• Xiting Yan, Jen-Hwa Chu, Jose Gomez, Maria Koenigs, Carole Holm, Xiaoxuan He, Mario F Perez, Hongyu Zhao, Shrikant Mane, Fernando D Martinez, Carole Ober, Dan L Nicolae, Kathleen C Barnes, Stephanie J London, Frank Gilliland, Scott T Weiss, Benjamin A Raby, Lauren Cohn, and Geoffrey L Chupp.
• 1 Section of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine.
• Am. J. Respir. Crit. Care Med.. 2015 May 15;191(10):1116-25.

RationaleThe airway transcriptome includes genes that contribute to the pathophysiologic heterogeneity seen in individuals with asthma.ObjectivesWe analyzed sputum gene expression for transcriptomic endotypes of asthma (TEA), gene signatures that discriminate phenotypes of disease.MethodsGene expression in the sputum and blood of patients with asthma was measured using Affymetrix microarrays. Unsupervised clustering analysis based on pathways from the Kyoto Encyclopedia of Genes and Genomes was used to identify TEA clusters. Logistic regression analysis of matched blood samples defined an expression profile in the circulation to determine the TEA cluster assignment in a cohort of children with asthma to replicate clinical phenotypes.Measurements And Main ResultsThree TEA clusters were identified. TEA cluster 1 had the most subjects with a history of intubation (P = 0.05), a lower prebronchodilator FEV1 (P = 0.006), a higher bronchodilator response (P = 0.03), and higher exhaled nitric oxide levels (P = 0.04) compared with the other TEA clusters. TEA cluster 2, the smallest cluster, had the most subjects that were hospitalized for asthma (P = 0.04). TEA cluster 3, the largest cluster, had normal lung function, low exhaled nitric oxide levels, and lower inhaled steroid requirements. Evaluation of TEA clusters in children confirmed that TEA clusters 1 and 2 are associated with a history of intubation (P = 5.58 × 10(-6)) and hospitalization (P = 0.01), respectively.ConclusionsThere are common patterns of gene expression in the sputum and blood of children and adults that are associated with near-fatal, severe, and milder asthma.

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