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Published on: January 26, 2019
Respiratory viruses are associated with serum metabolome among infants hospitalized for bronchiolitis: A multicenter
Michimasa Fujiogi1, Carlos A Camargo1, Yoshihiko Raita1
1Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Insights
Infant bronchiolitis severity and outcomes differ based on the specific respiratory virus. Distinct serum metabolomic profiles, particularly in lipid metabolism, are linked to different risks of acute and chronic morbidities in infants hospitalized with bronchiolitis.
Area of Science:
- Metabolomics
- Virology
- Pediatric Respiratory Medicine
Background:
- Bronchiolitis is a primary cause of infant hospitalization in the U.S.
- Evidence suggests bronchiolitis is heterogeneous, but virus-metabolism links are unclear.
- Understanding these interrelationships is crucial for disease pathobiology.
Purpose of the Study:
- To investigate the distinct serum metabolomic profiles in infants hospitalized with bronchiolitis caused by different respiratory viruses.
- To identify specific metabolites associated with varying risks of acute and chronic outcomes.
- To elucidate the role of host systemic metabolism in bronchiolitis pathobiology.
Main Methods:
- A multicenter prospective cohort study of 113 infants hospitalized with bronchiolitis.
- Serum metabolome profiling of infants infected with Respiratory Syncytial Virus (RSV), Rhinovirus-A (RV-A), or Rhinovirus-C (RV-C).
- Sparse partial least squares discriminant analysis to identify discriminatory metabolites and their association with clinical outcomes.
Main Results:
- Serum metabolomic profiles differed significantly between RSV-RV-A and RSV-RV-C infections (P<0.05).
- Lipid metabolism pathways (sphingolipids, carnitines, glycerophosphocholines) were predominantly implicated.
- Discriminatory metabolites were associated with risks of recurrent wheezing and need for positive pressure ventilation.
Conclusions:
- Respiratory virus species exhibit distinct serum metabolomic signatures in infants with bronchiolitis.
- These signatures correlate with differential risks of acute and chronic bronchiolitis morbidities.
- Findings advance understanding of virus-host interactions and systemic metabolic responses in bronchiolitis.
Background:
Bronchiolitis is the leading cause of infant hospitalizations in the United States. Growing evidence supports the heterogeneity of bronchiolitis. However, little is known about the interrelationships between major respiratory viruses (and their species), host systemic metabolism, and disease pathobiology.
Methods:
In an ongoing multicenter prospective cohort study, we profiled the serum metabolome in 113 infants (63 RSV-only, 21 RV-A, and 29 RV-C) hospitalized with bronchiolitis. We identified serum metabolites that are most discriminatory in the RSV-RV-A and RSV-RV-C comparisons using sparse partial least squares discriminant analysis. We then investigated the association between discriminatory metabolites with acute and chronic outcomes.
Results:
In 113 infants with bronchiolitis, we measured 639 metabolites. Serum metabolomic profiles differed in both comparisons (Ppermutation < 0.05). In the RSV-RV-A comparison, we identified 30 discriminatory metabolites, predominantly in lipid metabolism pathways (eg, sphingolipids and carnitines). In multivariable models, these metabolites were significantly associated with the risk of clinical outcomes (eg, tricosanoyl sphingomyelin, OR for recurrent wheezing at age of 3 years = 1.50; 95% CI: 1.05-2.15). In the RSV-RV-C comparison, the discriminatory metabolites were also primarily involved in lipid metabolism (eg, glycerophosphocholines [GPCs], 12,13-diHome). These metabolites were also significantly associated with the risk of outcomes (eg, 1-stearoyl-2-linoleoyl-GPC, OR for positive pressure ventilation use during hospitalization = 0.47; 95% CI: 0.28-0.78).
Conclusion:
Respiratory viruses and their species had distinct serum metabolomic signatures that are associated with differential risks of acute and chronic morbidities of bronchiolitis. Our findings advance research into the complex interrelations between viruses, host systemic response, and bronchiolitis pathobiology.
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