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Meta-Analysis
. 2012 Nov 14;11(11):CD008395.
doi: 10.1002/14651858.CD008395.pub2.

Nebulised deoxyribonuclease for viral bronchiolitis in children younger than 24 months

Annabelle Enriquez  1 , I-Wen Chu, Craig Mellis, Wan-Yu Lin
Affiliations
Meta-Analysis

Nebulised deoxyribonuclease for viral bronchiolitis in children younger than 24 months

Annabelle Enriquez et al. Cochrane Database Syst Rev. .

Abstract

Background: Bronchiolitis is one of the most common respiratory problems in the first year of life. The sputum of infants with bronchiolitis has increased deoxyribonucleic acid (DNA) content, leading to mucous plugging and airway obstruction. Recombinant human deoxyribonuclease (rhDNase), an enzyme that digests extracellular DNA, might aid the clearance of mucus and relieve peripheral airway obstruction.

Objectives: To determine the effect of nebulised rhDNase on the severity and duration of viral bronchiolitis in children younger than 24 months of age in the hospital setting.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2012, Issue 7 which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to July Week 4, 2012), EMBASE (1974 to August 2012) and LILACS (1982 to August 2012).

Selection criteria: Randomised controlled trials (RCTs) using nebulised rhDNase alone or with concomitant therapy in children younger than 24 months of age hospitalised with acute bronchiolitis.

Data collection and analysis: Two review authors independently performed literature searches, assessed trial quality and extracted data. We obtained unpublished data from trial authors. We used Review Manager 5.1 to pool treatment effects expressed as the mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI).

Main results: Three RCTs (333 participants) were identified, two of which were multicentre trials comprising only participants positive for respiratory syncytial virus (RSV). The other trial enrolled participants clinically diagnosed with bronchiolitis from a hospital in Italy. All studies used 2.5 mL (1 mg/mL) of nebulised rhDNase compared with placebo either as a daily or a twice daily dose. Adjunctive therapy included nebulised salbutamol, steroids, supplemental oxygen, intravenous fluids or tube feeding, nasal washing, nasal decongestants and antibiotics.Overall, nebulised rhDNase showed no benefit in clinically meaningful outcomes. Meta-analysis favoured the control group with a shorter duration of hospital stay (MD 0.50; 95% CI 0.10 to 0.90, P = 0.01) and better clinical score improvement (SMD -0.24; 95% CI -0.50 to 0.01, P = 0.06). The largest trial showed no difference in supplemental oxygen use or intensive care unit (ICU) admission.In one RCT, four out of 11 patients in the treatment group had atelectasis. Two of these patients showed distinctive clinical improvement after nebulised rhDNase.There was no significant difference in adverse events. These included temporary desaturation, temporary coughing, increased coughing, facial rash, hoarseness, dyspnoea and bad taste, reported in a total of 11 patients from both treatment groups.

Authors' conclusions: The results based on the three included studies in this review did not support the use of nebulised rhDNase in children under 24 months of age hospitalised with acute bronchiolitis. In these patients, treatment did not shorten the length of hospitalisation or improve clinical outcomes. It might have a role in severe bronchiolitis complicated by atelectasis, but further clinical studies would need to be performed.

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Conflict of interest statement

None known.

Figures

1
1
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
Forest plot of comparison: duration of hospitalisation
3
3
Forest plot of comparison: change in total clinical score
4
4
Forest plot of comparison: change in respiratory rate score
5
5
Forest plot of comparison: change in wheezing score
6
6
Forest plot of comparison: change in retraction score
1.1
1.1. Analysis
Comparison 1 Nebulised rhDNase versus control, Outcome 1 Duration of hospitalisation.
2.1
2.1. Analysis
Comparison 2 Nebulised rhDNase versus control, Outcome 1 Change in clinical score.
3.1
3.1. Analysis
Comparison 3 Nebulised rhDNase versus control, Outcome 1 Change in respiratory rate score.
4.1
4.1. Analysis
Comparison 4 Nebulised rhDNase versus control, Outcome 1 Change in wheezing score.
5.1
5.1. Analysis
Comparison 5 Nebulised rhDNase versus control, Outcome 1 Change in retraction score.
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References

References to studies included in this review

Boogaard 2007 {published and unpublished data}
    1. Boogaard R, Hulsmann AR, Hop WCJ, Merkus PJF. Efficacy of recombinant human deoxyribonuclease (Rh‐DNase) in infants hospitalised with respiratory syncytial virus bronchiolitis a multicentre randomised double blind clinical trial [Abstract]. European Respiratory Journal 2006;28(Suppl 50):758s [4365].
    1. Boogaard R, Hulsmann AR, Veen L, Vaessen‐Verberne AAPH, Yap YN, Sprij AJ, et al. Recombinant human deoxyribonuclease in infants with respiratory syncytial virus bronchiolitis. Chest 2007;131(3):788‐95. - PubMed
Nasr 2001 {published data only (unpublished sought but not used)}
    1. Nasr S, Strouse P, Soskolne E, Maxvold N, Garver K, Rubin B, et al. Efficacy of recombinant human DNase I in the management of RSV bronchiolitis [abstract]. American Journal of Respiratory and Critical Care Medicine 2000;161(3 Suppl):A339.
    1. Nasr SZ, Strouse PJ, Soskolne E, Maxvold N, Garver KA, Rubin BK, et al. Efficacy of recombinant human deoxyribonuclease I in the hospital management of respiratory syncytial virus bronchiolitis. Chest 2001;120:203‐8. - PubMed
Nenna 2010 {published and unpublished data}
    1. Corazzesi E, Nenna R, Tromba V, Tuccinardi R, Piacenti S, Scalercio F, et al. Recombinant human deoxyribonuclease treatment in hospital management of infants with moderate to severe bronchiolitis. European Respiratory Journal 2006;28(Suppl 50):758s [4367].
    1. Nenna R, Tromba V, Berardi R, Angelis D, Papoff P, Sabbatino G, et al. Recombinant human deoxyribonuclease treatment in hospital management of infants with moderate‐severe bronchiolitis. European Journal of Inflammation 2009;7(3):169‐74.

References to studies excluded from this review

Merkus 2001 {published data only}
    1. Merkus PJFM, Hoog M, Gent R, Jongste JC. DNase treatment for atelectasis in infants with severe respiratory syncytial virus bronchiolitis. European Respiratory Journal 2001;18(4):734‐7. - PubMed

Additional references

Armstrong 1950
    1. Armstrong JB, White JC. Liquefaction of viscous purulent exudate by deoxyribonuclease. Lancet 1950;256(6641):739‐42. - PubMed
Boogaard 2007a
    1. Boogaard R, Jongste JC, Merkus PJ. Pharmacotherapy of impaired mucociliary clearance in non‐CF pediatric lung disease. A review of the literature. Pediatric Pulmonology 2007;42(11):989‐1001. [PUBMED: 17902149] - PubMed
Boogaard 2007b
    1. Boogaard R, Hulsmann AR, Veen L, Vaessen‐Verberne AAPH, Yap YN, Sprij AJ, et al. Recombinant human deoxyribonuclease in infants with respiratory syncytial virus bronchiolitis. Chest 2007;131(3):788‐95. - PubMed
Calogero 2007
    1. Calogero C, Sly PD. Acute viral bronchiolitis: to treat or not to treat ‐ that is the question. Journal of Pediatrics 2007;151(3):235‐7. - PubMed
Corneli 2007
    1. Corneli HM, Zorc JJ, Mahajan P, Shaw KN, Holubkov R, Reeves SD, et al. Bronchiolitis Study Group of the Pediatric Emergency Care Applied Research Network (PECARN). A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis. New England Journal of Medicine 2007;357(4):331‐9. [PUBMED: 17652648] - PubMed
Deshpande 2003
    1. Deshpande SA, Northern V. The clinical and health economic burden of respiratory syncytial virus disease among children under 2 years of age in a defined geographical area. Archives of Disease in Childhood 2003;88(12):1065‐9. [PUBMED: 14670770] - PMC - PubMed
Erdeve 2007
    1. Erdeve O, Uras N, Atasay B, Arsan S. Efficacy and safety of nebulized recombinant human DNase as rescue treatment for persistent atelectasis in newborns: case‐series. Croatian Medical Journal 2007;48:234‐9. - PMC - PubMed
Fernandes 2010
    1. Fernandes RM, Bialy LM, Vandermeer B, Tjosvold L, Plint AC, Patel H, et al. Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database of Systematic Reviews 2010, Issue 10. [DOI: 10.1002/14651858.CD004878.pub2] - DOI - PubMed
Gadomski 2010
    1. Gadomski AM, Brower M. Bronchodilators for bronchiolitis. Cochrane Database of Systematic Reviews 2010, Issue 12. [DOI: 10.1002/14651858.CD001266.pub2] - DOI - PubMed
Greally 1995
    1. Greally P. Human recombinant DNase for mucus plugging in status asthmaticus. Lancet 1995;346:1423‐4. - PubMed
Hall 2009
    1. Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, et al. The burden of respiratory syncytial virus infection in young children. New England Journal of Medicine 2009;360(6):588‐98. [PUBMED: 19196675] - PMC - PubMed
Hartling 2011
    1. Hartling L, Bialy LM, Vandermeer B, Tjosvold L, Johnson DW, Plint AC, et al. Epinephrine for bronchiolitis. Cochrane Database of Systematic Reviews 2011, Issue 6. [DOI: 10.1002/14651858.CD003123.pub2] - DOI - PubMed
Hendriks 2005
    1. Hendriks T, Hoog M, Lequin MH, Devos AS, Merkus PJ. DNase and atelectasis in non‐cystic fibrosis pediatric patients. Critical Care 2005;9(4):341‐2. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Kupeli 2003
    1. Kupeli S, Teksam O, Dogru D, Yurdakok M. Use of recombinant human DNase in a premature infant with recurrent atelectasis. Pediatrics International 2003;45:584‐6. - PubMed
Leader 2003
    1. Leader S, Kohlhase K. Recent trends in severe respiratory syncytial virus (RSV) among US infants, 1997 to 2000. Journal of Pediatrics 2003;143(Suppl 5):127‐32. - PubMed
Manoha 2007
    1. Manoha C, Espinosa S, Aho SL, Huet F, Pothier P. Epidemiological and clinical features of hMPV, RSV and RVs infections in young children. Journal of Clinical Virology 2007;38(3):221‐6. - PubMed
Nenna 2009
    1. Nenna R, Tromba V, Berardi R, Angelis D, Papoff P, Sabbatino G, et al. Recombinant human deoxyribonuclease treatment in hospital management of infants with moderate‐severe bronchiolitis. European Journal of Inflammation 2009;7(3):169‐74.
Patel 2000
    1. Patel A, Harrison E, Durward A, Murdoch IA. Intratracheal recombinant human deoxyribonuclease in acute life‐threatening asthma refractory to conventional treatment. British Journal of Anaesthesia 2000;84:505‐7. - PubMed
Perrotta 2007
    1. Perrotta C, Ortiz Z, Roque M. Chest physiotherapy for acute bronchiolitis in paediatric patients between 0 and 24 months old. Cochrane Database of Systematic Reviews 2007, Issue 1. [DOI: 10.1002/14651858.CD004873.pub3] - DOI - PubMed
Puterman 1997
    1. Puterman AS, Weinberg EG. rhDNase in acute asthma. Pediatric Pulmonology 1997;23:316‐7. - PubMed
RevMan 2011 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.
Shak 1990
    1. Shak S, Capon DJ, Hellmiss R, Marsters SA, Baker CL. Recombinant human DNase reduces the viscosity of cystic fibrosis sputum. Proceedings of the National Academy of Sciences of the United States of America 1990;87(23):9188‐92. [PUBMED: 2251263] - PMC - PubMed
Suri 2002
    1. Suri R, Grieve R, Normand C, Metcalfe C, Thompson S, Wallis C, et al. Effects of hypertonic saline, alternate day and daily rhDNase on healthcare use, costs and outcomes in children with cystic fibrosis. Thorax 2002;57(10):841‐6. [PUBMED: 12324668] - PMC - PubMed
ten Berge 1999
    1. Berge M, Brinkhorst G, Kroon AA, Jongste JC. DNase treatment in primary ciliary dyskinesia ‐ assessment by nocturnal pulse oximetry. Pediatric Pulmonology 1999;27:59‐61. - PubMed
Wang 1992
    1. Wang EE, Milner RA, Navas L, Maj H. Observer agreement for respiratory signs and oximetry in infants hospitalized with lower respiratory infections. American Review of Respiratory Disease 1992;145:106‐9. - PubMed
Wohl 2003
    1. Wohl ME, Chernick V. Treatment of acute bronchiolitis. New England Journal of Medicine 2003;349:82‐3. - PubMed
Zhang 2011
    1. Zhang L, Mendoza‐Sassi RA, Wainwright C, Klassen TP. Nebulized hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database of Systematic Reviews 2011, Issue 3. [DOI: 10.1002/14651858.CD006458.pub2] - DOI

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