August, 2008-Discovery of Molecular Phenotypes of Severe Asthma
Severe asthma is a chronic inflammatory disease characterized by relative resistance to corticosteroid therapy; these patients and constitute those with the greatest morbidity and admissions to the Intensive Care Unit. Previous work has shown that severe asthmatics show distinct patterns of cellular (neutrophilic) inflammation, and show evidence of impaired innate immunity. A collaborative project by SCMM investigators measured panels of cytokines from bronchoalveolar lavage from 41 severe asthmatics vs. a matched group of nonsevere asthmatics. Using powerful unbiased bioinformatics analyses, distinct subgroups of asthmatics could be identified that significantly differ in lung function and dynamic responses to airway challenge solely based on hierarchical clustering of the BAL cytokine expression patterns. These investigators further sought as proof-of-principle to use the BAL cytokine panels to see if BAL cytokine patterns could predict which individuals were hyper-responsive to methacholine. This analysis involved predictive model building using a machine-learning technique of decision tree analysis, where methacholine hyper-responders could be identified and group into three distinct classes. These exciting findings indicate that protein signatures in BAL can be used for more accurate classification of asthma subtypes, thereby stimulating clinical research in personalized medicine. Use of molecular phenotyping information could lead to more robust identification of subgroups that may have distinct prognoses or be responsive to selective therapy. Read the article.
January, 2008-Dr. Allan Brasier's group recently published paper in Journal of Allergy and Clinical Immunology has made some headlines in the personalized medicine front for asthma. It was featured as an editors choice in the same magazine, and has hit the NIH news.
Brasier, A.R., Victor, S., Boetticher, G.D., Ju, H, Lee, C., Bleecker, E.R., Castro, M., Busse, W.W. and Calhoun W.J. Molecular Phenotyping Of Severe Asthma Using Pattern Recognition of Bronchoalveolar Lavage-Derived Cytokines. Journal of Clinical Allergy and Immunology, 121: 30-37, 2008.