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Three Part Question

In [an infant with RSV positive bronchiolitis] [Does treatment with DNase] [improve the clinical outcome]

Clinical Scenario

A 9-week-old infant was admitted to the paediatric ward with 5-day history of cough, coryza and wheeze. During his stay in the hospital, he became progressively dyspnoeic. His oxygen requirement gradually increased. Nasopharyngeal aspirate confirmed Respiratory Syncitial Virus. Chest X ray performed at this stage confirmed partial atelectasis of his right upper lobe. Do you give him DNase at this stage to improve his clinical state? If so what is the evidence behind this therapy?

Search Strategy

Medline using Dialog datastar (1951-2004
Medline using OVID interface(1966-10/04
Cochrane database
Medline (Dialog datastar) -"(( pulmozyme OR DNase OR Dornase OR deoxyribonuclease ) AND ( CHILD OR INFANT )) AND (( RSV OR respiratory ADJ syncitial ADJ virus OR bronchiolitis OR atelectasis ) AND ( CHILD OR INFANT))":
Medline (OVID)- DNase or deoxyribonuclease or pulmozyme or dornase).mp. and (bronchiolitis or RSV or respiratory syncitial virus or atelectasis).mp

Search Outcome

Dialog Datastar -11 references of which only 2 were considered relevant to answer the 3 part question.
OVID interface-194 references of which only one article was deemed relevant(Same was also found in dialog superstar).No additional relevant articles found.
Cochrane database-none relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Samya et al July 2001 USA	Previously healthy, hospitalised infants with proven RSV positive bronchiolitis between Feb 1996 and May 1998 (86 infants were enrolled of which only 75 were included in the analysis because of missing data in 11 other patients)	Randomised, double blind trial	CXR difference score	Significant improvement in CXR score in the rhDNase group while significant worsening in the score in placebo group (p-value<0.001)
			Clinical assessment score and length of hospital stay	No change observed in study and control group as the result was statistically insignificant. (Respiratory score-p value=0.56, Wheezing score- p value=0.41 Length of hospital stay-p value=0.97)
Merkus et al Oct 2001 Netherlands	5 cases of RSV positive bronchiolitis (3 on mechanical ventilation).	Case report	Clinical outcome	Marked improvement was seen in CXR, cardiac frequency, and PaCO2 in all 3 ventilated infants. Need for mechanical ventilation was avoided in other 2 infants.	It is difficult to generalize the outcome of this case report to all infants with RSV positive bronchiolitis as few other larger studies are needed to support this.

Comment(s)

Bronchiolitis is the commonest cause of respiratory tract infection and contributes to majority of hospital admissions particularly in infants. Severity of illness can vary from a mild respiratory illness to a life threatening one especially in infants with underlying cardiac or respiratory problems. Much controversy exists about the different therapeutic options currently available for bronchiolitis. One of the options being the use of DNase, even though the evidence to support its use in bronchiolitis is still less as only 2 studies have been published to date supporting this. DNase is an enzyme, which cleaves DNA and thereby reduces the viscoelasticity of mucopurulent secretions. Cochrane review has proven that the use of DNase in children with Cystic fibrosis is associated with improved lung function. The RCT by Samya Z etal.. showed difference in chest X ray but not clinical factors. This could show that Chest X ray changes are irrelevant, or that more major differences are needed for them to produce a clinical impact. There are number of factors which needs to be answered with the use of DNase in bronchiolitis There is limited experience about the use of DNase in children younger than 5 years old-hence more studies are needed to demonstrate the safety and efficacy of DNase in infants. Routine use of DNase in all cases of bronchiolitis is still questionable as the study from Nasr et al failed to show any clinical improvement in infants with RSV positive bronchiolitis. Probably it is better to predict at this stage that the DNase could be tried in those infants with severe bronchiolitis although we need randomised controlled trials in support of this. It is unclear from the currently available evidence about the appropriate duration of treatment required with DNase for treating bronchiolitis.

Clinical Bottom Line

From the evidence presented, DNase has shown no clinical benefit and its routine use in all cases of bronchiolitis is questionable. It needs to be used only within the context of randomised controlled trials.

References

1. Samya Z Nasr, Peter J. Strouse, Errol Soskolne, Norma J. Maxvold, Kimberly A. Garver, Bruce K. Rubin. Efficacy of Recombinant Human Deoxyribonuclease I in the Hospital Management of Respiratory Syncytial Virus Bronchiolitis. Chest 2001;120:203-208.
2. Merkus PJ, de Hoog M, van Gent R, de Jongste JC. DNase treatment for atelectasis in infants with severe respiratory syncytial virus bronchiolitis. European Respiratory Journal 2001 Oct;18(4):734-7.