#00057Effect of elexacaftor/tezacaftor/ivacaftor on body plethysmography measurements in patients with cystic fibrosis and advanced lung disease.

Premuda 1, Gramegna 1, Alicandro 2, Lucca 3, Retucci 4, Volpi 3, Cipolli 3, Blasi 1.
1Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy - Milano (Italy), 2Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Cystic Fibrosis Paediatric Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy - Milano (Italy), 3Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, Verona - Verona (Italy), 4Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Healthcare Professions Department, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy - Milano (Italy).

Abstract

INTRODUCTION. The heterogeneity of the ventilatory response to elexacator/tezacaftor/ivacaftor (ETI) and its magnitude are the side of the coin that has remained largely unexplored, especially in patients with cystic fibrosis (CF) and severe lung disease.
METHODS. We conducted a multicenter, observational, prospective study at two major CF Centers in Italy, enrolling 47 adults with CF and advanced lung disease (FEV1 <40% or actively listed for lung transplant) undergoing ETI treatment. At treatment initiation and after 12 months, patients underwent body plethysmography and we compared values at the two time points.

RESULTS. After 12 months of ETI treatment, there was a significant increase in FEV1 from a median value of 36 (25th-75th percentile: 33-39) to 52 (43-61) (P<0.001). IC/TLC ratio also increased from 32.0 (28.6-36.9) to 36.3 (33.4-41.3) (P<0.001). SRaw decreased from 263 (182-405) to 207 (120-258) (P<0.001). FRC/TLC ratio decreased from 68.2 (63.3-71.9) to 63.9 (58.8-67.1) (P<0.001), and RV/TLC ratio decreased from 53.1 (48.3-59.4) to 45.6 (39.4-49.8) (P<0.001).  Changes in FEV1 negatively correlated with baseline FRC/TLC ratio (r= -0.38, P= 0.009) and RV/TLC ratio (r= -0.42, P= 0.004). After adjustment for age at treatment initiation and CFTR genotype, we estimated that for each 10-unit increase in baseline RV/TLC ratio the expected median change in FEV1 decreased by 2.3 (95% CI: -5.8; -0.8).

CONCLUSIONS. ETI therapy effectively reduces hyperinflation in patients with CF and severe lung disease. Furthermore, plethysmography measurements suggestive of hyperinflation are predictive of lower treatment-induced changes in FEV1.