Epidemiology of Alpha-1 Antitrypsin Deficiency in the Veterans Health Administration.

Rationale: Alpha-1 antitrypsin (AAT) deficiency (AATD) is a known but underrecognized genetic cause of chronic obstructive pulmonary disease (COPD) and liver disease. Little is known about the epidemiology and burden of AATD among U.S. Veterans.

Objectives: To examine the Veteran characteristics and epidemiology of AATD and severe AATD throughout the Veterans Health Administration (VHA).

Methods: Data was obtained from the electronic health record to describe demographic, clinical, testing outcomes, and geographic data for Veterans between January 1, 2010 through December 31, 2019. Multivariable logistic regression analysis was performed to evaluate Veteran characteristics associated with AATD. We defined intermediate AATD as a serum AAT level >57 and <100 mg/dL or any allelic combination other than PI*MM, PI*MS, PI*SZ, or PI*ZZ. Severe AATD was defined by either PI*ZZ and PI*SZ genotypes as well as any combination with a serum level ≤57 mg/dL (≤11 µmol/L).

Results: Among 12 million Veterans enrolled during the study period, 175,508 were tested for AATD, and 8,832 were diagnosed with intermediate AATD and 3,088 were diagnosed with severe AATD. The positivity rate of AATD varied year-to-year ranging from 62 - 76 cases per 1,000 persons tested. AATD occurred in 57 cases per 1,000 persons tested with COPD, and there were 66 cases of AATD per 1,000 persons tested with liver disease; however, testing rates of COPD (4.04%) or liver disease (17.91%) were low. There was a heterogenous distribution of AATD throughout the United States. Factors associated with detection and diagnosis of AATD included younger age, White race, and no history of tobacco use.

Conclusions: This study represents a national analysis of AATD in the Veterans Health Administration. Although the annual positivity rates of AATD among those tested varied over the decade, it confirmed AATD is prevalent in Veterans. However, the number of eligible Veterans tested is low, which highlights the need for increased awareness of this condition.