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Progression and Augmentation Therapy in PiSZ and PiZZ Alpha-1 Antitrypsin Deficiency: A Longitudinal Functional and
Soha Esmaili1,2, Juan Luis Rodríguez Hermosa1,3,4, Gianna Vargas Centanaro1,3,4
1Pulmonology Department, Hospital Clínico San Carlos, 28040 Madrid, Spain.
Biomolecules
|April 30, 2025
Summary
Alpha-1 antitrypsin deficiency (AATD) patients with the PiZZ genotype show faster disease progression than PiSZ. Augmentation therapy slows decline in both, especially when started early, highlighting personalized AATD treatment needs.
Area of Science:
- Pulmonology
- Genetics
- Pharmacology
Background:
- Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder linked to chronic obstructive pulmonary disease (COPD).
- The PiZZ genotype is well-studied, but the PiSZ genotype's disease progression is less understood.
- This study investigates genotype-specific AATD progression and augmentation therapy effects.
Purpose of the Study:
- To compare the clinical and structural disease progression between PiSZ and PiZZ genotypes of AATD.
- To evaluate the impact of augmentation therapy on disease trajectory in AATD patients.
- To identify factors influencing disease acceleration in AATD.
Main Methods:
- A prospective observational cohort study included 74 AATD patients (41 PiSZ, 33 PiZZ), stratified by augmentation therapy.
- Lung function (FEV1, DLCO, KCO) and lung density (PD-15, HU-950) were assessed over two years.
- Mixed-effects models and regression analyses were used to determine genotype-specific progression and treatment effects.
Main Results:
- PiZZ individuals had significantly faster declines in lung function and density than PiSZ individuals.
- Augmentation therapy significantly reduced PD-15 decline in both genotypes, with greater benefits in PiZZ and early-diagnosed patients.
- Smoking and frequent exacerbations were independent risk factors for accelerated disease progression.
Conclusions:
- PiZZ genotype AATD follows a more aggressive course than PiSZ without treatment.
- Augmentation therapy is effective in slowing disease progression for both genotypes, particularly when initiated early.
- Genotype-specific monitoring and personalized treatment strategies are crucial for optimizing AATD outcomes.
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