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  • Title: Transcriptome analysis of sputum cells reveals two distinct molecular phenotypes of "asthma and chronic obstructive pulmonary disease overlap" in the elderly.
    Author: Lee SY, Lee HS, Park HW.
    Journal: Eur J Med Res; 2022 Oct 28; 27(1):215. PubMed ID: 36307832.
    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.
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