Prevalence, type, and clinical implications of CFTR variants in bronchiectasis

Prevalence, type, and clinical implications of CFTR variants in bronchiectasis Andrea Gramegnaa,b, Lucia Allavenaa,b, Gianfranco Alicandroa,c, Elisa Canellaa,b, Mattia Nigrod,e, Chiara Premudaa,b, Margherita Orib, Martina Santambrogiob, Luigi Porcarof, Daniele Pratig, Luca Valentia,g, Stefano Alibertid,e and Francesco Blasia,b aDepartment of Pathophysiology and Transplantation, University of Milan, Milan, Italy; bRespiratory Unit and Cystic Fibrosis Center, Internal Medicine Department, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; cMother and Child Department, Cystic Fibrosis, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; dDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; eRespiratory Unit, IRCCS Humanitas Research Hospital, Milan, Italy; fMedical Genetics Laboratory, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; gDepartment of Transfusion Medicine and Biological Resource Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy ABSTRACT Background and objective: Bronchiectasis is a chronic lung condition characterised by persistent respiratory symptoms and permanent bronchial dilation. CFTR variants are commonly reported in patients with bronchiectasis with unclear clinical implications. This study aims to investigate the prevalence of CFTR variants in people with bronch- iectasis and their association with clinical characteristics. Methods: Patients were recruited from two centres in Milan, Italy and screened for CFTR variants. The prevalence of CFTR variants in people with bronchiectasis was compared to that of a control group of healthy blood donors. Sweat chloride levels, pulmonary function tests, airway microbiology, disease severity and respiratory symptoms were compared between CFTR variant carriers and non-carriers. Results: The study included 454 adults with bronchiectasis and 250 individuals in the control group. Among those with bronchiectasis, 178 individuals (39.2%) carried at least one CFTR variant, with 41 (9.0%) identified as having a CF-causing variant. This preva- lence was higher than that observed in the control group (n = 10, 4%). The odds ratio of carrying a CF-causing variant among bronchiectasis patients was 2.83 (95% CI: 1.39–5.79, p = 0.004). No significant association was found between CFTR carrier status and clinical outcomes. Conclusions: CFTR variants are frequently observed in patients with bronchiectasis, although they are not associated with increased disease severity.