aggregation of data from studies was very limited. It is not possible to draw robust conclusions for this comparison and judgments should be reserved until further data are available.

Authors' conclusions: There is an indication from a single, large, unpublished study that inhaled mannitol increases time to first exacerbation in patients with bronchiectasis. In patients with near normal lung function, spirometry does not change dramatically with mannitol and adverse events are not more frequent than placebo. Further investigation is required in a patient population with impaired lung function.It is not possible to draw firm conclusions regarding the effect of nebulised hypertonic saline due to significant differences in the methodology, patient groups, and findings amongst the limited data available. The data suggest that it is unlikely to have benefit over isotonic saline in patients with milder disease, and hence future studies should test its use in those with more severe disease.

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Conflict of interest statement

None known.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Inhaled mannitol versus placebo, Outcome 1 Change from baseline in health‐related quality of life (SGRQ). Total.
1.2
1.2. Analysis
Comparison 1 Inhaled mannitol versus placebo, Outcome 2 Change from baseline in health‐related quality of life (SGRQ). Symptoms.
1.3
1.3. Analysis
Comparison 1 Inhaled mannitol versus placebo, Outcome 3 Change from baseline in health‐related quality of life (SGRQ). Activity.
1.4
1.4. Analysis
Comparison 1 Inhaled mannitol versus placebo, Outcome 4 Change from baseline in health‐related quality of life (SGRQ). Impact.
1.5
1.5. Analysis
Comparison 1 Inhaled mannitol versus placebo, Outcome 5 Leicester Cough Questionnaire score after 12 weeks.
1.6
1.6. Analysis
Comparison 1 Inhaled mannitol versus placebo, Outcome 6 Bronchiectasis Symptoms Questionnaire score at week 12.
1.7
1.7. Analysis
Comparison 1 Inhaled mannitol versus placebo, Outcome 7 Change in FEV1 (% predicted).
1.8
1.8. Analysis
Comparison 1 Inhaled mannitol versus placebo, Outcome 8 FEV1 (L) at 12 weeks.
1.9
1.9. Analysis
Comparison 1 Inhaled mannitol versus placebo, Outcome 9 Adverse events.
1.10
1.10. Analysis
Comparison 1 Inhaled mannitol versus placebo, Outcome 10 FEF25‐75(L/s) after 12 weeks.
1.11
1.11. Analysis
Comparison 1 Inhaled mannitol versus placebo, Outcome 11 Change in 24 hr sputum weight from baseline.
1.12
1.12. Analysis
Comparison 1 Inhaled mannitol versus placebo, Outcome 12 Antibiotic use.
1.13
1.13. Analysis
Comparison 1 Inhaled mannitol versus placebo, Outcome 13 Incremental Shuttle Walk (metres) at week 12.
1.14
1.14. Analysis
Comparison 1 Inhaled mannitol versus placebo, Outcome 14 FVC (L) at 12 weeks.
1.15
1.15. Analysis
Comparison 1 Inhaled mannitol versus placebo, Outcome 15 Serious adverse events.
2.1
2.1. Analysis
Comparison 2 Hypertonic saline versus isotonic saline, Outcome 1 SGRQ Symptom.
2.2
2.2. Analysis
Comparison 2 Hypertonic saline versus isotonic saline, Outcome 2 SGRQ Activity.
2.3
2.3. Analysis
Comparison 2 Hypertonic saline versus isotonic saline, Outcome 3 SGRQ Impact.
2.4
2.4. Analysis
Comparison 2 Hypertonic saline versus isotonic saline, Outcome 4 Leicester Cough Questionnaire Physical.
2.5
2.5. Analysis
Comparison 2 Hypertonic saline versus isotonic saline, Outcome 5 Leicester Cough Questionnaire Psychological.
2.6
2.6. Analysis
Comparison 2 Hypertonic saline versus isotonic saline, Outcome 6 Leicester Cough Questionnaire Social.
2.7
2.7. Analysis
Comparison 2 Hypertonic saline versus isotonic saline, Outcome 7 FEV1 (L).
2.8
2.8. Analysis
Comparison 2 Hypertonic saline versus isotonic saline, Outcome 8 FVC.
2.9
2.9. Analysis
Comparison 2 Hypertonic saline versus isotonic saline, Outcome 9 FEF25‐75.
2.10
2.10. Analysis
Comparison 2 Hypertonic saline versus isotonic saline, Outcome 10 Adverse events.
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References

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