title: Asthma-COPD overlap. Clinical relevance of genomic signatures of type 2 inflammation in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. 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). The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced in Th2-high asthma, was evaluated in these COPD cohorts. 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. A higher T2S score was associated with decreased lung function (P < 0.001), but not asthma history, in both COPD cohorts. 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. 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 cannot be identified by clinical history of asthma.
authors.affiliation: 1 Department of Medicine, Division of Pulmonary, Critical Care, Allergy, and Sleep and.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Christenson
authors.forename: Katrina
authors.initials: K
authors.lastname: Steiling
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Berge
authors.forename: Kahkeshan
authors.initials: K
authors.lastname: Hijazi
authors.forename: Pieter S
authors.initials: PS
authors.lastname: Hiemstra
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Marc E
authors.initials: ME
authors.lastname: Lenburg
authors.forename: Avrum
authors.initials: A
authors.lastname: Spira
authors.forename: Prescott G
authors.initials: PG
authors.lastname: Woodruff
mesh_terms: D001249:Asthma / Q000235:genetics*; D015331:Cohort Studies; D066264:Datasets as Topic; D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*
keywords: biological markers; chronic obstructive pulmonary disease; gene expression profiling