Distribution of SERPINA1 gene mutations in patients with spontaneous pneumothorax: A cross-sectional study from a tertiary chest diseases clinic in Turkiye

Spontaneous pneumothorax (SP) is characterized by air accumulation between the visceral and parietal pleural layers without traumatic or iatrogenic causes. Although its etiology is not fully understood, risk factors include low body mass index, tall stature, smoking, and male sex. Alpha-1 antitrypsin deficiency (AATD), caused by SERPINA1 mutations, may contribute to secondary SP (SSP) through mechanisms such as alveolar destruction and emphysema development. This study aimed to determine the frequency and distribution of SERPINA1 gene mutations in individuals diagnosed with SP and to assess the distribution of these mutations according to pneumothorax type - primary SP (PSP) versus SSP. This cross-sectional descriptive study was conducted at the Pulmonology Clinic of Samsun Training and Research Hospital between January 1, 2022, and December 31, 2024. A total of 100 patients aged over 18 years who were diagnosed with SP and provided informed consent were included. Dried blood spot samples were collected for SERPINA1genotyping (AlphaKits® GE Healthcare Ltd, Cardiff, UK), performed at the Progenika Clinical Diagnostics Laboratory (Spain). Demographic characteristics, smoking status, pneumothorax type, and thoracic CT findings were analyzed. One hundred patients (86% male) with a mean age of 38.8 ± 17.2 years were included. Sixty-six percent were smokers, 23% were nonsmokers, and 11% were ex-smokers. Among them, 55% had SSP and 45% had PSP. The underlying cause of SSP was emphysema in 43 patients (78.1%) and bronchiectasis in 12 patients (21.9%). SERPINA1 gene mutations associated with AATD were identified in 2 patients (2%), both in the SSP group. No mutations were detected in PSP cases. The genotype detected in both cases was PI*M/I, and both patients were smokers with emphysematous changes on thoracic CT. In conclusion, Screening strategies based solely on A1AT serum levels are insufficient as some carriers may have near-normal levels. However, routine genotyping of all SP patients is not supported by our data. Large prospective studies should clarify the role of targeted genetic testing in selected patient subgroups.