EC Pulmonology and Respiratory Medicine

Alpha-1 antitrypsin deficiency (AATD) is a hereditary condition that produces two distinct clinical problems depending on genotype and the organ affected. In the lungs, low-circulating alpha-1 antitrypsin (AAT) produces unchecked enzyme activity that destroys elastic lung tissue and sustains inflammation, leading to chronic obstructive pulmonary disease (COPD), emphysema and bronchiectasis [1]. In the liver, misfolded AAT accumulates inside liver cells and can cause neonatal hepatitis, cirrhosis in children and adults, and hepatocellular carcinoma [2].

Genetic variants determine risk. People with two severely deficient copies, such as the PiZZ genotype or null variants, have the lowest blood levels of AAT and the highest risk of both liver and lung disease. Heterozygous states, such as PiMZ, are carrier or intermediate states with variable risk that is strongly influenced by smoking, metabolic liver disease and other exposures [1].

Clinical presentation is often non-specific and overlaps with common respiratory and hepatic diagnoses. As a result, many patients experience prolonged and fragmented diagnostic pathways. Diagnostic delay typically exceeds five years, and the average age at diagnosis is around 45 years [3].

After diagnosis, management focuses on respiratory risk modification and liver surveillance. For eligible patients with severe deficiency and established emphysema, intravenous augmentation therapy is the only disease-modifying, commercially available option, but it carries practical burdens, and its availability varies by country. Clinical trial participation offers alternative avenues but is constrained by genotype-based eligibility, travel burdens and inconsistent access pathways.

A patient-centred understanding of these pathways can, therefore, guide more equitable testing, care delivery and research design. This article provides a clearer understanding of the AATD patient journey and examines how the regional differences in testing, clinical infrastructure and reimbursement can shape patient outcomes.

 Keywords: Alpha-1 Antitrypsin Deficiency; Alpha-1 Antitrypsin; Chronic Obstructive Pulmonary Disease; Rare Diseases; Genetic Disorders; Pulmonology; Hepatology; Augmentation Therapy; Genotypes; Clinical Trials

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