Thorax 2013;68:670-676 doi:10.1136/thoraxjnl-2012-201871

• Review

Blood fibrinogen as a biomarker of chronic obstructive pulmonary disease

1. Annelyse Duvoix1, 
2. Jenny Dickens1, 
3. Imran Haq1, 
4. David Mannino2, 
5. Bruce Miller3,
6. Ruth Tal-Singer3, 
7. David A Lomas1

+Author Affiliations

1. ¹Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Cambridge, UK
2. ²Department of Preventive Medicine and Environmental Health, University of Kentucky College of Public Health, Lexington, Kentucky, USA
3. ³GlaxoSmithKline, King of Prussia, Pennsylvania, USA

1. Correspondence toProfessor David Lomas, Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, UK;dal16@cam.ac.uk

• Received 12 March 2012
• Accepted 30 May 2012
• Published Online First 28 June 2012

Abstract

Background Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterised by airflow obstruction that is not fully reversible and is a major global cause of morbidity and mortality. The most widely used marker of disease severity and progression is FEV₁. However, FEV₁ correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterise individuals with COPD. Fibrinogen is an acute phase plasma protein that has emerged as a promising biomarker in COPD. Here we review the current clinical evidence linking fibrinogen with COPD and its associated co-morbidities and discuss its potential utility as a biomarker.

Methods Searches for appropriate studies were undertaken on PubMed using search terms fibrinogen, COPD, emphysema, chronic bronchitis, FEV₁, cardiovascular disease, exacerbation and mortality.

Results There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and with mortality. Fibrinogen is associated with disease severity but does not predict lung function decline, a measure used as a surrogate for disease activity. The role of fibrinogen in identifying inflammatory co morbidities, particularly cardiovascular disease, remains unclear. Fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations.

Conclusions Fibrinogen is likely to be a useful biomarker to stratify individuals with COPD into those with a high or low risk of future exacerbations and may identify those with a higher risk of mortality.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/3.0/ andhttp://creativecommons.org/licenses/by-nc/3.0/legalcode

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Thorax 2013;68:691-694 doi:10.1136/thoraxjnl-2012-202646

• Chest clinic

• Opinion

Multidimensional assessment and tailored interventions for COPD: respiratory utopia or common sense?

1. Vanessa M McDonald1,2,3, 
2. Isabel Higgins1, 
3. Lisa G Wood3,4, 
4. Peter G Gibson2,4,5

+Author Affiliations

1. ¹School of Nursing and Midwifery, University of Newcastle, Newcastle, New South Wales, Australia
2. ²School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia
3. ³Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, John Hunter Hospital, New Lambton, New South Wales, Australia
4. ⁴School of Biomedical Science, University of Newcastle, Newcastle, New South Wales, Australia
5. ⁵Woolcock Institute of Medical Research, Sydney, New South Wales, Australia

1. Correspondence toPeter G Gibson, Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, John Hunter Hospital, Locked Bag #1000, New Lambton, NSW 2305, Australia;peter.gibson@hnehealth.nsw.gov.au

• Received 27 August 2012
• Revised 7 February 2013
• Accepted 11 February 2013
• Published Online First 16 March 2013

Abstract

Introduction The rising disease burden from chronic obstructive pulmonary disease (COPD) requires new approaches.

Method We suggest an approach based around three elements: inflammometry and multidimensional assessment to identify therapeutic targets and case management to design and implement an individualised treatment programme based on these assessments.

Discussion This tailored approach to treatment would maximise efficacy, limit cost and permit a better risk–benefit ratio of treatment. The advantages include the ability to add up the benefits of individual therapies leading to a cumulative therapeutic benefit that is greater than each individual therapy alone. We can now design a multifaceted inflammometry intervention for airway diseases based on targeting eosinophilic inflammation, non-eosinophilic pathways and systemic inflammation. COPD is a complex and challenging disease. The use of inflammometry and multidimensional assessment is necessary to identify relevant treatment targets and maximise the scope of therapy while limiting unnecessary use of drugs. An individualised programme of management can be designed and coordinated by using a case manager. This new approach may provide tangible benefits to people with COPD.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/3.0/ andhttp://creativecommons.org/licenses/by-nc/3.0/legalcode

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Role of Microglia in CNS Autoimmunity

Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 208093, 8 pages
http://dx.doi.org/10.1155/2013/208093

Review Article

Role of Microglia in CNS Autoimmunity

Tobias Goldmann¹ and Marco Prinz^1,2

¹Institute of Neuropathology, University of Freiburg, Breisacher Straße 64, 79106 Freiburg, Germany
²BIOSS Centre for Biological Signalling Studies, University of Freiburg, Breisacher Straße 64, 79106 Freiburg, Germany

Received 10 May 2013; Accepted 28 May 2013

Academic Editor: Wolfgang J. Streit

Copyright © 2013 Tobias Goldmann and Marco Prinz. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS) in the Western world. The disease is characterized histologically by the infiltration of encephalitogenic 1/17-polarized CD4⁺ T cells, B cells, and a plethora of myeloid cells, resulting in severe demyelination ultimately leading to a degeneration of neuronal structures. These pathological processes are substantially modulated by microglia, the resident immune competent cells of the CNS. In this overview, we summarize the current knowledge regarding the highly diverse and complex function of microglia during CNS autoimmunity in either promoting tissue injury or tissue repair. Hence, understanding microglia involvement in MS offers new exciting paths for therapeutic intervention.

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Increased Expression of RhoA in Epithelium and Smooth Muscle of Obese Mouse Models

Journal of Allergy
Volume 2013 (2013), Article ID 740973, 11 pages
http://dx.doi.org/10.1155/2013/740973

Research Article

Increased Expression of RhoA in Epithelium and Smooth Muscle of Obese Mouse Models: Implications for Isoprenoid Control of Airway Smooth Muscle and Fibroblasts

Kristie R. Ross,¹ Rebecca J. Darrah,^2,3 Craig A. Hodges,^1,3 LaTresa Lang,¹ and Thomas J. Kelley^1,4

¹Departments of Pediatrics, Case Western Reserve University and Rainbow Babies and Children’s Hospital, 10900 Euclid Avenue, Cleveland, OH 44106-4948, USA
²Frances Payne Bolton School of Nursing, Case Western Reserve University, 8th Floor BRB, 10900 Euclid Avenue, Cleveland, OH 44106-4948, USA
³Department of Genetics and Genome Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4948, USA
⁴Department of Pharmacology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4948, USA

Received 8 February 2013; Revised 22 April 2013; Accepted 21 May 2013

Academic Editor: Balram Ghosh

Copyright © 2013 Kristie R. Ross et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The simultaneous rise in the prevalence of asthma and obesity has prompted epidemiologic studies that establish obesity as a risk factor for asthma. The alterations in cell signaling that explain this link are not well understood and warrant investigation so that therapies that target this asthma phenotype can be developed. We identified a significant increase in expression of the small GTPase RhoA in nasal epithelial cells and tracheal smooth muscle cells from leptin-deficient (ob/ob) mice compared to their wild-type counterparts. Since RhoA function is dependent on isoprenoid modification, we sought to determine the role of isoprenoid-mediated signaling in regulating the viability and proliferation of human airway smooth muscle cells (ASM) and normal human lung fibroblasts (NHLF). Inhibiting isoprenoid signaling with mevastatin significantly decreased the viability of ASM and NHLF. This inhibition was reversed by geranylgeranyl pyrophosphate (GGPP), but not farnesyl pyrophosphate (FPP), suggesting specificity to the Rho GTPases. Conversely, increasing isoprenoid synthesis significantly increased ASM proliferation and RhoA protein expression. RhoA expression is inherently increased in airway tissue from ob/ob mice, and obesity-entrained alterations in this pathway may make it a novel therapeutic target for treating airway disease in the obese population.

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INVITED REVIEW SERIES: STEM CELLS AND THE LUNG

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Lung stem cells: Do they exist?

1. Ivan Bertoncello^*, 
2. Jonathan L. McQualter

Article first published online: 25 APR 2013

DOI: 10.1111/resp.12073

© 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology

Issue

Respirology

Volume 18, Issue 4, pages 587–595, May 2013

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Keywords:

• adult stem cell;
• airway epithelium;
• animal model;
• cell biology;
• lung regeneration

Abstract

Recognition of the potential of stem cell-based therapies for alleviating intractable lung diseases has provided the impetus for research aimed at identifying regenerative cells in the adult lung, understanding how they are organized and regulated, and how they could be harnessed in lung regenerative medicine. In this review, we describe the attributes of adult stem and progenitor cells in adult organs and how they are regulated by the permissive or restrictive microenvironment in which they reside. We describe the power and limitations of experimental models, cell separative strategies and functional assays used to model the organization and regulation of adult airway and alveolar stem cells in the adult lung. The review summarizes recent progress and obstacles in defining endogenous lung epithelial stem and progenitor cells in mouse models and in translational studies.

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