- •A randomised, controlled pilot study in school-age children with cystic fibrosis.
- •One month's withdrawal of dornase alfa caused a significant increase in LCI.
- •Short-term discontinuation of dornase alfa may affect LCI values.
- •When using LCI as endpoint, dornase alfa adherence optimally needs to be addressed.
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.
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.
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.
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.
Abbreviations:LCI (lung clearance index), CF (cystic fibrosis), FEV1 (forced expired volume in 1 second), FEF25–75 (the forced expired flow at 25–75% of the forced vital capacity), CFQ-R (cystic fibrosis questionnaire-revised), MBW (multiple breath washout), CFTR (cystic fibrosis transmembrane conductance regulator), IQR (interquartile range), 95%CI (95% confidence interval), OSM (online supplementary material), n (number), SD (standard deviation)
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Published online: February 19, 2021
Accepted: February 7, 2021
Received in revised form: January 31, 2021
Received: November 28, 2020
© 2021 Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.