Short-term recombinant human DNase in bronchiectasis. Effect on clinical state and in vitro sputum transportability. Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase I. rhDNase Study Group. Role of bromhexine in exacerbations of bronchiectasis. Double-blind randomized multicenter study versus placebo.
We report a double blind placebo-controlled phase II study of the efficacy and safety of nebulized recombinant human DNase (rhDNase) administered for 14 d to adults with bronchiectasis not caused by cystic fibrosis. All were in a stable clinical state at the commencement of the study, and they received (1) rhDNase 2.5 mg twice daily, (2) rhDNase once daily, or (3) placebo (excipient only) inhalation. The outcome measures were spirometry, subjective quality of life/dyspnea, and safety. We also measured the ciliary transportability of the sputum expectorated before and after the treatment period, using the mucus-depleted bovine trachea. The drug was well tolerated, but it produced no significant change in any of the outcome variables or in sputum transportability. When the drug was incubated with bronchiectatic sputum in vitro, a fall in transportability was observed. We discuss possible explanations for the lack of a measurable benefit from rhDNase in this study population, which appears to contrast with the improvements shown in cystic fibrosis using studies of similar design. To study the safety and efficacy of aerosolized recombinant human DNase I in the treatment of idiopathic bronchiectasis.
                Double-blind, randomized, placebo-controlled, multicenter study.
                Three hundred forty-nine adult outpatients in stable condition with idiopathic bronchiectasis from 23 centers in North America, Great Britain, and Ireland.
                Study patients received aerosolized rhDNase or placebo twice daily for 24 weeks. Primary end points were incidence of pulmonary exacerbations and mean percent change in FEV1 from baseline over the treatment period.
                Pulmonary exacerbations were more frequent and FEV1 decline was greater in patients who received rhDNase compared with placebo during this 24-week trial.
                rhDNase was ineffective and potentially harmful in this group of adult outpatients in stable condition with idiopathic bronchiectasis. This contrasts with previously published results that demonstrated efficacy of rhDNase in patients with cystic fibrosis bronchiectasis. The effectiveness of bromhexine in the treatment of patients with bronchiectasis, in a stage of clinical exacerbation, was assessed in a double-blind, placebo-controlled trial involving 88 in-patients. Bronchiectasis was diagnosed by bronchography and/or CT scan. Bromhexine or matched placebo was administered as 30-mg capsules three times daily per os. Ceftazidine, 1 g i.m., was given to all patients once a day for the first week only. Bromhexine seemed to improve the clinical picture, with significantly positive trends for expectoration, quantity of sputum and auscultatory findings. It also increased the FEV1 and was well-tolerated. Both patients and investigators judged it efficacious.
There is not enough evidence to evaluate the routine use of mucolytics for bronchiectasis. High doses of bromhexine coupled with antibiotics may help with sputum production and clearance.