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Title: Protease-antiprotease imbalance in bronchiectasis
Authors: Oriano, Martina
Amati, Francesco
Gramegna, Andrea
De Soyza, Anthony
Mantero, Marco
Sibila, Oriol
Chotirmall, Sanjay Haresh
Voza, Antonio
Marchisio, Paola
Blasi, Francesco
Aliberti, Stefano
Keywords: Science::Medicine
Issue Date: 2021
Source: Oriano, M., Amati, F., Gramegna, A., De Soyza, A., Mantero, M., Sibila, O., Chotirmall, S. H., Voza, A., Marchisio, P., Blasi, F. & Aliberti, S. (2021). Protease-antiprotease imbalance in bronchiectasis. International Journal of Molecular Sciences, 22(11), 5996-.
Journal: International Journal of Molecular Sciences 
Abstract: Airway inflammation plays a central role in bronchiectasis. Protease-antiprotease balance is crucial in bronchiectasis pathophysiology and increased presence of unopposed proteases activity may contribute to bronchiectasis onset and progression. Proteases' over-reactivity and antiprotease deficiency may have a role in increasing inflammation in bronchiectasis airways and may lead to extracellular matrix degradation and tissue damage. Imbalances in serine proteases and matrix-metallo proteinases (MMPs) have been associated to bronchiectasis. Active neutrophil elastase has been associated with disease severity and poor long-term outcomes in this disease. Moreover, high levels of MMPs have been associated with radiological and disease severity. Finally, severe deficiency of α1-antitrypsin (AAT), as PiSZ and PiZZ (proteinase inhibitor SZ and ZZ) phenotype, have been associated with bronchiectasis development. Several treatments are under study to reduce protease activity in lungs. Molecules to inhibit neutrophil elastase activity have been developed in both oral or inhaled form, along with compounds inhibiting dipeptydil-peptidase 1, enzyme responsible for the activation of serine proteases. Finally, supplementation with AAT is in use for patients with severe deficiency. The identification of different targets of therapy within the protease-antiprotease balance contributes to a precision medicine approach in bronchiectasis and eventually interrupts and disrupts the vicious vortex which characterizes the disease.
ISSN: 1661-6596
DOI: 10.3390/ijms22115996
Rights: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (
Fulltext Permission: open
Fulltext Availability: With Fulltext
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