α1-Antitrypsin deficiency (AATD) is a genetic disorder that predisposes to the development of early pulmonary emphysema, especially in smokers. Episodes of exacerbations are frequent in patients with emphysema due to AATD and are associated with a deficient antiprotease screen in the airways compared with that of non-deficient COPD patients [1]. As a consequence, exacerbations have great impact on the evolution of the lung disease in AATD, measured in terms of decline in gas transfer [2], in health status [2, 3], and in lung function over time [4, 5]. To date, the only specific treatment for AATD-related emphysema is the intravenous infusion of purified α1-antitrypsin (AAT) derived from plasma donors, so-called augmentation therapy. Previous randomised clinical trials (RCTs) have consistently shown the efficacy of augmentation therapy in slowing the progression of pulmonary emphysema measured by computed tomography densitometry in individuals with severe AATD [6, 7]. However, evidence of the effect of augmentation on exacerbations is very limited and comes exclusively from a couple of observational studies that described a reduction in the frequency of exacerbations in patients after initiation of therapy [8, 9]. The lack of effect of augmentation therapy on exacerbations observed in RCTs can be due to different reasons: 1) the studies were not powered for exacerbations; 2) the patient populations were not enriched for exacerbators; and 3) augmentation per se may not have an effect on the prevention of exacerbations, but may help to preserve lung integrity in case of an exacerbation.
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