Idiopathic pulmonary fibrosis: emerging concepts on pharmacotherapy

Expert Opin Pharmacother. 2004 Aug;5(8):1671-86. doi: 10.1517/14656566.5.8.1671.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrosing disease of the distal air spaces of the lung of unknown aetiology. IPF is usually fatal with a median survival of < 3 years. There are currently no effective pharmacotherapeutic agents for the treatment of IPF. In this review, unifying concepts on the pathogenesis of IPF based on understanding of host responses to tissue injury are presented. These host responses involve tightly regulated and contextually orchestrated inflammatory and repair processes. Dysregulation of either of these processes can lead to pathological outcomes. Fibrosis results from an exaggerated or dysregulated repair process that proceeds 'uncontrolled' even after inflammatory responses have subsided. Disease heterogeneity may arise when inflammation and repair are in different (dys)regulatory phases, thus accounting for regional disparity. Usual interstitial pneumonia (UIP), the histopathological correlate of clinical IPF, represents a more fibrotic tissue reaction pattern and for which anti-inflammatory agents are ineffective. Emerging 'antifibrotic' drugs and strategies for UIP/IPF are discussed. The importance of accurately phenotyping a highly heterogeneous disease process that may require individualised and 'combined' therapies is emphasised.

Publication types

  • Review

MeSH terms

  • Acetylcysteine / therapeutic use
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antibodies, Monoclonal / therapeutic use
  • Connective Tissue Growth Factor
  • Eicosanoids / metabolism
  • Endothelin-1 / antagonists & inhibitors
  • Humans
  • Immediate-Early Proteins / antagonists & inhibitors
  • Intercellular Signaling Peptides and Proteins
  • Interferon-gamma / therapeutic use
  • Molybdenum / therapeutic use
  • Protein Kinase Inhibitors / therapeutic use
  • Proteins / antagonists & inhibitors
  • Pulmonary Fibrosis / drug therapy*
  • Pulmonary Fibrosis / physiopathology
  • Pyridones / therapeutic use
  • Recombinant Proteins / therapeutic use
  • Relaxin / therapeutic use
  • Renin-Angiotensin System / drug effects
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Monoclonal
  • CCN2 protein, human
  • Eicosanoids
  • Endothelin-1
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Protein Kinase Inhibitors
  • Proteins
  • Pyridones
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Connective Tissue Growth Factor
  • Molybdenum
  • Interferon-gamma
  • Relaxin
  • tetrathiomolybdate
  • pirfenidone
  • Acetylcysteine