PMID- 38046982 OWN - NLM STAT- MEDLINE DCOM- 20231205 LR - 20231217 IS - 1178-2005 (Electronic) IS - 1176-9106 (Print) IS - 1176-9106 (Linking) VI - 18 DP - 2023 TI - An Alpha-1 Antitrypsin Deficiency Screening Study in Patients with Chronic Obstructive Pulmonary Disease, Bronchiectasis, or Asthma in Turkey. PG - 2785-2794 LID - 10.2147/COPD.S425835 [doi] AB - PURPOSE: Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition characterized by decreased serum alpha-1 antitrypsin (AAT) levels. We aim to identify AATD in patients with chronic obstructive pulmonary disease (COPD), bronchiectasis, or asthma and to report the frequency of AAT variants in Turkey. PATIENTS AND METHODS: This non-interventional, multicenter, prospective study was conducted between October 2021 and June 2022. Adult patients with COPD, bronchiectasis, asthma, liver symptoms, or family members with AATD were included. Demographic and clinical characteristics, pulmonary diagnosis, respiratory symptoms, and AAT serum levels were assessed. Whole blood samples were collected as dried blood spots, and the most common AATD mutations were simultaneously tested by allele-specific genotyping. RESULTS: A total of 1088 patients, mainly diagnosed with COPD (92.7%) and shortness of breath (78.7%), were assessed. Fifty-one (5%) were found to have AATD mutations. Fifteen (29.4%) patients had Pi*S or Pi*Z mutations, whereas 36 (70.6%) patients carried rare alleles Pi*M malton (n=18, 35.3% of mutations), Pi*I (n=8, 16%), Pi*P lowell (n=7, 14%), Pi*M heerlen (n=2, 4%), and Pi*S iiyama (n=1, 2%). The most common heterozygous combinations were Pi*M/Z (n=12, 24%), and Pi*M/M malton (n=11, 22%). Ten patients with severe AATD due to two deficiency alleles were identified, two with the Pi*Z/Z genotype, four with the genotype Pi*M malton/M malton, three with Pi*Z/M malton, and one with Pi*Z/M heerlen. CONCLUSION: Our results identified AATD mutations as a genetic-based contributor to lung disease in patients with COPD or bronchiectasis and assessed their frequency in a population of Turkish patients. CI - (c) 2023 Tural Onur et al. FAU - Tural Onur, Seda AU - Tural Onur S AUID- ORCID: 0000-0002-0657-0392 AD - Department of Pulmonology, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, University of Health Sciences, Istanbul, Turkiye. FAU - Natoli, Antonino AU - Natoli A AD - Scientific and Medical Affairs, Scientific Innovation Office, Grifols, Frankfurt, Deutschland. FAU - Dreger, Bettina AU - Dreger B AD - Scientific and Medical Affairs, Scientific Innovation Office, Grifols, Frankfurt, Deutschland. FAU - Arinc, Sibel AU - Arinc S AD - Clinic of Chest Diseases, University of Health Sciences Turkey, S.B.U. Sureyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkiye. FAU - Sarioglu, Nurhan AU - Sarioglu N AD - Department of Pulmonology, Balikesir University Faculty of Medicine, Pulmonology Clinic, Balikesir, Turkiye. FAU - Cortuk, Mustafa AU - Cortuk M AD - Department of Pulmonology, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, University of Health Sciences, Istanbul, Turkiye. FAU - Karadogan, Dilek AU - Karadogan D AUID- ORCID: 0000-0001-5321-3964 AD - Department of Chest Diseases, Recep Tayyip Erdogan University, School of Medicine, Rize, Turkiye. FAU - Senyigit, Abdurrahman AU - Senyigit A AD - Department of Chest Diseases, Dicle University Faculty of Medicine Hospital, Diyarbakir, Turkiye. FAU - Yildiz, Birsen Pinar AU - Yildiz BP AUID- ORCID: 0000-0002-6650-1495 AD - Department of Pulmonology, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, University of Health Sciences, Istanbul, Turkiye. FAU - Kokturk, Nurdan AU - Kokturk N AUID- ORCID: 0000-0002-2889-7265 AD - Department of Pulmonary Medicine, Gazi University, School of Medicine, Ankara, Turkiye. FAU - Argun Baris, Serap AU - Argun Baris S AD - Department of Pulmonary Diseases, Faculty of Medicine, Kocaeli University, Kocaeli, Turkiye. FAU - Kodalak Cengiz, Sumeyye AU - Kodalak Cengiz S AUID- ORCID: 0000-0002-5174-6457 AD - Department of Pulmonary Medicine, Gazi University, School of Medicine, Ankara, Turkiye. FAU - Polatli, Mehmet AU - Polatli M AUID- ORCID: 0000-0001-7917-4297 AD - Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Turkiye. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20231128 PL - New Zealand TA - Int J Chron Obstruct Pulmon Dis JT - International journal of chronic obstructive pulmonary disease JID - 101273481 RN - 0 (alpha 1-Antitrypsin) SB - IM MH - Adult MH - Humans MH - *Pulmonary Disease, Chronic Obstructive/diagnosis/genetics/epidemiology MH - Prospective Studies MH - Turkey/epidemiology MH - *alpha 1-Antitrypsin Deficiency/complications/diagnosis/epidemiology MH - alpha 1-Antitrypsin/genetics MH - *Bronchiectasis/diagnosis/epidemiology/genetics MH - *Asthma PMC - PMC10693271 OTO - NOTNLM OT - alpha-1 antitrypsin deficiency OT - chronic obstructive pulmonary disease OT - diagnosis OT - genotype COIS- AN and BD are full-time employees of Grifols. DK reports honoraria paid to her institution, as speaker, from AstraZeneca, Abdi Ibrahim, Novartis and Grifols, outside the submitted work. The remaining authors have no conflicts of interest to declare for this work. EDAT- 2023/12/04 06:42 MHDA- 2023/12/05 17:44 PMCR- 2023/11/28 CRDT- 2023/12/04 05:15 PHST- 2023/06/14 00:00 [received] PHST- 2023/10/27 00:00 [accepted] PHST- 2023/12/05 17:44 [medline] PHST- 2023/12/04 06:42 [pubmed] PHST- 2023/12/04 05:15 [entrez] PHST- 2023/11/28 00:00 [pmc-release] AID - 425835 [pii] AID - 10.2147/COPD.S425835 [doi] PST - epublish SO - Int J Chron Obstruct Pulmon Dis. 2023 Nov 28;18:2785-2794. doi: 10.2147/COPD.S425835. eCollection 2023.