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

ivacaftor (ETI) therapy. Methods: We measured and 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 and 3 months after initiation of ETI and 15 age-matched healthy controls. Results: Patients with PCD showed increased viscoelastic properties (G’ and G’’ P<0.001) of airway mucus and elevated levels of airway inflammation markers, including free neutrophil serine protease activity (free NE, CatG, PR3 P<0.001), IL-1β and IL-8 (P<0.001), compared to healthy controls, but lower than observed in CF patients at baseline (free proteases, IL-1β, G’ and G’’ P<0.001, IL-8 P<0.05). Significant differences in sputum viscoelastic properties, airway inflammation and the sputum proteome between PCD patients and CF patients on ETI therapy were no longer observed. Conclusions: Clinically stable patients with PCD exhibit abnormalities in sputum viscoelastic properties, inflammation markers and the proteome that are less severe than in patients with CF without ETI, but similar to observed under ETI therapy.