To the editor,
Airway mucus dehydration from loss of cystic fibrosis transmembrane
conductance regulator (CFTR) activity leads to excessive airway
muco-inflammation that drives the onset and progression of lung disease
in cystic fibrosis (CF.)1,2 Previous studies with the
highly effective modulator therapy (HEMT) ivacaftor have demonstrated
improvement in CFTR function and substantial clinical benefits. However,
clinical studies of ivacaftor therapy in people with CF (PwCF) with
eligible genotypes have not consistently demonstrated a significant
reduction in markers of airway inflammation.3,4 This
somewhat unanticipated result suggests that airway inflammation may
persist in PwCF on HEMT and could benefit from anti-inflammatory
therapies.
Recently, elexacaftor-tezacaftor-ivacaftor (ETI, Trikafta) was approved
as a HEMT available to a larger fraction of PwCF. While in vitroevidence suggests that ETI treatment may alter inflammatory pathways in
CF5, there is little information regarding the impact
of ETI on airway inflammation in treated individuals. To address this
issue, we identified PwCF who underwent bronchoscopy with
bronchoalveolar lavage (BAL) after starting ETI therapy. To avoid
confounding by indication, the study population was limited to those who
had surveillance procedures before and after starting ETI therapy. BAL
markers of inflammation and infection obtained during these procedures
were then compared.