- Title
- Transcriptional phenotypes of asthma defined by gene expression profiling of induced sputum samples
- Creator
- Baines, Katherine J.; Simpson, Jodie L.; Wood, Lisa G.; Scott, Rodney J.; Gibson, Peter G.
- Relation
- Journal of Allergy and Clinical Immunology Vol. 127, Issue 1, p. 153-160.e9
- Publisher Link
- http://dx.doi.org/10.1016/j.jaci.2010.10.024
- Publisher
- Mosby
- Resource Type
- journal article
- Date
- 2011
- Description
- Background: Previous studies have identified clinical or inflammatory phenotypes of asthma on the basis of clinical and demographic parameters or sputum cell counts; however, few studies have defined transcriptional phenotypes of asthma. Objective: To investigate asthma phenotypes at a transcriptional level by using gene expression profiling of induced sputum. Methods: Induced sputum samples were collected from 59 people with asthma with a mean age of 58 years and an FEV1% predicted of 76%, and 69% were taking inhaled corticosteroids. Thirteen healthy controls without asthma were also assessed. Inflammatory cell counts were performed, and RNA was extracted from selected sputum. Transcriptional profiles were generated (Illumina Humanref-8 V2) and analyzed by using GeneSpring GX11. Results: Unsupervised hierarchical clustering of gene expression profiles in asthma revealed 3 distinct groups. The first transcriptional phenotype (n = 21) had lower FEV1% predicted and higher asthma control questionnaire scores, exhaled nitric oxide, and sputum eosinophils. The second transcriptional phenotype (n = 14) had lower FEV1% predicted and forced vital capacity % predicted and higher sputum neutrophils compared with a third transcriptional phenotype (n = 24) that had higher sputum macrophages and resembled healthy controls. Differentially expressed genes between transcriptional asthma phenotypes were related to inflammatory and immune responses. Genes in the IL-1 and TNF-α/nuclear factor-κB pathways were overexpressed and correlated with clinical parameters and neutrophilic airway inflammation. Conclusion: Gene expression profiling provides a novel means to investigate the molecular mechanisms and classifications of asthma phenotypes. There are 3 distinct transcriptional phenotypes of asthma that relate to both clinical and inflammatory parameters.
- Subject
- asthma phenotypes; gene expression profiling; induced sputum; IL 1; TNF α; neutrophils; eosinophils
- Identifier
- http://hdl.handle.net/1959.13/1043411
- Identifier
- uon:14184
- Identifier
- ISSN:0091-6749
- Language
- eng
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