Prevalence of ALPHA-1 antitrypsin deficiency in patients with chronic obstructive pulmonary disease (COPD) in Manisa province

Introduction Chronic obstructive pulmonary disease (COPD) is considered a major public health issue worldwide, particularly among individuals who smoke and are exposed to environmental factors. However, genetic factors also play a role in the development of COPD in some individuals. The most significant genetic risk factor identified for COPD is mutations in the SERPINA1 gene, which lead to alpha-1 antitrypsin (AAT) deficiency. AAT is a serum antiprotease that inhibits the effects of neutrophil elastase, one of the most common serine proteases. AAT deficiency can lead to the development of respiratory diseases, including COPD. The World Health Organization recommends that all individuals diagnosed with COPD, regardless of smoking history or phenotype, be evaluated for AAT deficiency. The objective of this study is to determine the prevalence of alpha-1 antitrypsin deficiency (AATD) in COPD patients in Manisa province. By performing AATD genotyping tests, the study aims to investigate the genetic status of COPD patients and examine the prevalence of AAT deficiency, as well as its relationship with the development of COPD. The study also seeks to provide new insights into the genetic origins of COPD and contribute to regional health policies. Methodology The study was conducted between December 15, 2023, and February 15, 2024, involving patients aged 18 years and older who were diagnosed with Chronic Obstructive Pulmonary Disease (COPD) according to the current GOLD guidelines. These patients presented to the outpatient clinic and inpatient service of the Department of Pulmonology at Manisa Celal Bayar University Hafsa Sultan Hospital.. Informed consent was obtained from all participants, and demographic data such as age, gender, smoking status, comorbidities, and medication use were recorded. Physical examination and vital signs were evaluated. The number of emergency department visits, exacerbations, and mMRC scores of the patients in the past year were assessed. Blood samples were collected from the participants, and the biological samples were anonymized and coded. These samples were then sent to Progenika Biopharma, S.A. for AATD genotyping, which involved the detection of mutations associated with AAT deficiency in the SERPINA1 gene using Polymerase Chain Reaction (PCR) amplification. The obtained data were analyzed using xPONENT® software, and genotype results were determined. Statistical analyses were performed to evaluate the data and estimate the regional prevalence of AAT deficiency. Results A total of 419 COPD patients were included in the study. The mean age of the participants was 65.54 ± 10.45 years, with 91.4% being male. Regarding smoking status, 47.3% of participants were current smokers (n = 198), 48.2% were former smokers (n = 202), and 4.5% had never smoked (n = 19). Most participants lived in urban areas, and a large proportion worked as laborers or farmers. In terms of comorbidities, 60.1% had one or more additional health conditions (n = 252), while 39.9% had no comorbidities (n = 167). Mutations associated with alpha-1 antitrypsin (AAT) deficiency were identified in 1.91% of participants (n = 8). Among the 8 mutation-positive patients, 3 had the M/Z mutation, 3 had the M/P Lowell mutation, 1 had the M/I mutation, and 1 had the M/S mutation. No Pi*ZZ homozygous mutations were detected. All mutation-positive patients were male. While the overall mean age of the patients was 65.54 years, the mean age of those with AAT deficiency mutations was 61 years. Furthermore, no statistically significant differences were observed between the mutation-positive and mutation-negative groups in terms of pulmonary function, mMRC scores, or hospitalization rates. Conclusion In this study, the prevalence of alpha-1 antitrypsin deficiency among 419 COPD patients in Manisa was determined to be 1.91% (n = 8). AATD should be considered a significant factor in COPD patients, and genetic screening may play an important role in early diagnosis. Keywords: COPD, genetics, alpha-1 antitrypsin