Comparison between conventional and "clinical" assessment of experimental lung fibrosis

Kjetil Ask^*¹^,2 , Renee Labiris^*² , Laszlo Farkas² , Antje Moeller² , Aaron Froese² , Troy Farncombe³ , Grant B McClelland⁴ , Mark Inman² , Jack Gauldie¹ and Martin RJ Kolb¹^,2

¹Department of Pathology and Molecular Medicine, Center for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada

²Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario, Canada

³Department of Nuclear Medicine, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada

⁴Department of Biology, Life Sciences, McMaster University, Hamilton, Ontario, Canada

author email corresponding author email* Contributed equally

Journal of Translational Medicine 2008, 6:16doi:10.1186/1479-5876-6-16


Published:	10 April 2008

Abstract

Background

Idiopathic pulmonary fibrosis (IPF) is a treatment resistant disease with poor prognosis. Numerous compounds have been demonstrated to efficiently prevent pulmonary fibrosis (PF) in animal models but only a few were successful when given to animals with established fibrosis. Major concerns of current PF models are spontaneous resolution and high variability of fibrosis, and the lack of assessment methods that can allow to monitor the effect of drugs in individual animals over time. We used a model of experimental PF in rats and compare parameters obtained in living animals with conventional assessment tools that require removal of the lungs.

Methods

PF was induced in rats by adenoviral gene transfer of transforming growth factor-beta. Morphological and functional changes were assessed for up to 56 days by micro-CT, lung compliance (measured via a mechanical ventilator) and VO₂max and compared to histomorphometry and hydroxyproline content.

Results

Standard histological and collagen assessment confirmed the persistent fibrotic phenotype as described before. The histomorphological scores correlated both to radiological (r²= 0.29, p < 0.01) and functional changes (r²= 0.51, p < 0.0001). VO₂max did not correlate with fibrosis.

Conclusion

The progression of pulmonary fibrosis can be reliably assessed and followed in living animals over time using invasive, non-terminal compliance measurements and micro-CT. This approach directly translates to the management of patients with IPF and allows to monitor therapeutic effects in drug intervention studies.