Chest
Volume 131, Issue 3, March 2007, Pages 788-795
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Original Research: Infections
Recombinant Human Deoxyribonuclease in Infants With Respiratory Syncytial Virus Bronchiolitis

https://doi.org/10.1378/chest.06-2282Get rights and content

Abstract

Background:Treatment of hospitalized infants with respiratory syncytial virus (RSV) bronchiolitis is mainly supportive. Bronchodilators and systemic steroids are often used but do not reduce the length of hospital stay. Because hypoxia and airways obstruction develop secondary to viscous mucus in infants with RSV bronchiolitis, and because free DNA is present in RSV mucus, we tested the efficacy of the mucolytic drug recombinant human deoxyribonuclease (rhDNase).

Methods:In a multicenter, randomized, double-blind, controlled clinical trial, 225 oxygen-dependent infants admitted to the hospital for RSV bronchiolitis were randomly assigned to receive 2.5 mg bid of nebulized rhDNase or placebo until discharge. The primary end point was length of hospital stay. Secondary end points were duration of supplemental oxygen, improvement in symptom score, and number of intensive care admissions.

Results:There were no significant differences between the groups with regard to the length of hospital stay (p = 0.19) or the duration of supplemental oxygen (p = 0.07). The ratio (rhDNase/placebo) of geometric means of length of stay was 1.12 (95%confidence interval, 0.96 to 1.33);for the duration of supplemental oxygen, the ratio was 1.28 (95%confidence interval, 0.97 to 1.68). There were no significant differences in the rate of improvement of the symptom score or in the number of intensive care admissions.

Conclusions:Administration of rhDNase did not reduce the length of hospital stay or the duration of supplemental oxygen in oxygen-dependent infants with RSV bronchiolitis.

Section snippets

Setting and Participants

For entry into this study, we considered infants < 12 months of age with proven RSV bronchiolitis requiring supplemental oxygen, who were admitted to 1 of the 10 participating hospitals between November 2002 and February 2006: Erasmus MC-Sophia Children's Hospital, Rotterdam; Amphia Hospital, Breda; Reinier de Graaf Gasthuis, Delft; Albert Schweitzer Hospital, Dordrecht; HagaTeaching Hospital/Juliana Children's Hospital, the Hague; Medisch Centrum Alkmaar, Alkmaar; Catharina Hospital,

Results

A total of 225 infants were assigned to treatment: 113 infants to rhDNase and 112 infants to placeboFig 1. Two patients withdrew from the study after the first dose of study medication (one in each group) and consequently had no follow-up data available. During the first two RSV seasons of the study, patients were recruited in 4 hospitals; during the last two RSV seasons, patients were recruited from a total of 10 hospitals. In terms of demographic variables, there were no significant

Discussion

We report the first large, randomized, double-blind, controlled trial of rhDNase in infants with RSV bronchiolitis. This study demonstrates that the mucolytic rhDNase does not shorten length of hospital stay or duration of supplemental oxygen in hypoxemic infants with RSV bronchiolitis. Neither was the rate of clinical improvement better in infants treated with rhDNase than in those receiving a placebo.

Because mucus plugs play an important role in the pathophysiology of RSV bronchiolitis,27and

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    Roche BV, the Netherlands, provided an unrestricted grant for this study and financed the study medication. Romedic BV, the Netherlands, donated the nebulizing equipment. The study sponsors had no role in the study design, the collection, analysis or interpretation of data, the writing of the report, or the decision to submit for publication.

    The principal investigators had full access to all study data and had final responsibility to submit for publication.

    The authors have no conflicts of interest to disclose.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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