Intravenous alpha-1 antitrypsin (IV-AAT) increases survival among patients with severe alpha-1 antitrypsin deficiency (AATD), according to a study published in the American Journal of Respiratory and Critical Care Medicine. 

IV-AAT as augmentation therapy has been found to increase AAT levels in the body, leading to improved outcomes. However, some studies have been unable to validate these findings, partly because AATD is such a rare genetic disease. 

Scientists have proposed various metrics to evaluate the efficacy of IV-AAT, including lung function tests such as forced expiratory volume in 1 second. However, the only test that has demonstrated the efficacy of IV-AAT is lung densitometry measured via computed tomography (CT). The authors of the study sought to evaluate the efficacy of IV-AAT by studying a large cohort of individuals with severe AATD. 

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The research team analyzed lung function decline and deaths among patients with severe AATD in 3 countries: Ireland, Switzerland, and Austria. All 3 countries share similar socialized healthcare systems. The research team accessed AATD registries in these 3 countries and identified patients with severe AATD, defined as having a genotype of any combination of Z, functional Z-like mutations, or null (Q0) mutations. 

Read more about AATD etiology 

A total of 615 individuals with severe AATD were included in the study. Among them, 250 received IV-AAT, with 213 still active. The research team found a significant survival benefit in patients actively receiving IV-AAT compared with those who have never received this form of therapy. IV-AAT was associated with a higher survival probability, whereas increased age and poor lung index status had the opposite effect. 

The researchers also determined that forced expiratory volume in 1 second is not useful in assessing the efficacy of IV-AAT because patients tend to be diagnosed late, meaning that lung function decline has plateaued and treatment is unlikely to show a marked improvement in this parameter. 

“Detecting people with severe AATD as early as possible and initiating therapy before the establishment of chronic obstructive pulmonary disease should be the goal to improve survival,” the authors concluded. 


Fraughen DD, Ghosh AJ, Hobbs BD, et al. Augmentation therapy for severe alpha-1 antitrypsin deficiency improves survival and is decoupled from spirometric decline — a multi-national registry analysis. Am J Respir Crit Care Med. Published online August 25, 2023. doi:10.1164/rccm.202305-0863OC