α1-Antitrypsin Deficiency Testing Barely Reached a Small Fraction of Patients With COPD and Asthma
In a national Veterans Health Administration cohort of more than 2.3 million adults with chronic obstructive pulmonary disease or asthma, α1-antitrypsin deficiency testing remained strikingly uncommon. Only 138,278 patients, or 5.8%, underwent testing during the study period. The low rate is difficult to reconcile with longstanding guidance supporting broad evaluation in obstructive lung disease, especially when the diagnosis can change management, family counseling, and the tempo of lung injury.
The cohort was large and clinically diverse: mean age was 64.2 years, 7.5% were female, and the racial and ethnic makeup included 15.3% Black or African American patients, 0.7% American Indian or Alaska Native patients, 0.7% Asian patients, 0.9% Native Hawaiian or Pacific Islander patients, and 82.4% White patients. Even inside a health system with integrated records, the screening gap remained substantial. A disease that is actionable in principle was being missed in practice.
Comorbidities Drove Testing More Than Pulmonary Diagnosis Alone
The strongest signals for testing came from conditions that may prompt clinicians to search for a unifying explanation. Cirrhosis was associated with the highest odds of testing, with an adjusted odds ratio of 6.40, and bronchiectasis also increased testing substantially, with an adjusted odds ratio of 3.73. Those two comorbidities fit the biology of the disorder: AATD can injure both liver and lung, so clinicians confronted with hepatic disease or destructive airway changes may be more likely to order the test.
Older age moved in the opposite direction. So did active tobacco use. Smoking is common in patients with COPD, and it can obscure the possibility of an inherited contributor by making the lung disease look entirely exposure-driven. In busy respiratory care, that diagnostic shortcut has consequences. Patients whose symptoms appear easily explained may never get the one test that would clarify whether a hereditary protease-antiprotease imbalance is part of the problem.
Longer drive time to specialty care also tracked with lower testing. Compared with patients who lived within 30 minutes of specialty care, those with drive times greater than 90 minutes had lower odds of testing, with an adjusted odds ratio of 0.63. The association was graded rather than abrupt, which suggests a practical barrier rather than random noise. Distance can slow referral, reduce specialist contact, and delay the cascade of confirmatory workup that follows a suspicious pulmonary history.
Rural-urban residence and the Social Vulnerability Index did not show meaningful differences across categories in the fully adjusted models. The access signal in this dataset was driven more clearly by travel time than by those broader geographic or vulnerability measures.
Treatment Followed the Same Pattern, Only at an Even Lower Level
Among 8,564 patients with an AATD diagnosis, only 320, or 3.7%, received augmentation therapy. The treatment gap was even more sobering than the testing gap because it reflects not just diagnosis, but movement from diagnosis to disease-specific therapy. Once the condition was recognized, many patients still did not reach augmentation treatment.
The same clinical and structural patterns appeared again. Augmentation therapy was less common among patients from minoritized racial and ethnic groups, among those actively using tobacco, and among those with longer drive times to specialty care. It was more common in patients with cirrhosis and bronchiectasis. The repetition matters because it points to a care pathway shaped by who gets seen, who gets tested, and who then advances to specialty treatment.
This is not a subtle failure. It is a deep underuse of a targeted therapy in a disorder where diagnosis itself can alter long-term pulmonary planning.
Why These Gaps Persist in a Disease With a Clear Genetic Signal
The pathophysiology of α1-antitrypsin deficiency makes the screening problem especially important. The disorder is inherited, and the resulting protein deficiency can accelerate emphysema and contribute to liver injury. In patients with COPD or asthma, the overlap with common disease phenotypes can make the inherited diagnosis easy to overlook, particularly when tobacco exposure is present. A smoker with chronic obstruction may be treated as a standard COPD case for years, even when the disease biology is not standard at all.
Comorbid cirrhosis and bronchiectasis functioned in this study as clinical clues. They likely triggered more testing because they suggest a broader systemic process, not just airway disease. Yet relying on such clues means the system is waiting for advanced or atypical disease before acting. That approach misses the point of broad testing recommendations, which are meant to identify patients before irreversible decline accumulates.
The access gradient tied to drive time is equally important. Specialty-based conditions often depend on referral momentum, and momentum weakens as distance increases. Patients farther from specialty hubs may need more steps to reach testing, interpretation, and treatment initiation. In a disease where earlier recognition can affect long-term lung preservation, those steps matter.
One sentence captures the central problem: the diagnostic and treatment pathways were both sparse.
A System-Level Miss, Not an Isolated Specialty Problem
These findings argue for system-level reform rather than isolated educational reminders alone. Electronic health record prompts, reflex testing pathways in COPD and asthma, and more deliberate attention to patients with chronic obstruction and liver or bronchiectatic disease could reduce missed diagnoses. The data also suggest that clinicians should be wary of the false reassurance that smoking history can provide. Tobacco exposure does not exclude inherited susceptibility; in some patients, it may coexist with it.
The cohort was drawn from a large national health system and used multivariable models that adjusted sequentially for demographics, comorbidities, tobacco use, rural-urban residence, Social Vulnerability Index, and drive time to specialty care. Even after those adjustments, the pattern held. Testing and treatment were profoundly low, and the gaps were not distributed evenly across the patient population.
The study leaves one practical question hanging over routine pulmonary care: how many patients with COPD or asthma are still being managed without ever being evaluated for a diagnosis that would change both prognosis and family risk assessment?