Biomarkers for Diagnosis and Treatment of COPD
Condition: COPD
Study type: Observational

Summary: 
      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
    

Detailed description: 
      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.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        An open label, parallel groups study, will be performed after it is approve by the Ethical
        committee and before the beginning of the study, all participants will be informed about
        the aim, procedures, risks and benefits of the study and they will provide a written
        informed consent
      
Biospecimen description: 
      blood