Beyond the diagnosis of idiopathic pulmonary fibrosis; the growing role of systems biology and stratified medicine

Curr Opin Pulm Med. 2013 Sep;19(5):460-5. doi: 10.1097/MCP.0b013e328363f4b7.

Abstract

Purpose of review: Idiopathic pulmonary fibrosis (IPF) is a progressive, invariably fatal condition with a median survival from diagnosis of only 3 years. Despite improvements in disease understanding, challenges remain in establishing a diagnosis and predicting prognosis in individual patients. Furthermore, limited understanding of the key pathogenetic mechanisms driving disease is hampering development of new therapies. This review outlines progress that has been made in applying systems biology to IPF and the insights into disease pathogenesis, diagnosis and monitoring that this research is providing.

Recent findings: Large-scale genome-wide association studies have highlighted polymorphisms in genes involved in epithelial integrity and host defense including MUC5B and TOLLIP. Whole blood transcriptomics points towards changes in immune cell regulation that influence the progression of fibrosis. Proteomic studies have identified serum proteins, including matrix metalloproteinase 7 and CC chemokine ligand (CCL)-18, which associate with disease severity and predict prognosis.

Summary: Use of molecular research techniques in large populations of well-phenotyped patients is leading to major advances in understanding of IPF. As new treatments for IPF emerge, it is to be hoped that careful application of these findings will enable the targeting of therapy to individuals based on the predominant mechanisms driving progression of their disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Gene Expression Profiling*
  • Humans
  • Idiopathic Pulmonary Fibrosis / diagnosis*
  • Idiopathic Pulmonary Fibrosis / genetics*
  • Idiopathic Pulmonary Fibrosis / therapy
  • Intracellular Signaling Peptides and Proteins / genetics
  • Mucin-5B / genetics
  • Polymorphism, Genetic / genetics
  • Prognosis
  • Proteomics*
  • Severity of Illness Index
  • Systems Biology*

Substances

  • Intracellular Signaling Peptides and Proteins
  • MUC5B protein, human
  • Mucin-5B
  • TOLLIP protein, human