Targeting fibrosis in respiratory lung disease

Over the years, many factors have been proposed as potential targets for therapeutic intervention in pulmonary fibrosis, and many compounds have been reported to have ‘antifibrotic’ effects. However, till date none of these molecules have had success in delaying the progression of human idiopathic pulmonary fibrosis (IPF). The targets are mostly derived from animal models of lung fibrosis, all of which demonstrate certain aspects of the complex pathobiology. Still, none of the models truly represent human IPF, which could be one of the reasons why targeting these factors has provided ineffective therapies. Another impediment to finding appropriate antifibrotic targets is that the factors responsible for the onset of disease are not necessarily the same as the factors involved in driving the progression. To effectively treat lung fibrosis, several questions need to be addressed, in addition to the identification of appropriate target molecules. Is it possible to efficiently repair or regenerate human lung tissue? What is the importance of circulating progenitor cells in fibrotic disorders? How does the mechanical tension inherent to fibrotic scar tissue modify the pathobiological progression? How does the interpretation of experimental models affect the understanding of human disease? This review will focus on some of these questions and briefly summarize current areas of investigation. We argue that the identification of factors implicated in the progression of pulmonary fibrosis is best assessed in vivo, with the use of animal models that mimic specific (but not all) aspects relevant to human pathobiology. The utilization of stringent ‘preclinical trials’ in animal models will potentially allow us to better characterize factors involved in the progression of fibrosis and establish efficient therapeutic strategies.Section editor:Martin Braddock – AstraZeneca R&D, Charnwood, Loughborough, UK