Measuring the effect of elexacaftor/tezacaftor/ivacaftor combination therapy on the respiratory pump in people with CF using dynamic chest radiography

Background: The CFTR modulator elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) leads to significant improvement in the symptoms and spirometry of people with cystic fibrosis (pwCF), but little evidence exists to understand its effect on respiratory pump function. Dynamic chest radiography (DCR) is a novel cineradiographic tool that identifies and tracks the chest wall and diaphragm throughout the breathing cycle, alongside fluoroscopic images of the chest of diagnostic quality. Methods: In this observational work, we examined the spirometry and DCR of 24 pwCF before and after starting ELX/TEZ/IVA. DCR automatically tracked the hemidiaphragm midpoints and projected lung area (PLA) during tidal and deep breathing manoeuvres. Results: ppFEV 1 (61 +/- 18 to 73 +/- 22, P<0.001) and ppFVC (77 +/- 16 to 88 +/- 15, P< 0.001) improved significantly. DCR demonstrated a significant increase in hemidiaphragm excursion on both the right (18 +/- 11 to 26 +/- 9 mm, P<0.001) and left (21 +/- 11 to 31 +/- 11 mm, P<0.001) sides, as well as maximum hemidiaphragm speed during inspiration (right 22 +/- 14 to 31 +/- 11 mm/s, P=0.03; left 28 +/- 11 to 37 +/- 16 mm/s, P=0.02). PLA at end-expiration was significantly reduced (334 +/- 71 to 290 +/- 72cm(2), P<0.001), with a significant increase in Delta PLA (83 +/- 40 to 117 +/- 36cm2, P<0.001). Conclusions: DCR demonstrated significant improvements in hemidiaphragm excursion and Delta PLA in pwCF started on ELX/TEZ/IVA. These changes likely reflect a reduction in air trapping and improved elastic recoil of the chest, and are consistent with improvements seen in spirometry. The changes seen with DCR are physiologically plausible and correlate well with spirometry. DCR warrants further investigation as a tool for assessing the impact of CFTR-modulating therapies. (c) 2022 The Authors. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)