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respiratory syncytial virus infection in high-risk infants and young children. Journal of Immunology (Baltimore, MD) (1950). 2007;**179**:3171-3177. DOI:

10.4049/jimmunol.179.5.3171

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clim.2007.03.003

ajrcmb.23.5.3771

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[77] Janssen R, Bont L, Siezen CLE, Hodemaekers HM, Ermers MJ,

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INF.0b013e31818e2aa9

nrmicro.2016.45

10.1086/420830

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Nature Reviews. Microbiology. 2016;**14**:360-373. DOI: 10.1038/

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[80] Tal G, Mandelberg A,

adc.72.1.16

[76] Zomer-Kooijker K,

Uiterwaal CSPM, van der GAC, Wilbrink B, Bont LJ, van der

**20**

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[89] Saleeby CME, Li R, Somes GW, Dahmer MK, Quasney MW, DeVincenzo JP. Surfactant protein A2 polymorphisms and disease severity in a respiratory syncytial virus-infected population. The Journal of Pediatrics. 2010;**156**:409-414. e4. DOI: 10.1016/j. jpeds.2009.09.043

[90] Villenave R, Thavagnanam S, Sarlang S, Parker J, Douglas I, Skibinski G, et al. In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo. Proceedings of the National Academy of Sciences of the United States of America. 2012;**109**:5040-5045. DOI: 10.1073/pnas.1110203109

[91] Oshansky CM, Barber JP, Crabtree J, Tripp RA. Respiratory syncytial virus F and G proteins induce interleukin 1alpha, CC, and CXC chemokine responses by normal human bronchoepithelial cells. The Journal of Infectious Diseases. 2010;**201**:1201-1207. DOI: 10.1086/651431

[92] Bueno SM, González PA, Pacheco R, Leiva ED, Cautivo KM, Tobar HE, et al. Host immunity during RSV pathogenesis. International Immunopharmacology. 2008;**8**:1320- 1329. DOI: 10.1016/j.intimp.2008.03.012

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[95] Sheeran P, Jafri H, Carubelli C, Saavedra J, Johnson C, Krisher K, et al. Elevated cytokine concentrations in the nasopharyngeal and tracheal secretions of children with respiratory syncytial virus disease. The Pediatric Infectious Disease Journal. 1999;**18**:115-122

[96] Bermejo-Martin JF, Garcia-Arevalo MC, De Lejarazu RO, Ardura J, Eiros JM, Alonso A, et al. Predominance of Th2 cytokines, CXC chemokines and innate immunity mediators at the mucosal level during severe respiratory syncytial virus infection in children. European Cytokine Network. 2007;**18**:162-167. DOI: 10.1684/ecn.2007.0096

[97] Garcia C, Soriano-Fallas A, Lozano J, Leos NB, Gomez AM, Ramilo O, et al. Decreased innate immune cytokine responses correlate with disease severity in children with respiratory syncytial virus and human rhinovirus bronchiolitis. ET Journal. 2012;**31**:86-89. DOI: 10.1097/ INF.0b013e31822dc8c1

[98] Díaz PV, Valdivia G, Gaggero AA, Bono MR, Zepeda G, Rivas M, et al. Pro-inflammatory cytokines in nasopharyngeal aspirate from hospitalized children with respiratory syncytial virus infection with or without rhinovirus bronchiolitis, and use of the cytokines as predictors of illness severity. Medicine (Baltimore). 2015;**94**:e1512. DOI: 10.1097/ MD.0000000000001512

[99] Garofalo RP, Olszewska-Pazdrak B, Ogra PL, Welliver RC. Betachemokines in nasal secretions of infants with respiratory syncytial

virus-induced respiratory infections. Pediatric Asthma, Allergy and Immunology. 2001;**15**:89-96. DOI: 10.1089/088318701753436880

[100] Walsh EE, Peterson DR, Kalkanoglu AE, Lee FE-H, Falsey AR. Viral shedding and immune responses to respiratory syncytial virus infection in older adults. The Journal of Infectious Diseases. 2013;**207**:1424-1432. DOI: 10.1093/infdis/jit038

[101] Hornsleth A, Loland L, Larsen LB. Cytokines and chemokines in respiratory secretion and severity of disease in infants with respiratory syncytial virus (RSV) infection. Journal of Clinical Virology: The Official Publication of the Pan American Society for Clinical Virology. 2001;**21**:163-170

[102] Tian M, Liu F, Wen G, Shi S, Chen R, Zhao D. Effect of variation in RANTES promoter on serum RANTES levels and risk of recurrent wheezing after RSV bronchiolitis in children from Han, Southern China. European Journal of Pediatrics. 2009;**168**:963-967. DOI: 10.1007/s00431-008-0870-3

[103] Hattori S, Shimojo N, Mashimo T, Inoue Y, Ono Y, Kohno Y, et al. Relationship between RANTES polymorphisms and respiratory syncytial virus bronchiolitis in a Japanese infant population. Japanese Journal of Infectious Diseases. 2011;**64**:242-245

[104] Sigurs N, Bjarnason R, Sigurbergsson F. Eosinophil cationic protein in nasal secretion and in serum and myeloperoxidase in serum in respiratory syncytial virus bronchiolitis: Relation to asthma and atopy. Acta Paediatrica (Oslo, Norway: 1992). 1994;**83**:1151-1155

[105] Kim HH, Lee MH, Lee JS. Eosinophil cationic protein and chemokines in nasopharyngeal secretions of infants with respiratory syncytial virus (RSV) bronchiolitis and non-RSV bronchiolitis. Journal of Korean Medical Science. 2007;**22**:37-42. DOI: 10.3346/jkms.2007.22.1.37

[106] Garofalo R, Dorris A, Ahlstedt S, Welliver RC. Peripheral blood eosinophil counts and eosinophil cationic protein content of respiratory secretions in bronchiolitis: Relationship to severity of disease. Pediatric Allergy and Immunology: The Official Publication of the European Society of Pediatric Allergy and Immunology. 1994;**5**:111-117

[107] Brandenburg AH, Groen J, van Steensel-Moll HA, Claas EC, Rothbarth PH, Neijens HJ, et al. Respiratory syncytial virus specific serum antibodies in infants under six months of age: Limited serological response upon infection. Journal of Medical Virology. 1997;**52**:97-104

[108] Kasel JA, Walsh EE, Frank AL, Baxter BD, Taber LH, Glezen WP. Relation of serum antibody to glycoproteins of respiratory syncytial virus with immunity to infection in children. Viral Immunology. 1987;**1**:199-205. DOI: 10.1089/vim.1987.1.199

[109] Nishimura T, Suzue J, Kaji H. Breastfeeding reduces the severity of respiratory syncytial virus infection among young infants: A multicenter prospective study. Pediatrics International (Pediatr Int): Official English Journal of the Japan Pediatric Society. 2009;**51**:812-816. DOI: 10.1111/j.1442-200X.2009.02877.x

[110] Watt PJ, Zardis M,

Lambden PR. Age related IgG subclass response to respiratory syncytial virus fusion protein in infected infants. Clinical and Experimental Immunology. 1986;**64**:503-509

[111] Wagner DK, Nelson DL, Walsh EE, Reimer CB, Henderson FW, Murphy BR. Differential immunoglobulin G subclass

**23**

1995;**8**:22-33

*Disease Severity in Respiratory Syncytial Virus Infection: Role of Viral and Host Factors*

[118] Fishaut M, Tubergen D, McIntosh K. Cellular response to respiratory viruses with particular reference to children with disorders of cell-mediated immunity. The Journal of

Pediatrics. 1980;**96**:179-186

1987;**62**:133-138

[119] Cannon MJ, Stott EJ, Taylor G, Askonas BA. Clearance of persistent respiratory syncytial virus infections in immunodeficient mice following transfer of primed T cells. Immunology.

[120] Cannon MJ, Openshaw PJ, Askonas BA. Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus. The Journal of Experimental Medicine. 1988;**168**:1163-1168. DOI:

[121] Heidema J, Lukens MV, van MWWC, van DMEA, Otten HG,

in Bronchoalveolar lavage fluid and peripheral blood mononuclear cells of infants with severe primary respiratory syncytial virus infections. Journal of Immunology. 2007;**179**:8410-8417. DOI:

10.4049/jimmunol.179.12.8410

DOI: 10.1038/ncomms10224

2003;**8**:223-246

[123] Kidd P. Th1/Th2 balance: The hypothesis, its limitations, and implications for health and disease. Alternative Medicine Review: A Journal of Clinical Therapeutics.

[124] Reithinger R, Dujardin J-C, Louzir H, Pirmez C, Alexander B, Brooker S. Cutaneous leishmaniasis. The Lancet Infectious Diseases. 2007;**7**:581-596. DOI: 10.1016/ S1473-3099(07)70209-8

[122] Jozwik A, Habibi MS, Paras A, Zhu J, Guvenel A, Dhariwal J, et al. RSVspecific airway resident memory CD8<sup>+</sup> T cells and differential disease severity after experimental human infection. Nature Communications. 2015;**6**:10224.

T cell responses

10.1084/jem.168.3.1163

van VAJ, et al. CD8+

*DOI: http://dx.doi.org/10.5772/intechopen.88782*

antibody titers to respiratory syncytial virus F and G glycoproteins in adults. Journal of Clinical Microbiology.

[112] Murphy BR, Graham BS, Prince GA, Walsh EE, Chanock RM, Karzon DT, et al. Serum and nasal-wash immunoglobulin G and A antibody response of infants and children to respiratory syncytial virus F and G glycoproteins following primary infection. Journal of Clinical Microbiology. 1986;**23**:1009-1014

[113] Murphy BR, Alling DW, Snyder MH, Walsh EE, Prince GA, Chanock RM, et al. Effect of age and preexisting antibody on serum antibody response of infants and children to the F and G glycoproteins during respiratory syncytial virus infection. Journal of Clinical Microbiology.

[114] Graham BS, Bunton LA, Wright PF, Karzon DT. Reinfection of mice with respiratory syncytial virus. Journal of Medical Virology. 1991;**34**:7-13

[115] Walsh EE, Wang L, Falsey AR, Qiu X, Corbett A, Holden-Wiltse J, et al. Virus-specific antibody, viral load, and disease severity in respiratory syncytial virus infection. The Journal of Infectious Diseases. 2018;**218**:208-217.

[116] Forbes ML, Kumar VR, Yogev R, Wu X, Robbie GJ, Ambrose CS. Serum palivizumab level is associated with decreased severity of respiratory syncytial virus disease in highrisk infants. Human Vaccines and Immunotherapeutics. 2014;**10**:2789-

DOI: 10.1093/infdis/jiy106

2794. DOI: 10.4161/hv.29635

[117] Hemming VG, Prince GA,

Clinical Microbiology Reviews.

Groothuis JR, Siber GR. Hyperimmune globulins in prevention and treatment of respiratory syncytial virus infections.

1986;**24**:894-898

1987;**25**:748-750

*Disease Severity in Respiratory Syncytial Virus Infection: Role of Viral and Host Factors DOI: http://dx.doi.org/10.5772/intechopen.88782*

antibody titers to respiratory syncytial virus F and G glycoproteins in adults. Journal of Clinical Microbiology. 1987;**25**:748-750

*The Burden of Respiratory Syncytial Virus Infection in the Young*

syncytial virus (RSV) bronchiolitis and non-RSV bronchiolitis. Journal of Korean Medical Science. 2007;**22**:37-42.

Ahlstedt S, Welliver RC. Peripheral blood eosinophil counts and eosinophil cationic protein content of respiratory secretions in bronchiolitis: Relationship

DOI: 10.3346/jkms.2007.22.1.37

to severity of disease. Pediatric

[107] Brandenburg AH, Groen J, van Steensel-Moll HA, Claas EC, Rothbarth PH, Neijens HJ, et al. Respiratory syncytial virus specific serum antibodies in infants under six months of age: Limited serological response upon infection. Journal of Medical Virology. 1997;**52**:97-104

[108] Kasel JA, Walsh EE, Frank AL, Baxter BD, Taber LH, Glezen WP. Relation of serum antibody to glycoproteins of respiratory syncytial virus with immunity to infection in children. Viral Immunology. 1987;**1**:199-205. DOI:

[109] Nishimura T, Suzue J, Kaji H. Breastfeeding reduces the severity of respiratory syncytial virus infection among young infants: A multicenter prospective study. Pediatrics International (Pediatr Int): Official English Journal of the Japan Pediatric Society. 2009;**51**:812-816. DOI: 10.1111/j.1442-200X.2009.02877.x

10.1089/vim.1987.1.199

[110] Watt PJ, Zardis M,

1986;**64**:503-509

Lambden PR. Age related IgG subclass response to respiratory syncytial virus fusion protein in infected infants. Clinical and Experimental Immunology.

[111] Wagner DK, Nelson DL, Walsh EE, Reimer CB, Henderson FW, Murphy BR. Differential immunoglobulin G subclass

1994;**5**:111-117

Allergy and Immunology: The Official Publication of the European Society of Pediatric Allergy and Immunology.

[106] Garofalo R, Dorris A,

virus-induced respiratory infections. Pediatric Asthma, Allergy and Immunology. 2001;**15**:89-96. DOI: 10.1089/088318701753436880

Kalkanoglu AE, Lee FE-H, Falsey AR. Viral shedding and immune responses to respiratory syncytial virus infection in older adults. The Journal of Infectious Diseases. 2013;**207**:1424-1432. DOI:

Larsen LB. Cytokines and chemokines in respiratory secretion and severity of disease in infants with respiratory syncytial virus (RSV) infection. Journal of Clinical Virology: The Official

Publication of the Pan American Society for Clinical Virology. 2001;**21**:163-170

[102] Tian M, Liu F, Wen G, Shi S, Chen R, Zhao D. Effect of variation in RANTES promoter on serum RANTES levels and risk of recurrent wheezing after RSV bronchiolitis in children from Han, Southern China. European Journal of Pediatrics. 2009;**168**:963-967. DOI:

10.1007/s00431-008-0870-3

[103] Hattori S, Shimojo N,

[104] Sigurs N, Bjarnason R,

[105] Kim HH, Lee MH, Lee JS. Eosinophil cationic protein and chemokines in nasopharyngeal secretions of infants with respiratory

Sigurbergsson F. Eosinophil cationic protein in nasal secretion and in serum and myeloperoxidase in serum in respiratory syncytial virus bronchiolitis: Relation to asthma and atopy. Acta Paediatrica (Oslo, Norway: 1992).

2011;**64**:242-245

1994;**83**:1151-1155

Mashimo T, Inoue Y, Ono Y, Kohno Y, et al. Relationship between RANTES polymorphisms and respiratory syncytial virus bronchiolitis in a Japanese infant population. Japanese Journal of Infectious Diseases.

[100] Walsh EE, Peterson DR,

10.1093/infdis/jit038

[101] Hornsleth A, Loland L,

**22**

[112] Murphy BR, Graham BS, Prince GA, Walsh EE, Chanock RM, Karzon DT, et al. Serum and nasal-wash immunoglobulin G and A antibody response of infants and children to respiratory syncytial virus F and G glycoproteins following primary infection. Journal of Clinical Microbiology. 1986;**23**:1009-1014

[113] Murphy BR, Alling DW, Snyder MH, Walsh EE, Prince GA, Chanock RM, et al. Effect of age and preexisting antibody on serum antibody response of infants and children to the F and G glycoproteins during respiratory syncytial virus infection. Journal of Clinical Microbiology. 1986;**24**:894-898

[114] Graham BS, Bunton LA, Wright PF, Karzon DT. Reinfection of mice with respiratory syncytial virus. Journal of Medical Virology. 1991;**34**:7-13

[115] Walsh EE, Wang L, Falsey AR, Qiu X, Corbett A, Holden-Wiltse J, et al. Virus-specific antibody, viral load, and disease severity in respiratory syncytial virus infection. The Journal of Infectious Diseases. 2018;**218**:208-217. DOI: 10.1093/infdis/jiy106

[116] Forbes ML, Kumar VR, Yogev R, Wu X, Robbie GJ, Ambrose CS. Serum palivizumab level is associated with decreased severity of respiratory syncytial virus disease in highrisk infants. Human Vaccines and Immunotherapeutics. 2014;**10**:2789- 2794. DOI: 10.4161/hv.29635

[117] Hemming VG, Prince GA, Groothuis JR, Siber GR. Hyperimmune globulins in prevention and treatment of respiratory syncytial virus infections. Clinical Microbiology Reviews. 1995;**8**:22-33

[118] Fishaut M, Tubergen D, McIntosh K. Cellular response to respiratory viruses with particular reference to children with disorders of cell-mediated immunity. The Journal of Pediatrics. 1980;**96**:179-186

[119] Cannon MJ, Stott EJ, Taylor G, Askonas BA. Clearance of persistent respiratory syncytial virus infections in immunodeficient mice following transfer of primed T cells. Immunology. 1987;**62**:133-138

[120] Cannon MJ, Openshaw PJ, Askonas BA. Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus. The Journal of Experimental Medicine. 1988;**168**:1163-1168. DOI: 10.1084/jem.168.3.1163

[121] Heidema J, Lukens MV, van MWWC, van DMEA, Otten HG, van VAJ, et al. CD8+ T cell responses in Bronchoalveolar lavage fluid and peripheral blood mononuclear cells of infants with severe primary respiratory syncytial virus infections. Journal of Immunology. 2007;**179**:8410-8417. DOI: 10.4049/jimmunol.179.12.8410

[122] Jozwik A, Habibi MS, Paras A, Zhu J, Guvenel A, Dhariwal J, et al. RSVspecific airway resident memory CD8<sup>+</sup> T cells and differential disease severity after experimental human infection. Nature Communications. 2015;**6**:10224. DOI: 10.1038/ncomms10224

[123] Kidd P. Th1/Th2 balance: The hypothesis, its limitations, and implications for health and disease. Alternative Medicine Review: A Journal of Clinical Therapeutics. 2003;**8**:223-246

[124] Reithinger R, Dujardin J-C, Louzir H, Pirmez C, Alexander B, Brooker S. Cutaneous leishmaniasis. The Lancet Infectious Diseases. 2007;**7**:581-596. DOI: 10.1016/ S1473-3099(07)70209-8

[125] Burke ML, Jones MK, Gobert GN, Li YS, Ellis MK, McManus DP. Immunopathogenesis of human schistosomiasis. Parasite Immunology. 2009;**31**:163-176. DOI: 10.1111/j.1365-3024.2009.01098.x

[126] Everard ML, Swarbrick A, Wrightham M, McIntyre J, Dunkley C, James PD, et al. Analysis of cells obtained by bronchial lavage of infants with respiratory syncytial virus infection. Archives of Disease in Childhood. 1994;**71**:428-432. DOI: 10.1136/adc.71.5.428

[127] Alwan WH, Openshaw PJ. Distinct patterns of T- and B-cell immunity to respiratory syncytial virus induced by individual viral proteins. Vaccine. 1993;**11**:431-437

[128] Alwan WH, Kozlowska WJ, Openshaw PJ. Distinct types of lung disease caused by functional subsets of antiviral T cells. The Journal of Experimental Medicine. 1994;**179**:81-89. DOI: 10.1084/jem.179.1.81

[129] Stack AM, Malley R, Saladino RA, Montana JB, MacDonald KL, Molrine DC. Primary respiratory syncytial virus infection: Pathology, immune response, and evaluation of vaccine challenge strains in a new mouse model. Vaccine. 2000;**18**:1412-1418

[130] Fernández JA, Tapia L, Palomino MA, Larrañaga C, Peña M, Jaramillo H. Plasma interferon-gamma, interleukin-10 and soluble markers of immune activation in infants with primary adenovirus (ADV) and respiratory syncytial virus (RSV) infection. European Cytokine Network. 2005;**16**:35-40

[131] Semple MG, Dankert HM, Ebrahimi B, Correia JB, Booth JA, Stewart JP, et al. Severe respiratory syncytial virus bronchiolitis in infants is associated with reduced airway interferon gamma and substance

P. PLoS One. 2007;**2**:e1038. DOI: 10.1371/journal.pone.0001038

[132] Ye Q, Shao W-X, Shang S-Q, Pan Y-X, Shen H-Q, Chen X-J. Epidemiological characteristics and immune status of children with respiratory syncytial virus. Journal of Medical Virology. 2015;**87**:323-329. DOI: 10.1002/jmv.24047

[133] Pinto RA, Arredondo SM, Bono MR, Gaggero AA. Díaz PV. T helper 1/T helper 2 cytokine imbalance in respiratory syncytial virus infection is associated with increased endogenous plasma cortisol. Pediatrics. 2006;**117**:e878-e886. DOI: 10.1542/ peds.2005-2119

[134] Bont L, Heijnen CJ, Kavelaars A, van Aalderen WM, Brus F, Draaisma JM, et al. Local interferon-gamma levels during respiratory syncytial virus lower respiratory tract infection are associated with disease severity. The Journal of Infectious Diseases. 2001;**184**:355-358. DOI: 10.1086/322035

[135] Midulla F, Tromba V, Lo Russo L, Mileto F, Sabatino G, Sgarrella M, et al. Cytokines in the nasal washes of children with respiratory syncytial virus bronchiolitis. International Journal of Immunopathology and Pharmacology. 2006;**19**:231-235

[136] Alonso Fernández J, Roine I, Vasquez A, Cáneo M. Soluble interleukin-2 receptor (sCD25) and interleukin-10 plasma concentrations are associated with severity of primary respiratory syncytial virus (RSV) infection. European Cytokine Network. 2005;**16**:81-90

[137] Vieira RA, Diniz EM de A, Ceccon MEJR. Correlation between inflammatory mediators in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection caused by respiratory syncytial virus and disease severity.

**25**

*Disease Severity in Respiratory Syncytial Virus Infection: Role of Viral and Host Factors*

*DOI: http://dx.doi.org/10.5772/intechopen.88782*

O Jornal Brasileiro de Pneumologia é publicação oficial da Sociedade Brasileira de Pneumologia e Tisiologia.

[138] Hassan MA, Eldin AME. Ahmed MM. T-helper2/T-helper1 imbalance in respiratory syncytial virus bronchiolitis in relation to disease severity and outcome. The Egyptian Journal of Immunology.

[139] Caballero MT, Serra ME, Acosta PL, Marzec J, Gibbons L, Salim M, et al. TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization. The Journal of Clinical Investigation. 2015;**125**:571-582. DOI: 10.1172/

[140] Shalev I, Schmelzle M, Robson SC, Levy G. Making sense of regulatory T cell suppressive function. Seminars in Immunology. 2011;**23**:282-292. DOI:

cells limit pulmonary immunopathology by modulating the CD8 T cell response during respiratory syncytial virus infection. Journal of Immunology (Baltimore, MD) (1950). 2010;**185**:2382- 2392. DOI: 10.4049/jimmunol.1000423

Payasliàn F, Anderson M, Rivarola N, Ferrero F, et al. Depletion of circulating

regulatory T cells during severe respiratory syncytial virus infection in Young children. American Journal of Respiratory and Critical Care Medicine.

2014;**189**:865-868. DOI: 10.1164/

[143] Paramore LC, Ciuryla V, Ciesla G, Liu L. Economic impact of respiratory syncytial virus-related illness in the US. PharmacoEconomics.

10.2165/00019053-200422050-00001

rccm.201311-1977LE

2004;**22**:275-284. DOI:

CD4 regulatory T

10.1016/j.smim.2011.04.003

[142] Raiden S, Pandolfi J,

Varga SM. Foxp3+

[141] Fulton RB, Meyerholz DK,

2010;**36**:59-66

2008;**15**:153-160

JCI75183

*Disease Severity in Respiratory Syncytial Virus Infection: Role of Viral and Host Factors DOI: http://dx.doi.org/10.5772/intechopen.88782*

O Jornal Brasileiro de Pneumologia é publicação oficial da Sociedade Brasileira de Pneumologia e Tisiologia. 2010;**36**:59-66

*The Burden of Respiratory Syncytial Virus Infection in the Young*

P. PLoS One. 2007;**2**:e1038. DOI: 10.1371/journal.pone.0001038

[132] Ye Q, Shao W-X, Shang S-Q, Pan Y-X, Shen H-Q, Chen X-J. Epidemiological characteristics and immune status of children with respiratory syncytial virus. Journal of Medical Virology. 2015;**87**:323-329. DOI:

[133] Pinto RA, Arredondo SM, Bono MR, Gaggero AA. Díaz PV. T helper 1/T helper 2 cytokine imbalance

in respiratory syncytial virus

infection is associated with increased endogenous plasma cortisol. Pediatrics. 2006;**117**:e878-e886. DOI: 10.1542/

[134] Bont L, Heijnen CJ, Kavelaars A, van Aalderen WM, Brus F, Draaisma JM, et al. Local interferon-gamma levels during respiratory syncytial virus lower respiratory tract infection are associated with disease severity. The Journal of Infectious Diseases. 2001;**184**:355-358.

[135] Midulla F, Tromba V, Lo Russo L, Mileto F, Sabatino G, Sgarrella M, et al. Cytokines in the nasal washes of

children with respiratory syncytial virus bronchiolitis. International Journal of Immunopathology and Pharmacology.

Roine I, Vasquez A, Cáneo M. Soluble interleukin-2 receptor (sCD25) and interleukin-10 plasma concentrations are associated with severity of primary respiratory syncytial virus (RSV) infection. European Cytokine Network.

[137] Vieira RA, Diniz EM de A, Ceccon MEJR. Correlation between inflammatory mediators in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection caused by respiratory syncytial virus and disease severity.

10.1002/jmv.24047

peds.2005-2119

DOI: 10.1086/322035

2006;**19**:231-235

2005;**16**:81-90

[136] Alonso Fernández J,

[125] Burke ML, Jones MK, Gobert GN,

Immunology. 2009;**31**:163-176. DOI: 10.1111/j.1365-3024.2009.01098.x

Dunkley C, James PD, et al. Analysis of cells obtained by bronchial lavage of infants with respiratory syncytial virus infection. Archives of Disease in Childhood. 1994;**71**:428-432. DOI:

[127] Alwan WH, Openshaw PJ. Distinct patterns of T- and B-cell immunity to respiratory syncytial virus induced by individual viral proteins. Vaccine.

[128] Alwan WH, Kozlowska WJ, Openshaw PJ. Distinct types of lung disease caused by functional subsets of antiviral T cells. The Journal of Experimental Medicine. 1994;**179**:81-89.

[129] Stack AM, Malley R, Saladino RA,

DOI: 10.1084/jem.179.1.81

Montana JB, MacDonald KL, Molrine DC. Primary respiratory syncytial virus infection: Pathology, immune response, and evaluation of vaccine challenge strains in a new mouse model. Vaccine. 2000;**18**:1412-1418

[130] Fernández JA, Tapia L,

[131] Semple MG, Dankert HM, Ebrahimi B, Correia JB, Booth JA, Stewart JP, et al. Severe respiratory syncytial virus bronchiolitis in infants is associated with reduced airway interferon gamma and substance

Palomino MA, Larrañaga C, Peña M, Jaramillo H. Plasma interferon-gamma, interleukin-10 and soluble markers of immune activation in infants with primary adenovirus (ADV) and respiratory syncytial virus (RSV) infection. European Cytokine Network.

Li YS, Ellis MK, McManus DP. Immunopathogenesis of human schistosomiasis. Parasite

[126] Everard ML, Swarbrick A, Wrightham M, McIntyre J,

10.1136/adc.71.5.428

1993;**11**:431-437

**24**

2005;**16**:35-40

[138] Hassan MA, Eldin AME. Ahmed MM. T-helper2/T-helper1 imbalance in respiratory syncytial virus bronchiolitis in relation to disease severity and outcome. The Egyptian Journal of Immunology. 2008;**15**:153-160

[139] Caballero MT, Serra ME, Acosta PL, Marzec J, Gibbons L, Salim M, et al. TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization. The Journal of Clinical Investigation. 2015;**125**:571-582. DOI: 10.1172/ JCI75183

[140] Shalev I, Schmelzle M, Robson SC, Levy G. Making sense of regulatory T cell suppressive function. Seminars in Immunology. 2011;**23**:282-292. DOI: 10.1016/j.smim.2011.04.003

[141] Fulton RB, Meyerholz DK, Varga SM. Foxp3+ CD4 regulatory T cells limit pulmonary immunopathology by modulating the CD8 T cell response during respiratory syncytial virus infection. Journal of Immunology (Baltimore, MD) (1950). 2010;**185**:2382- 2392. DOI: 10.4049/jimmunol.1000423

[142] Raiden S, Pandolfi J, Payasliàn F, Anderson M, Rivarola N, Ferrero F, et al. Depletion of circulating regulatory T cells during severe respiratory syncytial virus infection in Young children. American Journal of Respiratory and Critical Care Medicine. 2014;**189**:865-868. DOI: 10.1164/ rccm.201311-1977LE

[143] Paramore LC, Ciuryla V, Ciesla G, Liu L. Economic impact of respiratory syncytial virus-related illness in the US. PharmacoEconomics. 2004;**22**:275-284. DOI: 10.2165/00019053-200422050-00001

**27**

Section 2

RSV and Late Preterm

Infants

Section 2
