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

• Grant number: 18/02537-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: September 01, 2019
• End date: August 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Iolanda de Fátima Lopes Calvo Tibério
• Grantee: Iolanda de Fátima Lopes Calvo Tibério
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: Fernanda Degobbi Tenorio Quirino dos Santos Lopes
• Associated researchers: Beatriz Mangueira Saraiva ; Carla Máximo Prado ; Clarice Rosa Olivo ; Edna Aparecida Leick ; Isabela Judith Martins Bensenor ; Marco Antonio Maximo Prado ; Maria Luiza Vilela Oliva ; Milton de Arruda Martins ; Paulo Andrade Lotufo ; Renato Fraga Righetti
• Associated scholarship(s): 23/13626-7 - EXPRESSION OF STATS PROTEINS IN THE DIFFERENTIATION OF NAIVE TCD4+ CELLS IN AN EXPERIMENTAL MODEL OF OVERLAPPING ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE., BP.IC; 23/10674-0 - PREVENTIVE EFFECT OF THYMIC STROMAL LYMPHOPOIETIN INHIBITION IN AN EXPERIMENTAL MODEL OF CHRONIC ALLERGIC PULMONARY INFLAMMATION EXACERBATED BY LIPOPOLYSACCHARIDE, BP.IC; 23/06746-6 - The effects of anti-IL-17 on bronchial vascular remodeling in an asthma and COPD overlap model (ACO), BP.IC; + associated scholarships 22/02510-5 - The role of cholinergic antiinflammatory pathway in a model of Asthma-COPD Overlap Syndrome (ACOS) modelo experimental, BP.DD; 20/12863-7 - The effects of anti-IL17 antibody administration in asma-copd association syndrome (Acos), using a cigarette smoke exposure model, BP.DR; 21/02477-5 - The role of SOCS and STATs proteins in the differentiation of TCD4+ naive cells in an experimental model of Asthma and Chronic Obstructive Pulmonary Disease, BP.PD; 20/11716-0 - Therapeutic effect of melathonin on bronchial hiperresponsiveness to methacoline, airway inflammation and remodeling in Asthma, COPD and Asthma-COPD association of experimental models, BP.IC; 20/07359-8 - Effects of the synthetic peptide derived from the reactive site of Bauhinia bauhinioides Kallikrein Proteinase Inhibitor (BbKI) on inflammation, remodeling and oxidative stress in a model of asma-COPD overlay syndrome (ACOS), BP.IC; 19/27807-8 - Effects of the synthetic peptide derived from the reactive site of EcTI on inflammation, renovation and oxidative stress in a model of Asthma-COPD Overlay Syndrome (ACOS), BP.IC; 19/26449-0 - Effects of anti-IL17 on inflammation, remodeling oxidative stress in an ASMA-COPD Overlay Syndrome (ACOS) model, BP.PD; 19/23249-0 - Characterization of ASMA-COPD Overlay Syndrome (ACOS): experimental and clinical studies, BP.TT - associated scholarships

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)

Scientific publications

(24)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

OLIVO, C. R.; CASTRO, T. B. P.; RIANE, A.; REGONHA, T.; RIVERO, D. H. R. F.; VIEIRA, R. P.; SARAIVA-ROMANHOLO, B. M.; LOPES, F. D. T. Q. S.; TIBERIO, I. F. L. C.; MARTINS, M. A.; et al. The effects of exercise training on the lungs and cardiovascular function of animals exposed to diesel exhaust particles and gases. Environmental Research, v. 203, JAN 2022. (18/02537-5, 18/06088-0, 18/01531-3)

ALMEIDA, FRANCINE MARIA; OLIVEIRA, ROSELAINE MARIA; QUEIROZ, VITORIA CAROLINE; OLIVO, CLARICE ROSA; SARAIVA-ROMANHOLO, BEATRIZ MANGUEIRA; LOTUFO, PAULO A.; BENSENOR, ISABELA; SANTOS, ITAMAR SOUZA; LOPES CALVO TIBERIO, IOLANDA FATIMA. Pulmonary function evaluation on Asthma-COPD overlap from ELSA-Brasil cohort study.. European Respiratory Journal, v. 62, p. 3-pg., 2023-09-09. (19/26449-0, 22/02510-5, 18/02537-5)

SCHEFFER, V.; RIBEIRO, C.; CAMARGO, L.; FUKUZAKI, S.; RIGHETTI, R.; BEZERRA, S.; SARAIVA-ROMANHOLO, B.; ALMEIDA, F.; TIBERIO, I.; LEICK, E.. Therapeutic Effect of Melatonin on Pulmonary Inflammatory Response in Experimental Models of Asthma, COPD and Asthma-COPD Overlap. American Journal of Respiratory and Critical Care Medicine, v. 205, p. 2-pg., 2022-05-01. (20/11716-0, 18/02537-5)

CAMARGO, LEANDRO DO NASCIMENTO; DOS SANTOS, TABATA MARUYAMA; DE ANDRADE, FELIPP COSTA PINTO; FUKUZAKI, SILVIA; DOS SANTOS LOPES, FERNANDA DEGOBBI TENORIO QUIRINO; DE ARRUDA MARTINS, MILTON; PRADO, CARLA MAXIMO; LEICK, EDNA APARECIDA; RIGHETTI, RENATO FRAGA; TIBERIO, IOLANDA DE FATIMA LOPES CALVO. Bronchial Vascular Remodeling Is Attenuated by Anti-IL-17 in Asthmatic Responses Exacerbated by LPS. FRONTIERS IN PHARMACOLOGY, v. 11, p. 18-pg., 2020-09-04. (18/02537-5)

DA SILVA, ALEX FERREIRA; LIMA, FRANCIELE JESUS; MOREIRA, ALYNE RIANI; SILVA, CINTIA DO NASCIMENTO; DE OLIVEIRA, IVONE BRAGA; CALLERA, ALEXANDRA FERNANDES; PORFIRIO, ANA LUIZA; ALVES, LUAN HENRIQUE VASCONCELOS; TIBERIO, IOLANDA DE FATIMA LOPES CALVO; VELOSA, ANA PAULA PEREIRA; et al. Cigarette Smoke Exposure Leads to Organic and Mineral Bone Component Changes: The Importance of Rho Kinase Function in These Events. CELLS, v. 14, n. 7, p. 13-pg., 2025-03-28. (22/07357-0, 18/02537-5)

CAMARGO, LEANDRO DO NASCIMENTO; RIGHETTI, RENATO FRAGA; DE ALMEIDA, FRANCINE MARIA; DOS SANTOS, TABATA MARUYAMA; FUKUZAKI, SILVIA; MARTINS, NILO ARTHUR BEZERRA; BARBEIRO, MIGUEL CANTADORI; SARAIVA-ROMANHOLO, BEATRIZ MANGUEIRA; LOPES, FERNANDA DEGOBBI TENORIO QUIRINO DOS SANTOS; LEICK, EDNA APARECIDA; et al. Modulating asthma-COPD overlap responses with IL-17 inhibition. FRONTIERS IN IMMUNOLOGY, v. 14, p. 17-pg., 2023-10-27. (18/02537-5)

DOS SANTOS, TABATA MARUYAMA; RIGHETTI, RENATO FRAGA; CAMARGO, LEANDRO DO NASCIMENTO; LEICK, EDNA APARECIDA; FUKUZAKI, SILVIA; DE CAMPOS, ELAINE CRISTINA; GALLI, THIAGO TAFAREL; SARAIVA-ROMANHOLO, BEATRIZ MANGUEIRA; DA SILVA, LUANA LAURA SALES; BARBOSA, JESSICA ANASTACIA SILVA; et al. Effect of VAChT reduction on lung alterations induced by exposure to iron particles in an asthma model. Journal of Inflammation-London, v. 21, n. 1, p. 17-pg., 2024-07-03. (18/02537-5)

LOPES GONCALVES JOAO, JULIANA MORELLI; SILVA BARBOSA, JESSICA ANASTACIA; SALES DA SILVA, LUANA LAURA; DOS SANTOS, TABATA MARUYAMA; CAMARGO, LEANDR DO NASCIMENTO; DE CAMPOS, ELAINE CRISTINA; GALIL, THIAGO TAFAREL; SARAIVA-ROMANHOLO, BEATRIZ MANGUEIRA; MOREIRA BEZERRA, SUELLEN KAROLINE; SOBRAL HAMAGUCHI, SARA SUMIE; et al. Plant protease inhibitors compared to corticosteroids in mice with Asthma-COPD. European Respiratory Journal, v. 56, p. 2-pg., 2020-09-07. (18/02537-5)

DOS SANTOS, TABATA M.; RIGHETTI, RENATO F.; REZENDE, BIANCA G.; CAMPOS, ELAINE C.; CAMARGO, LEANDRO DO N.; SARAIVA-ROMANHOLO, BEATRIZ M.; FUKUZAKI, SILVIA; PRADO, CARLA M.; LEICK, EDNA A.; MARTINS, MILTON A.; et al. Effect of anti-IL17 and/or Rho-kinase inhibitor treatments on vascular remodeling induced by chronic allergic pulmonary inflammation. THERAPEUTIC ADVANCES IN RESPIRATORY DISEASE, v. 14, DEC 2020. (18/02537-5)

CAMARGO, L.; BARBOSA, J.; SILVA, L.; JOAO, J.; SANTOS, H.; SARAIVA-ROMANHOLO, B.; FUKUZAKI, S.; BEZERRA, S.; PRADO, C.; LOPES, F.; et al. Does Treatment with a Plant Proteinase Inhibitor, Enterolobium Contortisiliquum Contribute to the Control of Inflammation, Remodeling and Oxidative Stress in Mice with Asthma-COPD Overlap (ACO)?. American Journal of Respiratory and Critical Care Medicine, v. 205, p. 2-pg., 2022-05-01. (18/02537-5, 19/27807-8)

DE GENARO, ISABELLA SANTOS; DE ALMEIDA, FRANCINE MARIA; QUIRINO DOS SANTOS LOPES, FERNANDA DEGOBBI TENORIO; HIZUME KUNZLER, DEBORAH DE CAMARGO; BUSOLETTO TRIPODE, BRUNA GABRYELA; KURDEJAK, ADRIANA; NAKAMURA CORDEIRO, BRUNA; PANDOLPHO, RENATA; MACCHIONE, MARIANGELA; BRUGGEMANN, THAYSE REGINA; et al. Low-dose chlorine exposure impairs lung function, inflammation and oxidative stress in mice. Life Sciences, v. 267, FEB 15 2021. (14/26829-4, 18/02537-5, 12/15165-2)

TIBERIO, I. C.; SANTOS, T. M.; RIGHETTI, R. F.; CAMARGO, L. D.; LEICK, E. A.; FUKUSAKI, S.; CAMPOS, E. C.; TAFAREL, T. G.; SARAIVA-ROMANHOLO, B. M.; SILVA, L. L. S.; et al. Effects of Exposure to Environmental Pollution From Iron Ore Pelletization on the Lungs of Genetically Modified Animals. American Journal of Respiratory and Critical Care Medicine, v. 209, p. 2-pg., 2024-05-01. (18/02537-5)

DE MACEDO, JACQUELINE CARLA; OLIVO, CLARICE ROSA; BARNABE, VIVIANI; DIAS, EDUARDO DATI; DE MORAES, IBIS ARIANA PENA; TIBERIO, IOLANDA DE FATIMA LOPES CALVO; DE CARVALHO, CELSO RICARDO FERNANDES; SARAIVA-ROMANHOLO, BEATRIZ MANGUEIRA. Short-Term Effects of Conventional Chest Physiotherapy and Expiratory Flow Increase Technique on Respiratory Parameters, Heart Rate, and Pain in Mechanically Ventilated Premature Neonates: A Randomized Controlled Trial. HEALTHCARE, v. 12, n. 23, p. 13-pg., 2024-12-01. (14/26829-4, 18/02537-5)

DA SILVA, LUANA LAURA SALES; BARBOSA, JESSICA ANASTACIA SILVA; JOAO, JULIANA MORELLI LOPES GONCALVES; FUKUZAKI, SILVIA; CAMARGO, LEANDRO DO NASCIMENTO; DOS SANTOS, TABATA MARUYAMA; DE CAMPOS, ELAINE CRISTINA; COSTA, ARTHUR SILVA; SARAIVA-ROMANHOLO, BEATRIZ MANGUEIRA; BEZERRA, SUELLEN KAROLINE MOREIRA; et al. Effects of a Peptide Derived from the Primary Sequence of a Kallikrein Inhibitor Isolated from Bauhinia bauhinioides (pep-BbKI) in an Asthma-COPD Overlap (ACO) Model. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 14, p. 26-pg., 2023-07-01. (18/02537-5)

ALMEIDA, F. M.; MOREIRA, T. C. L.; OLIVEIRA, L. M.; RIGHETTI, R. F.; LOPES, F. D. T. Q. S.; ALENCAR, A. P.; MAUAD, T.; GOUVEIA, N. C.; LOTUFO, P. A.; BENSENOR, I.; et al. Effects of Air Pollution in S($)over-tilde-$ao Paulo on Asthma and COPD symptoms. European Respiratory Journal, v. 60, p. 2-pg., 2022-09-04. (19/26449-0, 18/02537-5)

ALMEIDA, F. M.; CAMARGO, L. N.; MARTINS, N.; LOURENCO, J. D.; BEZERRA, S. K. M.; SARAIVA-ROMANHOLO, B.; LEICK, E. A.; LOPES, F. D. Q. S.; PRADO, C. M.; RIGHETTI, R. F.; et al. Effects of anti-IL 17 on inflammation in Asthma, COPD and Asthma-COPD models. European Respiratory Journal, v. 60, p. 2-pg., 2022-09-04. (19/26449-0, 18/02537-5)

JOAO, JULIANA MORELLI LOPES GONCALVES; BARBOSA, JESSICA ANASTACIA SILVA; DA SILVA, LUANA LAURA SALES; FUKUZAKI, SILVIA; DE CAMPOS, ELAINE CRISTINA; CAMARGO, LEANDRO DO NASCIMENTO; SANTOS, TABATA MARUYAMA DOS; BEZERRA, SUELLEN KAROLINE MOREIRA; DE ALMEIDA, FRANCINE MARIA; SARAIVA-ROMANHOLO, BEATRIZ MANGUEIRA; et al. Effects of plant protease inhibitors (Pep-3-EcTI, Pep-BbKI, and Pep-BrTI) versus corticosteroids on inflammation, remodeling, and oxidative stress in an asthma-COPD (ACO) model. FRONTIERS IN PHARMACOLOGY, v. 15, p. 21-pg., 2024-05-07. (18/02537-5)

RAMPINELLI, B. A.; CAMARGO, L. D.; SANTOS, T. M.; FUKUZAKI, S.; SARAIVA ROMANHOLO, B. MANGUEIRA; LIGERO, A. DOS SANTOS; PRADO, C. M.; LOPES, F. D.; LEICK, E. A.; RIGHETTI, R. F.; et al. Modulating Bronchial Vascular Remodeling in an Experimental Asthma-COPD Overlap Model Through IL-17 Inhibition. American Journal of Respiratory and Critical Care Medicine, v. 209, p. 1-pg., 2024-05-01. (18/02537-5)

SANTANA, LAURIANA ALVES; MOREIRA BEZERRA, SUELLEN KAROLINE; SARAIVA-ROMANHOLO, BEATRIZ MANGUEIRA; YAMAGUTI, WELLINGTON PEREIRA; LOPES CALVO TIBERIO, IOLANDA DE FATIMA; DOS SANTOS, TABATA MARUYAMA; RIGHETTI, RENATO FRAGA. Cold bubble humidification of low-flow oxygen does not prevent acute changes in inflammation and oxidative stress at nasal mucosa. SCIENTIFIC REPORTS, v. 11, n. 1, JUL 12 2021. (18/02537-5)

TIBERIO, I. C.; FUKUZAKI, S.; SANTOS, T. M.; CAMPOS, E. C.; SILVA, L. L. S.; BARBOSA, J. A. S.; JOAO, J. M. L. G.; CAMARGO, L. N.; BEZERRA, S. K. M.; CIRILLO, J. V. O.; et al. Effects of Exposure to Environmental Pollution From Iron Ore Pellets on Elastase-induced Lung Inflammation: Evaluation of the Effect of Reduced Acetylcholine Transporter Expression in Mice. American Journal of Respiratory and Critical Care Medicine, v. 207, p. 2-pg., 2023-05-01. (18/02537-5)

RIGHETTI, R. F.; JOAO, J.; BARBOSA, J.; SILVA, L.; FUKUZAKI, S.; CAMARGO, L.; SARAIVA-ROMANHOLO, B.; BEZERRA, S.; PRADO, C. M.; LOPES, F. D.; et al. Plant Protease Inhibitors Had an Effect on Controlling Lung Inflammation, Remodeling and Oxidative Stress in Mice with ASTHMA-COPD Overlap: Comparison with Corticosteroid. American Journal of Respiratory and Critical Care Medicine, v. 205, p. 2-pg., 2022-05-01. (18/02537-5)

PIGATI, PATRICIA ANGELI DA SILVA; RIGHETTI, RENATO FRAGA; NISIAYMAMOTO, BRUNA TIEMI CUNHA; SARAIVA-ROMANHOLO, BEATRIZ MANGUEIRA; TIBERIO, IOLANDA DE FATIMA LOPES CALVO. Resilience and its impact on the mental health of physiotherapists during the COVID-19 pandemic in Sa?o Paulo, Brazil. Journal of Affective Disorders, v. 310, p. 7-pg., 2022-08-01. (18/02537-5)

DA SILVA PIGATI, PATRICIA ANGELI; RIGHETTI, RENATO FRAGA; DOURADO, VICTOR ZUNIGA; CUNHA NISIAYMAMOTO, BRUNA TIEMI; SARAIVA-ROMANHOLO, BEATRIZ MANGUEIRA; LOPES CALVO TIBERIO, IOLANDA DE FATIMA. Resilience Improves the Quality of Life and Subjective Happiness of Physiotherapists during the COVID-19 Pandemic. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, v. 19, n. 14, p. 22-pg., 2022-07-01. (18/02537-5)

BANZATO, ROSANA; PINHEIRO, NATHALIA M.; OLIVO, CLARICE R.; SANTANA, FERNANDA R.; LOPES, FERNANDA D. T. Q. S.; CAPERUTO, LUCIANA C.; CAMARA, NIELS O.; MARTINS, MILTON A.; TIBERIO, IOLANDA F. L. C.; PRADO, MARCO ANTONIO M.; et al. Long-term endogenous acetylcholine deficiency potentiates pulmonary inflammation in a murine model of elastase-induced emphysema. SCIENTIFIC REPORTS, v. 11, n. 1, AUG 5 2021. (18/06088-0, 11/15817-7, 18/02537-5, 18/15738-9, 13/02881-4)