Prevalence of SERPINA1 mutations in a bronchiectasis cohort: implications of extended screening for alpha-1...

To evaluate the prevalence of alpha-1 antitrypsin (AAT) variants through SERPINA1 genotyping in patients with non-cystic fibrosis bronchiectasis, and assess their clinical, functional and radiological characteristics. AAT deficiency is underdiagnosed, and an etiology to be considered when evaluating bronchiectasis.

A cross-sectional study was conducted at an outpatient clinic focused on bronchiectasis in a tertiary hospital. Data from patients followed between 2005 and 2023 were collected. Genotyping for AAT was performed. Demographic, clinical, pulmonary function tests, serum AAT levels and chest CT data were analyzed.

A total of 136 patients were included, predominantly female (72.1%), with a median age of 56.6 years. The prevalence of SERPINA1 gene mutations was 25.7% (n=35). Among the detected variant genotypes were Pi*MS (15.4%), Pi*MZ (5,1%), Pi*SS (1,5%), Pi*ZZ (1,5%), Pi*MI (0,7%), Pi*SZ (0,7%) and Pi*ZMMalton (0,7%). When comparing patients with and without SERPINA1 mutations, significant differences were observed in AAT serum levels, emphysema type (panlobular) and distribution (diffuse and lower-lobe predominant). No other clinical, microbiological, functional or radiological differences were found, including emphysema presence or absence. Notably, 16 (45.7%) of individuals carrying SERPINA1 mutations exhibited normal serum AAT levels.

AAT variants are not uncommon among patients with bronchiectasis. Presence of panlobular, diffuse or lower-lobe predominant emphysema should prompt AATD diagnostic consideration. However, the absence of emphysema does not exclude the diagnosis. Moreover, SERPINA1 variants may occur along with normal AAT serum levels. Clinicians should consider genotyping in patients with normal AAT levels, particularly when bronchiectasis remains unexplained.