The spectrum of CFTR dysfunction in patients with nontuberculous mycobacterial pulmonary disease

Dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein is a potential but undercharacterized risk factor for nontuberculous mycobacterial pulmonary disease (NTM-PD). We reviewed health records to identify clinical features of NTM-PD patients who exhibited CFTR dysfunction, defined by sweat chloride concentration (SCC) ≥30 mmol/L. CFTR genotyping was performed in those with elevated SCC. Among 40 patients, 77.5 % were female, and the median age was 70 years (IQR 54.3-73). M. avium complex was most frequently isolated (87.5 %). Median SCC was 31 mmol/L (IQR 22.3-51.8), with 23 patients (57.5 %) showing elevated levels. Patients with elevated SCC were often female, with low BMI, history of tobacco use, bronchiectasis, and small airway disease, and were likely to initiate antimycobacterial therapy. Clinically relevant CFTR variants were found in 5 (29 %) patients. These findings suggest CFTR dysfunction may contribute to NTM-PD pathogenesis. Comprehensive molecular and functional studies are warranted to elucidate underlying mechanisms.