Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has an extremely poor prognosis and there is currently no effective treatment for this condition. Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) improves oxygenation, but it is unclear whether treatment of AE-IPF with PMX-DHP affects survival. This study elucidated the effectiveness and safety of PMX-DHP for the treatment of AE-IPF. This study included 31 patients with 41 episodes of AE-IPF. All patients received steroids. Of 31, 14 patients (20 episodes) were treated with PMX-DHP. The laboratory and physiological test results after the start of therapy and survival were retrospectively compared between patients treated with and without PMX-DHP. Patients treated with PMX-DHP had a significantly greater change in PaO₂/FiO₂ ratio (mean ± SEM, 58.2 ± 22.5 vs. 0.7 ± 13.3, p = 0.034) and a smaller change in white blood cell count (−630 ± 959 /μL vs. 4500 ± 1190 /μL, p = 0.002) after 2 days of treatment than patients treated without PMX-DHP. The 12-month survival rate was significantly higher in patients treated with PMX-DHP (48.2% vs. 5.9%, p = 0.041). PMX-DHP was effective in patients with more severe underlying disease (GAP stages II or III; 12-month survival rate 57.1% with PMX-DHP vs. 0% without PMX-DHP, p = 0.021). Treatment with PMX-DHP was an independent predictor of better prognosis (hazard ratio 0.345, p = 0.037). Mild pulmonary thromboembolism occurred in one patient treated with PMX-DHP. Treatment of AE-IPF with PMX-DHP is tolerable and improves 12-month survival.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis and no curative therapies. SCF-Skp2 E3 ligase is a target for cancer therapy, but there have been no reports about Skp2 as a target for IPF. Here we demonstrate that Skp2 is a promising therapeutic target for IPF. We examined whether disrupting Skp2 suppressed pulmonary fibrosis in a bleomycin (BLM)-induced mouse model and found that pulmonary fibrosis was significantly suppressed in Skp2-deficient mice compared with controls. The pulmonary accumulation of fibrotic markers such as collagen type 1 and fibronectin in BLM-infused mice was decreased in Skp2-deficient mice. Moreover, the number of bronchoalveolar lavage fluid cells accompanied with pulmonary fibrosis was significantly diminished. Levels of the Skp2 target p27 were significantly decreased by BLM-administration in wild-type mice, but recovered in Skp2^−/− mice. In vimentin-positive mesenchymal fibroblasts, the decrease of p27-positive cells and increase of Ki67-positive cells by BLM-administration was suppressed by Skp2-deficency. As these results suggested that inhibiting Skp2 might be effective for BLM-induced pulmonary fibrosis, we next performed a treatment experiment using the Skp2 inhibitor SZL-P1-41. As expected, BLM-induced pulmonary fibrosis was significantly inhibited by SZL-P1-41. Moreover, p27 levels were increased by the SZL-P1-41 treatment, suggesting p27 may be an important Skp2 target for BLM-induced pulmonary fibrosis. Our study suggests that Skp2 is a potential molecular target for human pulmonary fibrosis including IPF.