Chronic obstructive pulmonary disease (COPD) remains highly prevalent among veterans, but the contribution of alpha-1 antitrypsin deficiency (AAT deficiency or AATD) to this patient population remains unclear and likely underdiagnosed, according to data from more than 2 million veterans presented at the American College of Chest Physicians (CHEST) 2025 Annual Meeting.

AATD is a genetic condition increases the risk for both lung disease and liver disease, according to the National Library of Medicine. AAT is produced by the liver but helps the lungs defend against inflammation and outside irritants such as smoke or other environmental exposures.

“COPD prevalence is especially high in the veteran population compared to the general population, making it essential to understand the rate of alpha-1 antitrypsin deficiency diagnosis and identify missed opportunities for screening in this group,” said lead author Arianne K. Baldomero, MD, pulmonologist and assistant professor of medicine at the University of Minnesota, Minneapolis, in an interview.

Baldomero and colleagues reviewed national data from Veterans’ Administration electronic health records, from 2004 to 2024. The study population included 2,384,913 veterans with COPD and/or asthma, based on two or more International Classification of Diseases codes and/or spirometry (forced expiratory volume in 1 second/forced vital capacity of < 0.7).

Overall, AATD was diagnosed in 8564 individuals (0.36% of the study population). Those diagnosed were significantly younger than the population overall, with a mean age of 57 years vs 64 years. A combination of COPD and asthma was more common among patients with AATD than those without AATD (20.8% vs 10.7%), while the proportion with either COPD or asthma alone was higher among patients without AATD (73.5% vs 64.4% and 15.8% vs 14.8%, respectively).

Individuals with AATD also were more likely than those without AATD to have cirrhosis (21.59% vs 5.38%) but less likely to have coronary artery disease (35.1% vs 41.4%). The AATD group also had fewer active smokers and more never smokers than the group without AATD (24.39% vs 30.4% and 30.34% vs 26.4%, respectively).

Although cirrhosis, hepatocellular carcinoma, and bronchiectasis were significantly associated with higher odds of an AATD diagnosis, active smoking compared to never smoking was associated with lower odds of AATD diagnosis.

“The extremely low rate of AATD diagnosis was striking, but consistent with known testing gaps in clinical practice, highlighting systemic under-screening even within an integrated healthcare system,” Baldomero told Medscape Medical News. “Clinicians should maintain a high index of suspicion for AATD in veterans with COPD, liver disease, or bronchiectasis and ensure guideline-recommended testing is performed regardless of smoking status or geography,” she said.

More individuals with AATD than those without reported possible exposure to toxic or hazardous substances during military service ( 33.8% vs 23.6%). Additionally, longer drive times to secondary care (> 90 minutes vs ≤ 30 minutes) were associated with lower odds of an AATD diagnosis.

“Future work should explore barriers to AATD testing, evaluate implementation strategies to increase screening adherence, and assess outcomes associated with earlier diagnosis and treatment among veterans,” Baldomero added.

Put AATD On the Radar in Clinical Practice

COPD is commonly seen in smokers, but many physicians are not familiar with the guidelines that all individuals with COPD, emphysema, and unexplained liver disease should be tested for alpha-1 AT deficiency,” said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

“Physicians assume that patients are unlikely to have alpha-1 deficiency unless they are presenting very young,” said Chatila, who was not involved in the study. Therefore, many physicians don’t routinely test for it, which likely contributed to the underdiagnosis seen in the current study, he said.

Hazardous environment exposure, bronchiectasis, and liver disease are well-known to be associated with the deficiency, Chatila noted.

The fact that smoking was protective was somewhat surprising, but can likely be explained by the fact that smokers were less likely to be tested, and therefore undiagnosed, Chatila said. “The fact that patients with alpha-1 were younger indicates that they got sicker at a younger age,” he noted. In addition, these patients may no longer be active smokers because of their respiratory problems, he added. The association between longer drive time and lower odds of AATD diagnoses also was not surprising, as less access to specialty care means fewer diagnoses, he said.

In practice, the results highlight the need for clinicians to know the guidelines and screen patients who are at risk, even those who are not typical patients with COPD, or many patients with the deficiency will remain undiagnosed, Chatila said.

“More research is needed to clarify the impact of underdiagnosis of these patients and provide interventions to mitigate the harm that is caused by delays in the proper diagnosis,” he added.

The study received no outside funding. Baldomero and Chatila disclosed having no financial conflicts of interest.