alpha1-Antitrypsin augmentation therapy for PI*MZ heterozygotes: a cautionary note

Area of Science:

• Pulmonology
• Genetics
• Pharmacology

Background:

• Intravenous (IV) augmentation therapy with plasma-derived alpha1-antitrypsin (AAT) is the established treatment for severe AAT deficiency-related pulmonary disease.
• Physicians are increasingly prescribing this therapy for individuals with a single abnormal AAT gene, specifically the PI*MZ genotype.

Purpose of the Study:

• To address concerns regarding the prescription of AAT augmentation therapy for individuals with the PI*MZ genotype.
• To evaluate the evidence supporting the efficacy of AAT augmentation therapy in this patient population.

Main Methods:

• Review of current treatment standards for AAT deficiency.
• Analysis of the evidence base for AAT augmentation therapy in heterozygote individuals (PI*MZ genotype).
• Discussion of alternative and primary therapeutic interventions for PI*MZ individuals.

Main Results:

• There is a lack of evidence demonstrating the effectiveness of AAT augmentation therapy in patients with the PI*MZ genotype.
• The primary interventions for PI*MZ individuals remain smoking cessation and mitigating other lung disease risk factors.

Conclusions:

• Clinicians should refrain from prescribing AAT augmentation therapy to individuals with the PI*MZ genotype.
• Focus should remain on established risk factor modification for managing lung disease in this population.