Tetrandrine slows the radiographic progression of progressive massive fibrosis in pneumoconiosis: a retrospective cohort study.

OBJECTIVE: This study aims to explore the clinical effect of Tetrandrine (Tet) on progressive massive fibrosis (PMF) of pneumoconiosis. METHODS: This retrospective study collected 344 pneumoconiosis patients with PMF, and 127 were eligible for the final analysis, including 57 patients in the Tet group and 70 patients in the control group. The progress of imaging and lung function were compared between the two groups. RESULTS: After 13 months (median) of treatment, the size of PMF was smaller in the Tet group than that in the control group (1526 vs. 2306, p=0.001), and the size was stable in the Tet group (1568 vs. 1526, p= 0.381), while progressed significantly in the control group (2055 vs. 2306, p=0.000). The small nodule profusion and emphysema were also milder than that in the control group (6.0 vs. 7.5, p=0.046 and 8.0 vs. 12, p=0.016 respectively). Pulmonary ventilation function parameters FVC and FEV1 improved in the Tet group (3222 vs. 3301, p=0.021; 2202 vs. 2259, p=0.025 respectively) and decreased in the control group (3272 vs. 3185, p= 0.00; 2094 vs. 1981, p=0.00 respectively). FEV1/FVC was also significantly higher in the Tet group than that in the control group (68.45vs. 60.74, p=0.001). However, similar result was failed to observed for DLco%, which showed a significant decrease in both groups. CONCLUSION: Tet has shown great potential in the treatment of PMF by slowing the progression of pulmonary fibrosis and the decline of lung function.

Mitochondrial folate pathway regulates myofibroblast differentiation and silica-induced pulmonary fibrosis.

BACKGROUND: Silica-induced pulmonary fibrosis (silicosis) is a diffuse interstitial fibrotic disease characterized by the massive deposition of extracellular matrix in lung tissue. Fibroblast to myofibroblast differentiation is crucial for the disease progression. Inhibiting myofibroblast differentiation may be an effective way for pulmonary fibrosis treatment. METHODS: The experiments were conducted in TGF-ß treated human lung fibroblasts to induce myofibroblast differentiation in vitro and silica treated mice to induce pulmonary fibrosis in vivo. RESULTS: By quantitative mass spectrometry, we revealed that proteins involved in mitochondrial folate metabolism were specifically upregulated during myofibroblast differentiation following TGF-ß stimulation. The expression level of proteins in mitochondrial folate pathway, MTHFD2 and SLC25A32, negatively regulated myofibroblast differentiation. Moreover, plasma folate concentration was significantly reduced in patients and mice with silicosis. Folate supplementation elevated the expression of MTHFD2 and SLC25A32, alleviated oxidative stress and effectively suppressed myofibroblast differentiation and silica-induced pulmonary fibrosis in mice. CONCLUSION: Our study suggests that mitochondrial folate pathway regulates myofibroblast differentiation and could serve as a potential target for ameliorating silica-induced pulmonary fibrosis.

[Establishment of transbronchoscope whole lung lavage and its comparison with bronchoalveolar lavage and whole lung lavage].

OBJECTIVE: To establish the technical specifications of transbronchoscope whole lung lavage (TBWLL) and to compare the clinical efficacy between TBWLL and bronchoalveolar lavage (BAL) or whole lung lavage (WLL). METHODS: A total of 133 patients with pneumoconiosis admitted to Hunan Prevention and Treatment Institute for Occupational Diseases from 2009 to 2014 were divided into TBWLL group (n=43), BAL group (n=45), and WLL group (n=45). Patients in the TBWLL group received conventional BAL of both lungs under a fiber bronchoscope, as well as sedation and anesthesia; lavage was performed twice in each course. TBWLL was compared with the BAL and WLL in terms of lavage volume. The clinical symptoms, pulmonary function, and blood gas before and after treatment and the safety were evaluated. RESULTS: The TBWLL group had significantly relieved cough and limitation of activity after lavage (P<0.05). Compared with the BAL group, the TBWLL group had significantly increased single lavage volumes and total lavage volume and a significantly shortened length of hospital stay (P<0.05). The three groups showed no significant short-term changes in clinical symptoms and pulmonary function after lavage. The TBWLL and WLL groups had a significantly lower incidence of postoperative complications than the BAL group (P<0.05). CONCLUSION: TBWLL has good clinical efficacy, with the advantages of BAL and WLL, and is highly feasible, safe, and effective.