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


CONCLUSIONS
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.
Ask
Kjetil
K
Department of Pathology and Molecular Medicine, Center for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada. askkj@mcmaster.ca
Labiris
Renee
R
Farkas
Laszlo
L
Moeller
Antje
A
Froese
Aaron
A
Farncombe
Troy
T
McClelland
Grant B
GB
Inman
Mark
M
Gauldie
Jack
J
Kolb
Martin R J
MR
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D018014:Gene Transfer Techniques; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012129:Respiratory Function Tests; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D015291:Transforming Growth Factors / Q000235:genetics
D015291:Transforming Growth Factors; D003094:Collagen; D006909:Hydroxyproline