Nasopharyngeal fungal subtypes of infant bronchiolitis and disease severity riskResearch in context
Summary: Background: Bronchiolitis is a leading cause of infant hospitalization. Recent research suggests the heterogeneity within bronchiolitis and the relationship of airway viruses and bacteria with bronchiolitis severity. However, little is known about the pathobiological role of fungi. We aime...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396423003079 |
| _version_ | 1797762830768799744 |
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| author | Ryohei Shibata Zhaozhong Zhu Michihito Kyo Tadao Ooka Robert J. Freishtat Jonathan M. Mansbach Marcos Pérez-Losada Carlos A. Camargo, Jr. Kohei Hasegawa |
| author_facet | Ryohei Shibata Zhaozhong Zhu Michihito Kyo Tadao Ooka Robert J. Freishtat Jonathan M. Mansbach Marcos Pérez-Losada Carlos A. Camargo, Jr. Kohei Hasegawa |
| author_sort | Ryohei Shibata |
| collection | DOAJ |
| description | Summary: Background: Bronchiolitis is a leading cause of infant hospitalization. Recent research suggests the heterogeneity within bronchiolitis and the relationship of airway viruses and bacteria with bronchiolitis severity. However, little is known about the pathobiological role of fungi. We aimed to identify bronchiolitis mycotypes by integrating fungus and virus data, and determine their association with bronchiolitis severity and biological characteristics. Methods: In a multicentre prospective cohort study of 398 infants (age <1 year, male 59%) hospitalized for bronchiolitis, we applied clustering approaches to identify mycotypes by integrating nasopharyngeal fungus (detected in RNA-sequencing data) and virus data (respiratory syncytial virus [RSV], rhinovirus [RV]) at hospitalization. We examined their association with bronchiolitis severity—defined by positive pressure ventilation (PPV) use and biological characteristics by nasopharyngeal metatranscriptome and transcriptome data. Results: In infants hospitalized for bronchiolitis, we identified four mycotypes: A) fungiM.restrictavirusRSV/RV, B) fungiM.restrictavirusRSV, C) fungiM.globosavirusRSV/RV, D) funginot-detectedvirusRSV/RV mycotypes. Compared to mycotype A infants (the largest subtype, n = 211), mycotype C infants (n = 85) had a significantly lower risk of PPV use (7% vs. 1%, adjOR, 0.21; 95% CI, 0.02–0.90; p = 0.033), while the risk of PPV use was not significantly different in mycotype B or D. In the metatranscriptome and transcriptome data, mycotype C had similar bacterial composition and microbial functions yet dysregulated pathways (e.g., Fc γ receptor-mediated phagocytosis pathway and chemokine signaling pathway; FDR <0.05). Interpretation: In this multicentre cohort, fungus-virus clustering identified distinct mycotypes of infant bronchiolitis with differential severity risks and unique biological characteristics. Funding: This study was supported by the National Institutes of Health. |
| first_indexed | 2024-03-12T19:33:00Z |
| format | Article |
| id | doaj.art-e87c8fd0a5384e46a8b566686d929375 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-03-12T19:33:00Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-e87c8fd0a5384e46a8b566686d9293752023-08-02T04:24:38ZengElsevierEBioMedicine2352-39642023-09-0195104742Nasopharyngeal fungal subtypes of infant bronchiolitis and disease severity riskResearch in contextRyohei Shibata0Zhaozhong Zhu1Michihito Kyo2Tadao Ooka3Robert J. Freishtat4Jonathan M. Mansbach5Marcos Pérez-Losada6Carlos A. Camargo, Jr.7Kohei Hasegawa8Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Corresponding author. Department of Emergency Medicine, Massachusetts General Hospital, 125 Nashua Street, Suite 920, Boston, MA 02114-1101, USA.Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USADepartment of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USADepartment of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Health Science, University of Yamanashi, Chuo, Yamanashi, JapanCenter for Genetic Medicine Research, Children’s National Research Institute, Washington, DC, USA; Division of Emergency Medicine, Children’s National Hospital, Washington, DC, USA; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USADepartment of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USAComputational Biology Institute, Department of Biostatistics and Bioinformatics, The George Washington University, Washington, DC, USADepartment of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USADepartment of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USASummary: Background: Bronchiolitis is a leading cause of infant hospitalization. Recent research suggests the heterogeneity within bronchiolitis and the relationship of airway viruses and bacteria with bronchiolitis severity. However, little is known about the pathobiological role of fungi. We aimed to identify bronchiolitis mycotypes by integrating fungus and virus data, and determine their association with bronchiolitis severity and biological characteristics. Methods: In a multicentre prospective cohort study of 398 infants (age <1 year, male 59%) hospitalized for bronchiolitis, we applied clustering approaches to identify mycotypes by integrating nasopharyngeal fungus (detected in RNA-sequencing data) and virus data (respiratory syncytial virus [RSV], rhinovirus [RV]) at hospitalization. We examined their association with bronchiolitis severity—defined by positive pressure ventilation (PPV) use and biological characteristics by nasopharyngeal metatranscriptome and transcriptome data. Results: In infants hospitalized for bronchiolitis, we identified four mycotypes: A) fungiM.restrictavirusRSV/RV, B) fungiM.restrictavirusRSV, C) fungiM.globosavirusRSV/RV, D) funginot-detectedvirusRSV/RV mycotypes. Compared to mycotype A infants (the largest subtype, n = 211), mycotype C infants (n = 85) had a significantly lower risk of PPV use (7% vs. 1%, adjOR, 0.21; 95% CI, 0.02–0.90; p = 0.033), while the risk of PPV use was not significantly different in mycotype B or D. In the metatranscriptome and transcriptome data, mycotype C had similar bacterial composition and microbial functions yet dysregulated pathways (e.g., Fc γ receptor-mediated phagocytosis pathway and chemokine signaling pathway; FDR <0.05). Interpretation: In this multicentre cohort, fungus-virus clustering identified distinct mycotypes of infant bronchiolitis with differential severity risks and unique biological characteristics. Funding: This study was supported by the National Institutes of Health.http://www.sciencedirect.com/science/article/pii/S2352396423003079BronchiolitisFungiMetatranscriptomeMycotypeSeverityTranscriptome |
| spellingShingle | Ryohei Shibata Zhaozhong Zhu Michihito Kyo Tadao Ooka Robert J. Freishtat Jonathan M. Mansbach Marcos Pérez-Losada Carlos A. Camargo, Jr. Kohei Hasegawa Nasopharyngeal fungal subtypes of infant bronchiolitis and disease severity riskResearch in context EBioMedicine Bronchiolitis Fungi Metatranscriptome Mycotype Severity Transcriptome |
| title | Nasopharyngeal fungal subtypes of infant bronchiolitis and disease severity riskResearch in context |
| title_full | Nasopharyngeal fungal subtypes of infant bronchiolitis and disease severity riskResearch in context |
| title_fullStr | Nasopharyngeal fungal subtypes of infant bronchiolitis and disease severity riskResearch in context |
| title_full_unstemmed | Nasopharyngeal fungal subtypes of infant bronchiolitis and disease severity riskResearch in context |
| title_short | Nasopharyngeal fungal subtypes of infant bronchiolitis and disease severity riskResearch in context |
| title_sort | nasopharyngeal fungal subtypes of infant bronchiolitis and disease severity riskresearch in context |
| topic | Bronchiolitis Fungi Metatranscriptome Mycotype Severity Transcriptome |
| url | http://www.sciencedirect.com/science/article/pii/S2352396423003079 |
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