Clinical Characteristics and Health Care Resource Utilization Among Individuals Undergoing Alpha-1 Antitrypsin Testing in a Quaternary Health System.

Rationale: Alpha-1 antitrypsin deficiency (AATD) is a genetically inherited condition that can result in serious lung and liver disease. It is unclear whether testing for common alleles is sufficient or if testing for rare variants is helpful in identifying clinically significant disease.

Methods: A retrospective review was performed on adult patients who had AAT phenotyping from January 2016 through December 2021. We recorded clinical characteristics and then grouped patients based on PI*types: Normal, PI*Z-heterozygotes (het), PI*ZZ, PI*S-hets, and defined a PI*Non-S/Non-Z group to include other identified PI*types. Chi Square and Kruskal-Wallis tests were used for bivariate analyses, generalized linear models for modeling forced expiratory volume in 1-second (FEV1), and logistic regression modeling for healthcare utilization outcomes adjusted for race, age, and sex.

Results: 1,772 tests were ordered from January 2016 through December 2021. Testing identified 79.5% Pi*MM, 8.4% PI*Z-het, 8.4% Pi*S-het, 3.3% PI*Non-S/Non-Z, and 0.5% PI*ZZ. FEV1 to forced vital capacity (FEV1/FVC) and FEV1 percent predicted were lowest in the PI*Non-S/Non-Z group compared to the other groups. PI*Non-S/Non-Z group had higher mean neutrophil lymphocyte ratio (NLR) compared to the other groups (p=0.021), higher hospitalization for acute respiratory events (27.6%; p=0.019), ICU utilization (15.3%, p=0.011) and death (25.4%, p=0.041) compared to the other groups.

Conclusion: AATD PI*typing identified several allelic combinations not previously linked with clinical disease. Compared to other PI*type groups, PI*'Non-S/Non-Z' group had impairments in pulmonary function, elevated inflammatory markers, higher health care utilization, and death. Our results underpin the need to explore relationships between rare allelic combinations and clinical outcomes.