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Viral and Host-Related Factors in the Nasal Inflammatory Response to Critical Bronchiolitis in Infants and Children
Alex L Sliwicki1, Jordan E Kreger2, Saly N Essoh2
1Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Michigan, Ann Arbor, MI.
Insights
Children with critical bronchiolitis show a strong inflammatory response, regardless of the specific virus. This response involves increased interferons and immune cytokines, with some pathways downregulating ciliary function.
Area of Science:
- Pediatric critical care medicine
- Immunology
- Respiratory viral infections
Background:
- Bronchiolitis is a common pediatric respiratory illness, with critical cases requiring intensive care.
- Understanding the host inflammatory response is crucial for managing severe bronchiolitis.
Purpose of the Study:
- To evaluate the inflammatory cytokine response in children with critical bronchiolitis.
- To compare inflammatory profiles based on viral etiology (RSV, rhinovirus, polyviral).
- To examine the link between clinical risk factors and the host inflammatory response.
Main Methods:
- Prospective cohort study in a pediatric intensive care unit (PICU).
- Analysis of nasal aspirates from 42 patients with critical bronchiolitis and 9 healthy controls.
- Cytokine measurement via ELISA and exploratory RNA sequencing (RNASeq).
Main Results:
- Patients with critical bronchiolitis showed increased interferons and type 1/2 immunity cytokines.
- No significant cytokine differences were found between RSV and rhinovirus infections.
- Multiple bronchiolitis admissions correlated with lower inflammatory cytokine levels.
- RNASeq revealed upregulated proinflammatory and downregulated ciliary function pathways.
Conclusions:
- Critical bronchiolitis elicits a robust inflammatory response irrespective of the causative virus.
- Transcriptomic data support observed clinical features, highlighting both pro-inflammatory and impaired ciliary pathways.
Objectives:
We aimed to evaluate the inflammatory cytokine response in children with critical bronchiolitis. Our secondary aims included: 1) understanding differences in inflammatory profiles between respiratory syncytial virus (RSV), rhinovirus, and polyviral infection, and 2) examining the association between clinical risk factors and the host inflammatory response.
Design:
A single-center, prospective cohort study of PICU patients with critical bronchiolitis.
Setting:
Medium-sized academic PICU from October 2021 to July 2024.
Patients:
Forty-two patients with critical bronchiolitis and nine healthy control patients.
Interventions:
None.
Measurements And Main Results:
Nasal aspirates were obtained and cytokines measured by enzyme-linked immunosorbent assay. The influence of viral type and host factors was assessed by nonparametric testing. In an exploratory analysis, cells from the nasal aspirates of a select group of patients underwent next-generation RNA sequencing (RNASeq). The nasal samples from patients with critical bronchiolitis exhibited an increase in interferons, type 1, and type 2 immunity-related cytokines. We did not identify differences in cytokine levels when comparing patients with rhinovirus to those with RSV infection. Patients with multiple (> 1) bronchiolitis admissions exhibited lower levels of inflammatory cytokines compared with patients during their first bronchiolitis admission. Using RNASeq, a subgroup of patients with rhinovirus or RSV exhibited similar upregulation of gene pathways associated with leukocyte chemotaxis, interferon signaling, and tumor necrosis factor superfamily cytokines compared with healthy controls. Pathways associated with ciliary function were downregulated compared with controls with RSV inducing a more pronounced downregulation than rhinovirus.
Conclusions:
These data demonstrate that patients with critical bronchiolitis exhibit a robust host inflammatory response independent of viral etiology. Our exploratory transcriptomic analysis showed upregulation of proinflammatory genes and downregulation of ciliary genes consistent with clinical characteristics of these patients at the bedside.
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