25611785
BACKGROUND	Chronic obstructive pulmonary disease ( COPD ) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma .
BACKGROUND	Studying asthma-associated gene expression changes in COPD could add insight into COPD pathogenesis and reveal biomarkers that predict a favorable response to corticosteroids .
OBJECTIVE	To determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features .
METHODS	We compared disease-associated airway epithelial gene expression alterations in an asthma cohort ( n = 105 ) and two COPD cohorts ( n = 237 , 171 ) .
METHODS	The T helper type 2 ( Th2 ) signature ( T2S ) score , a gene expression metric induced in Th2-high asthma , was evaluated in these COPD cohorts .
METHODS	The T2S score was correlated with asthma-related features and response to corticosteroids in COPD in a randomized , placebo-controlled trial , the Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease ( GLUCOLD ; n = 89 ) .
RESULTS	The 200 genes most differentially expressed in asthma versus healthy control subjects were enriched among genes associated with more severe airflow obstruction in these COPD cohorts ( P < 0.001 ) , suggesting significant gene expression overlap .
RESULTS	A higher T2S score was associated with decreased lung function ( P < 0.001 ) , but not asthma history , in both COPD cohorts .
RESULTS	Higher T2S scores correlated with increased airway wall eosinophil counts ( P = 0.003 ) , blood eosinophil percentage ( P = 0.03 ) , bronchodilator reversibility ( P = 0.01 ) , and improvement in hyperinflation after corticosteroid treatment ( P = 0.019 ) in GLUCOLD .
CONCLUSIONS	These data identify airway gene expression alterations that can co-occur in asthma and COPD .
CONCLUSIONS	The association of the T2S score with increased severity and `` asthma-like '' features ( including a favorable corticosteroid response ) in COPD suggests that Th2 inflammation is important in a COPD subset that can not be identified by clinical history of asthma .

