Nasal microRNA signatures for disease severity in infants with respiratory syncytial virus bronchiolitis: a multicentre prospective study.

Humans MicroRNAs / genetics Prospective Studies Respiratory Syncytial Virus Infections / genetics Infant Male Female Severity of Illness Index Bronchiolitis / genetics Bronchiolitis, Viral / genetics Infant, Newborn RNA, Messenger / metabolism Gene Expression Profiling
critical care non invasive ventilation respiratory infection viral infection

Journal

BMJ open respiratory research
ISSN: 2052-4439
Titre abrégé: BMJ Open Respir Res
Pays: England
ID NLM: 101638061

Informations de publication

Date de publication:
31 Jul 2024
Historique:
received: 31 12 2023
accepted: 28 06 2024
medline: 2 8 2024
pubmed: 2 8 2024
entrez: 1 8 2024
Statut: epublish

Résumé

Respiratory syncytial virus (RSV) bronchiolitis contributes to a large morbidity and mortality burden globally. While emerging evidence suggests that airway microRNA (miRNA) is involved in the pathobiology of RSV infection, its role in the disease severity remains unclear. In this multicentre prospective study of infants (aged<1 year) hospitalised for RSV bronchiolitis, we sequenced the upper airway miRNA and messenger RNA (mRNA) at hospitalisation. First, we identified differentially expressed miRNAs (DEmiRNAs) associated with higher bronchiolitis severity-defined by respiratory support (eg, positive pressure ventilation, high-flow oxygen therapy) use. We also examined the biological significance of miRNAs through pathway analysis. Second, we identified differentially expressed mRNAs (DEmRNAs) associated with bronchiolitis severity. Last, we constructed miRNA-mRNA coexpression networks and determined hub mRNAs by weighted gene coexpression network analysis (WGCNA). In 493 infants hospitalised with RSV bronchiolitis, 19 DEmiRNAs were associated with bronchiolitis severity (eg, miR-27a-3p, miR-26b-5p; false discovery rate<0.10). The pathway analysis using miRNA data identified 1291 bronchiolitis severity-related pathways-for example, regulation of cell adhesion mediated by integrin. Second, 1298 DEmRNAs were associated with bronchiolitis severity. Last, of these, 190 DEmRNAs were identified as targets of DEmiRNAs and negatively correlated with DEmiRNAs. By applying WGCNA to DEmRNAs, four disease modules were significantly associated with bronchiolitis severity-for example, microtubule anchoring, cell-substrate junction. The hub genes for each of these modules were also identified-for example, In infants hospitalised for RSV bronchiolitis, airway miRNA-mRNA coexpression network contributes to the pathobiology of bronchiolitis severity.

Sections du résumé

BACKGROUND BACKGROUND
Respiratory syncytial virus (RSV) bronchiolitis contributes to a large morbidity and mortality burden globally. While emerging evidence suggests that airway microRNA (miRNA) is involved in the pathobiology of RSV infection, its role in the disease severity remains unclear.
METHODS METHODS
In this multicentre prospective study of infants (aged<1 year) hospitalised for RSV bronchiolitis, we sequenced the upper airway miRNA and messenger RNA (mRNA) at hospitalisation. First, we identified differentially expressed miRNAs (DEmiRNAs) associated with higher bronchiolitis severity-defined by respiratory support (eg, positive pressure ventilation, high-flow oxygen therapy) use. We also examined the biological significance of miRNAs through pathway analysis. Second, we identified differentially expressed mRNAs (DEmRNAs) associated with bronchiolitis severity. Last, we constructed miRNA-mRNA coexpression networks and determined hub mRNAs by weighted gene coexpression network analysis (WGCNA).
RESULTS RESULTS
In 493 infants hospitalised with RSV bronchiolitis, 19 DEmiRNAs were associated with bronchiolitis severity (eg, miR-27a-3p, miR-26b-5p; false discovery rate<0.10). The pathway analysis using miRNA data identified 1291 bronchiolitis severity-related pathways-for example, regulation of cell adhesion mediated by integrin. Second, 1298 DEmRNAs were associated with bronchiolitis severity. Last, of these, 190 DEmRNAs were identified as targets of DEmiRNAs and negatively correlated with DEmiRNAs. By applying WGCNA to DEmRNAs, four disease modules were significantly associated with bronchiolitis severity-for example, microtubule anchoring, cell-substrate junction. The hub genes for each of these modules were also identified-for example,
CONCLUSIONS CONCLUSIONS
In infants hospitalised for RSV bronchiolitis, airway miRNA-mRNA coexpression network contributes to the pathobiology of bronchiolitis severity.

Identifiants

DOI: 10.1136/bmjresp-2023-002288 PMID: 39089741
pubmed: 39089741
pii: 11/1/e002288
doi: 10.1136/bmjresp-2023-002288
pii:
doi:

Substances chimiques

MicroRNAs 0
RNA, Messenger 0

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Michihito Kyo (M)

Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA mkyo@hiroshima-u.ac.jp.
ORCID: 0000-0002-2559-6440

Zhaozhong Zhu (Z)

Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
ORCID: 0000-0001-5662-1541

Ryohei Shibata (R)

Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
ORCID: 0000-0002-6195-441X

Tadao Ooka (T)

Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Health Science, University of Yamanashi, Kofu, Yamanashi, Japan.

Jonathan M Mansbach (JM)

Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Brennan Harmon (B)

Centre for Genetic Medicine Research, Children's National Hospital, Washington, District of Columbia, USA.

Andrea Hahn (A)

Centre for Genetic Medicine Research, Children's National Hospital, Washington, District of Columbia, USA.
Department of Paediatrics, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Division of Infectious Diseases, Children's National Hospital, Washington, District of Columbia, USA.

Marcos Pérez-Losada (M)

Computational Biology Institute, Department of Biostatistics and Bioinformatics, The George Washington University, Washington, District of Columbia, USA.

Carlos A Camargo (CA)

Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Kohei Hasegawa (K)

Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Nasal microRNA signatures for disease severity...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › microARN › Nasal microRNA signatures for disease severity...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Nasal microRNA signatures for disease severity...
questionsmedicales.fr › Infection › Maladies virales › Infections à virus à ARN › Infections à Mononegavirales › Infections à Paramyxoviridae › Infections à pneumovirus › Infections à virus respiratoire syncytial › Nasal microRNA signatures for disease severity...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › Nasal microRNA signatures for disease severity...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Enquêtes et questionnaires › Enquêtes de santé › Indicateurs d'état de santé › Acuité des besoins du patient › Indice de gravité de la maladie › Nasal microRNA signatures for disease severity...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Bronchite › Bronchiolite › Nasal microRNA signatures for disease severity...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Bronchite › Bronchiolite › Bronchiolite virale › Nasal microRNA signatures for disease severity...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › Nouveau-né › Nasal microRNA signatures for disease severity...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › Nasal microRNA signatures for disease severity...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Nasal microRNA signatures for disease severity...