Nome del progetto:
Pre-natal and early life origin of chronic obstructive lung respiratory diseases: identification of novel diagnostic biomarkers and therapeutic targets by applying the metabolomic approach

Principal Investigator:
Prof. Eugenio Baraldi.  Date of birth: March 1, 1957

Co-Principal Investigators:
Prof. G. Perilongo,
Prof. L. Chiandetti,
Dr. M.T. Gervasi

Inizio progetto – Fine progetto: 01/05/2013-30/04/2017

Budget: 200.000 €

Staff:

  • Giorgio Perilongo
  • Lino Chiandetti
  • Maria Teresa Gervasi
  • Roberto Romero
  • Silvia Carraro
  • Antonella Gucciardi
  • Paola Cogo
  • Giuseppe Giordano
  • Davide Grisalfi
  • Paola Pirillo
  • Enrico Valerio
  • Patrizia Zaramella

 

Finanziamenti:

fond-cariparo    IRP

 

Abstract:

Background

Biomarkers are set to become one of the main driving forces of scientific research in the coming years. Metabolomics, one of the core disciplines of systems biology, is a high-dimensional biology method that may allow hypothesis-free profiling of biomarkers. It is an innovative methodology that takes a non-selective approach (un-target approach, hypothesis-generating) enabling the simultaneous, quantitative analysis of thousands of different metabolites within a given sample.

Chronic obstructive lung diseases are among the leading causes of morbidity and mortality in the pediatric and adult age. Moreover, lung insult, starting early during the peri-natal, neonatal and pediatric growth, can have a strong impact on adult lung function.  The investigation of chronic complex diseases requires the simultaneous assessment of several biomarkers inasmuch as each single biomarker can reflect only a limited part of the pathological process. The transition toward the study of biomarker profiles has been facilitated by the development of high-throughputtechnologies, as metabolomics, supported by advanced statistical methodologies. Among the “-omic sciences” metabolomic is considered the closest to phenotype expression since it enables the study of the products of the interaction between environment and genetic individual background.

In our Department we have recently set up a metabolomics laboratory equipped with a latest generation liquid chromatography tandem mass spectrometry (UPLC Q-Tof Synapt G2 HDMS-Waters)

Aims of the project

In the present research project we aim at applying the metabolomic approach in the study of early origins (pre-natal and neonatal, infancy) of chronic obstructive respiratory diseases (bronchopulmonary dysplasia (BPD), asthma, chronic obstructive pulmonary diseases (COPD)). The general objective of the research project is to apply the metabolomic approach to the study of respiratory conditions that occur early in life, starting from the pre-natal and neonatal period, and precede the development of chronic obstructive pulmonary diseases. By means of the metabolomic approach we aim at characterizing patterns of biomarkers (studied in the amniotic fluid, blood, urine, exhaled breath condensate) that can predict the development of BPD and asthma. In addition we aim at identifying within these characteristic biomarker profiles, potential targets for the development of new therapeutic strategies.

 

Description of the project

The research project includes the following workpackages:

1)  Early origin of chronic respiratory disease: prematurity and bronchopulmonary dysplasia (BPD)

a)   Metabolomic profiling  of amniotic fluid  to assess the risk of preterm delivery and BPD development.

We will recruite a group of women with impeding pretem delivery. The aim of the study is to evaluate whether the metabolic profiling of the amniotic fluid is related to preterm labor and to the development of BPD. These data could serve as the basis for the development of rapid tests to identify the patients at risk of preterm birth.

  1. Metabolomic characterization of bronchopulmonary dysplasia

We will recruit a group of premature newborns to establish whether a biomarker profile exists at birth, capable of predicting the development of BPD. The metabolomic analysis will be applied on urine and blood samples collected during the first 3 days of life.

In a second part of the study we will recruit a group of preterm BPD infants, a group of preterm non-BPD infants and a group of healthy infants to compare their biochemical-metabolic characteristics.

2) Early origins of asthma: bronchiolitis and recurrent wheezing

We will recruit a group of infants with acute bronchiolitis in whom the metabolomic urinary profile will be studied to evaluate whether a biomarker patterns exists that can discriminate among infants with acute bronchiolitis those at high risk of recurrent wheeze and asthma development in the following 5 years.

 

Expected results 

We expect to identify, within the metabolomic profile of different biofluids (amniotic fluid, urine, blood, exhaled breath condensate), new biomarkers capable to predict the early origins of prematurity and chronic obstructive respiratory diseases with the potential for discovering unknown biological pathways and developing new targeted therapies. These finding could have a significant impact on the prevention and management of chronic obstructive respiratory diseases providing a potential tool to guide the preventive and therapeutic strategies in the view of a more personalized therapy.

In addition the present project will lead to the establishment of a technical platform for metabolomic analysis, optimized for several biofluids, that will lay the groundwork for pediatric research projects conducted in all the different pediatric subspecialities (oncology, cardiology, organ transplant, diabetes, nutrition, pharmacology).