TY - JOUR
T1 - Noninvasive analysis of the sputum transcriptome discriminates clinical phenotypes of asthma
AU - Yan, Xiting
AU - Chu, Jen Hwa
AU - Gomez, Jose
AU - Koenigs, Maria
AU - Holm, Carole
AU - He, Xiaoxuan
AU - Perez, Mario F.
AU - Zhao, Hongyu
AU - Mane, Shrikant
AU - Martinez, Fernando D.
AU - Ober, Carole
AU - Nicolae, Dan L.
AU - Barnes, Kathleen C.
AU - London, Stephanie J.
AU - Gilliland, Frank
AU - Weiss, Scott T.
AU - Raby, Benjamin A.
AU - Cohn, Lauren
AU - Chupp, Geoffrey L.
PY - 2015/5/15
Y1 - 2015/5/15
N2 - RATIONALE: The airway transcriptome includes genes that contribute to the pathophysiologic heterogeneity seen in individuals with asthma.OBJECTIVES: We analyzed sputum gene expression for transcriptomic endotypes of asthma (TEA), gene signatures that discriminate phenotypes of disease.METHODS: Gene 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 RESULTS: Three 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.CONCLUSIONS: There 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.
AB - RATIONALE: The airway transcriptome includes genes that contribute to the pathophysiologic heterogeneity seen in individuals with asthma.OBJECTIVES: We analyzed sputum gene expression for transcriptomic endotypes of asthma (TEA), gene signatures that discriminate phenotypes of disease.METHODS: Gene 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 RESULTS: Three 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.CONCLUSIONS: There 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.
KW - RNA
KW - genomic
KW - molecular endotyping
KW - pathway analysis
KW - severe asthma
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U2 - 10.1164/rccm.201408-1440OC
DO - 10.1164/rccm.201408-1440OC
M3 - Article
C2 - 25763605
AN - SCOPUS:84964698860
SN - 1073-449X
VL - 191
SP - 1116
EP - 1125
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 10
ER -