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Evidence summaries

Mucolytics for Non-Cystic Fibrosis Bronchiectasis

In patients with non-cystic fibrosis bronchiectasis, high doses of bromhexine coupled with antibiotics may help sputum production and clearance during an acute infective exacerbation. Recombinant human DNase may not be effective and possibly harmful, and there is not enough evidence from controlled trials to evaluate the routine use of other mucolytics for bronchiectasis. Level of evidence: "C"

A Cochrane review [Abstract] 1 included 4 studies with a total of 528 adult subjects with bronchiectasis but not cystic fibrosis. One study (n=88) compared bromhexine versus placebo during an acute infective exacerbation. High doses of bromhexine with antibiotics eased difficulty in expectoration (MD -0.53, 95% CI -0.81 to -0.25 at 16 days). A reduction in sputum production was noted with bromhexine (MD -21.5%, 95% CI -38.9 to -4.1 at day 16). No significant differences between bromhexine and placebo were observed with respect to reported adverse events (OR 2.93, 95% CI 0.12 to 73.97). In a single small, blinded but not placebo-controlled study of older (> 55 years) participants with stable bronchiectasis and mucus hypersecretion, erdosteine combined with physiotherapy over a 15-day period improved spirometry and sputum purulence more effectively compared with physiotherapy alone. The spirometric improvement was small (MD 200 mL in FEV1 and 300 mL in FVC) and was apparent only at day 15, not at earlier time points.

The remaining 2 studies (n=410) compared recombinant human DNase (RhDNase) versus placebo: 1 study was a 2-week study of 61 participants, and the other ran for 24 weeks and included 349 participants. Compared with placebo, recombinant human DNase showed no difference in FEV1 or FVC in the smaller study but showed a significant negative effect on FEV1 in the larger and longer study. For reported adverse events, no significant differences between recombinant human DNase and placebo were noted. but none of their data could be aggregated in a meta analysis. Compared to placebo, high doses of bromhexine with antibiotics eased difficulty in expectoration (WMD -0.53, 95% CI -0.81 to -0.25 at 16 days). There was also a reduction in sputum production with bromhexine (WMD -21.5%, 95% CI -38.9% to -4.1% at day 16). There was no difference in forced expiratory volume. Compared to placebo, recombinant human DNase showed no difference in forced expiratory volume or forced vital capacity in one study and was reported to have a significant negative effect on forced expiratory volume in another study. Adverse effects, including influenza-like symptoms, were more common in the group receiving recombinant human DNase.

Comment: The quality of evidence is downgraded by study limitations (unclear allocation concealment) and by imprecise results (few patients and wide confidence intervals).

    References

    • Wilkinson M, Sugumar K, Milan SJ et al. Mucolytics for bronchiectasis. Cochrane Database Syst Rev 2014;(5):CD001289. [PubMed]

Primary/Secondary Keywords