Advancing our understanding of infant bronchiolitis through phenotyping and endotyping: clinical and molecular approaches

References

• Hasegawa K, Mansbach JM, Camargo CA Jr. Infectious pathogens and bronchiolitis outcomes. Exp Rev Anti Infect Ther. 2014;12(7):817–828.
   PubMed Web of Science ®Google Scholar
• Ralston SL, Lieberthal AS, Meissner HC, et al. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014;134(5):e1474–1502.
   PubMed Web of Science ®Google Scholar
• Ricci V, Delgado Nunes V, Murphy MS, et al., Guideline Development G, Technical T. Bronchiolitis in children: summary of NICE guidance. Bmj. 2015;350:h2305.
   PubMed Web of Science ®Google Scholar
• Australian Clinical Practice Guidelines. Clinical guidelines: management of bronchiolitis in children. 2012. [cited 2016 June 13]. Available from: https://www.clinicalguidelines.gov.au/print/3278
   Google Scholar
• Agusti A, Bel E, Thomas M, et al. Treatable traits: toward precision medicine of chronic airway diseases. Eur Respir J. 2016;47(2):410–419.
   PubMed Web of Science ®Google Scholar
• Vanfleteren LE, Kocks JW, Stone IS, et al. Moving from the Oslerian paradigm to the post-genomic era: are asthma and COPD outdated terms? Thorax. 2014;69(1):72–79.
   PubMed Web of Science ®Google Scholar
• Nair H, Nokes DJ, Gessner BD, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010;375(9725):1545–1555.
   PubMed Web of Science ®Google Scholar
• Hasegawa K, Tsugawa Y, Brown DF, et al. Temporal trends in emergency department visits for bronchiolitis in the United States, 2006-2010. Pediatr Infect Dis J. 2014;33(1):11–18.
   PubMed Web of Science ®Google Scholar
• Hasegawa K, Tsugawa Y, Brown DF, et al. Trends in bronchiolitis hospitalizations in the United States, 2000–2009. Pediatrics. 2013;132(1):28–36.
   PubMed Web of Science ®Google Scholar
• Hasegawa K, Tsugawa Y, Cohen A, et al. Infectious disease-related emergency department visits among children in the US. Pediatr Infect Dis J. 2015;34(7):681–685.
   PubMed Web of Science ®Google Scholar
• Nair H, Simoes EA, Rudan I, et al. Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis. Lancet. 2013;381(9875):1380–1390.
   PubMed Web of Science ®Google Scholar
• Parrott RH, Kim HW, Arrobio JO, et al. Epidemiology of respiratory syncytial virus infection in Washington, D.C. II. Infection and disease with respect to age, immunologic status, race and sex. Am J Epidemiol. 1973;98(4):289–300.
   PubMed Web of Science ®Google Scholar
• Meissner HC. Selected populations at increased risk from respiratory syncytial virus infection. Pediatr Infect Dis J. 2003;22(2 Suppl):S40-44; discussion S44-45.
   Web of Science ®Google Scholar
• Gadomski AM, Scribani MB. Bronchodilators for bronchiolitis. Cochrane Database Syst Rev. 2014;6:CD001266.
   PubMed Web of Science ®Google Scholar
• Fernandes RM, Bialy LM, Vandermeer B, et al. Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database Syst Rev. 2013;6:CD004878.
   PubMed Web of Science ®Google Scholar
• Mansbach JM, Clark S, Piedra PA, et al. Hospital course and discharge criteria for children hospitalized with bronchiolitis. J Hosp Med. 2015;10(4):205–211.
   PubMed Web of Science ®Google Scholar
• Hasegawa K, Mansbach JM, Teach SJ, et al. Multicenter study of viral etiology and relapse in hospitalized children with bronchiolitis. Pediatr Infect Dis J. 2014;33(8):809–813.
   PubMed Web of Science ®Google Scholar
• Vereen S, Gebretsadik T, Hartert TV, et al. Association between breast-feeding and severity of acute viral respiratory tract infection. Pediatr Infect Dis J. 2014;33(9):986–988.
   PubMed Web of Science ®Google Scholar
• Mansbach JM, Piedra PA, Teach SJ, et al. Prospective multicenter study of viral etiology and hospital length of stay in children with severe bronchiolitis. Arch Pediatr Adolesc Med. 2012;166(8):700–706.
   PubMedGoogle Scholar
• Miller EK, Gebretsadik T, Carroll KN, et al. Viral etiologies of infant bronchiolitis, croup and upper respiratory illness during 4 consecutive years. Pediatr Infect Dis J. 2013;32(9):950–955.
   PubMed Web of Science ®Google Scholar
• Jartti T, Aakula M, Mansbach JM, et al. Hospital length-of-stay is associated with rhinovirus etiology of bronchiolitis. Pedatr Infect Dis J. 2014;33(8):829–834.
   PubMed Web of Science ®Google Scholar
• Marguet C, Lubrano M, Gueudin M, et al. In very young infants severity of acute bronchiolitis depends on carried viruses. PLoS One. 2009;4(2):e4596.
   PubMed Web of Science ®Google Scholar
• Hasegawa K, Jartti T, Mansbach JM, et al. Respiratory syncytial virus genomic load and disease severity among children hospitalized with bronchiolitis: Multicenter cohort studies in the US and Finland. J Infect Dis. 2015;211(10):1550–1559.
   PubMed Web of Science ®Google Scholar
• Alansari K, Sakran M, Davidson BL, et al. Oral dexamethasone for bronchiolitis: a randomized trial. Pediatrics. 2013;132(4):e810–816.
   PubMed Web of Science ®Google Scholar
• Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nature Med. 2012;18(5):716–725.
   PubMed Web of Science ®Google Scholar
• Fitzpatrick AM, Teague WG, Meyers DA, et al. Heterogeneity of severe asthma in childhood: confirmation by cluster analysis of children in the National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program. J Allergy Clin Immunol. 2011;127(2):382-389 e381-313.
   Web of Science ®Google Scholar
• Just J, Gouvis-Echraghi R, Rouve S, et al. Two novel, severe asthma phenotypes identified during childhood using a clustering approach. Eur Respir J. 2012;40(1):55–60.
   PubMed Web of Science ®Google Scholar
• Garden FL, Simpson JM, Mellis CM, et al. Change in the manifestations of asthma and asthma-related traits in childhood: a latent transition analysis. Eur Respir J. 2016;47(2):499–509.
   PubMed Web of Science ®Google Scholar
• Dumas O, Mansbach J, Hasegawa K, et al. Clustering approach to identify bronchiolitis profiles among children hospitalized with bronchiolitis [Abstract]. Am J Respir Crit Care Med. 2015;4:5.
   Google Scholar
• George BJ, Reif DM, Gallagher JE, et al. Data-driven asthma endotypes defined from blood biomarker and gene expression data. PLoS One. 2015;10(2):e0117445.
   Web of Science ®Google Scholar
• Williams-DeVane CR, Reif DM, Hubal EC, et al. Decision tree-based method for integrating gene expression, demographic, and clinical data to determine disease endotypes. BMC Systems Biol. 2013;7:119.
   PubMed Web of Science ®Google Scholar
• Modena BD, Tedrow JR, Milosevic J, et al. Gene expression in relation to exhaled nitric oxide identifies novel asthma phenotypes with unique biomolecular pathways. Am J Respir Crit Care Med. 2014;190(12):1363–1372.
   PubMed Web of Science ®Google Scholar
• Hinks TS, Brown T, Lau LC, et al. Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3-like protein 1. J Allergy Clin Immunol. 2016. [Epub ahead of print].
   PubMedGoogle Scholar
• Comhair SA, McDunn J, Bennett C, et al. Metabolomic endotype of asthma. J Immunol. 2015;195(2):643–650.
   PubMed Web of Science ®Google Scholar
• Lotvall J, Akdis CA, Bacharier LB, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011;127(2):355–360.
   PubMed Web of Science ®Google Scholar
• Larkin EK, Hartert TV. Genes associated with RSV lower respiratory tract infection and asthma: the application of genetic epidemiological methods to understand causality. Future Virol. 2015;10(7):883–897.
   PubMed Web of Science ®Google Scholar
• Thomsen SF, Stensballe LG, Skytthe A, et al. Increased concordance of severe respiratory syncytial virus infection in identical twins. Pediatrics. 2008;121(3):493–496.
   PubMed Web of Science ®Google Scholar
• Alvarez AE, Marson FA, Bertuzzo CS, et al. Epidemiological and genetic characteristics associated with the severity of acute viral bronchiolitis by respiratory syncytial virus. J Pediatr. 2013;89(6):531–543.
   Web of Science ®Google Scholar
• Choi EH, Lee HJ, Chanock SJ. Human genetics and respiratory syncytial virus disease: current findings and future approaches. Curr Top Microbiol Immunol. 2013;372:121–137.
   PubMed Web of Science ®Google Scholar
• Janssen R, Bont L, Siezen CL, et al. Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. J Infect Dis. 2007;196(6):826–834.
   PubMed Web of Science ®Google Scholar
• Wu P, Larkin EK, Reiss SS, et al. beta2-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study. BMC Med Gene. 2015;16:82.
   PubMed Web of Science ®Google Scholar
• Bunyavanich S, Schadt EE. Systems biology of asthma and allergic diseases: a multiscale approach. J Allergy Clin Immunol. 2015;135(1):31–42.
   PubMed Web of Science ®Google Scholar
• Mejias A, Dimo B, Suarez NM, et al. Whole blood gene expression profiles to assess pathogenesis and disease severity in infants with respiratory syncytial virus infection. PLoS Med. 2013;10(11):e1001549.
   PubMed Web of Science ®Google Scholar
• Fjaerli HO, Bukholm G, Skjaeret C, et al. Cord blood gene expression in infants hospitalized with respiratory syncytial virus bronchiolitis. J Infect Dis. 2007;196(3):394–404.
   PubMed Web of Science ®Google Scholar
• Fjaerli HO, Bukholm G, Krog A, et al. Whole blood gene expression in infants with respiratory syncytial virus bronchiolitis. BMC Infect Dis. 2006;6:175.
   PubMed Web of Science ®Google Scholar
• Bucasas KL, Mian AI, Demmler-Harrison GJ, et al. Global gene expression profiling in infants with acute respiratory syncytial virus broncholitis demonstrates systemic activation of interferon signaling networks. Pediatr Infect Dis J. 2013;32(2):e68–76.
   PubMed Web of Science ®Google Scholar
• Van Den Kieboom CH, Ahout IM, Zomer A, et al. Nasopharyngeal gene expression, a novel approach to study the course of respiratory syncytial virus infection. Eur Respir J. 2015;45(3):718–725.
   PubMed Web of Science ®Google Scholar
• Globinska A, Pawelczyk M, Kowalski ML. MicroRNAs and the immune response to respiratory virus infections. Exp Rev Clin Immunol. 2014;10(7):963–971.
   PubMed Web of Science ®Google Scholar
• Leahy TR, McManus R, Doherty DG, et al. Interleukin-15 is associated with disease severity in viral bronchiolitis. Eur Respir J. 2016;47(1):212–222.
   PubMed Web of Science ®Google Scholar
• Bakre A, Mitchell P, Coleman JK, et al. Respiratory syncytial virus modifies microRNAs regulating host genes that affect virus replication. J Gen Virol. 2012;93(Pt 11):2346–2356.
   PubMed Web of Science ®Google Scholar
• Buggele WA, Johnson KE, Horvath CM. Influenza A virus infection of human respiratory cells induces primary microRNA expression. J Biol Chem. 2012;287(37):31027–31040.
   PubMed Web of Science ®Google Scholar
• Dalmasso G, Nguyen HT, Yan Y, et al. Microbiota modulate host gene expression via microRNAs. PLoS One. 2011;6(4):e19293.
   PubMed Web of Science ®Google Scholar
• Maudet C, Mano M, Eulalio A. MicroRNAs in the interaction between host and bacterial pathogens. FEBS Lett. 2014;588(22):4140–4147.
   PubMed Web of Science ®Google Scholar
• Collison A, Siegle JS, Hansbro NG, et al. Epigenetic changes associated with disease progression in a mouse model of childhood allergic asthma. Dis Model Mech. 2013;6(4):993–1000.
   PubMed Web of Science ®Google Scholar
• Conenello GM, Zamarin D, Perrone LA, et al. A single mutation in the PB1-F2 of H5N1 (HK/97) and 1918 influenza A viruses contributes to increased virulence. PLoS Pathog. 2007;3(10):1414–1421.
   PubMed Web of Science ®Google Scholar
• Moore ML, Stokes KL, Hartert TV. The impact of viral genotype on pathogenesis and disease severity: respiratory syncytial virus and human rhinoviruses. Curr Opin Immunol. 2013;25(6):761–768.
   PubMed Web of Science ®Google Scholar
• Tran DN, Pham TM, Ha MT, et al. Molecular epidemiology and disease severity of human respiratory syncytial virus in Vietnam. PLoS One. 2013;8(1):e45436.
   PubMed Web of Science ®Google Scholar
• Martinello RA, Chen MD, Weibel C, et al. Correlation between respiratory syncytial virus genotype and severity of illness. J Infect Dis. 2002;186(6):839–842.
   PubMed Web of Science ®Google Scholar
• Villenave R, Thavagnanam S, Sarlang S, et al. In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo. Proc Natl Acad Sci U S A. 2012;109(13):5040–5045.
   PubMed Web of Science ®Google Scholar
• Hasegawa K, Linnemann RW, Avadhanula V, et al. Detection of respiratory syncytial virus and rhinovirus in healthy infants. BMC Res Notes. 2015;8(1):718.
   PubMedGoogle Scholar
• Miller EK, Williams JV, Gebretsadik T, et al. Host and viral factors associated with severity of human rhinovirus-associated infant respiratory tract illness. J Allergy Clin Immunol. 2011;127(4):883–891.
   PubMed Web of Science ®Google Scholar
• Huang T, Wang W, Bessaud M, et al. Evidence of recombination and genetic diversity in human rhinoviruses in children with acute respiratory infection. PLoS One. 2009;4(7):e6355.
   PubMed Web of Science ®Google Scholar
• Linsuwanon P, Payungporn S, Samransamruajkit R, et al. High prevalence of human rhinovirus C infection in Thai children with acute lower respiratory tract disease. J Infect. 2009;59(2):115–121.
   PubMed Web of Science ®Google Scholar
• Lau SK, Yip CC, Lin AW, et al. Clinical and molecular epidemiology of human rhinovirus C in children and adults in Hong Kong reveals a possible distinct human rhinovirus C subgroup. J Infect Dis. 2009;200(7):1096–1103.
   PubMed Web of Science ®Google Scholar
• Lee WM, Lemanske RF Jr, Evans MD, et al. Human rhinovirus species and season of infection determine illness severity. Am J Respir Crit Care Med. 2012;186(9):886–891.
   PubMed Web of Science ®Google Scholar
• Lynch SV. Viruses and microbiome alterations. Ann Am Thorac Soc. 2014;11(Suppl 1):S57–60.
   PubMedGoogle Scholar
• Hyde ER, Petrosino JF, Piedra PA, et al. Nasopharyngeal Proteobacteria are associated with viral etiology and acute wheezing in children with severe bronchiolitis. J Allergy Clin Immunol. 2014;133(4):1220–1222.
   PubMed Web of Science ®Google Scholar
• Mansbach JM, Hasegawa K, Henke DM, et al. Respiratory syncytial virus and rhinovirus severe bronchiolitis are associated with distinct nasopharyngeal microbiota. J Allergy Clin Immunol. 2016. [ Epub ahead of print].
   PubMed Web of Science ®Google Scholar
• Hasegawa K, Linnemann RW, Mansbach JM, et al. The fecal microbiota profile and bronchiolitis in infants. Pediatrics. Forthcoming 2016. [ Epub ahead of print].
   PubMed Web of Science ®Google Scholar
• Herbst T, Sichelstiel A, Schar C, et al. Dysregulation of allergic airway inflammation in the absence of microbial colonization. Am J Respir Crit Care Med. 2011;184(2):198–205.
   PubMed Web of Science ®Google Scholar
• Olszak T, An D, Zeissig S, et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science. 2012;336(6080):489–493.
   PubMed Web of Science ®Google Scholar
• Hollams EM, Hales BJ, Bachert C, et al. Th2-associated immunity to bacteria in teenagers and susceptibility to asthma. Eur Respir J. 2010;36(3):509–516.
   PubMed Web of Science ®Google Scholar
• Folsgaard NV, Schjorring S, Chawes BL, et al. Pathogenic bacteria colonizing the airways in asymptomatic neonates stimulates topical inflammatory mediator release. Am J Respir Crit Care Med. 2013;187(6):589–595.
   PubMed Web of Science ®Google Scholar
• Huang YJ, Nariya S, Harris JM, et al. The airway microbiome in patients with severe asthma: associations with disease features and severity. J Allergy Clin Immunol. 2015;136(4):874–884.
   PubMed Web of Science ®Google Scholar
• Teo Shu M, Mok D, Pham K, et al. The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development. Cell Host Microbe. 2015;17(5):704–715.
   PubMed Web of Science ®Google Scholar
• Biesbroek G, Tsivtsivadze E, Sanders EA, et al. Early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children. Am J Respir Crit Care Med. 2014;190(11):1283–1292.
   PubMed Web of Science ®Google Scholar
• Kloepfer KM, Lee WM, Pappas TE, et al. Detection of pathogenic bacteria during rhinovirus infection is associated with increased respiratory symptoms and asthma exacerbations. J Allergy Clin Immunol. 2014;133(5):1301–1307.
   PubMed Web of Science ®Google Scholar
• Carlsson CJ, Vissing NH, Sevelsted A, et al. Duration of wheezy episodes in early childhood is independent of the microbial trigger. J Allergy Clin Immunol. 2015;136(5):1208–1214 e1205.
   PubMed Web of Science ®Google Scholar
• Vissing NH, Chawes BL, Bisgaard H. Increased risk of pneumonia and bronchiolitis after bacterial colonization of the airways as neonates. Am J Respir Crit Care Med. 2013;188(10):1246–1252.
   PubMed Web of Science ®Google Scholar
• Von Linstow ML, Schonning K, Hoegh AM, et al. Neonatal airway colonization is associated with troublesome lung symptoms in infants. Am J Respir Crit Care Med. 2013;188(8):1041–1042.
   PubMed Web of Science ®Google Scholar
• Rosas-Salazar C, Shilts MH, Tovchigrechko A, et al. Nasopharyngeal microbiome in RSV resembles profile associated with increased childhood asthma risk. Am J Respir Crit Care Med. Forthcoming 2016. [ Epub ahead of print].
   PubMed Web of Science ®Google Scholar
• Herberth G, Offenberg K, Rolle-Kampczyk U, et al. Endogenous metabolites and inflammasome activity in early childhood and links to respiratory diseases. J Allergy Clin Immunol. 2015;136(2):495–497.
   PubMed Web of Science ®Google Scholar
• Turi KN, Steinhoff M, Watanabe M, et al. Metabolomics Approach to Understanding the Pathogenesis of Respiratory Syncytial Virus Infection. Ann Am Thoracic Soc. 2016.
   Google Scholar
• Schadt EE, Bjorkegren JL. NEW: network-enabled wisdom in biology, medicine, and health care. Sci Transl Med. 2012;4(115):115rv111.
   Web of Science ®Google Scholar
• Larkin EK, Gebretsadik T, Moore ML, et al. Objectives, design and enrollment results from the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure Study (INSPIRE). BMC Puml Med. 2015;15:45.
   PubMed Web of Science ®Google Scholar