Table 1 Summary points for/against the working hypothesis regarding the use of AAT augmentation therapy in individuals with the PI*MZ genotype

AAT deficiency in PI*MZ individuals represents an abnormal state that leads to a compromised response to inflammation and predisposition to a disease state; thus, in cases of poorly-controlled disease, correcting AAT deficiency may be beneficial

Augmentation therapy is not a cure, and is a life-long commitment; in PI*MZ individuals, there is little basis for potential clinical benefit to outweigh the burden of treatment

Additional genetic factors, such as ELANE expression, may contribute to a phenotype of PI*MZ individuals with greater protease/antiprotease imbalance and increased inflammation, potentially leading to rapid lung function decline

The only established risk modifier in PI*MZ individuals is smoking; smoking cessation should, therefore, be the focus of treatment

The prevalence of the PI*MZ genotype makes it a relatively common risk factor for COPD; the high prevalence along with high disease heterogeneity may suggest that general recommendations may not apply to each particular case and that there may be a subset of patients who could benefit from AAT augmentation therapy

The high prevalence of the PI*MZ genotype could create significant strain on the supply of a costly, plasma-derived therapy; the focus should be on improving the evidence for use of AAT augmentation therapy in PI*ZZ patients and increasing access to treatment for patients with severe AATD