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  1. Article ; Online: Sputum trypsin-like protease activity relates to clinical outcome in cystic fibrosis.

    Reihill, James / Moffitt, Kelly / Douglas, Lisa / Stuart Elborn, J / Jones, Andrew / Lorraine Martin, S

    Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

    2020  Volume 19, Issue 4, Page(s) 647–653

    Abstract: 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 ... ...

    Abstract 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
    Results: TLP activity inversely correlated with percent predicted FEV
    Conclusions: Sputum TLP activity may represent a novel non-invasive biomarker and/or therapeutic target for CF lung disease.
    MeSH term(s) Adult ; Biomarkers/metabolism ; Clinical Chemistry Tests/methods ; Cystic Fibrosis/metabolism ; Cystic Fibrosis/mortality ; Cystic Fibrosis/physiopathology ; Epithelial Sodium Channels/metabolism ; Female ; Humans ; Immunoenzyme Techniques/methods ; Ion Transport/physiology ; Male ; Reproducibility of Results ; Respiratory Function Tests/methods ; Respiratory Mucosa/metabolism ; Respiratory Mucosa/physiopathology ; Serine Endopeptidases/metabolism ; Sputum/metabolism ; Survival Analysis
    Chemical Substances Biomarkers ; Epithelial Sodium Channels ; trypsin-like serine protease ; Serine Endopeptidases (EC 3.4.21.-)
    Language English
    Publishing date 2020-01-11
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2084724-5
    ISSN 1873-5010 ; 1569-1993
    ISSN (online) 1873-5010
    ISSN 1569-1993
    DOI 10.1016/j.jcf.2019.12.014
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  2. Article ; Online: Neutrophil elastase as a biomarker for bacterial infection in COPD.

    Thulborn, Samantha J / Mistry, Vijay / Brightling, Christopher E / Moffitt, Kelly L / Ribeiro, David / Bafadhel, Mona

    Respiratory research

    2019  Volume 20, Issue 1, Page(s) 170

    Abstract: Background: Chronic obstructive pulmonary disease (COPD) is predominantly associated with neutrophilic inflammation. Active neutrophil elastase (NE) is a serine proteinase, secreted by neutrophils, in response to inflammation and pathogen invasion. We ... ...

    Abstract Background: Chronic obstructive pulmonary disease (COPD) is predominantly associated with neutrophilic inflammation. Active neutrophil elastase (NE) is a serine proteinase, secreted by neutrophils, in response to inflammation and pathogen invasion. We sought to investigate if NE could be used as a biomarker for bacterial infection in patients with COPD.
    Methods: NE was quantified using ProteaseTag® Active NE Immunoassay (ProAxsis, Belfast) from the sputum of COPD subjects at stable state, exacerbation and 2 weeks post treatment visit.
    Results: NE was measured in 90 samples from 30 COPD subjects (18 males) with a mean (range) age of 65 (45-81) years and mean (SD) FEV
    Conclusion: NE is elevated during exacerbations of COPD. NE may be a viable biomarker for distinguishing a bacterial exacerbation in patients with COPD.
    Trial registration: Leicestershire, Northamptonshire and Rutland ethics committee (reference number: 07/H0406/157).
    MeSH term(s) Aged ; Aged, 80 and over ; Bacterial Infections/diagnosis ; Bacterial Infections/enzymology ; Bacterial Infections/epidemiology ; Biomarkers/metabolism ; Female ; Humans ; Leukocyte Elastase/analysis ; Leukocyte Elastase/metabolism ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive/diagnosis ; Pulmonary Disease, Chronic Obstructive/enzymology ; Pulmonary Disease, Chronic Obstructive/epidemiology ; Sputum/chemistry ; Sputum/enzymology
    Chemical Substances Biomarkers ; ELANE protein, human (EC 3.4.21.37) ; Leukocyte Elastase (EC 3.4.21.37)
    Language English
    Publishing date 2019-07-30
    Publishing country England
    Document type Clinical Trial ; Journal Article
    ZDB-ID 2041675-1
    ISSN 1465-993X ; 1465-9921
    ISSN (online) 1465-993X
    ISSN 1465-9921
    DOI 10.1186/s12931-019-1145-4
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  3. Article ; Online: Evaluating the sensitivity and specificity of NEATstik technology compared to an activity-based immunoassay in sputum samples from participants with COPD.

    Thulborn, Samantha J / Cane, Jennifer L / Connolly, Clare / Borg, Catherine / Moffitt, Kelly L / Ribeiro, David / Robb, Charlene / Russell, Richard E K / Bafadhel, Mona

    The European respiratory journal

    2020  Volume 55, Issue 5

    MeSH term(s) Aged ; Aged, 80 and over ; Female ; Humans ; Immunoassay ; Leukocyte Elastase/metabolism ; Male ; Middle Aged ; Neutrophils/metabolism ; Pulmonary Disease, Chronic Obstructive/physiopathology ; Respiratory Function Tests ; Sensitivity and Specificity ; Sputum/metabolism
    Chemical Substances Leukocyte Elastase (EC 3.4.21.37)
    Language English
    Publishing date 2020-05-27
    Publishing country England
    Document type Comparative Study ; Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 639359-7
    ISSN 1399-3003 ; 0903-1936
    ISSN (online) 1399-3003
    ISSN 0903-1936
    DOI 10.1183/13993003.02412-2019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.MO 292: Show issues

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  4. Article ; Online: Proteases implicated in apoptosis: old and new.

    Moffitt, Kelly L / Martin, S Lorraine / Walker, Brian

    The Journal of pharmacy and pharmacology

    2010  Volume 62, Issue 5, Page(s) 563–576

    Abstract: Objectives: The role of proteases in the regulation of apoptosis is becoming increasingly apparent. Whilst many of these proteases are already characterised, some have yet to be identified. Traditionally caspases held the traditional role as the prime ... ...

    Abstract Objectives: The role of proteases in the regulation of apoptosis is becoming increasingly apparent. Whilst many of these proteases are already characterised, some have yet to be identified. Traditionally caspases held the traditional role as the prime mediators of apoptosis; however, attention is now turning towards the contribution made by serine proteases.
    Key findings: As unregulated apoptosis is implicated in various disease states, the emergence of this proteolytic family as apoptotic regulators offers novel and alterative opportunities for therapeutic targets.
    Summary: This review presents a brief introduction and overview of proteases in general with particular attention given to those involved in apoptotic processing.
    MeSH term(s) Apoptosis/physiology ; Humans ; Peptide Hydrolases/metabolism ; Serine Proteases/metabolism
    Chemical Substances Peptide Hydrolases (EC 3.4.-) ; Serine Proteases (EC 3.4.-)
    Language English
    Publishing date 2010-05
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 3107-0
    ISSN 2042-7158 ; 0022-3573 ; 0373-1022
    ISSN (online) 2042-7158
    ISSN 0022-3573 ; 0373-1022
    DOI 10.1211/jpp.62.05.0002
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  5. Article ; Online: From sentencing to execution--the processes of apoptosis.

    Moffitt, Kelly L / Martin, S Lorraine / Walker, Brian

    The Journal of pharmacy and pharmacology

    2010  Volume 62, Issue 5, Page(s) 547–562

    Abstract: Objectives: Cell proliferation and apoptosis play a major role in maintaining homeostasis and as such any disruption within these processes can lead to disease states. Apoptosis occurs in three non-distinct phases--induction, effector and degradation-- ... ...

    Abstract Objectives: Cell proliferation and apoptosis play a major role in maintaining homeostasis and as such any disruption within these processes can lead to disease states. Apoptosis occurs in three non-distinct phases--induction, effector and degradation--and can be executed through both the extrinsic and intrinsic pathways in addition to recognised sub-pathways such as the p53 and lysosomal pathways. This review article highlights these pathways, incorporating an overview of the molecular regulators of apoptosis.
    Key findings: These regulators include the prominent apoptotic players 'the caspases' in addition to the main regulators of the Bcl-2 family. Increased understanding of the physiological processes of apoptosis at the molecular level not only offers an insight in disease pathogenesis but, in addition, allows for the development of diagnostic, prognostic and therapeutic tools.
    Summary: While apoptosis remains the key player in cellular death, other processes cannot be dismissed. Many other proteins, in addition to caspases, within apoptotic pathways have been identified. Research continues into establishing the precise aspects of their molecular mechanisms of action and inter-relationships. Inappropriate apoptosis due to dysregulation of cell death pathways provides a plethora of molecular checkpoints that can be targeted and modulated as part of therapeutic intervention. Increased research into these areas will prove useful for the design of novel chemotherapeutic drugs, an area that is particularly important due to increased risk of chemoresistance.
    MeSH term(s) Apoptosis/physiology ; Caspases/metabolism ; Cell Proliferation ; Homeostasis ; Humans ; Mitochondria/physiology ; Proteins/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Signal Transduction
    Chemical Substances Proteins ; Proto-Oncogene Proteins c-bcl-2 ; Caspases (EC 3.4.22.-)
    Language English
    Publishing date 2010-05
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 3107-0
    ISSN 2042-7158 ; 0022-3573 ; 0373-1022
    ISSN (online) 2042-7158
    ISSN 0022-3573 ; 0373-1022
    DOI 10.1211/jpp.62.05.0001
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  6. Article ; Online: A point-of-care neutrophil elastase activity assay identifies bronchiectasis severity, airway infection and risk of exacerbation.

    Shoemark, Amelia / Cant, Erin / Carreto, Luis / Smith, Alexandria / Oriano, Martina / Keir, Holly R / Perea, Lidia / Canto, Elisabet / Terranova, Leonardo / Vidal, Silvia / Moffitt, Kelly / Aliberti, Stefano / Sibila, Oriol / Chalmers, James D

    The European respiratory journal

    2019  Volume 53, Issue 6

    Abstract: Introduction: Neutrophil elastase activity in sputum can identify patients at high risk of airway infection and exacerbations in bronchiectasis. Application of this biomarker in clinical practice is limited, because no point-of-care test is available. ... ...

    Abstract Introduction: Neutrophil elastase activity in sputum can identify patients at high risk of airway infection and exacerbations in bronchiectasis. Application of this biomarker in clinical practice is limited, because no point-of-care test is available. We tested whether a novel semi-quantitative lateral flow device (neutrophil elastase airway test stick - NEATstik®) can stratify bronchiectasis patients according to severity, airway infection and exacerbation risk.
    Methods: Sputum samples from 124 patients with stable bronchiectasis enrolled in the UK and Spain were tested using the NEATstik®, which scores neutrophil elastase concentration from 0 (<8 µg·mL
    Measurements and main results: Patients had a median age of 69 years and forced expiratory volume in 1 s (FEV
    Conclusions: A novel lateral flow device provides assessment of neutrophil elastase activity from sputum in minutes and identifies patients at increasing risk of airway infection and future exacerbations.
    MeSH term(s) Aged ; Biomarkers/metabolism ; Bronchiectasis/diagnosis ; Bronchiectasis/physiopathology ; Cohort Studies ; Disease Progression ; Female ; Forced Expiratory Volume ; Humans ; Leukocyte Elastase/metabolism ; Linear Models ; Lung/physiopathology ; Male ; Middle Aged ; Neutrophils/metabolism ; Point-of-Care Testing ; Severity of Illness Index ; Spain ; Sputum/metabolism ; United Kingdom
    Chemical Substances Biomarkers ; Leukocyte Elastase (EC 3.4.21.37)
    Language English
    Publishing date 2019-06-13
    Publishing country England
    Document type Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't ; Validation Study
    ZDB-ID 639359-7
    ISSN 1399-3003 ; 0903-1936
    ISSN (online) 1399-3003
    ISSN 0903-1936
    DOI 10.1183/13993003.00303-2019
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  7. Article ; Online: Neutrophil Elastase Activity Is Associated with Exacerbations and Lung Function Decline in Bronchiectasis.

    Chalmers, James D / Moffitt, Kelly L / Suarez-Cuartin, Guillermo / Sibila, Oriol / Finch, Simon / Furrie, Elizabeth / Dicker, Alison / Wrobel, Karolina / Elborn, J Stuart / Walker, Brian / Martin, S Lorraine / Marshall, Sara E / Huang, Jeffrey T-J / Fardon, Thomas C

    American journal of respiratory and critical care medicine

    2016  Volume 195, Issue 10, Page(s) 1384–1393

    Abstract: Rationale: Sputum neutrophil elastase and serum desmosine, which is a linked marker of endogenous elastin degradation, are possible biomarkers of disease severity and progression in bronchiectasis. This study aimed to determine the association of ... ...

    Abstract Rationale: Sputum neutrophil elastase and serum desmosine, which is a linked marker of endogenous elastin degradation, are possible biomarkers of disease severity and progression in bronchiectasis. This study aimed to determine the association of elastase activity and desmosine with exacerbations and lung function decline in bronchiectasis.
    Methods: This was a single-center prospective cohort study using the TAYBRIDGE (Tayside Bronchiectasis Registry Integrating Datasets, Genomics, and Enrolment into Clinical Trials) registry in Dundee, UK. A total of 433 patients with high-resolution computed tomography-confirmed bronchiectasis provided blood samples for desmosine measurement, and 381 provided sputum for baseline elastase activity measurements using an activity-based immunosassay and fluorometric substrate assay. Candidate biomarkers were tested for their relationship with cross-sectional markers of disease severity, and with future exacerbations, mortality and lung function decline over 3 years.
    Measurement and main results: Elastase activity in sputum was associated with the bronchiectasis severity index (r = 0.49; P < 0.0001) and was also correlated with the Medical Research Council dyspnea score (r = 0.34; P < 0.0001), FEV
    Conclusions: Sputum neutrophil elastase activity is a biomarker of disease severity and future risk in adults with bronchiectasis.
    MeSH term(s) Aged ; Biomarkers/metabolism ; Bronchiectasis/metabolism ; Bronchiectasis/physiopathology ; Cohort Studies ; Desmosine/metabolism ; Disease Progression ; Female ; Humans ; Leukocyte Elastase/metabolism ; Lung/metabolism ; Lung/physiopathology ; Male ; Middle Aged ; Neutrophils/metabolism ; Prospective Studies ; Registries ; Severity of Illness Index ; Sputum/metabolism ; United Kingdom
    Chemical Substances Biomarkers ; Desmosine (11003-57-9) ; Leukocyte Elastase (EC 3.4.21.37)
    Language English
    Publishing date 2016-12-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1180953-x
    ISSN 1535-4970 ; 0003-0805 ; 1073-449X
    ISSN (online) 1535-4970
    ISSN 0003-0805 ; 1073-449X
    DOI 10.1164/rccm.201605-1027OC
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