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
Repositorio Institucional (UCA)
Institución
Pontificia Universidad Católica Argentina
OAI Identificador
oai:ucacris:123456789/10052

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oai_identifier_str oai:ucacris:123456789/10052
network_acronym_str RIUCA
repository_id_str 2585
network_name_str Repositorio Institucional (UCA)
spelling 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)
collection Repositorio Institucional (UCA)
instname_str 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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