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.