Abstract
Ever since the first studies, restoring proteinase imbalance in the lung has traditionally been considered as the main goal of alpha1 antitrypsin (AAT) replacement therapy. This strategy was therefore based on ensuring biochemical efficacy, identifying a protection threshold, and evaluating different dosage regimens. Subsequently, the publication of the results of the main clinical trials showing a decrease in the progression of pulmonary emphysema has led to a debate over a possible change in the main objective of treatment, from biochemical efficacy to clinical efficacy in terms of lung densitometry deterioration prevention. This new paradigm has produced a series controversies and unanswered questions which face clinicians managing AAT deficiency. In this review, the concepts that led to the approval of AAT replacement therapy are reviewed and discussed under a new prism of achieving clinical efficacy, with the reduction of lung deterioration as the main objective. Here, we propose the use of current knowledge and clinical experience to face existing challenges in different clinical scenarios, in order to help clinicians in decision-making, increase interest in the disease, and stimulate research in this field.
Highlights
Alpha1 antitrypsin deficiency (AATD) is a rare genetic condition that determines the appearance of pulmonary emphysema and liver damage in its severe forms [1]
Controversies and doubts may arise about the management of different aspects of this condition in daily clinical practice. This is evident when it comes to considering exogenous alpha1 antitrypsin (AAT) replacement therapy, which is known as augmentation therapy, for severely deficient patients
One major finding is the ability of AAT augmentation therapy to decrease emphysema progression as measured by lung densitometry [2,3,4]
Summary
Alpha antitrypsin deficiency (AATD) is a rare genetic condition that determines the appearance of pulmonary emphysema and liver damage in its severe forms [1]. Controversies and doubts may arise about the management of different aspects of this condition in daily clinical practice This is evident when it comes to considering exogenous alpha antitrypsin (AAT) replacement therapy, which is known as augmentation therapy, for severely deficient patients. The preservation of pulmonary density with exogenous AAT has sparked a debate over a potential change in the main aims of treatment from biochemical efficacy to clinical efficacy, based on emphysema progression evaluated by lung densitometry. Under this new paradigm, clinicians managing AATD are faced with a number of controversies and unanswered. The subsequent trial used the standard dose of 60 mg/kg in weekly infusions [8], which has been maintained until now
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