Abstract
Alpha-1 Antitrypsin Deficiency (AATD) has been historically under-recognised and under-diagnosed; recently it has begun to receive greater interest in terms of attempts at deeper elucidation of pathology and treatment options. However, the concept of disease phenotypes within AATD (emphysema, chronic bronchitis, bronchiectasis, or a combination of phenotypes) has not been proposed or studied. Of the 3 Neutrophil Serine Proteases (NSPs), Neutrophil Elastase (NE) was historically believed to be the sole contributor to disease pathology in AATD. Recently, Proteinase-3 (PR3) has been increasingly studied as an equal, if not greater, contributor to the disease process. Cathepsin G (CG), however, has not been extensively evaluated in this area. Matrix metalloproteinases (MMPs) have also been mentioned in the pathogenesis of AATD but have not been widely explored. This article considers the available evidence for differential protease activity in patients with AATD, including the contribution to distinct phenotypes of the disease. Due to limited literature in this area, extrapolations from studies of other chronic lung diseases with similar phenotypes, including chronic obstructive pulmonary disease (COPD) and bronchiectasis have been made. We consider a new framework of understanding defined by protease driven endotypes of disease which may lead to new opportunities for precision medicine.
Footnotes
This manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Fazleen has nothing to disclose.
Conflict of interest: Dr. Wilkinson reports grants and personal fees from AstraZeneca, during the conduct of the study; personal fees and other from MMH, grants and personal fees from GSK, grants and personal fees from AZ, personal fees from BI, grants and personal fees from Synairgen, outside the submitted work; .
This is a PDF-only article. Please click on the PDF link above to read it.
- Received August 5, 2021.
- Accepted September 9, 2021.
- Copyright ©The authors 2021
This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions{at}ersnet.org