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Published on: August 7, 2017
Nasopharyngeal fungal subtypes of infant bronchiolitis and disease severity risk
Ryohei Shibata1, Zhaozhong Zhu1, Michihito Kyo1
1Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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.
Insights
Fungal and viral co-infections in infant bronchiolitis define distinct mycotypes. Certain mycotypes, like fungi M.globosa with RSV/RV, are linked to reduced respiratory support needs and unique immune pathway alterations.
Area of Science:
- Pediatric Infectious Diseases
- Respiratory Virology
- Mycology
- Microbiome Research
Background:
- Bronchiolitis is a major cause of infant hospitalization, with known viral and bacterial associations.
- The role of fungi in bronchiolitis severity and pathogenesis remains largely unexplored.
- Understanding the interplay of fungi, viruses, and bacteria is crucial for deciphering disease heterogeneity.
Purpose of the Study:
- To identify distinct fungal-viral co-infection patterns (mycotypes) in infants hospitalized with bronchiolitis.
- To investigate the association of these mycotypes with bronchiolitis severity, including the need for positive pressure ventilation (PPV).
- To explore the biological characteristics and host immune responses associated with different mycotypes.
Main Methods:
- A multicentre prospective cohort study involving 398 infants under one year old hospitalized for bronchiolitis.
- Nasopharyngeal samples analyzed using RNA-sequencing to detect fungal and viral (RSV, RV) presence.
- Clustering approaches integrated fungal and viral data to define mycotypes; severity assessed by PPV use; biological characteristics analyzed via metatranscriptome and transcriptome data.
Main Results:
- Four distinct mycotypes were identified: fungi M.restricta/virus RSV/RV, fungi M.restricta/virus RSV, fungi M.globosa/virus RSV/RV, and fungi-negative/virus RSV/RV.
- Infants in the fungi M.globosa/virus RSV/RV mycotype showed a significantly lower risk of requiring PPV compared to the largest group (fungi M.restricta/virus RSV/RV).
- Mycotype C (fungi M.globosa/virus RSV/RV) exhibited similar bacterial composition but dysregulated immune pathways, including Fc γ receptor-mediated phagocytosis and chemokine signaling.
Conclusions:
- Fungus-virus co-infection patterns (mycotypes) are identifiable in infant bronchiolitis.
- These distinct mycotypes are associated with differential risks of severe disease requiring respiratory support.
- Specific mycotypes are linked to unique host immune pathway dysregulation, offering insights into bronchiolitis pathogenesis.
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