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PloS One 2015
PubMed: 26439742
DOI: 10.1371/journal.pone.0140288 -
Biomedicine & Pharmacotherapy =... Sep 2017Pulmonary fibrosis (PF) is a lethal, chronic and progressive respiratory disease leading to interstitial lung damage and serious breathing problems. The pathogenic... (Review)
Review
Pulmonary fibrosis (PF) is a lethal, chronic and progressive respiratory disease leading to interstitial lung damage and serious breathing problems. The pathogenic mechanism involves activation, migration, proliferation and differentiation of fibroblasts into myofibroblats inducing extracellular matrix accumulation that destroy lung parenchyma. Available antifibrotic treatment options are limited to Pirfenidone and Nintedanib that prevent deterioration without an improvement of this disease. The use of plant extracts and natural bioactive compounds for the treatment of PF has been known for more than thirty years in China. Nowadays, phytotherapy has gained a considerable attention in the treatment of PF both in vivo and in vitro using bleomycin (BLM)-induced lung inflammation, oxidative stress and pulmonary fibrosis in rats. In this review, we aimed to focus on the protective effects and the mechanisms of action of several plant extracts described by various research works for the treatment of PF.
Topics: Animals; Fibroblasts; Humans; Oxidative Stress; Phytotherapy; Plant Extracts; Pneumonia; Pulmonary Fibrosis
PubMed: 28688290
DOI: 10.1016/j.biopha.2017.06.052 -
Thorax Sep 2013Patients with fibrotic interstitial lung disease have symptom control and quality of life (QoL) needs. This review aims to evaluate the evidence for the use of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with fibrotic interstitial lung disease have symptom control and quality of life (QoL) needs. This review aims to evaluate the evidence for the use of interventions in improving dyspnoea, other symptoms and QoL.
METHODS
Eleven databases, relevant websites and key journals were hand-searched. Studies were assessed and data extracted independently by two researchers using standardised proformas. Meta-analyses were performed where possible with 95% CI.
RESULTS
34 papers with 19 interventions in 3635 patients were included. Meta-analyses showed no significant effect of interferon γ-1b or sildenafil on 6-minute walking distance (6MWD) or dyspnoea. Pulmonary rehabilitation and pirfenidone had a positive effect on 6MWD (mean difference (95% CI) 27.4 (4.1 to 50.7)) and 24.0 (4.3 to 43.7), respectively), and pulmonary rehabilitation had a mixed effect on dyspnoea. Both pulmonary rehabilitation and sildenafil showed a trend towards significance in improving QoL. There was weak evidence for the improvement of 6MWD using oxygen; dyspnoea using prednisolone, diamorphine, D-pencillamine and colchicine; cough using interferon α and thalidomide; anxiety using diamorphine; fatigue using pulmonary rehabilitation; and QoL using thalidomide and doxycycline. A wide range of outcome scales was used and there were no studies with economic evaluation.
CONCLUSIONS
There is strong evidence for the use of pulmonary rehabilitation and pirfenidone to improve 6MWD and moderate evidence for the use of sildenafil and pulmonary rehabilitation to improve QoL. Future recommendations for research would include careful consideration of the dichotomy of radical and palliative treatments when deciding on how symptom and QoL outcome measures are used and data presented.
Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Cough; Dyspnea; Exercise Test; Fibrosis; Glucocorticoids; Heroin; Humans; Immunologic Factors; Lung; Lung Diseases, Interstitial; Narcotics; Oxygen Inhalation Therapy; Piperazines; Prednisolone; Purines; Pyridones; Quality of Life; Sildenafil Citrate; Sulfones; Thalidomide; Tubulin Modulators
PubMed: 23204065
DOI: 10.1136/thoraxjnl-2012-202040 -
The Cochrane Database of Systematic... Sep 2010Idiopathic pulmonary fibrosis is a chronic progressive lung disease with poor outcome and no effective treatment to date. This is an update of a Cochrane Review first... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Idiopathic pulmonary fibrosis is a chronic progressive lung disease with poor outcome and no effective treatment to date. This is an update of a Cochrane Review first published in 2003.
OBJECTIVES
To assess the efficacy of non-steroid agents in adults with idiopathic pulmonary fibrosis.
SEARCH STRATEGY
We searched the Cochrane Airways Group Register (30 March 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2010), Ovid MEDLINE to March week 5, 2010, EMBASE to week 13, 2010 and PubMed to April 2010, with additional handsearching, including abstracts of international conferences. We also contacted pharmaceutical companies and researchers in the field.
SELECTION CRITERIA
Randomised studies comparing non-steroid drugs with placebo or steroids in adults with idiopathic pulmonary fibrosis.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality, extracted data and assessed risk of bias. We contacted pharmaceutical companies to obtain missing information, if any. We combined survival outcomes using Peto odds ratios or hazard ratios (HR).
MAIN RESULTS
Fifteen trials involving 10 different drugs were included. Two trials enrolling 1156 patients compared interferon gamma-1beta with placebo: interferon gamma-1beta did not significantly improve survival (HR 0.88, 95% CI 0.47 to 1.64; P = 0.68). Four trials involving 1155 patients compared pirfenidone with placebo. Three trials, conducted in 1046 patients, provided data on progression-free survival: pirfenidone significantly reduced the risk of disease progression by 30% (HR 0.70, 95% CI 0.56 to 0.88, P = 0.002). Data on the effect of pirfenidone on pulmonary function could only be assessed for two studies analysing 314 patients. Forced vital capacity or vital capacity was significantly improved by pirfenidone (mean difference 0.08 L, 95% CI 0.03 to 0.13, P = 0.0006).
AUTHORS' CONCLUSIONS
Based on available data, partly still unpublished, pirfenidone appears to improve progression-free survival and, to a lesser extent, pulmonary function in patients with idiopathic pulmonary fibrosis. More data are needed on overall survival and quality of life on treatment. From the studies in this review, interferon gamma-1beta has not been shown to affect survival. Other agents evaluated in single studies either failed to provide evidence for a benefit or need to be assessed in larger randomised controlled trials.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Colchicine; Cyclophosphamide; Humans; Immunosuppressive Agents; Interferon-gamma; Prednisone; Pulmonary Fibrosis; Pyridones; Randomized Controlled Trials as Topic; Recombinant Proteins
PubMed: 20824834
DOI: 10.1002/14651858.CD003134.pub2 -
European Respiratory Review : An... Jun 2012The magnitude of treatment effect can be assessed by a number of methods. One method of collectively analysing data is that used by the Cochrane Collaboration. Their... (Review)
Review
The magnitude of treatment effect can be assessed by a number of methods. One method of collectively analysing data is that used by the Cochrane Collaboration. Their systematic reviews identify, analyse and present research-based evidence in an accessible format. These reviews may contain meta-analyses combining data from multiple studies to provide robust evaluations of overall treatment effects. In 2003, Cochrane reviews of data for treatment with corticosteroids in idiopathic pulmonary fibrosis (IPF) found no evidence supporting their use; similarly, reviews of immunomodulatory agents found very little evidence to support their use. A recent update of these Cochrane reviews failed to identify any evidence supporting the use of corticosteroids in IPF; however, a review of non-steroid agents in the treatment of IPF identified 15 clinical trials suitable for analysis. Two trials of interferon-γ-1b were combined, and no treatment effect was observed in terms of survival. Two Japanese trials of treatment with pirfenidone were combined, and a positive effect of pirfenidone on pulmonary function decline was observed. Meta-analysis of three phase III studies suggested that pirfenidone significantly increased progression-free survival by 30%. The findings of this systematic review, although not presenting new original data, together with an acceptable safety profile, suggest that pirfenidone may have a role in IPF treatment.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Disease-Free Survival; Humans; Idiopathic Pulmonary Fibrosis; Interferon-gamma; Pyridones; Recombinant Proteins; Treatment Outcome
PubMed: 22654087
DOI: 10.1183/09059180.00000912 -
European Journal of Internal Medicine Jun 2008Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a clinical entity defined by rapid deterioration of IPF during the course of the disease that is not due... (Review)
Review
Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a clinical entity defined by rapid deterioration of IPF during the course of the disease that is not due to infections, pulmonary embolism, or heart failure. The condition needs to be differentiated from acute interstitial pneumonia (or Hamman-Rich syndrome), which occurs in patients with no underlying lung disease. The exact etiology and pathogenesis remain unknown, but the condition is characterized by diffuse alveolar damage (on a background of IPF) that probably occurs as a result of a massive lung injury due to some unknown etiologic agent. High-resolution computed tomography can help in prognostication and management of this condition. Once infections and other causes of worsening have been excluded, treatment involves enhanced immunosuppression with pulse doses of methylprednisolone and cytotoxic agents. Our systematic review shows that the outcome, however, is poor, with 1-month and 3-month mortality around 60% and 67%, respectively. Few studies have shown beneficial effects of cyclosporine, pirfenidone, and anticoagulants in the management and prevention of AE-IPF. The etiology, risk factors, pathogenesis, therapy, prognosis, and predictors need to be studied and the potential role of newer agents in the management and prevention of AE-IPF needs to be further clarified.
Topics: Cytotoxins; Humans; Immunosuppressive Agents; Methylprednisolone; Pulmonary Fibrosis; Severity of Illness Index; Treatment Outcome
PubMed: 18471669
DOI: 10.1016/j.ejim.2007.04.024 -
BMC Pulmonary Medicine Apr 2015The treatment landscape for idiopathic pulmonary fibrosis, a devastating lung disease, is changing. To investigate the effectiveness of treatments for idiopathic... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
The treatment landscape for idiopathic pulmonary fibrosis, a devastating lung disease, is changing. To investigate the effectiveness of treatments for idiopathic pulmonary fibrosis we undertook a systematic review, network meta-analysis and indirect comparison.
METHODS
We searched MEDLINE, EMBASE and The Cochrane library for relevant studies. Randomised controlled trials of pirfenidone, nintedanib or N-acetylcysteine were eligible. Predefined processes for selecting references, extracting data and assessing study quality were applied. Our network meta-analysis of published data used a fixed effect model. For forced vital capacity measures a standardised mean difference approach was used and converted to odds ratios for interpretation.
RESULTS
Of 1076 references, 67 were retrieved and 11 studies included. Studies were of reasonable size, populations were similar, and the overall quality was good. Only two treatments, pirfenidone (odds ratio 0.62, 95% credible interval 0.52, 0.74) and nintedanib (0.41, 95% credible interval 0.34, 0.51) produced a statistically significant slowing in the rate of forced vital capacity decline compared with placebo. In an indirect comparison, results indicate that nintedanib is statistically significantly better than pirfenidone in slowing forced vital capacity decline (odds ratio 0.67, 95% credible interval 0.51, 0.88). Results were stable in scenario analysis and random effects models. Indirect comparisons of mortality were not statistically significant between nintedanib and pirfenidone.
CONCLUSIONS
Two treatments show beneficial effects and when compared indirectly nintedanib appears to have superior benefit on forced vital capacity. Limitations to indirect comparisons should be considered when interpreting these results, however, our findings can be useful to inform treatment decisions.
Topics: Acetylcysteine; Anti-Inflammatory Agents, Non-Steroidal; Enzyme Inhibitors; Free Radical Scavengers; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Pyridones; Treatment Outcome
PubMed: 25927225
DOI: 10.1186/s12890-015-0034-y -
Chinese Medical Journal 2013To reveal interventions for chronic cyclosporine A nephrotoxicity (CCN) and provide new targets for further studies, we analyzed all relevant studies about interventions... (Review)
Review
OBJECTIVE
To reveal interventions for chronic cyclosporine A nephrotoxicity (CCN) and provide new targets for further studies, we analyzed all relevant studies about interventions in renal cell apoptosis.
DATA SOURCES
We collected all relevant studies about interventions for cyclosporine A (CsA)-induced renal cell apoptosis in Medline (1966 to July 2010), Embase (1980 to July 2010) and ISI (1986 to July 2010), evaluated their quality, extracted data following PICOS principles and synthesized the data.
STUDY SELECTION
We included all relevant studies about interventions in CsA-induced renal cell apoptosis no limitation of research design and language) and excluded the duplicated articles, meeting abstracts and reviews without specific data.
RESULTS
There were three kinds of intervention, include anti-oxidant (sulfated polysaccharides, tea polyphenols, apigenin, curcumin, spirulina, etc), biologics (recombinant human erythropoietin (rhEPO), a murine pan-specific transforming growth factor (TGF)-beta-neutralizing monoclonal antibody1D11, cartilage oligomeric matrix protein (COMP)-angiopoietin-1 and hepatocyte growth factor (HGF) gene), and other drugs (spironolactone, rosiglitazone, pirfenidone and colchicine). These interventions significantly improved the CCN, renal cell apoptosis and renal dysfunction through intervening in four apoptotic pathways in animals or protected renal cells from apoptosis induced by CsA and increased cell survival through respectively four pathways in vitro.
CONCLUSIONS
There are three group interventions for CCN. Especially anti-oxidant drugs can significantly improve CCN, renal cell apoptosis and renal dysfunction. Many drugs can improve CCN through intervening in Fas/Fas ligand or mitochondrial pathway with sufficient evidences. Angiotensin II, nitric oxide (NO) and endoplasmic reticulum (ER) pathways will be new targets for CCN.
Topics: Animals; Apoptosis; Chronic Disease; Cyclosporine; Humans; Immunosuppressive Agents; Kidney; Mitochondria; Nitric Oxide; Signal Transduction; fas Receptor
PubMed: 24112179
DOI: No ID Found -
Journal of Clinical Medicine Jan 2023Antifibrotic treatment has been approved for reducing disease progression in fibrotic interstitial lung disease (ILD). As a result of increased bleeding risk, some...
Impact of Antifibrotic Treatment on Postoperative Complications in Patients with Interstitial Lung Diseases Undergoing Lung Transplantation: A Systematic Review and Meta-Analysis.
Antifibrotic treatment has been approved for reducing disease progression in fibrotic interstitial lung disease (ILD). As a result of increased bleeding risk, some experts suggest cessation of antifibrotics prior to lung transplantation (LT). However, extensive knowledge regarding the impact of antifibrotic treatment on postoperative complications remains unclear. We performed a comprehensive search of several databases from their inception through to 30 September 2021. Original studies were included in the final analysis if they compared postoperative complications, including surgical wound dehiscence, anastomosis complication, bleeding complications, and primary graft dysfunction, between those with and without antifibrotic treatment undergoing LT. Of 563 retrieved studies, 6 studies were included in the final analysis. A total of 543 ILD patients completing LT were included, with 161 patients continuing antifibrotic treatment up to the time of LT and 382 without prior treatment. Antifibrotic treatment was not significantly associated with surgical wound dehiscence (RR 1.05; 95% CI, 0.31-3.60; = 0%), anastomotic complications (RR 0.88; 95% CI, 0.37-2.12; = 31%), bleeding complications (RR 0.76; 95% CI, 0.33-1.76; = 0%), or primary graft dysfunction (RR 0.87; 95% CI, 0.59-1.29; = 0%). Finally, continuing antifibrotic treatment prior to LT was not significantly associated with decreased 1-year mortality (RR 0.80; 95% CI, 0.41-1.58; = 0%). Our study suggests a similar risk of postoperative complications in ILD patients undergoing LT who received antifibrotic treatment compared to those not on antifibrotic therapy.
PubMed: 36675583
DOI: 10.3390/jcm12020655 -
Arthritis Research & Therapy Jun 2021New molecular mechanisms that can be targeted with specific drugs have recently emerged for the treatment of systemic sclerosis (SSc) patients. Over the past 3 years,... (Review)
Review
New molecular mechanisms that can be targeted with specific drugs have recently emerged for the treatment of systemic sclerosis (SSc) patients. Over the past 3 years, the achievement of one large phase 3 trial has led to the approval by drug agencies of the first drug licenced for SSc-related interstitial lung disease. Given this exciting time in the SSc field, we aimed to perform a systemic literature review of phase 1, phase 2 and phase 3 clinical trials and large observational studies about targeted therapies in SSc. We searched MEDLINE/PubMed, EMBASE, and ClinicalTrials.gov for clinical studies from 2016 with targeted therapies as the primary treatment in patients with SSc for skin or lung involvement as the primary clinical outcome measure. Details on the study characteristics, the trial drug used, the molecular target engaged by the trial drug, the inclusion criteria of the study, the treatment dose, the possibility of concomitant immunosuppression, the endpoints of the study, the duration of the study and the results obtained were reviewed. Of the 973 references identified, 21 (4 conference abstracts and 17 articles) were included in the systematic review. A total of 15 phase 1/phase 2 clinical trials, 2 phase 3 clinical trials and 2 observation studies were analysed. The drugs studied in phase 1/phase 2 studies included the following: inebilizumab, dabigatran, C-82, pomalidomide, rilonacept, romilkimab, tocilizumab, tofacitinib, pirfenidone, lenabasum, abatacept, belimumab, riociguat, SAR100842 and lanifibranor. All but 3 studies were performed in early diffuse SSc patients with different inclusion criteria, while 3 studies were performed in SSc patients with interstitial lung disease (ILD). Phase 3 clinical trials investigated nintedanib and tocilizumab. Nintedanib was investigated in SSc-ILD patients whereas tocilizumab focused on early diffuse SSc patients with inflammatory features. Two observational studies including > 50 patients with rituximab as the targeted drug were also evaluated. All these studies offer a real hope for SSc patients. The future challenges will be to customize patient-specific therapeutics with the goal to develop precision medicine for SSc.
Topics: Humans; Lung Diseases, Interstitial; Scleroderma, Diffuse; Scleroderma, Systemic
PubMed: 34074331
DOI: 10.1186/s13075-021-02536-5