Characterization of asthma-COPD overlap syndrome (ACOS): experimental and clinical studies

Abstract

Experimental therapy laboratory I (LIM-20) is a multidisciplinary group of researchers who have been working for several years on the mechanisms of asthma and chronic obstructive pulmonary disease (COPD) development, with a focus in the mechanisms of modulation and pathophysiology of these combining experimental and clinical studies in patients with asthma and COPD. Both in clinical practice and in scientific research, obstructive respiratory diseases - asthma and COPD - are widely studied, with defined criteria and pathophysiological mechanisms. However, in recent years a variant of these diseases has been described, and overlapping features common to both, with clinical manifestations similar to those observed in COPD, but with a significant response to the use of bronchodilators. This clinical entity was called asthma-COPD overlap syndrome (ACOS). Despite this classification, there is no consensus in the literature about the inflammatory profile, oxidative stress and pulmonary tissue remodeling in these patients, showing a lack of understanding of the pathophysiology of the disease and the mechanisms that could modulate these responses. ACOS is an airway disease characterized by a fixed airflow obstruction with features common to both asthma and COPD, but a more specific definition could not yet be established given the lack of scientific evidence on the subject. One of the most relevant implications in the diagnosis and understanding of the pathophysiology of ACOS is the therapeutics and modulation mechanisms to be adopted for these patients and based on all these similarities and differences in the definition and pathophysiology of ACOS, it is understandable that further investigations are necessary related to this disease. Thus, the central objective of this project is the development of a set of clinical and experimental studies that aims to deepen the mechanisms of modulation and pathophysiology of ACOS. In this way, we will carry out a clinical study, which will select patients from the Longitudinal Study of Adult Health (ELSA) who meet the diagnostic criteria for asthma and COPD defined by GINA and GOLD 2016 and thus characterize demographic, clinical and biochemical markers related to ACOS in the São Paulo subpopulation participating in ELSA and diagnosed according to the aforementioned criteria, comparing the markers characterized to those previously established in the pathogenesis of Asthma and COPD and also observed in patients with these diagnoses, describe prognostic outcomes - exacerbations, hospitalizations, need for supplementary oxygen therapy and mortality and to describe the impact that the diseases of interest of this work exert on the quality of life of the population of this study. We will perform seven experimental studies to evaluate the mechanisms of the effects of anti-IL17 action, peptide and protease inhibitors, cytokine signaling suppressor proteins (SOCS) and transcription activators (STAT), as well as occupational influences (chlorine and pollution) and interval training in the experimental model of asthma-COPD overlap syndrome (ACOS). (AU)