Augmentation therapy of alpha 1-antitrypsin deficiency.
Intravenous augmentation therapy with human plasma alpha 1AT represents the current "state of the art" form of therapy for alpha 1AT deficiency. Augmentation therapy is directed towards specific correction of the central abnormality of alpha 1AT deficiency i.e., to correct the insufficient anti-neutrophil elastase screen of the lung. By augmenting lung levels of functional alpha 1AT, the anti-neutrophil elastase protective screen of the lower respiratory tract is re-established, and the delicate alveolar structures are protected from elastolytic degradation. Weekly, monthly and plasma exchange-alpha 1AT infusion all share the same basic approach to augmenting lung anti-elastase defenses, and appear to be equally effective in re-establishing the anti-elastase screen of the lower respiratory tract. One important issue concerning augmentation therapy is the question of when to initiate therapy. Because the goal of augmentation therapy is to prevent lung destruction, it is rational to initiate therapy prior to the onset of significant lung destruction. Traditionally, pulmonary function testing and chest X-rays have been used to determine the degree of emphysema, but these methods are relatively insensitive when compared to newer evaluative methods, including computed tomography and ventilation-perfusion scanning. In view of the availability of these newer diagnostic modalities, and the desire to maximally preserve the lung through early initiation of augmentation therapy, the traditional concepts requiring the presence of lung function abnormalities as evidence of lung destruction may need to be re-evaluated for individuals with alpha 1AT deficiency. Aerosol augmentation therapy with human plasma alpha 1AT or with rAAT are attractive possible alternative approaches to increasing lung anti-neutrophil elastase defenses.(ABSTRACT TRUNCATED AT 250 WORDS)
Hubbard
R C
RC
Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Crystal
R G
RG
D000336:Aerosols; D004334:Drug Administration Schedule; D006801:Humans; D007262:Infusions, Intravenous; D011656:Pulmonary Emphysema / Q000188:drug therapy / Q000209:etiology; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage / Q000627:therapeutic use; D019896:alpha 1-Antitrypsin Deficiency
D000336:Aerosols; D000515:alpha 1-Antitrypsin