Persistence of static lung hyperinflation in adults with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor.

Abstract

Background: This study sought to describe the prevalence of lung hyperinflation in adults (≥18 years) with cystic fibrosis (awCF) and the effects of elexacaftor-tezacaftor-ivacaftor (ETI) on hyperinflation.

Methods: 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 > upper limit of normal (ULN) using the Global Lung Initiative reference values. Lung hyperinflation was defined as RV/TLC>ULN. Variables associated with hyperinflation prior to ETI initiation were identified using multivariate logistic regression analysis. Evolution of hyperinflation was examined by comparing data prior to and after 12 months on ETI.

Findings: Body plethysmography was available prior to ETI initiation in 297 awCF, of which 286 had also body plethysmography at 12 months after ETI initiation. Prior to ETI initiation, TLC, RV and RV/TLC ratio values greater than ULN were found in 14%, 69% and 76% of awCF, respectively. RV/TLC ratio inversely correlated with percent predicted forced expiratory volume in 1 s (ppFEV₁; r=-0.86). Increasing age and the number of days on intravenous antibiotics in the previous year were independently associated with RV/TLC>ULN. RV/TLC decreased after 12 months of ETI (median (IQR) absolute decrease; -5.4 (-10.3 to -0.3) %, p<0.0001; n=286) but remained above ULN in 65% of awCF, including in some with normal ppFEV₁.

Interpretation: Lung hyperinflation usually persists in awCF treated with ETI despite improvement in ppFEV₁ and lung volumes.