Perspectives on current practices and future research directions in alpha-1 antitrypsin deficiency

Alpha-1 antitrypsin deficiency (AATD) is a complex genetic condition that predisposes individuals to develop respiratory diseases, including chronic obstructive pulmonary disease (COPD). The clinical presentation of AATD varies between patients and disease progression is difficult to predict, presenting challenges for diagnosis and disease management. Additionally, a lack of AATD awareness among physicians has contributed to underdiagnosis and low testing rates. Consequently, there is a need to improve diagnostic algorithms to identify underlying AATD in respiratory patients. Strategies to increase physician awareness and promote systematic testing of patients with COPD may also improve testing rates. Additionally, implementing offsite sample testing may ease the testing process and alleviate the need for patients to travel to genetic testing facilities. Use of patient registries has enabled many advances in our understanding of AATD and continues to be an important asset for research. Advances in genetic sequencing technologies and data analysis capabilities, including artificial intelligence, are likely to improve our understanding of AATD and the variance observed between patients. Increasingly, the significance of different variants will be a topic for future research. Specific treatment for AATD is available and real-world evidence demonstrates a survival benefit of receiving intravenous alpha-1 antitrypsin (AAT) therapy; however, its precise mechanisms of clinical efficacy remain incompletely understood. This review summarises key advances in the genetics, clinical presentation, diagnosis, and treatment of AATD, while highlighting the benefits of AAT therapy and remaining research gaps. Despite the availability of specific treatment, assessing which patients to treat can be challenging, as many factors need to be considered. Individualisation of treatment decisions is crucial, supported by close monitoring and early initiation of treatment where appropriate. Improving access to AAT therapy, including self-administration options, may further enhance patient care. Emerging AATD therapies offer hope for disease modification, improved outcomes, and expanded treatment options for patients.