Results
1. Pirfenidone was
superior to nintedanib in improving lung function in mice with fibrotic
silicosis.
When administered as a preventive or early intervention measure, many
drugs have shown benefit in animal models, potentially due to their
involvement in the initial response though, quite different from real
clinical scenarios. To investigate the therapeutic effects of PFD and
BIBF on silicosis, we opted to establish a late-stage fibrotic silicosis
mouse model induced for 6 weeks, thereby enhancing the clinical
applicability of these two drugs in the treatment of silicosis (Fig 1A).
As commonly acknowledged, pulmonary fibrosis makes important influences
on lung functions (PFT animal lung function test system), which can
seriously affect lung volume indexes, flow rate indexes, as well as
resistance and compliance indexes. Compared with silicosis mice, both
low and high doses of PFD and BIBF served essentially the same purpose
in IC (Fig 1B), while in terms of FVC, PFD manifestly outperformed BIBF
(Fig 1C). With respect to pulmonary ventilation defects, as observed in
Figure 1D and E, PFD in a dose-dependent manner proved to be identical
to BIBF in improving forced
expiratory volume in FEV100, but more capable of meliorating MMEF than
BIBF. In pulmonary fibrosis, poor tissue stiffness can lead to
alterations in respiratory mechanical prosperities (compliance and
resistance). An increase in RI has been associated with the progression
of pulmonary fibrosis, however, BIBF inferiors to PFD, but still could
decrease this resistance to facilitate aerated lung in a dose-dependent
fashion (Fig 1F). Additionally, lung compliance composed of
Cdyn (Fig 1G) and Cchord (Fig 1H)
showed a strongly downward trend with fibrosis, which was elevated by
PFD or BIBF. Collectively, PFD significantly favored over BIBF, exerted
therapeutic effects on lung functions of silicosis mice. Moreover, these
therapeutic effects on lung function were enhanced with dose to a
certain extent.