Biomarkers for Diagnosis and Treatment of COPD (BmiRCOPD)
A Predictive "Molecular Biology Signature" for Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease
COPD is an inflammatory disease characterized by enhanced chronic airway and lung inflammatory responses to noxious agents (e.g. smoke, pollutants) and progressive airflow limitation. In COPD patients there is a spillover of peripheral lung inflammation into systemic circulation resulting in increased level of various inflammatory markers such as: IL-1β, IL-6, IL-8, and TNF-α.
Diagnosis, now, is based on clinical evaluation and spirometry test and COPD treatment includes the use of LABA, LAMA and corticosteroids.
To data no plasmatic marker able to identify the stage of COPD and the response to the treatment have been documented . The aim of this study is to evaluate in COPD patients the role of microRNA as predictive biomarker, of the disease in order to have a signature of miRs typically of COPD
研究概览
地位
条件
详细说明
Chronic obstructive pulmonary disease (COPD) is a heterogeneous respiratory disorder affecting more than 200 million patients worldwide. It is characterized by enhanced chronic airway and lung inflammatory responses to noxious agents (e.g. smoke, pollutants) and progressive airflow limitation.
Both, prevalence and incidence of this disease are continuously increasing, thus the investigators can predict that in 2020 it will be the third important cause of death in the world.
Several immune system cells (e.g. macrophages, eosinophils) and biochemical mediators (e.g. tumor necrosis factor-alpha, transforming growth factor beta, Interleukins and metalloproteases) are involved in its development and in symptom severity.
It has been suggested that in COPD patients there is a spillover of peripheral lung inflammation into systemic circulation resulting in increased level of various inflammatory markers such as: IL-1β, IL-6, IL-8, and TNF-α. Those biomolecules are responsible of various complication associated with COPD such as cardiovascular disease, hypertension and skeletal muscle weakness to name a few. It is worth to note that the increase of systemic inflammatory markers is also responsible of diabetes, obesity and metabolic syndrome development in COPD patients.
Diagnosis, now, is based on clinical evaluation and spirometry test and COPD treatment includes the use of LABA, LAMA and corticosteroids. Therefore, an early diagnosis in order to asses a specific treatment it is mandatory.
Sarioglu et al.,reported that systemic inflammatory markers levels (in plasma) TNFα, IL-6 and C-reactive protein, persist in the stable period in 110 COPD patients and the C-reactive protein levels correlate with the COPD Assessment Test.
However, C-reactive protein is not a specific marker, while to date more appropriate marker(s) could be represented by microRNA (miR) a key class of gene expression regulators, emerging as crucial players in various biological processes such as cellular proliferation and differentiation, development and apoptosis.
In this concern, Stolzenburg et al., documented, in an experimental model of COPD, that miR-1343 reduces the expression of both isoform of TGF-b receptor 1 and 2, directly targeting their 3' UTRs mRNA region, suggesting a role in the improvement of lung fibrosis.
To date, no other data have been performed yet on this topic. In the present project the investigators would like to screen with nCounter GX Human Inflammation Kit a comprehensive number of 249 human genes known to be differentially expressed in inflammation. The gene list represents a broad range of inflammation-related pathways. In parallel miRs screening will be performed (800 in a single reaction tube) using NanoString Technology Platform. This technology is robust and sensitive and today is used for the validation of New Generation Sequence (NGS) data. Our aim is to evaluate in COPD patients the role of miRs as predictive biomarker, of the disease in order to have a signature of miRs typically of COPD. The signature could be used to monitoring the therapeutic application of drugs used in COPD as well as to asses a Prediction COPD Diagnostic test.
The absence of a plasmatic marker able to identify the stage of disease and the response to the treatment leads to COPD exacerbation and progression, this represent, in the real life, a common problem during COPD treatment and is also related with an increase of sanitary health costs. Last year, the European health bill for COPD treatment increased by USD 10 million and the market is thought to increase up to USD 37.7 million by 2030.
研究类型
注册 (实际的)
联系人和位置
学习地点
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Catanzaro、意大利、88100
- UCCP
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Catanzaro
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Badolato、Catanzaro、意大利、88100
- UCCP
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Borgia、Catanzaro、意大利、88100
- UCCP
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
Inclusion Criteria:
- COPD diagnosed according to the GOLD criteria
Exclusion Criteria:
- allergy to corticosteroids or to bronchodilators
- neurodegenerative diseases
- autoimmune diseases
- inability to use inhalers
- progressive serious medical conditions (such as cancer, AIDS or end-stage renal disease)
- infectious diseases
学习计划
研究是如何设计的?
设计细节
队列和干预
团体/队列 |
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COPD-Untreated (Group 1)
In this Group will be enrolled patients of both sex and older than 40-years with COPD stage GOLD 2 and 3 that did not receive COPD treatment in the last 6 months (beta 2 agonists, corticosteroids, anticholinergics).
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COPD-uncontrolled (Group 2)
In this Group will be enrolled patients of both sex and older than 40-years with COPD stage GOLD 2 and 3 that receive a COPD treatment (e.g.
beta 2 agonists, corticosteroids, anticholinergics) but with a post-bronchodilator FEV1< 80% and an FEV1/FVC < 0.7 or with 1-2 exacerbation/year
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Control subjects (Group 3)
In this Group will be enrolled patients of both sex and older than 40 years; (2) will be free from lung disease as determined by a physician; (3) will have a normal spirometry (FEV1> 85% and FEV1/FVC > 0.7)
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Change of miR expression at 6 and 12 months
大体时间:6 and 12 months
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Change of miR expression in COPD-groups (Groups 1 and 2 ) vs control-Group
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6 and 12 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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correlation between miRs expression and clinical outcome
大体时间:6 and 12 months
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correlation between miRs and clinical outcome evaluated through the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) dispnea scale
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6 and 12 months
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correlation between miRs expression and the development of adverse drug reaction
大体时间:6 and 12 months
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correlation between miRs and clinical outcome evaluated through the Naranjo probability scale
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6 and 12 months
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correlation between miRs expression and inflammatory markers
大体时间:6 and 12 months
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correlation between miRs expression and plasma levels of ILs, TNF-Alpha, C reactive protein
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6 and 12 months
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合作者和调查者
调查人员
- 首席研究员:Luca Gallelli, MD、University of Catanzaro
出版物和有用的链接
一般刊物
- Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65. doi: 10.1164/rccm.201204-0596PP. Epub 2012 Aug 9.
- Garvey C. Recent updates in chronic obstructive pulmonary disease. Postgrad Med. 2016;128(2):231-8. doi: 10.1080/00325481.2016.1118352. Epub 2015 Dec 1. Erratum In: Postgrad Med. 2016;128(2):v.
- Barnes PJ. Chronic obstructive pulmonary disease: effects beyond the lungs. PLoS Med. 2010 Mar 16;7(3):e1000220. doi: 10.1371/journal.pmed.1000220.
- Sarioglu N, Hismiogullari AA, Bilen C, Erel F. Is the COPD assessment test (CAT) effective in demonstrating the systemic inflammation and other components in COPD? Rev Port Pneumol (2006). 2016 Jan-Feb;22(1):11-7. doi: 10.1016/j.rppnen.2015.08.007. Epub 2015 Oct 31.
- Stolzenburg LR, Wachtel S, Dang H, Harris A. miR-1343 attenuates pathways of fibrosis by targeting the TGF-beta receptors. Biochem J. 2016 Feb 1;473(3):245-56. doi: 10.1042/BJ20150821. Epub 2015 Nov 5.
- Watt J, Ganapathi P. COPD: Novel therapeutics and management strategies--SMi's 7th Annual Conference (October 19-20, 2015--London, UK). Drugs Today (Barc). 2015 Oct;51(10):613-7. doi: 10.1358/dot.2015.51.10.2409817.
- Agusti A, Edwards LD, Rennard SI, MacNee W, Tal-Singer R, Miller BE, Vestbo J, Lomas DA, Calverley PM, Wouters E, Crim C, Yates JC, Silverman EK, Coxson HO, Bakke P, Mayer RJ, Celli B; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PLoS One. 2012;7(5):e37483. doi: 10.1371/journal.pone.0037483. Epub 2012 May 18.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他研究编号
- COPD
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慢性阻塞性肺病的临床试验
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Bangabandhu Sheikh Mujib Medical University, Dhaka...完全的
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University College, LondonUniversity of Cambridge; National Institute for Health Research, United Kingdom; Royal Free Hampstead...未知
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Virginia Commonwealth UniversityFisher and Paykel Healthcare完全的
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AstraZeneca完全的
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Chiesi Farmaceutici S.p.A.完全的中度至重度慢性阻塞性肺疾病 (COPD)保加利亚, 德国, 匈牙利, 波兰, 俄罗斯联邦, 英国