A Short extension to multiple breath washout provides additional signal of distal airway disease in people with CF: A pilot study.

Background: Adding a slow vital capacity (SVC) to multiple breath washout (MBW) allows quantification of otherwise overlooked signal from under/un-ventilated lung units (UVLU) and may provide a more comprehensive assessment of airway disease than conventional lung clearance index (LCI _2.5 ).
Methods: We conducted a pilot study on people undergoing MBW tests: 10 healthy controls (HC) and 43 cystic fibrosis (CF) subjects performed an SVC after the standard end of test. We term the new outcome LCI with Short extension (LCI _ShX ). We assessed (i) CF/ HC differences, (ii) variability (iii) effect of pulmonary exacerbation (PEx)/treatment and (iv) relationship with CF computed tomography (CFCT) scores.
Results: HC/ CF group differences were larger with LCI _ShX than LCI _2.5 (P<0.001). Within the CF group UVLU was highly variable and when abnormal it did not correlate with corresponding LCI _2.5 . Signal showed little variability during clinical stability (n = 11 CF; 2 visits; median inter-test variability 2.6% LCI _ShX, 2.5% LCI _2.5 ). PEx signal was significantly greater for LCI _ShX both for onset and resolution. Both MBW parameters correlated significantly with total lung CT scores and hyperinflation but only LCI _ShX correlated with mucus plugging.
Conclusions: UVLU captured within the LCI _ShX varies between individuals; the lack of relationship with LCI _2.5 demonstrates that new, additional information is being captured. LCI _ShX repeatability during clinical stability combined with its larger signal around episodes of PEx may lend it superior sensitivity as an outcome measure. Further studies will build on this pilot data to fully establish its utility in monitoring disease status.
Competing Interests: Declaration of Competing Interest Christopher Short, Clare Saunders, Dominic Hughes, Samantha Irving, Laura Gardener, Mark Rosenthal and Paul Robinson report no conflicts of interest. Thomas Semple reports speakers fees - Vertex Pharmaceuticals. Research grants – Chiesi Pharmaceuticals. Consultancy fees - Boehringer-Ingelheim and Calyx. Prof. Jane Davies has performed clinical trial leadership roles, educational and/ or advisory activities for the following: Abbvie, Algipharma AS, Bayer AG, Boehringer Ingelheim Pharma GmbH & Co. KG, Eloxx, Enterprise, Galapagos NV, ImevaX GmbH, Ionis, Nivalis Therapeutics, Inc., Novartis, ProQR Therapeutics III B.V., Proteostasis Therapeutics, INC., Pulmocide Raptor Pharmaceuticals, Inc, Vertex Pharmaceuticals.
(Copyright © 2021. Published by Elsevier B.V.)