PMID- 27801710
OWN - NLM
STAT- MEDLINE
DCOM- 20180403
LR  - 20181202
IS  - 1531-6971 (Electronic)
IS  - 1070-5287 (Linking)
VI  - 23
IP  - 1
DP  - 2017 Jan
TI  - Glucocortiosteroid subsensitivity and asthma severity.
PG  - 78-88
AB  - PURPOSE OF REVIEW: Glucocorticosteroids (GCSs) remain the cornerstone of therapy 
      for treating the inflammatory component of asthma. Clinical response to GCS is 
      heterogeneous, varying both within asthma 'endotypes', as well as the same 
      individual. Different factors and micro-environment can alter the canonical 
      GCS-induced signalling pathways leading to reduced efficacy, collectively termed 
      as GCS subsensitivity, which includes the entire spectrum of steroid 
      insensitivity and steroid resistance. RECENT FINDINGS: In the past, steroid 
      subsensitivity has been associated with dysregulated expression of 
      glucocorticoid-receptor isoforms, neutrophilic inflammation and Th17 cytokines, 
      oxidative stress-inducing factors and their downstream effect on histone 
      deacetylase activities and gene expression. The review highlights recent 
      observations, such as GCS-induced dysregulation of key transcription factors 
      involved in host defence, role of airway infections altering expression of 
      critical regulatory elements like the noncoding microRNAs, and the importance of 
      interleukin (IL)-10 in reinstating steroid response in key immune cells. Further, 
      emerging concepts of autoimmunity triggered because of delayed resolution of 
      eosinophilic inflammation (due to GCS subsensitivity) and observed lymphopenia 
      (plausibly a side-effect of continued GCS use) are discussed. SUMMARY: This 
      review bridges concepts that have been known, and those under current 
      investigation, providing both molecular and clinical insights to aid therapeutic 
      strategies for optimal management of asthmatics with varying degree of steroid 
      subsensitivity and disease severity, with particular emphasis on the PI3 kinase 
      pathways.
FAU - Mukherjee, Manali
AU  - Mukherjee M
AD  - Department of Medicine, McMaster University & St Joseph's Healthcare, Hamilton, 
      Ontario, Canada.
FAU - Svenningsen, Sarah
AU  - Svenningsen S
FAU - Nair, Parameswaran
AU  - Nair P
LA  - eng
GR  - CIHR/Canada
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Curr Opin Pulm Med
JT  - Current opinion in pulmonary medicine
JID - 9503765
RN  - 0 (Glucocorticoids)
RN  - 0 (Receptors, Glucocorticoid)
SB  - IM
MH  - Asthma/*drug therapy/immunology
MH  - Glucocorticoids/*therapeutic use
MH  - Humans
MH  - Receptors, Glucocorticoid/immunology
MH  - Severity of Illness Index
MH  - Signal Transduction/drug effects
MH  - Th17 Cells/immunology
EDAT- 2016/11/02 06:00
MHDA- 2018/04/04 06:00
CRDT- 2016/11/02 06:00
PHST- 2016/11/02 06:00 [pubmed]
PHST- 2018/04/04 06:00 [medline]
PHST- 2016/11/02 06:00 [entrez]
AID - 10.1097/MCP.0000000000000337 [doi]
PST - ppublish
SO  - Curr Opin Pulm Med. 2017 Jan;23(1):78-88. doi: 10.1097/MCP.0000000000000337.