Titolo progetto: PRIN2022 PNRR - Central (cardiorespiratory) and peripheral (muscular) determinants of functional deterioration in COPD: new biomarkers for evaluating disease severity and acute exacerbations?

Programma di finanziamento: PRIN 2022

Responsabile scientifico: prof. Bruno Grassi 

Collaboratori: prof.ssa Miriam Isola

Ruolo del DAME: coordinatore

Descrizione generale:

Chronic obstructive pulmonary disease (COPD) is a major burden for health systems and may negatively affect the patients’ health status, quality of life and life expectancy. Functional impairment depends on both cardiorespiratory (systemic/central) and microvascular/skeletal muscle (peripheral) factors. Indeed, skeletal muscle dysfunction substantially contributes to exercise intolerance, a major hallmark of the disease, and it is associated with worse outcomes. Microvascular/endothelial impairments, chronic inflammation, oxidative stress, muscle atrophy, altered skeletal muscle oxidative metabolism, mitochondrial dysfunction, impaired capacity of muscle regeneration and other factors may contribute to muscular dysfunction. COPD patients are characterized by systemic inflammation, leading to muscle atrophy, reduced capacity of force production and impaired oxidative function. These phenomena are presumably related to the severity of COPD and the occurrence and severity of acute exacerbations, which are mainly responsible for the progressive clinical deterioration of patients. The role of “peripheral” factors in the pathogenesis of the disease has not been settled yet, and the use of biomarkers related to peripheral alterations in evaluating the severity of COPD has not been investigated so far. Longitudinal studies are lacking. The main aim of the present study is to identify, in COPD patients with different disease severity and acute exacerbations, systemic/central (cardiorespiratory) and peripheral (skeletal muscle) determinants of functional impairment in order to assess their potential use as biomarkers of the severity of COPD and of its acute exacerbations. A comparison will be made with accepted methods which usually neglect a specific analysis of muscular dysfunction. The approach will help to establish the pathophysiological mechanisms of the impairments, ideally allowing to define, in the future, personalized therapeutical or rehabilitation interventions. Patients with COPD of different severity will undergo, at a baseline examination, an evaluation of parameters of systemic/central impairments, mainly determined during a cardiopulmonary exercise test, as well as an evaluation of parameters of peripheral (microvascular/endothelial) and skeletal muscle impairments. Specific attention will be devoted to evaluating skeletal muscle oxidative metabolism and mitochondrial respiration, to the presence of inflammation, oxidative stress, muscle atrophy, mitochondrial dysfunction, skeletal muscle deterioration. During acute exacerbations of the disease the patients will undergo the same measurements mentioned above, except for the cardiopulmonary exercise test. Systemic/central and peripheral biomarkers of impairment will be compared between patients with different disease severity and a group of control subjects (cross-sectional study) and, in each patient, at baseline and during acute exacerbations (longitudinal study).

Partner del progetto:                                                                                

• Università degli studi di Udine
• Università degli studi di Verona
• Università degli studi di Pavia

Date inizio e fine progetto: 29.11.2023 – 28.11.2025

Budget totale del progetto: 86.205,00€

Sito web: https://prin.mur.gov.it/ 

Finanziato dall’Unione europea – Next Generation EU