Publications
Detailed Information
Transcriptome analysis of sputum cells reveals two distinct molecular phenotypes of asthma and chronic obstructive pulmonary disease overlap in the elderly
Cited 0 time in
Web of Science
Cited 0 time in Scopus
- Authors
- Issue Date
- 2022-10-28
- Publisher
- BMC
- Citation
- European Journal of Medical Research. 2022 Oct 28;27(1):215
- Keywords
- Asthma ; Chronic obstructive pulmonary disease ; Asthma-chronic obstructive pulmonary disease overlap ; syndrome, Sputum, Transcriptome, Cluster analysis
- Abstract
- Background
Little is known about the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO). This study examined the molecular phenotypes of ACO in the elderly.
Methods
A genome-wide investigation of gene expression in sputum cells from the elderly with asthma, ACO, or COPD was performed using gene set variation analysis (GSVA) with predefined asthma- or COPD-specific gene signatures. We then performed a subsequent cluster analysis using enrichment scores (ESs) to identify molecular clusters in the elderly with ACO. Finally, a second GSVA was conducted with curated gene signatures to gain insight into the pathogenesis of ACO associated with the identified molecular clusters.
Results
Seventy elderly individuals were enrolled (17 with asthma, 41 with ACO, and 12 with COPD). Two distinct molecular clusters of ACO were identified. Clinically, ACO cluster 1 (N = 23) was characterized by male and smoker dominance, more obstructive lung function, and higher proportions of both neutrophil and eosinophil in induced sputum compared to ACO cluster 2 (N = 18). ACO cluster 1 had molecular features similar to both asthma and COPD, with mitochondria and peroxisome dysfunction as important mechanisms in the pathogenesis of these diseases. The molecular features of ACO cluster 2 differed from those of asthma and COPD, with enhanced innate immune reactions to microorganisms identified as being important in the pathogenesis of this form of ACO.
Conclusion
Recognition of the unique biological pathways associated with the two distinct molecular phenotypes of ACO will deepen our understanding of ACO in the elderly.
- ISSN
- 2047-783X
- Language
- English
- Files in This Item:
- Appears in Collections:
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.