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Chest. 2017 Aug;152(2):249-262. doi: 10.1016/j.chest.2017.03.056. Epub 2017 Apr 23.

The Role of Neutrophil Elastase Inhibitors in Lung Diseases.

Author information

1
Institut Clínic Respiratori, Hospital Clinic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Ciber de Enfermedades Respiratorias, Barcelona, Spain.
2
Drug Discovery and Development, Polyphor Ltd., Allschwil, Switzerland.
3
Department of Pneumology, Hospital Clinic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Ciber de Enfermedades Respiratorias, Barcelona, Spain; Institut Clínic Respiratori, Hospital Clinic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Ciber de Enfermedades Respiratorias, Barcelona, Spain. Electronic address: atorres@clinic.ub.es.

Abstract

In many respiratory diseases characterized by an intense inflammatory response, the balance between proteolytic enzymes (proteases, including elastases) and their inhibitors (proteinases inhibitors) is not neutral. Excess activity of neutrophil elastase (NE) and similar proteases has been reported to cause tissue damage and to alter the remodeling process in many clinical conditions such as pneumonia, respiratory distress, and acute lung injury (ALI). Several experimental NE inhibitors have been tested in preclinical and clinical studies of different conditions of inflammatory lung injury such as ALI and pneumonia, with contrasting results. This study reviews the literature regarding NE inhibitors in the field of respiratory diseases and reflects on possible future developments. In particular, we highlight potential gaps in the scientific evidence and discuss potential strategies for focusing investigation on antielastases in clinical practice through the selection of targeted populations and proper outcomes.

KEYWORDS:

ARDS; airways inflammation; bronchiectasis; cystic fibrosis; neutrophil biology; neutrophil elastase; pneumonia

PMID:
28442313
DOI:
10.1016/j.chest.2017.03.056
[Indexed for MEDLINE]

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