5. PFD in combination with BIBF is more effective in improving pulmonary function than the monotherapy in late silicosis mice.
In consideration of the assessment findings from previous monotherapy experiments, our therapeutic approach in combination drug administration entails the utilization of high-dose PFD, high-dose BIBF, as well as the concurrent administration of PFD and BIBF at both high and low dosages (Fig 6A). Our evaluation commenced with an examination of pulmonary function as the initial parameter to gauge the effectiveness of the combination therapy at a holistic level. Primarily, by focusing on the pulmonary capacity indicator IC (Fig 6B) and FVC (Fig 6C), we observed that combination therapy outperformed monotherapy in augmenting lung volume. Importantly, the efficacy of the combined intervention remained relatively consistent across both high and low dosage regimens. The subsequent area of investigation pertained to the flow rate indicator, wherein it was found that combination therapy exhibited equivalent efficacy to PFD monotherapy in enhancing FEV100 (Fig 6D). However, combination therapy showed a significant superiority in the enhancement of MMEF (Fig 6E). Additionally, the combined administration approach also exhibited enhanced efficacy over monotherapy in terms of resistance and compliance, leading to reduced resistance (Fig 6F) and improved dynamic (Fig 6G) and static compliance (Fig 6H). From multiple perspectives, including lung capacity, flow rate, resistance, and compliance, the combined administration approach demonstrated superior outcomes. Hence, it is a promising candidate for novel antifibrotic therapy, warranting further investigation through clinical trials and potential implementation.