An Alpha-1 Antitrypsin Deficiency Screening Study in Patients with Chronic Obstructive Pulmonary Disease, Bronchiectasis, or Asthma in Turkey

Abstract

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.

Keywords:

• alpha-1 antitrypsin deficiency
• genotype
• diagnosis
• chronic obstructive pulmonary disease

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Acknowledgments

Eugenio Rosado, PhD, and Jordi Bozzo, PhD CMPP (Grifols), are acknowledged for medical writing and editorial support in the preparation of this manuscript. The authors wish to thank all the patients who contributed to this study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas and took part in drafting, revising, or critically reviewing the article. MP: conceptualization, study design, methodology, resources, data acquisition, data curation, investigation, writing – review and editing. STO, SA, NS, MÇ, DK, AŞ, BPY, NK, SAB, and SKC: study design, methodology, resources, data acquisition, data curation, validation, investigation, writing – review and editing. AN and BD: conceptualization, formal analysis, project administration, supervision, validation, visualization, writing – review and editing. All authors critically revised, edited, agreed, and approved the final version of the article before submission, and during the revision, of the manuscript. Authors agreed in the journal to which the article is submitted, take responsibility, and are accountable for the contents of the article.

Disclosure

AN and BD are full-time employees of Grifols. DK reports honoraria paid to her institution, as speaker, from AstraZeneca, Abdi İbrahim, Novartis and Grifols, outside the submitted work. The remaining authors have no conflicts of interest to declare for this work.

Additional information

Funding

This study was funded by Grifols, manufacturer of A1AT Genotyping Test and plasma-derived alpha-1 antitrypsin medicinal products.