Recombinant human deoxyribonuclease for the treatment of acute asthma in children

Ruben Boogaard ^1*, Frank Smit ², Ruud Schornagel ³, Anja APH Vaessen-Verberne ⁴, Jan M Kouwenberg ⁵, Marion Hekkelaan ⁶, Tom Hendriks ⁷, Sander WW Feith ⁸, Wim CJ Hop ⁹, Johan C de Jongste ¹ and Peter JFM Merkus ¹

¹ Erasmus MC-Sophia Children's Hospital, Netherlands
² Medisch Centrum Rijnmond Zuid, Netherlands
³ Albert Schweitzer Hospital, Netherlands
⁴ Amphia Hospital, Netherlands
⁵ HagaTeaching Hospital/Juliana Children's Hospital, Netherlands
⁶ Reinier de Graaf Gasthuis, Netherlands
⁷ Catharina Hospital, Netherlands
⁸ Sint Franciscus Gasthuis, Netherlands
⁹ Erasmus MC, Netherlands

^* To whom correspondence should be addressed. E-mail: r.boogaard{at}erasmusmc.nl.

Accepted 12 June 2007

Abstract

Background: Airway obstruction in acute asthma is the result of airway smooth muscle contraction, inflammation and mucus plugging. Case reports suggest that mucolytic therapy might be beneficial in acute asthma. The aim of this study was to determine the efficacy of the mucolytic drug recombinant human deoxyribonuclease (rhDNase) in addition to standard treatment at the emergency department in children with an asthma exacerbation.

Methods: In a multicenter randomized double-blind controlled clinical trial, 121 children brought to the emergency room for a moderate-to-severe asthma exacerbation were randomly assigned to receive either a single dose of 5 mg nebulized rhDNase or placebo following the second dose of bronchodilators. An asthma score (scale 5 to 15) was assessed at baseline and at 1, 2, 6, 12 and 24 hours. The primary outcome variable was the asthma score 1 hour after the study medication.

Results: One hour after the study medication, the asthma score in the rhDNase group showed a 1.0 (0.5 to 1.6) points adjusted mean decrease from baseline (95%CI), vs. 0.7 (0.3 to 1.2) points in the placebo group; mean difference (95% CI)= 0.4 (-0.2 to 1.0) points; P=0.23. The asthma score over the study period of 24 hours also did not significantly differ between the rhDNase and placebo group (mean difference = 0.2 (-0.3 to 0.7) points, P=0.40). Duration of oxygen supplementation and number of bronchodilator treatments in the first 24 hours were similar in both groups.

Conclusion: Adding a single dose of nebulized rhDNase to standard treatment in the emergency room has no beneficial effects in children with moderate-to-severe acute asthma. (Controlled-trials.com number, ISRCTN81874766)

Keywords: asthma exacerbation, controlled clinical trial, dornase alfa, pediatric, treatment

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