Specific treatment of pulmonary involvement in patients with AAT deficiency − why, how, and for whom?
For patients with emphysema and decreased lung function due to alpha-1-antitrypsin deficiency (AATD), there is an approved specific treatment which involves the i.v. administration of alpha-1-antitrypsin (AAT) derived from human plasma. This augmentation therapy slows the loss of lung tissue density. Its effects and impact on the frequency and duration of exacerbations, quality of life, lung functions, and patient mortality are less clear.
Alpha-1-Antitrypsin Deficiency
AAT deficiency typically manifests with pulmonary involvement. Some patients develop bronchiectasis, but the typical manifestation is emphysema and chronic obstructive pulmonary disease (COPD).
Non-Pharmacological Treatment of AATD
Treatment of patients with AATD includes both non-pharmacological and pharmacological approaches. Non-pharmacological treatment involves lifestyle modifications − avoiding polluted environments, not smoking, healthy nutrition, and adequate exercise as part of a comprehensive treatment program. Patients should follow the recommendations for non-pharmacological treatment of COPD.
Specific Pharmacological (Augmentation) Treatment
Specific pharmacological treatment in the form of AAT administration is indicated for patients with severe deficiency of this protein (serum AAT level < 0.5–0.8 g/l) and documented lung involvement – pulmonary emphysema with decreased lung function. Its aim is to increase the level of AAT in serum and in the fluid covering the lung epithelium, thus restoring balance disrupted by uninhibited protease activity. It is administered in i.v. infusions usually 1× per week, and this lifelong treatment.
According to available evidence, augmentation therapy leads to an increase in anti-elastase capacity and a reduction in inflammatory mediators in the lungs. Radiologically, it reduces the loss of lung tissue density over time, thereby slowing the progression of lung damage. It seems to have some benefit in terms of patient survival and slowing the decline of one-second vital capacity (FEV1) in patients with an FEV1 value in the range of 30–65 % of the predicted value. The treatment's effect on exacerbation frequency is not clearly established, but it appears to reduce their severity. Inhalation administration or less frequent i.v. applications with modified dosing are being explored to improve patient quality of life.
Who is Augmentation Therapy For
Currently, augmentation therapy for AATD is recommended only for patients with severe genotypes (e.g., PI*ZZ or PI*SZ) or with FEV1 ≤ 65 %, as only in these cases has its clear benefit been demonstrated. It is not recommended for mild genotypes, when FEV1 > 65 %, for individuals who continue to smoke, or for patients after liver transplantation.
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Source: Barjaktarevic I., Campos M. Management of lung disease in alpha-1 antitrypsin deficiency: what we do and what we do not know. Ther Adv Chronic Dis 2021 Jul 29; 12 (suppl.): 20406223211010172, doi: 10.1177/20406223211010172.
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