Transcriptome analysis of sputum cells reveals two distinct molecular phenotypes of "asthma and chronic obstructive pulmonary disease overlap" in the elderly
© 2022. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
European journal of medical research - 27(2022), 1 vom: 28. Okt., Seite 215 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lee, Suh-Young [VerfasserIn] |
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| Links: |
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| Themen: |
Asthma |
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| Anmerkungen: |
Date Completed 01.11.2022 Date Revised 01.11.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s40001-022-00861-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM348221231 |
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| 245 | 1 | 0 | |a Transcriptome analysis of sputum cells reveals two distinct molecular phenotypes of "asthma and chronic obstructive pulmonary disease overlap" in the elderly |
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| 500 | |a Date Completed 01.11.2022 | ||
| 500 | |a Date Revised 01.11.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Asthma | |
| 650 | 4 | |a Asthma-chronic obstructive pulmonary disease overlap syndrome | |
| 650 | 4 | |a Chronic obstructive pulmonary disease | |
| 650 | 4 | |a Cluster analysis | |
| 650 | 4 | |a Sputum | |
| 650 | 4 | |a Transcriptome | |
| 700 | 1 | |a Lee, Hyun-Seung |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Heung-Woo |e verfasserin |4 aut | |
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