<p>Obstacles to Early Diagnosis and Treatment of Alpha-1 Antitrypsin Deficiency: Current Perspectives</p>

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.

Structural characterization and conformational dynamics of alpha-1 antitrypsin pathogenic variants causing alpha-1-antitrypsin deficiency

“…A proportion of A1ATD patients develop liver cirrhosis, which may be caused by aggregates of alpha-1-antitrypsin proteins ( Köhnlein and Welte, 2008 ). While it is often undiagnosed ( Quinn et al, 2020 ), it causes emphysema, which can be exacerbated by tobacco smoke ( Tejwani and Stoller, 2021 ). It affects 1 in 2,500 people of European ancestry ( Greulich et al, 2017 ).…”

The impact of diagnostic delay on survival in alpha-1-antitrypsin deficiency: results from the Austrian Alpha-1 Lung Registry

“…However, recent evidence suggests that even many AATD patients with symptomatic lung disease are not correctly identified: Only 6% of the Pi*ZZ carriers in a large biobank were diagnosed although they had an eightfold increased risk of COPD, a sevenfold increased risk of emphysema and 2.4-fold increased risk of mortality, compared to wild-type (Pi*MM) [32]. One reason might be the low awareness of physicians and consequently low adherence to the guidelines [30,33]. Except earlier onset in some cases, the clinical presentation of COPD patients with or without AATD is similar which might be another obstacle for timely diagnosis [31,33].…”

“…One reason might be the low awareness of physicians and consequently low adherence to the guidelines [30,33]. Except earlier onset in some cases, the clinical presentation of COPD patients with or without AATD is similar which might be another obstacle for timely diagnosis [31,33].…”

Disease burden associated with alpha-1 antitrypsin deficiency: systematic and structured literature reviews

“…Recent reviews of AATD have focused on the epidemiology and distribution of genetic variants, disease screening, diagnosis and care, as well as AAT therapy [2,3,[15][16][17][18][19]. In contrast, comprehensive reviews that assess the burden of AATD on patients, caregivers and healthcare systems are lacking.…”