Meta-analysis of airway epithelium gene expression in asthma

Abstract

Differential gene expression in the airway epithelium of patients with asthma controls has been reported in several studies. However, there is no consensus on which genes are reproducibly affected in asthma. We sought to identify a consensus list of differentially expressed genes (DEGs) using a meta-analysis approach.We identified eight studies with data that met defined inclusion criteria. These studies comprised 355 cases and 193 controls and involved sampling either bronchial or nasal epithelium. We conductedstudy-level analyses, followed by a meta-analysis. Likewise, we applied a meta-analysis framework to the results of study-level pathway enrichment.We identified 1273 DEGs, 431 of which had not been identified in previous studies. 450 DEGs exhibited large effect sizes and were robust to study population differences in age, sex, race/ethnicity, medication use, smoking status and exacerbations. The magnitude of differential expression of these 450 genes was highly similar in bronchial and nasal airway epithelia. Meta-analysis of pathway enrichment revealed a number of consistently dysregulated biological pathways, including putative transcriptional and post-transcriptional regulators.In total, we identified a set of genes that is consistently dysregulated in asthma, that links to known and novel biological pathways, and that will inform asthma subtype identification.

Transcriptome-wide and differential expression network analyses of childhood asthma in nasal epithelium

“…We recently identified more than 7000 CpGs associated with atopic asthma in an epigenome-wide association study of nasal epithelium in Puerto Rican children, 1 and a recent meta-analysis of airway epithelial gene expression identified 1273 differentially expressed genes (DEGs) in asthma. 2 Here, we report a transcriptome-wide study of nasal epithelium and atopic asthma in Puerto Rican children, with replication in 3 separate cohorts.…”

“…It is well recognized that individuals with allergic diseases such as asthma and atopic dermatitis clear some viral infections poorly compared with healthy subjects. 1,2 Respiratory viral infections, including respiratory syncytial virus (RSV), influenza A virus (IAV), and rhinovirus, can promote asthma exacerbations and are associated with increased morbidity and mortality. Type I (a/b) and type III (l) interferons are critical for antiviral defense, inhibit viral replication, and mobilize host defense mechanisms.…”

Particulate matter and the airway epithelium: the special case of the underground?

“…Furthermore, asthma is associated with a background of pre-existing oxidative stress as well as increased susceptibility to ROS-associated damage [77,78]. Indeed, genetic polymorphisms in enzymes involved in cycling of the antioxidant glutathione have been associated with asthma [79], as have decreased levels of airway superoxide dismutase and catalase [80,81].…”

Dysregulation of sputum columnar epithelial cells and products in distinct asthma phenotypes

“…The bronchial epithelium is a critical site of asthma-related pathophysiological changes, and transcriptomic studies of bronchial brushings demonstrate altered bronchial epithelium activation status in asthma. [11][12][13] A three gene expression signature (composed of periostin, CLCA1 and SerpinB2) measured in bronchial brushings relating to IL-13 activation of bronchial epithelial cells, type 2 high asthma and airway eosinophilia can predict corticosteroid response in patients with mild asthma. 13,14 The use of epithelial gene signatures in the clinic has been limited by the highly invasive nature of bronchial brushing collection.…”