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Randomized Controlled Trial
. 2021 Nov;20(6):949-956.
doi: 10.1016/j.jcf.2021.02.004. Epub 2021 Feb 19.

Withdrawal of dornase alfa increases ventilation inhomogeneity in children with cystic fibrosis

Christian Voldby  1 , Kent Green  1 , Lue Philipsen  1 , Rikke Mulvad Sandvik  1 , Marianne Skov  1 , Frederik Buchvald  1 , Tacjana Pressler  2 , Kim Gjerum Nielsen  3
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Free article
Randomized Controlled Trial

Withdrawal of dornase alfa increases ventilation inhomogeneity in children with cystic fibrosis

Christian Voldby et al. J Cyst Fibros. 2021 Nov.
Free article

Abstract

Background: The lung clearance index (LCI) is increasingly used as an outcome in clinical trials of patients with mild cystic fibrosis (CF) lung disease. Yet, understanding the impact of standard CF respiratory therapy on LCI is needed. We assessed to what degree withdrawal of nebulised dornase alfa affected LCI in school-age children with CF not receiving CFTR modulators or hydrator therapy.

Methods: A single-centre, randomised, controlled, parallel group study to determine effects of one month's withdrawal of nebulised dornase alfa (intervention) in 5-18 years old children with CF. Remaining chronic maintenance therapy stayed unchanged. Outcome measures were assessed at two visits one month apart. Primary outcome was absolute change in LCI. Secondary outcomes were FEV1, FEF25-75 and CF Questionnaire-revised (CFQ-R) respiratory symptom score. Possible harmful effects were assessed by comparing the occurrence of pulmonary exacerbations between groups.

Results: Twenty-eight children (median age 10.4 [interquartile range: 7.6; 13.5] years) with CF received standard care (n = 14) or intervention (n = 14). Compared with the control group, LCI increased (worsened) 1.74 (95% confidence interval: 0.62; 2.86) during withdrawal of dornase alfa, while FEV1 (-6.8% predicted) and FEF25-75 (-13.1% predicted) decreased significantly. Change in CFQ-R respiratory symptom score and the occurrence of pulmonary exacerbations did not differ significantly between groups.

Conclusions: One month's withdrawal of dornase alfa caused increasing ventilation inhomogeneity and deteriorating FEV1 and FEF25-75 in school-age children with mild CF. Hence, adherence to dornase alfa optimally needs to be addressed when using LCI and spirometric parameters as endpoints, even in short-term clinical trials.

Keywords: Cystic fibrosis; Dornase alfa; Lung clearence index; Mulitple breath washout; Randomised controlled trial.

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Conflict of interest statement

Declaration of Competing Interest Christian Voldby reports grants from Tømrermester Jørgen Holm og hustru Elisa f. Hansens Mindelegat during the conduct of the study. Kim G. Nielsen reports grants from The John and Birthe Meyer Foundation, grants from Aase and Ejnar Danielsen's Foundation and grants from The Queen Louise Children's Hospital's Research Foundation during the conduct of the study. The funders had no role in study design, data collection, choice or interpretation of analyses, decision to publish, or preparation of the manuscript. Kent Green, Lue Philipsen, Rikke Mulvad Sandvik, Marianne Skov, Frederik Buchvald and Tacjana Pressler has nothing to disclose.

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