Clinical Characteristics and Health Care Resource Utilization Among Individuals Undergoing Alpha-1 Antitrypsin...

Area of Science:

• Pulmonology
• Genetics
• Internal Medicine

Background:

• Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder.
• AATD can lead to severe lung and liver disease.
• The clinical significance of rare AATD variants is not well understood.

Purpose of the Study:

• To investigate the clinical impact of rare Alpha-1 antitrypsin (AAT) alleles.
• To determine if testing beyond common AATD variants is clinically relevant.

Main Methods:

• Retrospective review of adult AAT phenotyping from 2016-2021.
• Patients grouped by PI*types: Normal, PI*Z-heterozygotes, PI*ZZ, PI*S-heterozygotes, and PI*Non-S/Non-Z.
• Statistical analyses included Chi Square, Kruskal-Wallis, generalized linear models (FEV1), and logistic regression (healthcare utilization).

Main Results:

• The PI*Non-S/Non-Z group showed the lowest FEV1/FVC and FEV1 percent predicted.
• This group exhibited higher neutrophil lymphocyte ratio (NLR), hospitalization rates for respiratory events, ICU utilization, and mortality.
• Common genotypes identified were Pi*MM (79.5%), PI*Z-het (8.4%), and Pi*S-het (8.4%).

Conclusions:

• AATD PI*typing identified novel allelic combinations associated with clinical disease.
• The PI*Non-S/Non-Z group experienced significant pulmonary function impairment, inflammation, and adverse outcomes.
• These findings emphasize the importance of investigating rare AATD variants for comprehensive patient care.