Subclinical phenotypes of asthma.
OBJECTIVE
Asthma is a heterogeneous disease. Identification of specific subphenotypes of asthma may further our understanding of pathophysiology and treatment response, leading to the better targeting of both existing and novel antiasthma therapies. An accurate and comprehensive clinicopathological classification system therefore remains an important priority for asthma research. The present review discusses the important recent literature in this field.


RESULTS
Cluster analysis in patients with severe asthma has suggested the presence of four distinct clinical phenotypes, two with eosinophilic airway inflammation, and two without. Patients with eosinophilic inflammation benefit most from a management strategy targeting the sputum eosinophil count. Molecular phenotying utilizing gene arrays in steroid-naive asthmatic individuals reveals two distinct subgroups (Th2-high and Th2-low) based on the expression of Th2 cytokine genes (IL-5, IL-13) and Th2-responsive genes. The Th2-high group exhibit clinical features typical of patients with eosinophilic disease. Targeting anti-IL-5 therapy to patients with evidence of eosinophilic airway inflammation and recurrent asthma exacerbations markedly reduces the asthma exacerbation rate, but day-to-day asthma symptoms remain unchanged.


CONCLUSIONS
The detailed phenotyping of asthma will allow the successful targeting of existing and novel therapies to those patients most likely to gain benefit.
Bradding
Peter
P
Institute for Lung Health and Department of Respiratory Medicine, Glenfield Hospital, UK. pbradding@hotmail.com
Green
Ruth H
RH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D002452:Cell Count; D002465:Cell Movement; D016000:Cluster Analysis; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D015848:Interleukin-5 / Q000276:immunology; D010641:Phenotype; D012137:Respiratory System / Q000276:immunology; D013183:Sputum / Q000166:cytology; D018418:Th2 Cells / Q000276:immunology
D000911:Antibodies, Monoclonal; D015848:Interleukin-5