Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: Relationship to disease severity

Rekha Chaudhuri; Charles McSharry; Jeffrey Brady; Iona Donnelly; Christal Grierson; Stephen McGuinness; Lisa Jolly; Christopher J Weir; C Martina Messow; Mark Spears; Gino Miele; Karl Nocka; Dan Crowther; Joyce Thompson; Maureen Brannigan; Jane Lafferty; Michael Sproule; William Macnee; Martin Connell; John T Murchison; Malcolm C Shepherd; Giora Feuerstein; Douglas K Miller; Neil C Thomson

doi:10.1016/j.jaci.2011.12.996

Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: Relationship to disease severity

Rekha Chaudhuri, Charles McSharry, Jeffrey Brady, Iona Donnelly, Christal Grierson, Stephen McGuinness, Lisa Jolly, Christopher J Weir, C Martina Messow, Mark Spears, Gino Miele, Karl Nocka, Dan Crowther, Joyce Thompson, Maureen Brannigan, Jane Lafferty, Michael Sproule, William Macnee, Martin Connell, John T MurchisonMalcolm C Shepherd, Giora Feuerstein, Douglas K Miller, Neil C Thomson

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Background
Matrix metalloproteinase (MMP)-12 has been implicated in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and asthma. The influence of disease severity on sputum MMP-12 concentrations and activity is not known.

Objectives
We sought to examine the relationship between disease severity assessed by means of lung function and computed tomography (CT) and induced sputum MMP-12 concentrations and activity in patients with asthma and COPD.

Methods
In 208 subjects (109 asthmatic patients, smokers and never smokers, mild, moderate, and severe; 53 patients with COPD, smokers and exsmokers, mild, moderate, and severe; and 46 healthy control subjects, smokers and never smokers), we measured induced sputum MMP-12 concentrations (ELISA) and enzyme activity (fluorescence resonance energy transfer), sputum cell MMP12 mRNA expression (quantitative PCR [qPCR]), diffusing capacity for carbon monoxide (Dlco), and CT assessment of emphysema (percentage of low-attenuation areas at less −950 Hounsfield units).

Results
Sputum MMP-12 concentrations are greater in patients with COPD and smokers with asthma than in healthy nonsmokers (P = .003 and P = .035, respectively) but similar to those seen in healthy smokers. In patients with COPD, disease severity, when measured by means of CT-assessed emphysema, but not by means of spirometry or Dlco values, is directly associated with sputum MMP-12 concentrations and activity. In the asthma groups there is no significant association between disease severity and sputum MMP-12 concentrations or activity.

Conclusions
Sputum MMP-12 concentrations and activity in patients with COPD are directly associated with the extent of emphysema measured by means of CT. This finding supports a role for MMP-12 in the pathogenesis of COPD and might suggest that blocking MMP-12 activity in patients with COPD could prevent the further development of emphysema.

Original language	English
Pages (from-to)	655-663.e8
Journal	Journal of Allergy and Clinical Immunology
Volume	129
Issue number	3
DOIs	https://doi.org/10.1016/j.jaci.2011.12.996
Publication status	Published - Mar 2012

Keywords / Materials (for Non-textual outputs)

Matrix metalloproteinase 12
tissue inhibitor of metalloproteinases 1 and 2
MMP12 expression
emphysema
chronic obstructive pulmonary disease
asthma
smoker

Access to Document

10.1016/j.jaci.2011.12.996

http://www.sciencedirect.com/science/article/pii/S009167491200070X

PhD STUDENT - JOANNE SIMPSON - Supervisor MOHINI GRAY
Iredale, J.
MRC
1/09/12 → 31/08/16
Project: Research
MRC HUB NETWORK WORK
Murray, G.
MRC
1/01/09 → 31/08/15
Project: Research

Cite this

Chaudhuri, R., McSharry, C., Brady, J., Donnelly, I., Grierson, C., McGuinness, S., Jolly, L., Weir, C. J., Messow, C. M., Spears, M., Miele, G., Nocka, K., Crowther, D., Thompson, J., Brannigan, M., Lafferty, J., Sproule, M., Macnee, W., Connell, M., ... Thomson, N. C. (2012). Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: Relationship to disease severity. Journal of Allergy and Clinical Immunology, 129(3), 655-663.e8. https://doi.org/10.1016/j.jaci.2011.12.996

@article{15dcf14d5fa64447a5b60471f7a303ef,

title = "Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: Relationship to disease severity",

abstract = "BackgroundMatrix metalloproteinase (MMP)-12 has been implicated in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and asthma. The influence of disease severity on sputum MMP-12 concentrations and activity is not known.ObjectivesWe sought to examine the relationship between disease severity assessed by means of lung function and computed tomography (CT) and induced sputum MMP-12 concentrations and activity in patients with asthma and COPD.MethodsIn 208 subjects (109 asthmatic patients, smokers and never smokers, mild, moderate, and severe; 53 patients with COPD, smokers and exsmokers, mild, moderate, and severe; and 46 healthy control subjects, smokers and never smokers), we measured induced sputum MMP-12 concentrations (ELISA) and enzyme activity (fluorescence resonance energy transfer), sputum cell MMP12 mRNA expression (quantitative PCR [qPCR]), diffusing capacity for carbon monoxide (Dlco), and CT assessment of emphysema (percentage of low-attenuation areas at less −950 Hounsfield units).ResultsSputum MMP-12 concentrations are greater in patients with COPD and smokers with asthma than in healthy nonsmokers (P = .003 and P = .035, respectively) but similar to those seen in healthy smokers. In patients with COPD, disease severity, when measured by means of CT-assessed emphysema, but not by means of spirometry or Dlco values, is directly associated with sputum MMP-12 concentrations and activity. In the asthma groups there is no significant association between disease severity and sputum MMP-12 concentrations or activity.ConclusionsSputum MMP-12 concentrations and activity in patients with COPD are directly associated with the extent of emphysema measured by means of CT. This finding supports a role for MMP-12 in the pathogenesis of COPD and might suggest that blocking MMP-12 activity in patients with COPD could prevent the further development of emphysema.",

keywords = "Matrix metalloproteinase 12 , tissue inhibitor of metalloproteinases 1 and 2, MMP12 expression, emphysema, chronic obstructive pulmonary disease, asthma, smoker",

author = "Rekha Chaudhuri and Charles McSharry and Jeffrey Brady and Iona Donnelly and Christal Grierson and Stephen McGuinness and Lisa Jolly and Weir, {Christopher J} and Messow, {C Martina} and Mark Spears and Gino Miele and Karl Nocka and Dan Crowther and Joyce Thompson and Maureen Brannigan and Jane Lafferty and Michael Sproule and William Macnee and Martin Connell and Murchison, {John T} and Shepherd, {Malcolm C} and Giora Feuerstein and Miller, {Douglas K} and Thomson, {Neil C}",

year = "2012",

month = mar,

doi = "10.1016/j.jaci.2011.12.996",

language = "English",

volume = "129",

pages = "655--663.e8",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Mosby ",

number = "3",

}

Chaudhuri, R, McSharry, C, Brady, J, Donnelly, I, Grierson, C, McGuinness, S, Jolly, L, Weir, CJ, Messow, CM, Spears, M, Miele, G, Nocka, K, Crowther, D, Thompson, J, Brannigan, M, Lafferty, J, Sproule, M, Macnee, W, Connell, M, Murchison, JT, Shepherd, MC, Feuerstein, G, Miller, DK & Thomson, NC 2012, 'Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: Relationship to disease severity', Journal of Allergy and Clinical Immunology, vol. 129, no. 3, pp. 655-663.e8. https://doi.org/10.1016/j.jaci.2011.12.996

TY - JOUR

T1 - Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: Relationship to disease severity

AU - Chaudhuri, Rekha

AU - McSharry, Charles

AU - Brady, Jeffrey

AU - Donnelly, Iona

AU - Grierson, Christal

AU - McGuinness, Stephen

AU - Jolly, Lisa

AU - Weir, Christopher J

AU - Messow, C Martina

AU - Spears, Mark

AU - Miele, Gino

AU - Nocka, Karl

AU - Crowther, Dan

AU - Thompson, Joyce

AU - Brannigan, Maureen

AU - Lafferty, Jane

AU - Sproule, Michael

AU - Macnee, William

AU - Connell, Martin

AU - Murchison, John T

AU - Shepherd, Malcolm C

AU - Feuerstein, Giora

AU - Miller, Douglas K

AU - Thomson, Neil C

PY - 2012/3

Y1 - 2012/3

N2 - BackgroundMatrix metalloproteinase (MMP)-12 has been implicated in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and asthma. The influence of disease severity on sputum MMP-12 concentrations and activity is not known.ObjectivesWe sought to examine the relationship between disease severity assessed by means of lung function and computed tomography (CT) and induced sputum MMP-12 concentrations and activity in patients with asthma and COPD.MethodsIn 208 subjects (109 asthmatic patients, smokers and never smokers, mild, moderate, and severe; 53 patients with COPD, smokers and exsmokers, mild, moderate, and severe; and 46 healthy control subjects, smokers and never smokers), we measured induced sputum MMP-12 concentrations (ELISA) and enzyme activity (fluorescence resonance energy transfer), sputum cell MMP12 mRNA expression (quantitative PCR [qPCR]), diffusing capacity for carbon monoxide (Dlco), and CT assessment of emphysema (percentage of low-attenuation areas at less −950 Hounsfield units).ResultsSputum MMP-12 concentrations are greater in patients with COPD and smokers with asthma than in healthy nonsmokers (P = .003 and P = .035, respectively) but similar to those seen in healthy smokers. In patients with COPD, disease severity, when measured by means of CT-assessed emphysema, but not by means of spirometry or Dlco values, is directly associated with sputum MMP-12 concentrations and activity. In the asthma groups there is no significant association between disease severity and sputum MMP-12 concentrations or activity.ConclusionsSputum MMP-12 concentrations and activity in patients with COPD are directly associated with the extent of emphysema measured by means of CT. This finding supports a role for MMP-12 in the pathogenesis of COPD and might suggest that blocking MMP-12 activity in patients with COPD could prevent the further development of emphysema.

AB - BackgroundMatrix metalloproteinase (MMP)-12 has been implicated in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and asthma. The influence of disease severity on sputum MMP-12 concentrations and activity is not known.ObjectivesWe sought to examine the relationship between disease severity assessed by means of lung function and computed tomography (CT) and induced sputum MMP-12 concentrations and activity in patients with asthma and COPD.MethodsIn 208 subjects (109 asthmatic patients, smokers and never smokers, mild, moderate, and severe; 53 patients with COPD, smokers and exsmokers, mild, moderate, and severe; and 46 healthy control subjects, smokers and never smokers), we measured induced sputum MMP-12 concentrations (ELISA) and enzyme activity (fluorescence resonance energy transfer), sputum cell MMP12 mRNA expression (quantitative PCR [qPCR]), diffusing capacity for carbon monoxide (Dlco), and CT assessment of emphysema (percentage of low-attenuation areas at less −950 Hounsfield units).ResultsSputum MMP-12 concentrations are greater in patients with COPD and smokers with asthma than in healthy nonsmokers (P = .003 and P = .035, respectively) but similar to those seen in healthy smokers. In patients with COPD, disease severity, when measured by means of CT-assessed emphysema, but not by means of spirometry or Dlco values, is directly associated with sputum MMP-12 concentrations and activity. In the asthma groups there is no significant association between disease severity and sputum MMP-12 concentrations or activity.ConclusionsSputum MMP-12 concentrations and activity in patients with COPD are directly associated with the extent of emphysema measured by means of CT. This finding supports a role for MMP-12 in the pathogenesis of COPD and might suggest that blocking MMP-12 activity in patients with COPD could prevent the further development of emphysema.

KW - Matrix metalloproteinase 12

KW - tissue inhibitor of metalloproteinases 1 and 2

KW - MMP12 expression

KW - emphysema

KW - chronic obstructive pulmonary disease

KW - asthma

KW - smoker

U2 - 10.1016/j.jaci.2011.12.996

DO - 10.1016/j.jaci.2011.12.996

M3 - Article

C2 - 22305682

SN - 0091-6749

VL - 129

SP - 655-663.e8

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 3

ER -

Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: Relationship to disease severity

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

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Projects

PhD STUDENT - JOANNE SIMPSON - Supervisor MOHINI GRAY

MRC HUB NETWORK WORK

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