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Original Research: Diffuse Lung Disease |

Fibulin-1 Predicts Disease Progression in Patients With Idiopathic Pulmonary FibrosisFibulin-1 Predicts Disease Progression

Jade Jaffar, BSc; Sofia Unger, BSc; Tamera J. Corte, MBBS, PhD; Michael Keller, MBBS; Paul J. Wolters, MD, PhD; Luca Richeldi, MD, PhD; Stefania Cerri, MD, PhD; Cecilia M. Prêle, PhD; Philip M. Hansbro, PhD; William Scott Argraves, PhD; Rema A. Oliver, PhD; Brian G. Oliver, PhD; Judith L. Black, MBBS, PhD; Janette K. Burgess, PhD
Author and Funding Information

From the Woolcock Institute of Medical Research, The University of Sydney (Mss Jaffar and Unger and Drs B. G. Oliver, Black, and Burgess), Glebe, NSW, Australia; Discipline of Pharmacology, The University of Sydney (Ms Jaffar and Drs Black and Burgess), Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, and Royal Prince Alfred Hospital (Sydney Local Health District) (Ms Jaffar and Drs Corte, Keller, and Burgess), Sydney, NSW, Australia; Cardiovascular Research Institute, University of California San Francisco (Dr Wolters), San Francisco, CA; Department of Respiratory Diseases, University Hospital of Modena, University of Modena and Reggio Emilia (Drs Richeldi and Cerri), Modena, Italy; Department of Interstitial Lung Disease, University of Southampton (Dr Richeldi), Southampton, England; Lung Institute of Western Australia, Centre for Asthma Allergy and Respiratory Research, The University of Western Australia (Dr Prêle), and Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia and Western Australian Institute for Medical Research (Dr Prêle), Perth, WA, Australia; Priority Research Centre for Asthma and Respiratory Disease, The University of Newcastle and Hunter Medical Research Institute (HMRI) (Dr Hansbro), New Lambton Heights, NSW, Australia; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina (Dr Argraves), Charleston, SC; Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School, University of New South Wales (Dr R. A. Oliver), Randwick, NSW, Australia; and School of Medical and Molecular Biosciences, The University of Technology Sydney (Dr B. G. Oliver), Sydney, NSW, Australia.

CORRESPONDENCE TO: Jade Jaffar, BSc, Woolcock Institute of Medical Research, 431 Glebe Point Rd, Level 3 Cell Biology, Glebe, NSW 2037, Australia; e-mail jade.jaffar@sydney.edu.au


Part of this article has been presented and published in abstract form at the American Thoracic Society Annual Scientific Conference, May 17-22, 2013, Philadelphia, PA (Jaffar J, Unger S, Corte T, et al. Am J Respir Crit Care Med. 2013;187[1_MeetingAbstracts]:A3382) and at the Thoracic Society of Australia and New Zealand Annual Scientific Conference, March 23-27, 2013, Darwin, Australia (Jaffar J, Tjin G, Unger S, Black JL, Oliver BG, Burgess JK. Respirology. 2013;18[suppl 2]:27).

FUNDING/SUPPORT: This work was supported by the National Health and Medical Research Council, Australia [Grant 1003263]. Ms Jaffar was supported by a Rebecca L Cooper PhD Scholarship. Dr Burgess was supported by an NHM RC Career Development Fellowship [1032695]. Dr Black was supported by a NHMRC Senior Principal Research [Fellowship 571098]. Dr B. G. Oliver was supported by an NHMRC Career Development [Fellowship 1026880]. Dr Argraves was supported by a National Institutes of Health [Grant HL095067]. Serum acquisition from San Francisco was funded by the Nina Ireland Lung Disease Program.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(4):1055-1063. doi:10.1378/chest.13-2688
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BACKGROUND:  The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fibrosis in IPF.

METHODS:  Serum, lung tissue, and lung function values were obtained from four independent locations (Sydney, NSW, and Perth, WA, Australia; San Francisco, CA; and Modena, Italy). Patients with IPF were followed for a minimum of 1 year and progression was defined as a significant decline in lung function or death. Primary parenchymal lung fibroblasts of 15 patients with and without IPF were cultured under nonstimulatory conditions. Fibulin-1 levels in serum, and secreted or deposited by fibroblasts, were measured by western blot and in lung tissue by immunohistochemistry.

RESULTS:  Serum fibulin-1 levels were increased in patients with IPF compared with subjects without lung disease (P = .006). Furthermore, tissue fibulin-1 levels were increased in patients with IPF (P = .02) and correlated negatively with lung function (r = −0.9, P < .05). Primary parenchymal fibroblasts from patients with IPF produced more fibulin-1 than those from subjects without IPF (P < .05). Finally, serum fibulin-1 levels at first blood draw predicted disease progression in IPF within 1 year (area under the curve , 0.71; 95% CI, 0.57-0.86; P = .012).

CONCLUSIONS:  Fibulin-1 is a novel potential biomarker for disease progression in IPF and raises the possibility that it could be used as a target for the development of new treatments.

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