Dornase alfa: Can it relieve persistent small airway obstruction in asthma?

Published Online: March 29, 2013

Up to half of children with asthma do not gain optimal asthma control or continue to show an obstructive lung function. Especially, the small airways continue to play an important role in these children. Dornase alfa is a mucolytic drug, used to treat airways obstructed by mucus in cystic fibrosis patients. Studies suggest that dornase alfa could be effective to treat persistent small airway disease in moderate to severe asthma. However, no controlled studies in these patients were performed to date.

In a Letter to the Editor recently published in The Journal of Allergy & Clinical Immunology (JACI), Bakker et al. hypothesized that dornase alfa might be useful in children with asthma who show persistent small airway obstruction despite standard asthma treatment. They performed a randomized controlled clinical trial in 60 children with asthma. Children were eligible to participate in the study if aged 6 to 18 years, had clinically stable asthma, maintenance treatment with at least 400 ug/day inhaled Budesonide or equivalent, and persistent small airways obstruction.

The study drug was administered using an innovative smart nebulizer, which is highly efficient in targeting the small airways. Using this nebulizer three aspects of inhalation therapy were optimized. Firstly, particle size could be controlled. In one study arm small particles were generated to efficiently target the small airways. Secondly, the settings of nebulizer were personalized to meet the patient’s lung function. To do so it was programmed to let the patient inhale dornase alfa with a deep and slow inhalation. Hence, the inhalation maneuver was tailored to the needs of the patient, and to obtain efficient deposition of medication in the small airways. Thirdly, adherence to treatment was electronically monitored. The primary endpoint in this study was forced expiratory flow at 75% of forced vital capacity (FEF75), which is a sensitive marker of small airway obstruction.

The authors found that dornase alfa has no additional value in the treatment of children with stable asthma and persistent small airways obstruction. There was no significant improvement in FEF75 or any other lung function parameter. Symptom scores also showed no significant benefit. The authors conclude that it is not useful to prescribe dornase alfa as an add-on drug in children with stable asthma and persistent airway obstruction. The smart nebulizer is an important inhalation therapy platform for proof of concept studies since it controls for therapy adherence, and inhalation competence.

COI Disclosure: Roche BV Netherlands supplied dornase alfa for use in this study, free of charge, and the study was supported by an unconditional grant by Roche BV Netherlands. Activaero GmbH supplied Akita²® APIXNEB devices and technical support. This was an investigator-initiated study; the sponsors did not have any influence on the design, data analysis, or reporting of the study.

The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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