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Editorials |

α1-Antitrypsin Deficiency : More Than a Protease Imbalance?

Mark D. Wewers, MD
Author and Funding Information

Affiliations: Columbus, OH
 ,  Dr. Wewers is John A. Prior Professor of Medicine, Deputy Director, Davis Heart and Lung Research Institute.

Correspondence to: Mark D. Wewers, MD, John A. Prior Professor of Medicine, Deputy Director, 110L Davis Heart and Lung Research Institute, DHLRI, 473 W. 12th Ave, Columbus, OH 43210; e-mail: wewers.2@osu.edu



Chest. 2004;125(5):1607-1609. doi:10.1378/chest.125.5.1607
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Does the protease-antiprotease concept need an update? The novel observation provided by the work from Mulgrew and colleagues in this issue of CHEST (see page 1948) suggests that the process is likely much more complex than originally conceived 4 decades ago. More about that later.

In 1963, Laurell and Eriksson1 demonstrated the connection between a deficiency of α1-antitrypsin and the fact that three of the first five individuals identified had unmistakable evidence of pulmonary emphysema. The recognition that the main function of α1-antitrypsin is to inhibit proteases (most specifically neutrophil elastase and proteinase 3), and the demonstration that these enzymes when instilled into the lung produce pulmonary emphysema, led to the genesis of this hypothesis. It has now been almost 2 decades since α1-antitrypsin infusions have been used clinically in an attempt to counterbalance the protease burden.2 Yet, to date there are only limited data to suggest that this treatment has impacted the natural history of α1-antitrypsin deficiency-associated emphysema. The largest comparison to date, the Alpha-1-Antitrypsin Deficiency Registry, which analyzed 927 subjects, failed to demonstrate an effect of augmentation therapy on FEV1 rate of decline.3 Is the concept of an imbalance between enzyme and inhibitor too simplistic? Why doesn’t augmentation therapy have a more dramatic effect on the progression of a disease that is the most classic example of the protease antiprotease hypothesis? These questions certainly raise a number of interesting possibilities.

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