☆ 4.5 Article

Respiratory viruses are associated with serum metabolome among infants hospitalized for bronchiolitis: A multicenter study

PEDIATRIC ALLERGY AND IMMUNOLOGY (2020)

Journal

PEDIATRIC ALLERGY AND IMMUNOLOGY

Volume 31, Issue 7, Pages 755-766

Publisher

WILEY

DOI: 10.1111/pai.13296

Keywords

bronchiolitis; infant; respiratory syncytial virus; rhinovirus; rhinovirus species; serum metabolome

Funding

NHLBI NIH HHS [R21 HL129909] Funding Source: Medline
NIAID NIH HHS [U19 AI104317, R01 AI108588, R01 AI134940, U01 AI087881, R01 AI137091, R01 AI127507, R01 AI114552] Funding Source: Medline
NIH HHS [R01 AI-127507, R01 AI-137091, UG3/UH3 OD-023253, UG3 OD023253, UH3 OD023253, R01 AI-114552, R01 AI-134940] Funding Source: Medline

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Abstract

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 (P-permutation < 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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Cytokine expression in rhinovirus- vs. respiratory syncytial virus-induced first wheezing episode and its relation to clinical course

Pekka Hurme, Miisa Komulainen, Marleena Tulkki, Annamari Leino, Beate Ruckert, Riitta Turunen, Tytti Vuorinen, Mubeccel Akdis, Cezmi A. Akdis, Tuomas Jartti

Summary: The cytokine profiles of Rhinovirus (RV) and respiratory syncytial virus (RSV)-induced first wheezing episode differ, with higher cytokine expression and longer hospitalization time in the RSV group. In the RV group, increased expression of I-309 (CCL1) and TARC is associated with fewer relapses.

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