Sputum trypsin-like protease activity relates to clinical outcome in cystic fibrosis.

Autor: Reihill J; School of Pharmacy, McClay Research Centre, Belfast BT9 7BL, United Kingdom., Moffitt K; School of Pharmacy, McClay Research Centre, Belfast BT9 7BL, United Kingdom., Douglas L; School of Pharmacy, McClay Research Centre, Belfast BT9 7BL, United Kingdom., Stuart Elborn J; Wellcome-Wolfson Institute For Experimental Medicine, Queen's University Belfast, Northern Ireland, BT9 7BL, United Kingdom., Jones A; Wythenshawe Hospital, Manchester Adult Cystic Fibrosis Centre, South Moor Road, Manchester, M23 9LT, United Kingdom., Lorraine Martin S; School of Pharmacy, McClay Research Centre, Belfast BT9 7BL, United Kingdom. Electronic address: l.martin@qub.ac.uk.
Jazyk: angličtina
Zdroj: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society [J Cyst Fibros] 2020 Jul; Vol. 19 (4), pp. 647-653. Date of Electronic Publication: 2020 Jan 11.
DOI: 10.1016/j.jcf.2019.12.014
Abstrakt: Background: In cystic fibrosis (CF) airways excessive levels of serine trypsin-like proteases (TLPs) activate the epithelial sodium channel (ENaC) resulting in airways dehydration and promotion of mucus secretion. Despite this the relationship of TLP activity and clinical outcome has not been studied.
Methods: We analysed supernatant (sol) prepared from CF sputum from adult CF patients in two study cohorts (29 and 33 samples, respectively). Protease activities were determined by measuring the hydrolysis of peptide-based substrates or by ELISA. Lung function was assessed by spirometry (FEV 1 ). Mortality data was retrospectively obtained and time in months until death or transplantation used for subsequent survival analysis.
Results: TLP activity inversely correlated with percent predicted FEV 1 (r = -0.4, p = 0.03) and was greater in individuals who did not survive beyond 5-years from the time of sample collection. A Kaplan-Meier analysis demonstrated significantly reduced survival (p = 0.04) for individuals with high TLP activity [hazard ratio (HR) of 7.21 per log unit TLP activity (p = 0.03)]. In contrast, neutrophil elastase displayed no significant associations with lung function or patient survival. Similar findings were evident in the second study cohort.
Conclusions: Sputum TLP activity may represent a novel non-invasive biomarker and/or therapeutic target for CF lung disease.
Competing Interests: Declaration of Competing Interest Prof. Martin is a co-founder of ProAxsis Ltd and has received research grants from ProAxsis Ltd. and Cystic Fibrosis Foundation Therapeutics Inc. Prof. Elborn has served as a medical advisor for ProAxsis Ltd, provided consultancy for Bayer and Vertex, and received a grant from Novartis. Dr Rehill, Dr Jones and Dr Moffitt declare no potential conflict of interest.
(Copyright © 2019. Published by Elsevier B.V.)
Databáze: MEDLINE
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