Detecting Alpha-1 Antitrypsin Deficiency: Current State, Impediments, Opportunities, and Future Directions

Alpha-1 antitrypsin deficiency (AATD) is an underrecognized condition with only a small minority of affected individuals diagnosed, long delays between initial symptoms and diagnosis, and evidence that affected individuals may see many physicians with suggestive symptoms before an initial diagnosis is made. In the context that failure to detect AATD confers harm and that specific therapy is currently available, there is a clear need for enhanced detection. Impediments to enhanced detection include inadequate knowledge about AATD by physicians caring for at-risk patients, inattention to guidelines that endorse testing, a sense of "therapeutic nihilism" among some physicians (i.e., the mistaken impression that, because specific therapy is unavailable, there is no imperative to diagnose), and concerns about the cost of testing. Various measures have been undertaken to address these impediments and to enhance detection, including educational programs, targeted detection programs (some with free and home-based confidential testing), and population-based and newborn screening pilot programs. The latter is not yet nationally endorsed for large-scale screening. Novel approaches are deploying features of the electronic medical record and of artificial intelligence to prompt testing in at-risk individuals. To the extent that underrecognition of AATD persists with stubbornly long, multiyear diagnostic delay intervals, none of the detection strategies deployed to date have been adequate. The path forward regards continued innovation with targeted detection approaches while efforts continue to assess the impact of population-based screening, hopefully toward ultimate endorsement on a broad national scale.