Obstacles to Early Diagnosis and Treatment of Alpha-1 Antitrypsin Deficiency: Current Perspectives

Abstract

This review summarizes the current research and outlooks regarding the obstacles to diagnosing and treating early alpha-1-antitrypsin deficiency (AATD). It draws on prior systematic reviews and expert surveys to discover precisely what difficulties exist in early diagnosis and treatment of AATD and elucidate potential solutions to ease these difficulties. The perceived rarity of AATD may translate to a condition poorly understood by primary care physicians, and even many respiratory physicians, which results in opportunities for diagnosis being missed, especially in mild or asymptomatic patients. There are diagnostic techniques involving biomarkers and home testing methods which could improve the rate of early diagnosis. With respect to treatment, AATD involves treating two separate pathologies, lung disease and liver disease. The only specific AATD treatment, augmentation therapy, has proven ability in treating lung disease but not liver disease. Alpha-1-antitrypsin (AAT) synthesized in the liver can form damaging polymers that also result in reduced circulating AAT levels and, whilst liver transplantation is used to effectively treat AATD, it is inappropriate in early disease. Novel therapeutic areas such as gene editing and increasing autophagy are therefore being researched as future treatments. Ultimately, diagnosis and treatment are intrinsically linked in AATD, with earlier diagnosis leading to better treatment options and thus better patient outcomes.

Keywords: chronic obstructive pulmonary disease; cirrhosis; diagnostic screening programs; emphysema.

Figure 1

Optimized detection of AATD, In the above system patients or healthcare professionals could access AATD testing, and it would also be automatically triggered by identification of emphysema or liver fibrosis on tests done for other reasons. Educated healthcare professionals would always test for AATD in relevant respiratory and hepatic presentations, and patients aware of (for example) a family history of AATD or COPD would know that they should get tested and would access it themselves either before or after a healthcare professional saw them. Referral to specialist centers would occur early after a positive laboratory test.