Real-Life Experience With Pirfenidone in Idiopathic Pulmonary Fibrosis in Argentina. A Retrospective Multicenter Study

Introduction

Pirfenidone was the first antifibrotic drug approved in Argentina for idiopathic pulmonary fibrosis (IPF). Outcomes in real life may differ from the results of clinical trials. The primary endpoint was to study the tolerance of pirfenidone in real life. Secondary endpoints were to analyze effectiveness and reasons for discontinuation.

中药方剂抗肺纤维化方治疗肺纤维化患者的临床研究

〔摘 要〕 目的：研究中药方剂抗肺纤维化方治疗肺纤维化（PF）患者的疗效。方法：选取福建中医药大学附属 第二人民医院 2020 年 3 月至 2021 年 10 月期间收治的 70 例 PF 患者，采用随机数字表法分为对照组与观察组，各 35 例。对照组患者采用常规西药治疗，观察组患者在常规西药治疗基础上采用中药方剂抗肺纤维化方治疗。比较两 组患者的临床疗效、治疗前及治疗 3 个月后中医证候积分、肺功能指标、肺纤维化指标、圣乔治呼吸疾病问卷（SGRQ）、 高分辨计算机断层扫描（HRCT）评分。结果：观察组患者治疗总有效率为 88.67 %，高于对照组的 62.86 %，差异具 有统计学意义（P ＜ 0.05）。治疗后观察组患者的乏力、呼吸气短、自汗、咳嗽评分均低于对照组，差异具有统计学 意义（P ＜ 0.05）。治疗后观察组患者的第 1 秒用力呼气容积（FEV1）、用力肺活量（FVC）、最大呼气流量（PEF） 均高于对照组，差异具有统计学意义（P ＜ 0.05）。治疗后观察组患者的透明质酸（HA）、层粘连蛋白（LN）、 Ⅲ型胶原（Ⅲ –Col）均低于对照组，差异具有统计学意义（P ＜ 0.05）。治疗后观察组患者的 SGRQ、HRCT 评分均 低于对照组，差异具有统计学意义（P ＜ 0.05）。结论：采用中药方剂抗肺纤维化方与常规西药联合治疗 PF 患者， 能进一步改善患者临床症状，降低肺纤维化程度，增强肺功能，提高临床疗效。     

氨氯地平对肺纤维化大鼠的影响研究

目的  研究氨氯地平对大鼠肺纤维化的保护作用和可能的分子机制,为肺纤维化的治疗寻找新的途径。方法  选取240只实验大鼠进行研究,随机分为空白组、模型组、吡非尼酮组和氨氯地平组,每组各60只。模型组、吡非尼酮组和氨氯地平组采用气管内灌注博来霉素建立肺纤维化大鼠模型,空白组则气管内灌注等量生理盐水;然后空白组和模型组大鼠给予相同量生理盐水处理,氨氯地平组大鼠则给予1/2量的氨氯地平和1/2量的生理盐水处理;吡非尼酮组给予1/2量的吡非尼酮和1/2量的生理盐水处理。采用单因素方差分析和u检验分析1、2及4周后4组大鼠肺泡炎、肺纤维化的评分,并分析大鼠的血小板反应蛋白1（TSP-1）、转化生长因子β1（TGF-β1）及I型胶原和III型胶原mRNA的含量变化情况。结果  氨氯地平组和吡非尼酮组大鼠各时间段的TSP-1、TGF-β1及I型胶原和III型胶原mRNA的含量均低于模型组（P <0.05）,且氨氯地平组较吡非尼酮组也降低（P <0.05）,大鼠的肺泡炎和肺纤维化评分结果显示氨氯地平组和吡非尼酮组低于模型组（P <0.05）,且氨氯地平组显著低于吡非尼酮组（P <0.05）。结论  氨氯地平可能通过抑制TGF-β1、TSP-1的生成水平和减少I型胶原和III型胶原mRNA的表达达到减轻大鼠肺组织肺泡炎及肺纤维化程度的临床效果。

     

p63 - Key molecule in the early phase of epithelial abnormality in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is the most common lung disease predisposing lung cancer. To clarify the early phase of epithelial abnormalities in IPF, we used an in vitro squamous metaplasia model, transforming growth factor beta1 (TGF beta1)-treated airway epithelial cells (BEAS-2B). The model repeated the expression of squamous epithelial character, such as involucrin, and keratin 6 and 14. DNA microarray analysis disclosed a unique expression signature in TGF beta1-treated airway epithelial cells, 20 specifically up-regulated genes including p63, jagged 1 (jag1) and the genes of structure proteins. Western blotting and RT-PCR analysis revealed that DeltaNp63alpha was the dominant isoform of p63 in our experimental model. Immunohistochemical analysis demonstrated the expression of p63 and jag1 in lung tissues of IPF. Inhibition of p63 with siRNA caused the down-regulation of jag1 expression, but not of involucrin, or keratin 6 and 14. Interestingly, the up-regulation of p63 was totally suppressed by N-acetyl-l-cysteine (NAC), but not by dexamethasone or pirfenidone. Thus, the p63-jag1 pathway may be up-regulated at an early phase of epithelial abnormalities in IPF, which can be overcome by NAC even in the TGF beta1-rich milieu.     

Effects of pirfenidone on experimental head injury in rats

Traumatic brain injury (TBI) continues to be a significant public healthcare concern. Neuroinflammation that occurs in the secondary phase of TBI leads to cognitive and physical dysfunction. A number of therapeutic modalities have been evaluated in an attempt to find a suitable treatment. The only drug approved for the treatment of idiopathic pulmonary fibrosis, pirfenidone, has been evaluated for its antifibrotic, anti-inflammatory, and anti-oxidant properties for various disorders, but this is the first study to examine its effects in an experimental TBI model. Twenty-four Wistar rats were randomly divided into three groups: control, trauma, and pirfenidone. The two latter groups underwent experimental diffuse cortical injury mimicking TBI. Neurological assessment was performed using the Garcia test, histological analysis was performed to examine neuroprotective and anti-inflammatory effects, and biochemical analyses of neuron-specific enolase (NSE), S-100B, caspase-3, and thiobarbituric acid reactive substances were performed. The pirfenidone group had a better Garcia test score (P=0.001), an increased anti-inflammatory effect (P<0.001), and an enhanced neuroprotective effect (P=0.007) along with decreased NSE, S100B, and TBARS levels compared to the trauma group. However, pirfenidone did not show a beneficial effect on caspase-3 levels. Pirfenidone may help decrease mortality and morbidity rates after TBI through its anti-inflammatory and antioxidant effects.     

Pirfenidone increases the epithelialization rate of skin graft donor sites

Background

Improving epithelialization of donor sites of split-thickness skin grafts (STSG) is extremely important in burned patients. We aimed to assess the efficacy of pirfenidone, a drug with anti-inflammatory, antifibrotic, and antioxidant effects, to accelerate wound healing. We hypothesized that pirfenidone accelerates the epithelialization rates in donor sites.

吡菲尼酮对牛血清蛋白诱导的肝纤维化大鼠肝损害的保护作用观察

目的探讨吡菲尼酮对牛血清蛋白诱导的大鼠肝纤维化的影响。方法雄性Wistar大鼠30只被随机分为3组,给予模型组腹腔注射牛血清白蛋白,正常对照组接受等量的生理盐水腹腔注射,治疗组在腹腔注射牛血清白蛋白5 w后,按200 mg·kg-1·d-1灌胃给药吡菲尼酮,治疗4 w后处死试验动物,留取肝脏组织,行HE和Masson染色,观察肝脏病理学改变,采用免疫组化法检测Smad6蛋白表达。结果与模型组比,吡菲尼酮治疗组肝组织纤维化S3和S4期病变较模型组明显减少,炎症细胞浸润明显减少,胶原纤维间隔缩小,着色变浅;模型组肝组织Smad6相对表达量为(108.2±33.6),显著低于吡菲尼酮治疗组[(329.4±39.2),P0.05]。结论吡菲尼酮可抑制牛血清蛋白诱导的大鼠肝纤维化,其机制与通过上调Smad 6蛋白表达有关。