Chronic stress and glucocorticoid receptor resistance in asthma
- Autores
- Palumbo, María Laura; Prochnik, Andrés; Wald, Miriam Ruth; Genaro, Ana María
- Año de publicación
- 2020
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión aceptada
- Descripción
- Fil: Palumbo, María Laura. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina
Fil: Palumbo, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Prochnik, Andrés. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomedicas; Argentina
Fil: Prochnik, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Wald, Miriam Ruth. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomedicas; Argentina
Fil: Wald, Miriam Rut. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Genaro, Ana María. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina
Abstract: Purpose: Chronic and persistent exposure to negative stress can lead to adverse consequences on health. Particularly, psychosocial factors were found to increase the risk and outcome of respiratory diseases like asthma. Glucocorticoids (GCs) are the most efficient anti-inflammatory therapy for asthma. However, a significant proportion of patients don’t respond adequately to GC administration. GC sensitivity is modulated by genetic and acquired disease-related factors. Additionally, it was proposed that endogenous corticosteroids may limit certain actions of synthetic GCs, contributing to insensitivity. Psychological and physiological stresses activate the hypothalamic-pituitary-adrenal axis, increasing cortisol levels. Here, we review the mechanism involved in altered GC sensitivity in asthmatic patients under stressful situations. Strategies for modulation GC sensitivity and improving GC therapy are discussed. Methods: PubMed was searched for publications on psychological chronic stress and asthma, GC resistance in asthma, biological mechanisms for GC resistance, and drugs for steroid-resistant asthma, including highly potent GCs. Findings: GC resistance in patients with severe disease remains a major clinical problem. In asthma, experimental and clinical evidence suggests that chronic stress induces inflammatory changes, contributing to a worse GC response. GC resistant patients can be treated with other broad-spectrum anti-inflammatory drugs, but these generally have major side effects. Different mechanisms of GC resistance have been described and might be useful for developing new therapeutic strategies against it. Novel drugs, such as highly potent GCs, phosphoinositide 3-kinase-delta inhibitors that reestablish histone deacetylase-2 function, decrease of GC receptor phosphorylation by p38 mitogenactivated protein kinase inhibitors, or phosphatase activators, are currently in clinical development and might be combined with GC therapy in the future. Furthermore, microRNAs (small noncoding RNA molecules) operate as posttranscriptional regulators, providing another level of control of GC receptor levels. Empirical results allow postulating that the detection and study of microRNAs might be a promising approach to better characterize and treat asthmatic patients. Implications: Many molecular and cellular pathobiological mechanisms are responsible of GC resistance. Therefore detecting specific biomarkers to help identify patients who would benefit from new therapies is crucial. Stress consitutes a negative aspect of current lifestyles that increase asthma morbidity and mortality. Adequate stress management could be an important and positive intervention. Key words: asthma, chronic stress, glucocorticoid resistance, pharmacologic strategies. - Fuente
- Clinical Therapeutics. 2020
- Materia
-
ASMA
CORTICOIDES
TRATAMIENTO MEDICO
TRATAMIENTO FARMACOLOGICO
ESTRES
FACTORES PSICOLOGICOS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/4.0/
- Repositorio
- Institución
- Pontificia Universidad Católica Argentina
- OAI Identificador
- oai:ucacris:123456789/10052
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Chronic stress and glucocorticoid receptor resistance in asthmaPalumbo, María LauraProchnik, AndrésWald, Miriam RuthGenaro, Ana MaríaASMACORTICOIDESTRATAMIENTO MEDICOTRATAMIENTO FARMACOLOGICOESTRESFACTORES PSICOLOGICOSFil: Palumbo, María Laura. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Palumbo, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Prochnik, Andrés. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomedicas; ArgentinaFil: Prochnik, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wald, Miriam Ruth. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomedicas; ArgentinaFil: Wald, Miriam Rut. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Genaro, Ana María. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; ArgentinaAbstract: Purpose: Chronic and persistent exposure to negative stress can lead to adverse consequences on health. Particularly, psychosocial factors were found to increase the risk and outcome of respiratory diseases like asthma. Glucocorticoids (GCs) are the most efficient anti-inflammatory therapy for asthma. However, a significant proportion of patients don’t respond adequately to GC administration. GC sensitivity is modulated by genetic and acquired disease-related factors. Additionally, it was proposed that endogenous corticosteroids may limit certain actions of synthetic GCs, contributing to insensitivity. Psychological and physiological stresses activate the hypothalamic-pituitary-adrenal axis, increasing cortisol levels. Here, we review the mechanism involved in altered GC sensitivity in asthmatic patients under stressful situations. Strategies for modulation GC sensitivity and improving GC therapy are discussed. Methods: PubMed was searched for publications on psychological chronic stress and asthma, GC resistance in asthma, biological mechanisms for GC resistance, and drugs for steroid-resistant asthma, including highly potent GCs. Findings: GC resistance in patients with severe disease remains a major clinical problem. In asthma, experimental and clinical evidence suggests that chronic stress induces inflammatory changes, contributing to a worse GC response. GC resistant patients can be treated with other broad-spectrum anti-inflammatory drugs, but these generally have major side effects. Different mechanisms of GC resistance have been described and might be useful for developing new therapeutic strategies against it. Novel drugs, such as highly potent GCs, phosphoinositide 3-kinase-delta inhibitors that reestablish histone deacetylase-2 function, decrease of GC receptor phosphorylation by p38 mitogenactivated protein kinase inhibitors, or phosphatase activators, are currently in clinical development and might be combined with GC therapy in the future. Furthermore, microRNAs (small noncoding RNA molecules) operate as posttranscriptional regulators, providing another level of control of GC receptor levels. Empirical results allow postulating that the detection and study of microRNAs might be a promising approach to better characterize and treat asthmatic patients. Implications: Many molecular and cellular pathobiological mechanisms are responsible of GC resistance. Therefore detecting specific biomarkers to help identify patients who would benefit from new therapies is crucial. Stress consitutes a negative aspect of current lifestyles that increase asthma morbidity and mortality. Adequate stress management could be an important and positive intervention. Key words: asthma, chronic stress, glucocorticoid resistance, pharmacologic strategies.Elsevier2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://repositorio.uca.edu.ar/handle/123456789/100520149-2918 (online)10.1016/j.clinthera.2020.03.002Palumbo, M. L., et al. Chronic stress and glucocorticoid receptor resistance in asthma [en línea]. Postprint del artículo publicado en Clinical Therapeutics. 2020. doi: 10.1016/j.clinthera.2020.03.002. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/10052Clinical Therapeutics. 2020reponame:Repositorio Institucional (UCA)instname:Pontificia Universidad Católica Argentinaenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/4.0/2025-07-03T10:57:21Zoai:ucacris:123456789/10052instacron:UCAInstitucionalhttps://repositorio.uca.edu.ar/Universidad privadaNo correspondehttps://repositorio.uca.edu.ar/oaiclaudia_fernandez@uca.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:25852025-07-03 10:57:22.281Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentinafalse |
dc.title.none.fl_str_mv |
Chronic stress and glucocorticoid receptor resistance in asthma |
title |
Chronic stress and glucocorticoid receptor resistance in asthma |
spellingShingle |
Chronic stress and glucocorticoid receptor resistance in asthma Palumbo, María Laura ASMA CORTICOIDES TRATAMIENTO MEDICO TRATAMIENTO FARMACOLOGICO ESTRES FACTORES PSICOLOGICOS |
title_short |
Chronic stress and glucocorticoid receptor resistance in asthma |
title_full |
Chronic stress and glucocorticoid receptor resistance in asthma |
title_fullStr |
Chronic stress and glucocorticoid receptor resistance in asthma |
title_full_unstemmed |
Chronic stress and glucocorticoid receptor resistance in asthma |
title_sort |
Chronic stress and glucocorticoid receptor resistance in asthma |
dc.creator.none.fl_str_mv |
Palumbo, María Laura Prochnik, Andrés Wald, Miriam Ruth Genaro, Ana María |
author |
Palumbo, María Laura |
author_facet |
Palumbo, María Laura Prochnik, Andrés Wald, Miriam Ruth Genaro, Ana María |
author_role |
author |
author2 |
Prochnik, Andrés Wald, Miriam Ruth Genaro, Ana María |
author2_role |
author author author |
dc.subject.none.fl_str_mv |
ASMA CORTICOIDES TRATAMIENTO MEDICO TRATAMIENTO FARMACOLOGICO ESTRES FACTORES PSICOLOGICOS |
topic |
ASMA CORTICOIDES TRATAMIENTO MEDICO TRATAMIENTO FARMACOLOGICO ESTRES FACTORES PSICOLOGICOS |
dc.description.none.fl_txt_mv |
Fil: Palumbo, María Laura. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina Fil: Palumbo, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Prochnik, Andrés. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomedicas; Argentina Fil: Prochnik, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Wald, Miriam Ruth. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomedicas; Argentina Fil: Wald, Miriam Rut. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Genaro, Ana María. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina Abstract: Purpose: Chronic and persistent exposure to negative stress can lead to adverse consequences on health. Particularly, psychosocial factors were found to increase the risk and outcome of respiratory diseases like asthma. Glucocorticoids (GCs) are the most efficient anti-inflammatory therapy for asthma. However, a significant proportion of patients don’t respond adequately to GC administration. GC sensitivity is modulated by genetic and acquired disease-related factors. Additionally, it was proposed that endogenous corticosteroids may limit certain actions of synthetic GCs, contributing to insensitivity. Psychological and physiological stresses activate the hypothalamic-pituitary-adrenal axis, increasing cortisol levels. Here, we review the mechanism involved in altered GC sensitivity in asthmatic patients under stressful situations. Strategies for modulation GC sensitivity and improving GC therapy are discussed. Methods: PubMed was searched for publications on psychological chronic stress and asthma, GC resistance in asthma, biological mechanisms for GC resistance, and drugs for steroid-resistant asthma, including highly potent GCs. Findings: GC resistance in patients with severe disease remains a major clinical problem. In asthma, experimental and clinical evidence suggests that chronic stress induces inflammatory changes, contributing to a worse GC response. GC resistant patients can be treated with other broad-spectrum anti-inflammatory drugs, but these generally have major side effects. Different mechanisms of GC resistance have been described and might be useful for developing new therapeutic strategies against it. Novel drugs, such as highly potent GCs, phosphoinositide 3-kinase-delta inhibitors that reestablish histone deacetylase-2 function, decrease of GC receptor phosphorylation by p38 mitogenactivated protein kinase inhibitors, or phosphatase activators, are currently in clinical development and might be combined with GC therapy in the future. Furthermore, microRNAs (small noncoding RNA molecules) operate as posttranscriptional regulators, providing another level of control of GC receptor levels. Empirical results allow postulating that the detection and study of microRNAs might be a promising approach to better characterize and treat asthmatic patients. Implications: Many molecular and cellular pathobiological mechanisms are responsible of GC resistance. Therefore detecting specific biomarkers to help identify patients who would benefit from new therapies is crucial. Stress consitutes a negative aspect of current lifestyles that increase asthma morbidity and mortality. Adequate stress management could be an important and positive intervention. Key words: asthma, chronic stress, glucocorticoid resistance, pharmacologic strategies. |
description |
Fil: Palumbo, María Laura. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentina |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
acceptedVersion |
dc.identifier.none.fl_str_mv |
https://repositorio.uca.edu.ar/handle/123456789/10052 0149-2918 (online) 10.1016/j.clinthera.2020.03.002 Palumbo, M. L., et al. Chronic stress and glucocorticoid receptor resistance in asthma [en línea]. Postprint del artículo publicado en Clinical Therapeutics. 2020. doi: 10.1016/j.clinthera.2020.03.002. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/10052 |
url |
https://repositorio.uca.edu.ar/handle/123456789/10052 |
identifier_str_mv |
0149-2918 (online) 10.1016/j.clinthera.2020.03.002 Palumbo, M. L., et al. Chronic stress and glucocorticoid receptor resistance in asthma [en línea]. Postprint del artículo publicado en Clinical Therapeutics. 2020. doi: 10.1016/j.clinthera.2020.03.002. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/10052 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/4.0/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/4.0/ |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
Clinical Therapeutics. 2020 reponame:Repositorio Institucional (UCA) instname:Pontificia Universidad Católica Argentina |
reponame_str |
Repositorio Institucional (UCA) |
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Repositorio Institucional (UCA) |
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Pontificia Universidad Católica Argentina |
repository.name.fl_str_mv |
Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentina |
repository.mail.fl_str_mv |
claudia_fernandez@uca.edu.ar |
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1836638351454633984 |
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13.070432 |