Changes in Sputum Viscoelastic Properties and Airway Inflammation in Primary Ciliary Dyskinesia are Comparable to Cystic Fibrosis on Elexacaftor/Tezacaftor/Ivacaftor Therapy.

BACKGROUND Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are muco-obstructive lung diseases that are caused by distinct genetically determined defects in mucociliary clearance, however, knowledge on the relative severity of airway mucus dysfunction and chronic inflammation remains limited. The aim of this study was therefore to compare sputum viscoelastic properties, inflammation markers and the proteome between patients with PCD and patients with CF before and under elexacaftor/tezacaftor/ivacaftor (ETI) therapy. METHODS We compared sputum rheology, inflammation markers and the proteome in 42 clinically stable adolescent and adult patients with PCD, 40 patients with CF with at least one F508del allele before (baseline) and 3 months after initiation of ETI and 15 age-matched healthy controls. RESULTS The elastic modulus (G') and viscous modulus (G″) of PCD sputum was increased compared to healthy controls (p<0.001), lower than in CF at baseline (p<0.001) and similar to CF on ETI. Inflammation markers in PCD sputum including neutrophil elastase (NE), free DNA, myeloperoxidase (MPO), interleukin (IL)-1β and IL-8 were also increased compared to healthy controls (all p<0.001), lower than in CF at baseline (p<0.05 to p<0.001) and comparable to CF on ETI. Similar, changes in the sputum proteome were less pronounced in PCD compared to CF at baseline, but comparable between PCD and CF on ETI. CONCLUSIONS Clinically stable patients with PCD show changes in sputum viscoelastic properties, inflammation markers and the proteome that are less severe than in patients with CF at baseline, but comparable to CF patients on ETI therapy.