Chronic stress and glucocorticoid receptor resistance in asthma
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 th...
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| Formato: | Artículo |
| Lenguaje: | Inglés |
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Elsevier
2020
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| Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/10052 |
| Aporte de: |
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I33-R139123456789-10052 |
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dspace |
| institution |
Universidad Católica Argentina |
| institution_str |
I-33 |
| repository_str |
R-139 |
| collection |
Repositorio Institucional de la Universidad Católica Argentina (UCA) |
| language |
Inglés |
| topic |
ASMA CORTICOIDES TRATAMIENTO MEDICO TRATAMIENTO FARMACOLOGICO ESTRES FACTORES PSICOLOGICOS |
| spellingShingle |
ASMA CORTICOIDES TRATAMIENTO MEDICO TRATAMIENTO FARMACOLOGICO ESTRES FACTORES PSICOLOGICOS Palumbo, María Laura Prochnik, Andrés Wald, Miriam Ruth Genaro, Ana María Chronic stress and glucocorticoid receptor resistance in asthma |
| topic_facet |
ASMA CORTICOIDES TRATAMIENTO MEDICO TRATAMIENTO FARMACOLOGICO ESTRES FACTORES PSICOLOGICOS |
| description |
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. |
| format |
Artículo |
| author |
Palumbo, María Laura Prochnik, Andrés Wald, Miriam Ruth Genaro, Ana María |
| author_facet |
Palumbo, María Laura Prochnik, Andrés Wald, Miriam Ruth Genaro, Ana María |
| author_sort |
Palumbo, María Laura |
| title |
Chronic stress and glucocorticoid receptor resistance in asthma |
| 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 |
| publisher |
Elsevier |
| publishDate |
2020 |
| url |
https://repositorio.uca.edu.ar/handle/123456789/10052 |
| work_keys_str_mv |
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| bdutipo_str |
Repositorios |
| _version_ |
1764820523881070594 |