The changing face of inflammation following CFTR modulation: identifying new phenotypes of innate immunity

Abstract

Triple combination therapy for people with cystic fibrosis (pwCF) restores the activity of defective cystic fibrosis transmembrane conductance regulator (CFTR) proteins. For those fortunate to receive this therapy, it has fundamentally changed the nature of the disease.1 CFTR modulators markedly improve clinical outcomes and symptoms, reversing or alleviating pathologies such as mucous plugging and overly acidic small intestine pH. However, other manifestations of disease persist (established bronchiectasis, chronic airway infections with organisms such as Pseudomonas aeruginosa ). Optimal management of pwCF depends on continued accumulation of knowledge regarding how CFTR therapy changes CF disease. 2 When the first CFTR modulator (ivacaftor) was introduced, several studies characterised how CF pathology changed following enhancement of CFTR activity3–5; however, since only a small fraction of pwCF were eligible for ivacaftor, studies were limited. The approval of elexacaftor-tezacaftor-ivacaftor (ETI) for pwCF with at least one F508del mutation meant that >90% of pwCF would be eligible for modulator therapy. Many studies were organised around the globe to capture specimens and measurements from pwCF before and after initiation of ETI. Much attention has been paid to ETI’s effects on clinical parameters and pulmonary inflammation and infection, but fewer studies have focused on the effects of ETI on systemic inflammation. In this edition of Thorax , Maher and colleagues6 describe changes in systemic inflammatory cells and …