α1 Antitrypsin deficiency: current best practice in testing and augmentation therapy

1 Antitrypsin deficiency (AATD) increases the risk of chronic obstructive pulmonary disease (COPD), liver disease and other conditions. Although it is not a rare disease, it is a condition rarely diagnosed because of unawareness by most healthcare providers who manage subjects at risk. Testing recommendations have been published and strongly suggest testing all subjects with confirmed COPD, cryptogenic liver cirrhosis, subjects with incompletely reversible airflow obstruction and siblings of affected individuals. Testing strategies usually imply a combination of measures of 1 antitrypsin (AAT) levels, phenotyping and genotyping, techniques that have been facilitated for in-office use by development of testing kits using dried blood spots. Early detection of subjects is crucial to apply effective preventive measures and early institution of therapy. The only specific Food and Drug Administration - approved therapy for this condition is lifelong weekly intravenous AAT replacement (augmentation therapy). Observational studies strongly suggest a beneficial effect of augmentation therapy in slowing lung function decline and randomized trials suggest a beneficial effect in slowing the progression of emphysema over time as measured by computed tomography. In addition, augmentation therapy has been shown to modulate systemic inflammatory responses and affect markers of elastin degradation. As new markers of disease progression are discovered, new doses of AAT replacement are tested and sub-phenotypes of disease are described, treatment recommendations are likely to change towards a more individualized therapeutic approach.