Researchers have found that alpha-1 antitrypsin (AAT) augmentation therapy in patients with alpha-1 antitrypsin deficiency (AATD) does not significantly alter long-term decline in forced expiratory volume in 1 second (FEV1), according to a study published in ERJ Open Research.

AATD predisposes a patient to develop lung disease, especially emphysema, that is marked by a sharp decline in FEV1. FEV1 is a valuable prognostic indicator, as a sharp, continuous decline corresponds with higher mortality. 

AAT augmentation therapy was introduced in the United States nearly 3 decades ago. It was predicated on the assumption that maintaining a threshold level of AAT would be protective against further progression of lung disease. It remains a recommended course of treatment by the American Thoracic Society and European Respiratory Society for AATD patients with low serum AAT levels. However, studies have contradictory findings on its efficacy in preventing FEV1 decline. 

Continue Reading

Read more about AATD etiology

Researchers hence set out to determine whether AAT augmentation therapy is effective in maintaining FEV1 levels. They studied data obtained from the Alpha-1 International Registry (AIR) database from 5 countries that had the most complete datasets: The Netherlands, Germany, Italy, the United Kingdom, and Spain.

Researchers chose to study patients who had the ZZ-AATD phenotype, the most common phenotype that can affect the lungs in drastically different ways. Researchers studied the postbronchodilator FEV1 values and compared the results of the group that received AAT augmentation therapy with the group that did not. 

There were 374 patients included in this study; 128 were treated with AAT augmentation therapy and 246 were not. The mean follow-up times were 8.59 years for the treated group and 8.60 years for the untreated group.

Through the use of mixed-effects model analysis, researchers found that the treated group experienced a mean FEV1 decline of −1.016% predicted per year, while the untreated group experienced a mean FEV1 decline of −0.931% predicted per year. Furthermore, the likelihood ratio test demonstrated no difference between the groups (P =.71). 


Schouten IGM, Kasteleyn MJ, Tsonaka R, et al. Long-term effect of α1-antitrypsin augmentation therapy on the decline of FEV1 in deficient patients: an analysis of the AIR database. ERJ Open Res. 2021;7(3):00194-2021.  doi:10.1183/23120541.00194-2021