Augmentation therapy of α1-antitrypsin deficiency

R. C. Hubbard, R. G. Crystal

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Intravenous augmentation therapy with human plasma α1AT represents the current 'state of the art' form of therapy for α1AT deficiency. Augmentation therapy is directed towards specific correction of the central abnormality of α1AT deficiency i.e., to correct the insufficient anti-neutrophil elastase screen of the lung. By augmenting lung levels of functional α1AT, 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-α1AT 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 α1AT deficiency. Aerosol augmentation therapy with human plasma α1AT or with rAAT are attractive possible alternative approaches to increasing lung anti-neutrophil elastase defenses. By directing targeting active anti-elastase protection to the lung via aerosol, this form of therapy offers the prospect of significantly more efficient delivery of equivalent therapy, and the possibility of patient self-administration, thus lessening the burden of the disease to patients. However, evaluation of aerosol therapy in the form of long-term study will be necessary before it is possible to recommend aerosol augmentation therapy as clinically equivalent to intravenous therapy. Gene therapy represents the likely future of augmentation therapy. As with liver transplantation, successful gene therapy would directly cure the deficiency state. Unlike liver transplantation, gene therapy would not be limited by the major practical constraints imposed by the limited availability of donor organs. Although considerable methodological hurdles remain prior to gene therapy becoming an established therapeutic modality for α1AT deficiency, it holds forth the promise of curative therapy, and will continue to be the subject of active investigation.

Original languageEnglish
Pages (from-to)44s-52s
JournalEuropean Respiratory Journal
Issue numberSUPPL. 9
Publication statusPublished - 1 Jan 1990


ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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