ABSTRACT
ABSTRACT Idiopathic pulmonary fibrosis (IPF) is a form of chronic interstitial lung disease of unknown cause, which predominantly affects elderly men who are current or former smokers. Even though it is an uncommon disease, it is of great importance because of its severity and poor prognosis. In recent decades, several pharmacological treatment modalities have been investigated for the treatment of this disease, and the classic concepts have therefore been revised. The purpose of these guidelines was to define evidence-based recommendations regarding the use of pharmacological agents in the treatment of IPF in Brazil. We sought to provide guidance on the practical issues faced by clinicians in their daily lives. Patients of interest, Intervention to be studied, Comparison of intervention and Outcome of interest (PICO)-style questions were formulated to address aspects related to the use of corticosteroids, N-acetylcysteine, gastroesophageal reflux medications, endothelin-receptor antagonists, phosphodiesterase-5 inhibitors, pirfenidone, and nintedanib. To formulate the PICO questions, a group of Brazilian specialists working in the area was assembled and an extensive review of the literature on the subject was carried out. Previously published systematic reviews with meta-analyses were analyzed for the strength of the compiled evidence, and, on that basis, recommendations were developed by employing the Grading of Recommendations Assessment, Development and Evaluation approach. The authors believe that the present document represents an important advance to be incorporated in the approach to patients with IPF, aiming mainly to improve its management, and can become an auxiliary tool for defining public policies related to IPF.
RESUMO A fibrose pulmonar idiopática (FPI) é uma forma de pneumopatia intersticial crônica fibrosante de causa desconhecida, que acomete preferencialmente homens idosos, com história atual ou pregressa de tabagismo. Mesmo sendo uma doença incomum, ela assume grande importância devido a sua gravidade e prognóstico reservado. Nas últimas décadas, diversas modalidades terapêuticas farmacológicas foram investigadas para o tratamento dessa doença, de tal modo que conceitos clássicos vêm sendo revisados. O objetivo destas diretrizes foi definir recomendações brasileiras baseadas em evidências em relação ao emprego de agentes farmacológicos no tratamento da FPI. Procurou-se fornecer orientações a questões de ordem prática, enfrentadas pelos clínicos no seu cotidiano. As perguntas PICO (acrônimo baseado em perguntas referentes aos Pacientes de interesse, Intervenção a ser estudada, Comparação da intervenção e Outcome [desfecho] de interesse) abordaram aspectos relativos ao uso de corticosteroides, N-acetilcisteína, tratamento medicamentoso do refluxo gastroesofágico, inibidores dos receptores da endotelina, inibidores da fosfodiesterase-5, pirfenidona e nintedanibe. Para a formulação das perguntas PICO, um grupo de especialistas brasileiros atuantes na área foi reunido, sendo realizada uma extensa revisão bibliográfica sobre o tema. As revisões sistemáticas com meta-análises previamente publicadas foram analisadas quanto à força das evidências compiladas e, a partir daí, foram concebidas recomendações seguindo a metodologia Grading of Recommendations Assessment, Development and Evaluation. Os autores acreditam que o presente documento represente um importante avanço a ser incorporado na abordagem de pacientes com FPI, objetivando principalmente favorecer seu manejo, e pode se tornar uma ferramenta auxiliar na definição de políticas públicas relacionadas à FPI.
Subject(s)
Humans , Male , Aged , Practice Guidelines as Topic , Idiopathic Pulmonary Fibrosis/drug therapy , Acetylcysteine/therapeutic use , Pyridones/therapeutic use , Brazil , Indoles/therapeutic use , Anti-Inflammatory Agents/therapeutic useABSTRACT
Objective To explore the effect of rapamycin on pulmonary fibrosis in rats and its mechanism.Methods Pulmonary fibrosis model was induced by intratracheal instillation of bleomycin (5mg/kg).Control group was treated by intratracheal instillation of saline (1.25 ml/kg) to obtain the negative control.The rats of the rapamycin-treated group were given rapamycin (1 mg/kg per day) by gastric perfusion for consecutive 10 days beginning on the third day after intratracheal instillation of bleomycin.On the 28th day,all rats were sacrificed and the peripheral blood and the lung tissues were harvested.Lung tissues were performed hematoxylin-eosin (HE) staining.The severity of pulmonary fibrosis in rats was assessed by Ashcroft score.Lung tissues were performed immunohistochemical staining to detect the expression of transforming growth factor beta (TGF-beta).The expression level was judged by integrated optical density.Results The severity of pulmonary fibrosis was improved in rats of rapamycin-treated group compared with the rats of bleomycin-treated group.A significant difference in Ashcroft score was found between rapamycin-treated group and bleomycin-treated group(2.92 ± 0.64 vs 5.76 ± 1.76,P ＜ 0.01).The expression level of TGF-β was increased in rapamycin-treated group compared with the normal control group (5520.00 ± 1614.20 vs 3370.00 ± 1478.14,P ＜0.01).The expression level of TGF-β was decreased in rapamycin-treated group compared with the bleomycin-treated group (5520.00 ± 1614.20 vs 7772.00 ±1526.46 P ＜0.01).Conclusions Rapamycin can prevent bleomycin-induced pulmonary fibrosis.