The timing of inhalation of dornase alfa in people with cystic fibrosis

Dentice R, Elkins M

Published Online:

May 11, 2011

Inhaling the enzyme dornase alfa reduces the stickiness of sputum and improves clinical outcomes in people with cystic fibrosis. It is not certain whether it is better to inhale dornase alfa before or after clearing the airways with physical techniques. It is also not clear whether it is better to inhale it in the morning or in the evening. We included five trials with a total of 122 participants. In these trials the length of treatment ranged from two to eight weeks. Four of the trials compared inhaling before to inhaling after the airways had been cleared and found no overall difference in clinical outcomes. However, in children with well-preserved lung function, inhaling of dornase alfa after airway clearance techniques was better for small airways function. However, this did not affect quality of life or other outcomes. In the remaining trial, morning versus evening inhalation had no impact on lung function or symptoms. Therefore, for many people with CF, the timing of dornase alfa inhalation (before or after airway clearance or the time of day) can be based on practical reasons or individual preference.

Abstract (click to read)

Background:

Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis.

Objectives:

To determine the effect of timing of dornase alfa inhalation on measures of clinical efficacy in people with cystic fibrosis (in relation to airway clearance techniques or time of day).

Search strategy:

Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), and international CF conference proceedings.

Search date: 6 October 2010.

Selection criteria:

Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the study with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation.

Data collection and analysis:

Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed.

Main results:

We identified 92 trial reports representing 47 studies, of which five studies (providing data on 122 participants) met our inclusion criteria. All five studies used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change FEV1. Similarly, FVC and quality of life were not significantly affected; FEF25 was significantly worse with dornase alfa inhalation after airway clearance, MD -0.17 litres (95% CI -0.28 to -0.05), based on the pooled data from two small studies in children (7 to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.

In one trial, morning versus evening inhalation had no impact on lung function or symptoms.

Authors' conclusions:

The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and studies with variable follow-up. Apart from this, the timing of dornase alfa inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day. Further research is warranted.

This record should be cited as:

Dentice R, Elkins M. Timing of dornase alfa inhalation for cystic fibrosis. Cochrane Database of Systematic Reviews 2011, Issue 5. Art. No.: CD007923. DOI: 10.1002/14651858.CD007923.pub2

Assessed as up to date:

April 1, 2011

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Primary Review Group:

Cystic Fibrosis and Genetic Disorders Group

Health topics:

Genetic disorders > Cystic fibrosis > Inhaled therapy & aerosol delivery

Genetic disorders > Cystic fibrosis > Mucolytic treatment

Lungs & airways > Cystic fibrosis > Inhaled therapy & aerosol delivery

Lungs & airways > Cystic fibrosis > Mucolytic treatment

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

The timing of inhalation of dornase alfa in people with cystic fibrosis

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