ObjectiveTo evaluate the clinical efficacy and safety of pirfenidone in Chinese patients with idiopathic pulmonary fibrosis (IPF). MethodsIn a multicenter,randomized,double-blind,comparative clinical trial,87 patients with IPF were randomly divided into two groups. Group A (43 patients) were treated with pirfenidone (1 200 mg per day) for 48 weeks,while Group B (44 patients) were treated with placebo. Clinical features were compared between two groups including efficacy indicators (pulmonary function,6MWT,and quality of life scores) and safety indicators (incidence of adverse events). ResultsForced vital capacity (FVC) was increased by (90±410)mL in Group A and decreased by (70±310)mL in Group B (P<0.05);In Group A,forced expiratory volume in 1 second was raised by (100±330)mL and (110±240)mL following 12 and 24 weeks after treatment,significantly different from group B (P<0.05). There were significant differences in 6MWT between two groups 36 and 48 weeks after treatment respectively(both P<0.05). Quality of life scores,including the St. George's score (excluding symptoms) and dyspnea score,were significantly higher in Group A than Group B (both P<0.05). There was no significant difference in the incidence of adverse events between Groups A and B (83.72% vs. 72.73%,P>0.05). ConclusionDomestic pirfenidone is clinically effective and safe for the treatment of IPF in Chinese patients.
ObjectiveTo evaluate the efficacy and safety of pirfenidone in patients with idiopathic pulmonary fibrosis. MethodsPubMed, Cochrane Library, CNKI, CBM, Wanfang, and VIP databases were searched for randomized controlled trials of pirfenidone as interventions for the treatment of idiopathic pulmonary fibrosis. According to the Cochrane system evaluation method, the methodological quality of included studies was evaluated and the effective data were extracted. The meta-analysis was performed with RevMan 5.2 software. ResultsSix studies were included with 1727 patients in total. Compared with placebo groups, pirfenidon could improve the changing rate of vital capacity at the end of the treatment[WMD=0.06, 95% CI (0.01, 0.12), Z=2.48, P=0.01; heterogeneity inspection χ2=1.03, P=0.31]. Pirfenidon could not improve the changing rate of lowest SpO2 in 6-minute walking test[WMD=0.82, 95% CI (-1.35, 2.98), Z=0.74, P=0.46; heterogeneity inspection χ2=8.90, P=0.003] and could not reduce the mortality[RR=0.62, 95% CI (0.37, 1.03), Z=1.85, P=0.06; heterogeneity inspection χ2=3.05, P=0.55]. The incidences of photosensitivity, dizziness, nausea, abdominal discomfort, joint pain, fatigue in pirfenidone group were more frequent than those in placebo group. ConclusionsBecause of lack of enough eligible studies and defects in design and reporting data in the studies, this meta-analysis can not evaluate pirfenidone's long-term efficacy and safety. Hence, the existed clinical evidences can't support pirfenidone to be the treatment of IPF medication.
Objective To investigate the effects of transforming growth factor beta (TGF-β) on airway remodeling in obese asthmatic mice and intervention effects of pirfenidone. Methods Seventy-five C57BL/6J mice were randomly divided into five groups, namely a blank control group (group A), an obese group (group B), an obese asthmatic group (group C), a budesonide treatment group (group D) and a pirfenidone treatment group (group E). The mice in the B, C, D, and E groups were fed with high fat diets, then the mice in the C, D, and E groups were sensitized and challenged with ovalbumin (OVA) to establish the model of chronic obese asthma. The mice in group A were fed with normal diets, sensitized and challenged with normal saline. The mice in group D were treated with budesonide (0.5 mg/ml), and the mice in group E were treated with pirfenidone (300 mg/kg). After 4 weeks of treatment, the total number of white cells as well as the percentage of leukocytes, eosinophils, neutrophils and macrophage in bronchoalveolar lavage fluid (BALF) were counted. ELISA and Western blot were used to evaluate the expression of TGF-β. The pathological changes of mice were observed under light microscope by HE and periodic acid-Schiff staining. Meanwhile the remodeling indices were measured including total bronchial wall area (WAt), smooth muscle area (WAm), and bronchial basement membrane perimeter (Pbm). Results The levels of leukocyte and eosinophils in BALF, expression of TGF-β, WAt/Pbm and WAm/Pbm in group C were higher than those in group A, B, D, and E (allP<0.05). The levels of eosinophils in BALF, WAt/Pbm in group E were lower than those in group D (allP<0.05). The level of TGF-β decreased in a sequence of group C>D>E>B>A (allP<0.05). The expression of TGF-β was in a positive correlation with eosinophil percentage in BALF (r=0.79,P<0.01). Conclusions The expression of TGF-β in the airway of obese asthmatic mice is closely related to airway inflammation, airway hyper-secretion and airway remodeling. Pirfenidone can effectively inhibit the expression of TGF-β and improve airway remodeling.
After pirfenidone and nintedanib showed efficacy, drug treatment for idiopathic pulmonary fibrosis began to focused on anti-fibrosis. Current research on idiopathic pulmonary fibrosis mainly focus on the pathogenesis and therapeutic targets, and more targeted drugs are gradually entering clinical trials. This article summarizes the results of recent studies on the treatment of idiopathic pulmonary fibrosis with pirfenidone and nintedanib alone or in combination by searching the literature, and reviews the mechanism and test results of the new target anti-fibrosis drugs based on molecular biology that are currently undergoing clinical research in various phases, and aims to provide a basis for how to choose drugs to treat idiopathic pulmonary fibrosis.