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

Ask K, Labiris R, Farkas L, Moeller A, Froese A, Farncombe T, McClelland GB, Inman M, Gauldie J, Kolb MR - J Transl Med (2008)

Bottom Line: 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).This approach directly translates to the management of patients with IPF and allows to monitor therapeutic effects in drug intervention studies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology and Molecular Medicine, Center for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada. askkj@mcmaster.ca

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.

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Correlations. Correlations between (A) histological fibrotic score and the parameter K (n = 57), (B) fibrotic score and absolute fibrotic volume (n = 20), (C) parameter K and absolute fibrotic volume (n = 18) and (D) fibrotic score and VO2max (n = 41).
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Figure 5: Correlations. Correlations between (A) histological fibrotic score and the parameter K (n = 57), (B) fibrotic score and absolute fibrotic volume (n = 20), (C) parameter K and absolute fibrotic volume (n = 18) and (D) fibrotic score and VO2max (n = 41).

Mentions: The histomorphology score (Ashcroft) was compared to lung function, and showed an excellent correlation to the parameter k (Fig 5A, p < 0.0001). The fibrotic volumes in micro-CT, defined as high dense voxels comprised between -100 to +200 HU, correlated both with the fibrotic score (p = 0.014, Figure 5B) and to the parameter k (p = 0.035, Figure 5C). There was no correlation to the decrease in VO2 max (Figure 5D).


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

Ask K, Labiris R, Farkas L, Moeller A, Froese A, Farncombe T, McClelland GB, Inman M, Gauldie J, Kolb MR - J Transl Med (2008)

Correlations. Correlations between (A) histological fibrotic score and the parameter K (n = 57), (B) fibrotic score and absolute fibrotic volume (n = 20), (C) parameter K and absolute fibrotic volume (n = 18) and (D) fibrotic score and VO2max (n = 41).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2365932&req=5

Figure 5: Correlations. Correlations between (A) histological fibrotic score and the parameter K (n = 57), (B) fibrotic score and absolute fibrotic volume (n = 20), (C) parameter K and absolute fibrotic volume (n = 18) and (D) fibrotic score and VO2max (n = 41).
Mentions: The histomorphology score (Ashcroft) was compared to lung function, and showed an excellent correlation to the parameter k (Fig 5A, p < 0.0001). The fibrotic volumes in micro-CT, defined as high dense voxels comprised between -100 to +200 HU, correlated both with the fibrotic score (p = 0.014, Figure 5B) and to the parameter k (p = 0.035, Figure 5C). There was no correlation to the decrease in VO2 max (Figure 5D).

Bottom Line: 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).This approach directly translates to the management of patients with IPF and allows to monitor therapeutic effects in drug intervention studies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology and Molecular Medicine, Center for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada. askkj@mcmaster.ca

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.

Show MeSH
Related in: MedlinePlus