Limited effectiveness of elexacaftor-tezacaftor-ivacaftor on lung hyperinflation in adults with cystic fibrosis

<bold>Background:</bold> This study sought to describe the prevalence of lung hyperinflation in adults (≥18 years) with CF (awCF) and the effects of elexacaftor-tezacaftor-ivacaftor (ETI) on hyperinflation. <bold>Methods:</bold> Consecutive awCF who initiated ETI at Cochin Hospital, Paris, France, and had performed body plethysmography within 12 months prior to ETI initiation were included. Abnormal lung volumes (including total lung capacity-TLC and residual volume-RV) were defined as greater than the upper limit of normal (ULN) using Global Lung Initiative reference values. Hyperinflation was defined as RV/TLC>ULN. Variables associated with hyperinflation were identified using a multivariate logistic regression analysis. Evolution of hyperinflation was examined using body plethysmography performed at 12 month-visit following ETI initiation. <bold>Findings:</bold> Body plethysmography was available within 12 months prior to ETI initiation and after 12 months of ETI treatment in 297 and 211 awCF, respectively. Prior to ETI initiation, TLC, RV, and RV/TLC values >ULN were found in 14%, 69% and 76% of awCF, respectively. RV/TLC strongly correlated with percent predicted forced expiratory volume in 1 sec (ppFEV₁; r2 = 0.78). Increasing age and days on intravenous antibiotics in the previous year were independently associated with RV/TLC>ULN. RV/TLC decreased after 12 months of ETI (median absolute decrease; -6.5 [−11.0; -1.0] %, P<0.0001; n=211), but remained >ULN in 69% of awCF. <bold>Interpretation:</bold> Lung hyperinflation is highly prevalent in awCF and strongly correlated with ppFEV₁. ETI was associated with decrease in RV/TLC, but hyperinflation persisted in most of awCF, especially in those with advanced lung disease.