TY - JOUR
T1 - Protease–antiprotease imbalance in bronchiectasis
AU - Oriano, Martina
AU - Amati, Francesco
AU - Gramegna, Andrea
AU - Soyza, Anthony De
AU - Mantero, Marco
AU - Sibila, Oriol
AU - Chotirmall, Sanjay H.
AU - Voza, Antonio
AU - Marchisio, Paola
AU - Blasi, Francesco
AU - Aliberti, Stefano
N1 - Funding Information:
Conflicts of Interest: M.O., F.A., A.G., M.M., O.S., S.H.C., A.V. and P.M. declare no conflict of interest. F.B. reports grants and personal fees from AstraZeneca, grants from Bayer, grants and personal fees from Chiesi, grants and personal fees from GlaxoSmithKline, personal fees from Grifols, personal fees from Guidotti, personal fees from Insmed, grants and personal fees from Menarini, personal fees from Novartis, grants and personal fees from Pfizer, personal fees from Zambon, personal fees from Vertex, outside the submitted work. S.A. reports personal fees from Bayer Healthcare, personal fees from Grifols, personal fees from AstraZeneca, personal fees from Zambon, grants and personal fees from Chiesi, grants and personal fees from Insmed, personal fees from GlaxoSmithKline, personal fees from Menarini, personal fees from ZetaCube Srl, grants from Fisher & Paykel, outside the submitted work. A.D.S. reports grants, speakers fees and travel support from AstraZeneca, Bayer, Chiesi, Forest labs, GSK, Insmed, Pfizer, Medimmune, Novartis and Zambon outside the submitted work.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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.
AB - 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.
KW - Bronchiectasis
KW - Neutrophilic inflammation
KW - Proteases
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U2 - 10.3390/ijms22115996
DO - 10.3390/ijms22115996
M3 - Review article
AN - SCOPUS:85106957968
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 11
M1 - 5996
ER -