Biomarkers for idiopathic pulmonary fibrosis identified

[Guest guest]

Biomarkers for idiopathic pulmonary fibrosis identified

Science Centric, Sofia Town,Bulgaria*

1 May 2008 18:38 GMT

http://www.sciencecentric.com/news/08050123.htm

The first evidence of a distinctive protein signature that could

help to transform the diagnosis and improve the monitoring of the

devastating lung disease idiopathic pulmonary fibrosis (IPF) is

being reported by University of Pittsburgh School of Medicine

researchers in this month's edition of PLoS Medicine, an open-access

journal of the Public Library of Science.

In the paper, Naftali Kaminski, M.D., director of the Dorothy P. and

P. Centre for Interstitial Lung Disease in the

Division of Pulmonary, Allergy and Critical Medicine at the

University of Pittsburgh School of Medicine, and his colleagues

describe a unique combination of blood proteins that appears to

distinguish IPF patients from normal controls with extraordinary

sensitivity and precision.

'Our findings suggest that we may be able to monitor what is

happening in the lungs by measuring certain proteins in the

peripheral blood,' explains senior author Dr Kaminski, who also is

associate professor of medicine. 'More study is needed to confirm

whether these biomarkers might be useful as a clinical blood test to

detect lung fibrosis. But right now, there is no straightforward

test for IPF. The lung is not highly accessible; biopsy procedures

carry risk, and while imaging is good, it can't follow the disease

biologically.'

IPF is a degenerative illness distinguished by progressive lung

scarring and diminished breathing capacity, typically leading to

death within about five years of diagnosis. It is estimated that 5

million people worldwide and 130,000 in the United States are

affected by pulmonary fibrosis and about 30,000 people die of the

disease every year.

For this study, researchers analysed the concentrations of 49

proteins in the plasma of 74 patients with IPF and 53 normal

controls. A combination of five proteins related to normal tissue

breakdown and remodelling and certain disease processes, including

arthritis and cancer, was found to be highly indicative of IPF.

Increases in two of the five, matrix metalloproteinases (MMP) 7 and

1, also were observed in tissue and fluid taken from the lungs of

IPF patients. Other proteins in the IPF signature are matrix

metalloproteinase 8, insulin-like growth factor binding protein 1

and tumour necrosis factor receptor superfamily member 1A.

'These proteins were increased in IPF patients, but not in patients

with lung illnesses such as chronic obstructive pulmonary disease,'

says Ivan O. s, M.D., first author on the study and assistant

professor of medicine, University of Pittsburgh School of Medicine.

Elevated MMP1 and MMP7 also distinguished IPF when compared to

levels associated with another disease that closely mimics IPF,

called subacute/chronic hypersensitivity pneumonia. In particular,

increased concentrations of MMP7 'may be indicative of asymptomatic

lung disease and perhaps reflect disease progression,' Dr s says.

'One of the challenges is to know whether a blood protein actually

reflects the situation in the lung,' notes J. s,

Ph.D., study co-first author and research assistant professor in the

Division of Pulmonary, Allergy and Critical Care Medicine,

University of Pittsburgh School of Medicine. The team evaluated all

the genes expressed in IPF-affected lung tissue to determine the

proteins in the peripheral blood on which they should focus. Based

on their detailed analysis, the team believes that increased levels

of these five proteins probably are reflective of the disease.

'IPF can have a slow progression, so drug companies may wait a long

time to see whether a particular drug is having any effect,' says Dr

Kaminski. 'But a blood biomarker could indicate whether a drug is

working earlier. The biomarkers also might be used for risk

assessment and for evaluation of disease progression.'

Some known causes of pulmonary fibrosis include occupational and

environmental exposure to asbestos, metal dust, farming chemicals

and mould, an inflammatory disease called sarcoidosis, radiation,

drug reactions, autoimmune disorders and possibly a genetic

predisposition, according to the American Lung Association.

Most cases are considered to be idiopathic, or of unknown origin.

There is no proven effective therapy for IPF, and most drug

interventions are considered experimental. Long-term benefit may be

possible with lung transplantation, a radical approach dependent

upon a limited number of donated organs.

Source: University of Pittsburgh Schools of the Health Sciences