PMID- 22515387
OWN - NLM
STAT- MEDLINE
DCOM- 20120815
LR  - 20120420
IS  - 1365-2222 (Electronic)
IS  - 0954-7894 (Linking)
VI  - 42
IP  - 5
DP  - 2012 May
TI  - Pathogenesis of severe asthma.
PG  - 625-37
LID - 10.1111/j.1365-2222.2012.03983.x [doi]
AB  - Patients with severe asthma have asthma symptoms which are difficult to control, 
      require high dosages of medication, and continue to experience persistent 
      symptoms, asthma exacerbations or airflow obstruction. Epidemiological and 
      clinical evidences point to the fact that severe asthma is not a single 
      phenotype. Cluster analyses have identified subclasses of severe asthma using 
      parameters such as patient characteristics, and cytokine profiles have also been 
      useful in classifying moderate and severe asthma. The IL-4/IL-13 signalling 
      pathway accounts for the symptoms experienced by a subset of severe asthmatics 
      with allergen-associated symptoms and high serum immunoglobulin E (IgE) levels, 
      and these patients are generally responsive to anti-IgE treatment. The IL-5/IL-33 
      signalling pathway is likely to play a key role in the disease pathogenesis of 
      those who are resistant to high doses of inhaled corticosteroid but responsive to 
      systemic corticosteroids and anti-IL5 therapy. The IL-17 signalling pathway is 
      thought to contribute to 'neutrophilic asthma'. Although traditionally viewed as 
      players in the defence mechanism against viral and intracellular bacterial 
      infection, mounting evidence supports a role for Th1 cytokines such as IL-18 and 
      IFN-gamma in severe asthma pathogenesis. Furthermore, these cytokine signalling 
      pathways interact to contribute to the spectrum of clinical pathological outcomes 
      in severe asthma. To date, glucocorticoids are the most effective anti-asthma 
      drugs available, yet severe asthma patients are typically resistant to the 
      effects of glucocorticoids. Glucocorticoid receptor dysfunction and histone 
      deacetylase activity reduction are likely to contribute to glucocorticoid 
      resistance in severe asthma patients. This review discusses recent development in 
      different cytokine signalling pathways, their interactions and steroid 
      resistance, in the context of severe asthma pathogenesis.
CI  - (c) 2012 Blackwell Publishing Ltd.
FAU - Poon, A H
AU  - Poon AH
AD  - Meakins-Christie Laboratories, McGill University Health Centre, Montreal, Quebec, 
      Canada.
FAU - Eidelman, D H
AU  - Eidelman DH
FAU - Martin, J G
AU  - Martin JG
FAU - Laprise, C
AU  - Laprise C
FAU - Hamid, Q
AU  - Hamid Q
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Clin Exp Allergy
JT  - Clinical and experimental allergy : journal of the British Society for Allergy 
      and Clinical Immunology
JID - 8906443
RN  - 0 (Anti-Asthmatic Agents)
RN  - 0 (Cytokines)
RN  - 0 (Glucocorticoids)
RN  - 0 (Histones)
SB  - IM
MH  - Acetylation
MH  - Animals
MH  - Anti-Asthmatic Agents/therapeutic use
MH  - Asthma/drug therapy/*etiology
MH  - Cytokines/genetics/immunology/metabolism
MH  - Drug Resistance
MH  - Glucocorticoids/therapeutic use
MH  - Histones/metabolism
MH  - Humans
MH  - Severity of Illness Index
MH  - Signal Transduction
EDAT- 2012/04/21 06:00
MHDA- 2012/08/16 06:00
CRDT- 2012/04/21 06:00
PHST- 2012/04/21 06:00 [entrez]
PHST- 2012/04/21 06:00 [pubmed]
PHST- 2012/08/16 06:00 [medline]
AID - 10.1111/j.1365-2222.2012.03983.x [doi]
PST - ppublish
SO  - Clin Exp Allergy. 2012 May;42(5):625-37. doi: 10.1111/j.1365-2222.2012.03983.x.