1. Asthma–COPD Overlap. Clinical Relevance of Genomic Signatures of Type 2 Inflammation in Chronic Obstructive Pulmonary Disease
- Author
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Christenson, Stephanie A, Steiling, Katrina, van den Berge, Maarten, Hijazi, Kahkeshan, Hiemstra, Pieter S, Postma, Dirkje S, Lenburg, Marc E, Spira, Avrum, and Woodruff, Prescott G
- Subjects
Asthma ,Lung ,Genetics ,Chronic Obstructive Pulmonary Disease ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Respiratory ,Cohort Studies ,Datasets as Topic ,Female ,Forced Expiratory Volume ,Gene Expression Profiling ,Humans ,Inflammation ,Male ,Pulmonary Disease ,Chronic Obstructive ,Transcriptome ,chronic obstructive pulmonary disease ,gene expression profiling ,biological markers ,Medical and Health Sciences ,Respiratory System - Abstract
RationaleChronic 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.ObjectivesTo determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features.MethodsWe 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).Measurements and main resultsThe 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.ConclusionsThese 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.
- Published
- 2015