PT  - JOURNAL ARTICLE
AU  - Wim A Wuyts
AU  - C Agostini
AU  - KM Antoniou
AU  - D Bouros
AU  - RC Chambers
AU  - V Cottin
AU  - JJ Egan
AU  - BN Lambrecht
AU  - R Lories
AU  - H Parfrey
AU  - A Prasse
AU  - C Robalo-Cordeiro
AU  - E Verbeken
AU  - JA Verschakelen
AU  - AU Wells
AU  - GM Verleden
TI  - The pathogenesis of pulmonary fibrosis: a moving target
AID  - 10.1183/09031936.00073012
DP  - 2012 Jan 01
TA  - European Respiratory Journal
PG  - erj00730-2012
4099  - http://erj.ersjournals.com/content/early/2012/10/25/09031936.00073012.short
4100  - http://erj.ersjournals.com/content/early/2012/10/25/09031936.00073012.full
AB  - Pulmonary fibrosis is the end stage of many diffuse parenchymal lung diseases. It is characterised by excessive matrix formation leading to destruction of the normal lung architecture and finally death. Despite an exponential increase in our understanding of potentially important mediators and mechanisms, the delineation of primary pathways has proven to be elusive.In this paper susceptibility and injurious agents such as viruses and gastroesophageal reflux and their likely role in initiating disease are discussed. Further topics that are elaborated are candidate ancillary pathways, including immune mechanisms, oxidative and endoplasmic reticulum stress, activation of the coagulation cascade and the potential role of stem cells. The paper will try to provide the reader with an integrated view on the current knowledge and attempts to provide a road map for future research.It is important to explore robust models of overall pathogenesis, reconciling a large number of clinical and scientific observations. We believe that the integration of current data into a "big picture" overview of fibrogenesis is essential for the development of effective antifibrotic strategies. The latter will likely consist of a combination of agents targeting a number of key pathways.