Chest
Original Research: InfectionsRecombinant Human Deoxyribonuclease in Infants With Respiratory Syncytial Virus 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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Cited by (49)
Serine proteases in neutrophil extracellular traps exhibit anti-Respiratory Syncytial Virus activity
2022, International ImmunopharmacologyCitation Excerpt :Several experimental models have described the beneficial local reduction of NETs using DNase. Specifically, for hRSV infection, the inhalation of DNase in children with bronchiolitis reduces lung collapse, but the therapy does not show evidence of clinical benefits when compared to patients with mild bronchiolitis [40,41]. Notably, the degradation of NETs can also have unintended consequences in the lungs since the release of enzymes such as elastase and proteinase 3 could expose the patient to the pathologic processes described above.
Rational use of mucoactive medications to treat pediatric airway disease
2020, Paediatric Respiratory ReviewsCitation Excerpt :As such, the use of the mucolytic dornase alfa, has been of interest [21,22]. Two randomized, placebo-controlled studies of nebulized dornase alfa in hospitalized children with mild to moderate bronchiolitis and a Cochrane review did not show a decrease in length of hospital stay or respiratory effort [20,23,24]. However, one study did show an improvement in chest radiograph defined atelectasis compared to placebo in young children with severe bronchiolitis [20].
Neutrophil Extracellular Traps in Respiratory Disease: guided anti-microbial traps or toxic webs?
2017, Paediatric Respiratory ReviewsCitation Excerpt :Indeed, both systemic and local (by inhalation) administration of DNase in mice is beneficial in septic lung injury and transfusion-related acute lung injury (TRALI)-models [71–73,90]. Treatment with recombinant DNase (dornase alfa) is often used clinically in patients with CF. Interestingly, although DNase reduces atelectasis in children with RSV bronchiolitis [91], so far, this therapy hasn’t shown further clinical benefit in randomized controlled trials among patients with mild bronchiolitis [92]. It is possible that DNase will be more effective in children with severe RSV disease in need of mechanical ventilation [93].
Successful treatment of atelectasis with Dornase alpha in a patient with congenital muscular dystrophy
2014, Revista Portuguesa de PneumologiaCitation Excerpt :In patients with cystic fibrosis rhDNase has proved extremely effective, with both aerosol administration7 and bronchoscopic instillation.8 Studies in newborns or in children have reported beneficial effects of rhDNase on atelectasis in non-cystic fibrosis patients,9,10 and anecdotal reports have suggested a beneficial effect in respiratory syncytial virus bronchiolitis11 and in atelectasis due to mucus plugs in newborns and children.12 Most of these studies were performed by instillating the drug directly into the trachea in intubated patients.
Viral bronchiolitis in children: A common condition with few therapeutic options
2013, Early Human DevelopmentCitation Excerpt :The therapy for bronchiolitis is mainly supportive [5], with supplemental oxygen, nasal washing, and intravenous (IV) fluids. Clinical trials, testing β 2-agonists [6,7], glucocorticoids [8], epinephrine [9], recombinant human DNase [10,11], and hypertonic saline [12] in bronchiolitis report highly controversial results. Bronchiolitis is the first acute lower respiratory tract viral infection affecting terminal and respiratory bronchioli in infants less than 12 months of age and resulting from bronchiole obstruction.
Treatment of bronchiolitis: State of the art
2013, Early Human Development
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).