Study of Diagnostic and Predictive Biomarkers of Idiopathic Pulmonary Fibrosis

Armen Hareyan's picture

The recent failure of the drug Actimmune as a treatment for idiopathic pulmonary fibrosis (IPF) in a late-stage clinical trial has highlighted the need for better diagnostic markers for the disease in earlier stage trials. Researchers at the Dorothy P. & Richard P. Simmons Center for Interstitial Lung Disease at the University of Pittsburgh School of Medicine are currently recruiting several hundred patients with IPF for a study of clinical, biochemical and genetic changes that may occur as the result of treatment or progression of the disease.

The aim of this study is to identify biological "markers" in blood samples that can be used to develop a simple blood test for diagnosing the disease and predicting its outcome. To achieve this aim, investigators at the Simmons Center will collect and analyze blood samples from a large cohort of people with IPF for a period of up to five years as they receive treatment according to the latest guidelines. The researchers also will provide ongoing, standard-care follow-up of patients every three to four months, evaluating them for signs of clinical changes. Where indicated, participants also will receive a computerized tomography scan and a lung biopsy to confirm their diagnosis.


IPF is a progressively debilitating lung disease for which there is no cure and few effective therapies. The cause of the disease is unknown, but the natural history is characterized by gradually worsening shortness of breath and diminished capacity for physical activity as a consequence of inflammation-related scarring, or fibrosis, in lung tissue and loss of lung function. The median survival of patients with biopsy-confirmed IPF is less than three years without a lung transplant. Nevertheless, the course of the disease often is variable from one patient to another.

IPF patients often don't receive an accurate diagnosis for months or years due to lack of clinical expertise in this disorder and because its symptoms are sometimes similar to other respiratory disorders. For some patients, an accurate diagnosis is only made after a lung biopsy, a painful and invasive procedure. Investigators at the Simmons Center, which is directed by Naftali Kaminski, M.D., associate professor of medicine and human genetics, and Kevin F. Gibson, M.D., associate professor of pulmonary, allergy and critical care medicine, at the University of Pittsburgh School of Medicine, are studying the use of advanced genetics and genomics tools to more accurately and less invasively diagnose and predict the course of IPF and other lung diseases.

To identify biological markers in the blood, the investigators will look for specific proteins known to be overabundant in the lungs of people with IPF and examine how they behave in the blood. The investigators will analyze the gene expression signatures of certain blood cells using genomic microarrays, a sophisticated assay for measuring the activity, or expression, of all the genes in the human genome. The microarray analyses will help the Simmons Center researchers determine if the genomic expression patterns of people with IPF have diagnostic value and are relevant to disease progression and treatment.

Ultimately, the investigators will examine how these findings differ between patients whose condition deteriorates during the course of the study and those whose condition does not deteriorate. By applying advanced bioinformatics approaches, they hope to identify markers that are predictive of disease outcome in IPF patients. They expect these observations will lead to the development of new and easily accessible diagnostic approaches for IPF. In addition, findings may yield exciting new insights about the role of natural immunity in IPF progression.