State of the Art
Respiratory syncytial virus prevention and therapy: Past, present, and future
Melvin Wright DO,
Giovanni Piedimonte MD,
Melvin Wright DO
Department of Pediatrics and Pediatric Research Institute, West Virginia University School of Medicine, Morgantown, West Virginia
Search for more papers by this authorCorresponding Author
Giovanni Piedimonte MD
Department of Pediatrics and Pediatric Research Institute, West Virginia University School of Medicine, Morgantown, West Virginia
Department of Pediatrics, West Virginia University School of Medicine, 1 Medical Center Drive, P.O. Box 9214, Morgantown, WV 26506-9214.Search for more papers by this authorMelvin Wright DO,
Giovanni Piedimonte MD,
Melvin Wright DO
Department of Pediatrics and Pediatric Research Institute, West Virginia University School of Medicine, Morgantown, West Virginia
Search for more papers by this authorCorresponding Author
Giovanni Piedimonte MD
Department of Pediatrics and Pediatric Research Institute, West Virginia University School of Medicine, Morgantown, West Virginia
Department of Pediatrics, West Virginia University School of Medicine, 1 Medical Center Drive, P.O. Box 9214, Morgantown, WV 26506-9214.Search for more papers by this authorAbstract
Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children worldwide. More than 50 years after its discovery, and despite relentless attempts to identify pharmacological therapies to improve the clinical course and outcomes of this disease, the most effective therapy remains supportive care. Although the quest for a safe and effective vaccine remains unsuccessful, pediatricians practicing during the past decade have been able to protect at least the more vulnerable patients with safe and effective passive prophylaxis. This review summarizes the history, microbiology, epidemiology, pathophysiology, and clinical manifestations of this infection in order to provide the reader with the background information necessary to fully appreciate the many challenges presented by the clinical management of young children with bronchiolitis. The last part of this article attempts an evidence-based review of the pharmacologic strategies currently available and those being evaluated, intentionally omitting highly experimental approaches not yet tested in clinical trials and, therefore, not likely to become available in the foreseeable future. Pediatr Pulmonol. 2011; 46:324–347. © 2010 Wiley-Liss, Inc.
REFERENCES
- 1Eberle J. A treatise on the diseases and physical education of children. Philadelphia: Lippincott, Grambo and Co; 1850. 548 p.
- 2Adams JM. Primary virus pneumonitis with cytoplasmic inclusion bodies. JAMA 1941; 116: 925–933.
- 3Adams JM, Green RG, Evans CA. Primary viral pneumonitis: a comparative study of two epidemics. J Pediatr 1942; 20: 405–420.
- 4Blount RE, Jr., Morris JA, Savage RE. Recovery of cytopathogenic agent from chimpanzees with coryza. Proc Soc Exp Biol Med 1956; 92: 544–549.
- 5Chanock R, Roizman B, Myers R. Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). I. Isolation, properties and characterization. Am J Hyg 1957; 66: 281–290.
- 6Chanock R, Finberg L. Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). II. Epidemiologic aspects of infection in infants and young children. Am J Hyg 1957; 66: 291–300.
- 7Chanock RM, Kim HW, Vargosko AJ, Deleva A, Johnson KM, Cumming C, Parrott RH. Respiratory syncytial virus. I. Virus recovery and other observations during 1960 outbreak of bronchiolitis, pneumonia, and minor respiratory diseases in children. JAMA 1961; 176: 647–653.
- 8Parrott RH, Vargosko AJ, Kim HW, Cumming C, Turner H, Huebner RJ, Chanock RM. Respiratory syncytial virus. II. Serologic studies over a 34-month period of children with bronchiolitis, pneumonia, and minor respiratory diseases. JAMA 1961; 176: 653–657.
- 9Johnson KM, Chanock RM, Rifkind D, Kravetz HM, Knight V. Respiratory syncytial virus. IV. Correlation of virus shedding, serologic response, and illness in adult volunteers. JAMA 1961; 176: 663–667.
- 10Kapikian AZ, Mitchell RH, Chanock RM, Shvedoff RA, Stewart CE. An epidemiologic study of altered clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an inactivated RS virus vaccine. Am J Epidemiol 1969; 89: 405–421.
- 11Prince GA, Jenson AB, Horswood RL, Camargo E, Chanock RM. The pathogenesis of respiratory syncytial virus infection in cotton rats. Am J Pathol 1978; 93: 771–791.
- 12Peters TR, Crowe JE, Jr. Respiratory syncytial virus. In: SS Long, editor. Principles and practice of pediatric infectious diseases, 3rd edition. Philadelphia, PA:
Churchill Livingstone; 2008. 1112–1117.
10.1016/B978-0-7020-3468-8.50231-5 Google Scholar
- 13Anderson LJ, Hierholzer JC, Tsou C, Hendry RM, Fernie BF, Stone Y, McIntosh K. Antigenic characterization of respiratory syncytial virus strains with monoclonal antibodies. J Infect Dis 1985; 151: 626–633.
- 14Mufson MA, Orvell C, Rafnar B, Norrby E. Two distinct subtypes of human respiratory syncytial virus. J Gen Virol 1985; 66: 2111–2124.
- 15Hall CB, Walsh EE, Schnabel KC, Long CE, McConnochie KM, Hildreth SW, Anderson LJ. Occurrence of groups A and B of respiratory syncytial virus over 15 years: associated epidemiologic and clinical characteristics in hospitalized and ambulatory children. J Infect Dis 1990; 162: 1283–1290.
- 16McConnochie KM, Hall CB, Walsh EE, Roghmann KJ. Variation in severity of respiratory syncytial virus infections with subtype. J Pediatr 1990; 117: 52–62.
- 17Papadopoulos NG, Gourgiotis D, Javadyan A, Bossios A, Kallergi K, Psarras S, Tsolia MN, Kafetzis D. Does respiratory syncytial virus subtype influences the severity of acute bronchiolitis in hospitalized infants? Respir Med 2004; 98: 879–882.
- 18Walsh EE, McConnochie KM, Long CE, Hall CB. Severity of respiratory syncytial virus infection is related to virus strain. J Infect Dis 1997; 175: 814–820.
- 19Gilca R, De Serres G, Tremblay M, Vachon ML, Leblanc E, Bergeron MG, Dery P, Boivin G. Distribution and clinical impact of human respiratory syncytial virus genotypes in hospitalized children over 2 winter seasons. J Infect Dis 2006; 193: 54–58.
- 20Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, Anderson LJ. Bronchiolitis-associated hospitalizations among US children, 1980–1996. JAMA 1999; 282: 1440–1446.
- 21Gilchrist S, Torok TJ, Gary HE, Jr., Alexander JP, Anderson LJ. National surveillance for respiratory syncytial virus, United States, 1985–1990. J Infect Dis 1994; 170: 986–990.
- 22Glezen WP, Taber LH, Frank AL, Kasel JA. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child 1986; 140: 543–546.
- 23 Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics 2006; 118: 1774–1793.
- 24Leader S, Kohlhase K. Respiratory syncytial virus-coded pediatric hospitalizations, 1997 to 1999. Pediatr Infect Dis J 2002; 21: 629–632.
- 25Sung RY, Murray HG, Chan RC, Davies DP, French GL. Seasonal patterns of respiratory syncytial virus infection in Hong Kong: a preliminary report. J Infect Dis 1987; 156: 527–528.
- 26Venkatesh MP, Weisman LE. Prevention and treatment of respiratory syncytial virus infection in infants: an update. Expert Rev Vaccines 2006; 5: 261–268.
- 27Ballow M, Cates KL, Rowe JC, Goetz C, Desbonnet C. Development of the immune system in very low birth weight (less than 1500 g) premature infants: concentrations of plasma immunoglobulins and patterns of infections. Pediatr Res 1986; 20: 899–904.
- 28Walsh EE, Peterson DR, Falsey AR. Risk factors for severe respiratory syncytial virus infection in elderly persons. J Infect Dis 2004; 189: 233–238.
- 29Boyce TG, Mellen BG, Mitchel EF, Jr., Wright PF, Griffin MR. Rates of hospitalization for respiratory syncytial virus infection among children in Medicaid. J Pediatr 2000; 137: 865–870.
- 30Wang EE, Law BJ, Boucher FD, Stephens D, Robinson JL, Dobson S, Langley JM, McDonald J, MacDonald NE, Mitchell I. Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of admission and management variation in patients hospitalized with respiratory syncytial viral lower respiratory tract infection. J Pediatr 1996; 129: 390–395.
- 31Navas L, Wang E, de Carvalho V, Robinson J. Improved outcome of respiratory syncytial virus infection in a high-risk hospitalized population of Canadian children. Pediatric Investigators Collaborative Network on Infections in Canada. J Pediatr 1992; 121: 348–354.
- 32King JC, Jr., Burke AR, Clemens JD, Nair P, Farley JJ, Vink PE, Batlas SR, Rao M, Johnson JP. Respiratory syncytial virus illnesses in human immunodeficiency virus- and noninfected children. Pediatr Infect Dis J 1993; 12: 733–739.
- 33Milner ME, de la Monte SM, Hutchins GM. Fatal respiratory syncytial virus infection in severe combined immunodeficiency syndrome. Am J Dis Child 1985; 139: 1111–1114.
- 34Hall CB, Powell KR, MacDonald NE, Gala CL, Menegus ME, Suffin SC, Cohen HJ. Respiratory syncytial viral infection in children with compromised immune function. N Engl J Med 1986; 315: 77–81.
- 35Simões EA. Maternal smoking, asthma, and bronchiolitis: clear-cut association or equivocal evidence? Pediatrics 2007; 119: 1210–1212.
- 36Howard TS, Hoffman LH, Stang PE, Simoes EA. Respiratory syncytial virus pneumonia in the hospital setting: length of stay, charges, and mortality. J Pediatr 2000; 137: 227–232.
- 37Simoes EA. Respiratory syncytial virus and subsequent lower respiratory tract infections in developing countries: a new twist to an old virus. J Pediatr 1999; 135: 657–661.
- 38Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003; 289: 179–186.
- 39Shay DK, Holman RC, Roosevelt GE, Clarke MJ, Anderson LJ. Bronchiolitis-associated mortality and estimates of respiratory syncytial virus-associated deaths among US children, 1979–1997. J Infect Dis 2001; 183: 16–22.
- 40Leader S, Kohlhase K. Recent trends in severe respiratory syncytial virus (RSV) among US infants, 1997 to 2000. J Pediatr 2003; 143: S127–S132.
- 41Stang P, Brandenburg N, Carter B. The economic burden of respiratory syncytial virus-associated bronchiolitis hospitalizations. Arch Pediatr Adolesc Med 2001; 155: 95–96.
- 42Falsey AR, Walsh EE. Respiratory syncytial virus infection in adults. Clin Microbiol Rev 2000; 13: 371–384.
- 43Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med 2005; 352: 1749–1759.
- 44Hall CB, Walsh EE, Long CE, Schnabel KC. Immunity to and frequency of reinfection with respiratory syncytial virus. J Infect Dis 1991; 163: 693–698.
- 45Henderson FW, Collier AM, Clyde WA, Jr., Denny FW. Respiratory-syncytial-virus infections, reinfections and immunity. A prospective, longitudinal study in young children. N Engl J Med 1979; 300: 530–534.
- 46Hall CB, Long CE, Schnabel KC. Respiratory syncytial virus infections in previously healthy working adults. Clin Infect Dis 2001; 33: 792–796.
- 47Sims DG, Downham MA, Gardner PS, Webb JK, Weightman D. Study of 8-year-old children with a history of respiratory syncytial virus bronchiolitis in infancy. Br Med J 1978; 1: 11–14.
- 48McConnochie KM, Roghmann KJ. Bronchiolitis as a possible cause of wheezing in childhood: new evidence. Pediatrics 1984; 74: 1–10.
- 49Mok JY, Simpson H. Outcome for acute bronchitis, bronchiolitis, and pneumonia in infancy. Arch Dis Child 1984; 59: 306–309.
- 50Murray M, Webb MS, O'Callaghan C, Swarbrick AS, Milner AD. Respiratory status and allergy after bronchiolitis. Arch Dis Child 1992; 67: 482–487.
- 51Osundwa VM, Dawod ST, Ehlayel M. Recurrent wheezing in children with respiratory syncytial virus (RSV) bronchiolitis in Qatar. Eur J Pediatr 1993; 152: 1001–1003.
- 52Noble V, Murray M, Webb MS, Alexander J, Swarbrick AS, Milner AD. Respiratory status and allergy nine to 10 years after acute bronchiolitis. Arch Dis Child 1997; 76: 315–319.
- 53Stein RT, Sherrill D, Morgan WJ, Holberg CJ, Halonen M, Taussig LM, Wright AL, Martinez FD. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet 1999; 354: 541–545.
- 54Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B. Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med 2000; 161: 1501–1507.
- 55Simões EA, Carbonell-Estrany X, Rieger CH, Mitchell I, Fredrick L, Groothuis JR. The effect of respiratory syncytial virus on subsequent recurrent wheezing in atopic and nonatopic children. J Allergy Clin Immunol 2010; 126: 256–262.
- 56Hall CB, Douglas RG, Jr., Geiman JM. Quantitative shedding patterns of respiratory syncytial virus in infants. J Infect Dis 1975; 132: 151–156.
- 57Hall CB, Douglas RG, Jr. Modes of transmission of respiratory syncytial virus. J Pediatr 1981; 99: 100–103.
- 58Hall CB, Douglas RG, Jr., Schnabel KC, Geiman JM. Infectivity of respiratory syncytial virus by various routes of inoculation. Infect Immune 1981; 33: 779–783.
- 59Hall CB, Douglas RG, Jr., Geiman JM. Possible transmission by fomites of respiratory syncytial virus. J Infect Dis 1980; 141: 98–102.
- 60Othumpangat S, Gibson L, Samsell L, Piedimonte G. NGF is an essential survival factor for bronchial epithelial cells during respiratory syncytial virus infection. PLoS ONE 2009; 4: e6444.
- 61Johnson JE, Gonzales RA, Olson SJ, Wright PF, Graham BS. The histopathology of fatal untreated human respiratory syncytial virus infection. Mod Pathol 2007; 20: 108–119.
- 62Hoffman SJ, Laham FR, Polack FP. Mechanisms of illness during respiratory syncytial virus infection: the lungs, the virus and the immune response. Microbes Infect 2004; 6: 767–772.
- 63Domurat F, Roberts NJ, Jr., Walsh EE, Dagan R. Respiratory syncytial virus infection of human mononuclear leukocytes in vitro and in vivo. J Infect Dis 1985; 152: 895–902.
- 64Panuska JR, Hertz MI, Taraf H, Villani A, Cirino NM. Respiratory syncytial virus infection of alveolar macrophages in adult transplant patients. Am Rev Respir Dis 1992; 145: 934–939.
- 65Krilov LR, Hendry RM, Godfrey E, McIntosh K. Respiratory virus infection of peripheral blood monocytes: correlation with ageing of cells and interferon production in vitro. J Gen Virol 1987; 68: 1749–1753.
- 66Englund JA, Sullivan CJ, Jordan MC, Dehner LP, Vercellotti GM, Balfour HH, Jr. Respiratory syncytial virus infection in immunocompromised adults. Ann Intern Med 1988; 109: 203–208.
- 67Padman R, Bye MR, Schidlow DV, Zaeri N, Severe RSV bronchiolitis in an immunocompromised child. Clin Pediatr (Phila) 1985; 24: 719–721.
- 68Aherne W, Bird T, Court SD, Gardner PS, McQuillin J. Pathological changes in virus infections of the lower respiratory tract in children. J Clin Pathol 1970; 23: 7–18.
- 69Kim HW, Canchola JG, Brandt CD, Pyles G, Chanock RM, Jensen K, Parrott RH. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol 1969; 89: 422–434.
- 70Chin J, Magoffin RL, Shearer LA, Schieble JH, Lennette EH. Field evaluation of a respiratory syncytial virus vaccine and a trivalent parainfluenza virus vaccine in a pediatric population. Am J Epidemiol 1969; 89: 449–463.
- 71Legg JP, Hussain IR, Warner JA, Johnston SL, Warner JO. Type 1 and type 2 cytokine imbalance in acute respiratory syncytial virus bronchiolitis. Am J Respir Crit Care Med 2003; 168: 633–639.
- 72Aung S, Rutigliano JA, Graham BS. Alternative mechanisms of respiratory syncytial virus clearance in perforin knockout mice lead to enhanced disease. J Virol 2001; 75: 9918–9924.
- 73Glezen WP, Paredes A, Allison JE, Taber LH, Frank AL. Risk of respiratory syncytial virus infection for infants from low-income families in relationship to age, sex, ethnic group, and maternal antibody level. J Pediatr 1981; 98: 708–715.
- 74Stensballe LG, Ravn H, Kristensen K, Agerskov K, Meakins T, Aaby P, Simoes EA. Respiratory syncytial virus neutralizing antibodies in cord blood, respiratory syncytial virus hospitalization, and recurrent wheeze. J Allergy Clin Immunol 2009; 123: 398–403.
- 75 The PREVENT Study Group. Reduction of respiratory syncytial virus hospitalization among premature infants and infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis. Pediatrics 1997; 99: 93–99.
- 76 Committee on Infectious Diseases and Committee of Fetus and Newborn. Prevention of respiratory syncytial virus infections: indications for the use of palivizumab and update on the use of RSV-IGIV. Pediatrics 1998; 102: 1211–1216.
- 77Chandwani S, Borkowsky W, Krasinski K, Lawrence R, Welliver R. Respiratory syncytial virus infection in human immunodeficiency virus-infected children. J Pediatr 1990; 117: 251–254.
- 78Welliver TP, Garofalo RP, Hosakote Y, Hintz KH, Avendano L, Sanchez K, Velozo L, Jafri H, Chavez-Bueno S, Ogra PL, McKinney L, Reed JL, Welliver RC, Sr. Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses. J Infect Dis 2007; 195: 1126–1136.
- 79Hu C, Wedde-Beer K, Auais A, Rodriguez MM, Piedimonte G. Nerve growth factor and nerve growth factor receptors in respiratory syncytial virus-infected lungs. Am J Physiol Lung Cell Mol Physiol 2002; 283: L494–L502.
- 80Tortorolo L, Langer A, Polidori G, Vento G, Stampachiacchere B, Aloe L, Piedimonte G. Neurotrophins overexpression in lower airways of infants with respiratory syncytial virus infection. Am J Respir Crit Care Med 2005; 172: 233–237.
- 81Renz H. Neurotrophins in bronchial asthma. Respir Res 2001; 2: 265–268.
- 82Urrego F, Scuri M, Auais A, Mothasham L, Piedimonte G. Combined effects of chronic nicotine and acute virus exposure on neurotrophin expression in rat lung. Pediatr Pulmonol 2009; 44: 1075–1084.
- 83Leon A, Buriani A, Dal Toso R, Fabris M, Romanello S, Aloe L, Levi-Montalcini R. Mast cells synthesize, store, and release nerve growth factor. Proc Nat Acad Sci USA 1994; 91: 3739–3743.
- 84Nilsson G, Forsberg-Nilsson K, Xiang Z, Hallbook F, Nilsson K, Metcalfe D. Human mast cells express functional TrkA and are a source of nerve growth factor. Eur J Immunol 1997; 27: 2295–2301.
- 85Ehrhard P, Erb P, Graumann U, Otten U. Expression of nerve growth factor and nerve growth factor receptor tyrosine kinase Trk in activated CD4-positive T-cell clones. Proc Nat Acad Sci USA 1993; 90: 10984–10988.
- 86Braun A, Lommatzsch M, Lewin GR, Virchow JC, Renz H. Neurotrophins: a link between airway inflammation and airway smooth muscle contractility in asthma. Int Arch Allergy Immunol 1999; 118: 163–165.
- 87Auais A, Adkins B, Napchan G, Piedimonte G. Immuno-modulatory effects of sensory nerves during respiratory syncytial virus infection in rats. Am J Physiol Lung Cell Mol Physiol 2003; 285: L105–L113.
- 88Mothasham L, Auais A, Piedimonte G. Nerve growth factor mediates steroid-resistant inflammation in respiratory syncytial virus infection. Pediatr Pulmonol 2007; 42: 496–504.
- 89Wedde-Beer K, Hu C, Rodriguez MM, Piedimonte G. Leukotrienes mediate neurogenic inflammation in lungs of young rats infected with respiratory syncytial virus. Am J Physiol Lung Cell Mol Physiol 2002; 282: L1143–L1150.
- 90Bauer O, Razin E. Mast cell–nerve interactions. News Physiol Sci 2000; 15: 213–218.
- 91van Schaik SM, Tristram DA, Nagpal IS, Hintz KM, Welliver RCI, Welliver RC. Increased production of IFN-gamma and cysteinyl leukotrienes in virus-induced wheezing. J Allergy Clin Immunol 1999; 103: 630–636.
- 92Volovitz B, Welliver RC, De Castro G, Krystofik D, Ogra PL. The release of leukotrienes in the respiratory tract during infection with respiratory syncytial virus: role in obstructive airway disease. Pediatr Res 1988; 24: 504–507.
- 93Piedimonte G, Renzetti G, Di Marco A, Auais A, Tripodi S, Colistro F, Villani A, Di Ciommo A, Cutrera R. Leukotriene synthesis during respiratory syncytial virus bronchiolitis: influence of age and atopy. Pediatr Pulmonol 2005; 40: 285–291.
- 94Bisgaard H. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am J Respir Crit Care Med 2003; 167: 379–383.
- 95Hall WJ, Hall CB, Speers DM. Respiratory syncytial virus infection in adults: clinical, virologic, and serial pulmonary function studies. Ann Intern Med 1978; 88: 203–205.
- 96Aujard Y, Fauroux B. Risk factors for severe respiratory syncytial virus infection in infants. Respir Med 2002; 96: S9–S14.
- 97Welliver RC. Review of epidemiology and clinical risk factors for severe respiratory syncytial virus (RSV) infection. J Pediatr 2003; 143: S112–S117.
- 98Finger R, Anderson LJ, Dicker RC, Harrison B, Doan R, Downing A, Corey L. Epidemic infections caused by respiratory syncytial virus in institutionalized young adults. J Infect Dis 1987; 155: 1335–1339.
- 99Parrott RH, Kim HW, Arrobio JO, Hodes DS, Murphy BR, Brandt CD, Camargo E, Chanock RM. 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: 289–300.
- 100Simpson W, Hacking PM, Court SD, Gardner PS. The radiological findings in respiratory syncytial virus infection in children. II. The correlation of radiological categories with clinical and virological findings. Pediatr Radiol 1974; 2: 155–160.
- 101Simpson W, Hacking PM, Court SD, Gardner PS. The radiological findings in respiratory syncytial virus infection in children. Part I. Definitions and interobserver variation in the assessment of abnormalities on the chest X-ray. Pediatr Radiol 1974; 2: 97–100.
- 102Friis B, Eiken M, Hornsleth A, Jensen A. Chest X-ray appearances in pneumonia and bronchiolitis. Correlation to virological diagnosis and secretory bacterial findings. Acta Paediatr Scand 1990; 79: 219–225.
- 103Kim HW, Arrobio JO, Brandt CD, Jeffries BC, Pyles G, Reid JL, Chanock RM, Parrott RH. Epidemiology of respiratory syncytial virus infection in Washington, D.C. I. Importance of the virus in different respiratory tract disease syndromes and temporal distribution of infection. Am J Epidemiol 1973; 98: 216–225.
- 104Walsh EE, Falsey AR, Hennessey PA. Respiratory syncytial and other virus infections in persons with chronic cardiopulmonary disease. Am J Respir Crit Care Med 1999; 160: 791–795.
- 105Bruhn FW, Mokrohisky ST, McIntosh K. Apnea associated with respiratory syncytial virus infection in young infants. J Pediatr 1977; 90: 382–386.
- 106Church NR, Anas NG, Hall CB, Brooks JG. Respiratory syncytial virus-related apnea in infants. Demographics and outcome. Am J Dis Child 1984; 138: 247–250.
- 107Hall CB, Hall WJ, Speers DM. Clinical and physiological manifestations of bronchiolitis and pneumonia. Outcome of respiratory syncytial virus. Am J Dis Child 1979; 133: 798–802.
- 108Anas N, Boettrich C, Hall CB, Brooks JG. The association of apnea and respiratory syncytial virus infection in infants. J Pediatr 1982; 101: 65–68.
- 109Kneyber MC, Brandenburg AH, de Groot R, Joosten KF, Rothbarth PH, Ott A, Moll HA. Risk factors for respiratory syncytial virus associated apnoea. Eur J Pediatr 1998; 157: 331–335.
- 110Willwerth BM, Harper MB, Greenes DS. Identifying hospitalized infants who have bronchiolitis and are at high risk for apnea. Ann Emerg Med 2006; 48: 441–447.
- 111Rayyan M, Naulaers G, Daniels H, Allegaert K, Debeer A, Devlieger H. Characteristics of respiratory syncytial virus-related apnoea in three infants. Acta Paediatr 2004; 93: 847–849.
- 112Sabogal C, Auais A, Napchan G, Suguihara C, Bancalari E, Piedimonte G. Effect of respiratory syncytial virus on apnea in weanling rats. Pediatr Res 2005; 57: 819–825.
- 113Perrotta C, Ortiz Z, Roque M. Chest physiotherapy for acute bronchiolitis in paediatric patients between 0 and 24 months old. Cochrane Database Syst Rev 2007; (1): CD004873.
- 114Downes JJ, Wood DW, Striker TW, Haddad C. Acute respiratory failure in infants with bronchiolitis. Anesthesiology 1968; 29: 426–434.
- 115Mansbach JM, McAdam AJ, Clark S, Hain PD, Flood RG, Acholonu U, Camargo CA, Jr. Prospective multicenter study of the viral etiology of bronchiolitis in the emergency department. Acad Emerg Med 2008; 15: 111–118.
- 116Stempel HE, Martin ET, Kuypers J, Englund JA, Zerr DM. Multiple viral respiratory pathogens in children with bronchiolitis. Acta Paediatr 2009; 98: 123–126.
- 117Midulla F, Scagnolari C, Bonci E, Pierangeli A, Antonelli G, De Angelis D, Berardi R, Moretti C. Respiratory syncytial virus, human bocavirus and rhinovirus bronchiolitis in infants. Arch Dis Child 2010; 95: 35–41.
- 118Miron D, Srugo I, Kra-Oz Z, Keness Y, Wolf D, Amirav I, Kassis I. Sole pathogen in acute bronchiolitis: is there a role for other organisms apart from respiratory syncytial virus? Pediatr Infect Dis J 2010; 29: e7–e10.
- 119Flores G, Horwitz RI. Efficacy of beta2-agonists in bronchiolitis: a reappraisal and meta-analysis. Pediatrics 1997; 100: 233–239.
- 120Gadomski AM, Bhasale AL. Bronchodilators for bronchiolitis. Cochrane Database Syst Rev 2006; 3: CD001266.
- 121Auais A, Wedde-Beer K, Piedimonte G. Anti-inflammatory effect of albuterol enantiomers during respiratory syncytial virus infection in rats. Pediatr Pulmonol 2005; 40: 228–234.
- 122Hartling L, Wiebe N, Russell K, Patel H, Klassen TP. Epinephrine for bronchiolitis. Cochrane Database Syst Rev 2004; (1): CD003123.
10.1002/14651858.CD003123.pub2 Google Scholar
- 123Wang EE, Milner R, Allen U, Maj H. Bronchodilators for treatment of mild bronchiolitis: a factorial randomised trial. Arch Dis Child 1992; 67: 289–293.
- 124Schuh S, Johnson D, Canny G, Reisman J, Shields M, Kovesi T, Kerem E, Bentur L, Levison H, Jaffe D. Efficacy of adding nebulized ipratropium bromide to nebulized albuterol therapy in acute bronchiolitis. Pediatrics 1992; 90: 920–923.
- 125Chowdhury D, al Howasi M, Khalil M, al-Frayh AS, Chowdhury S, Ramia S. The role of bronchodilators in the management of bronchiolitis: a clinical trial. Ann Trop Paediatr 1995; 15: 77–84.
- 126Karadag B, Ceran O, Guven G, Dursun E, Ipek IO, Karakoc F, Ersu RH, Bozaykut A, Inan S, Dagli E. Efficacy of salbutamol and ipratropium bromide in the management of acute bronchiolitis—a clinical trial. Respiration 2008; 76: 283–287.
- 127Patel H, Platt R, Lozano JM, Wang EE. Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database Syst Rev 2004; (3): CD004878.
- 128Teeratakulpisarn J, Limwattananon C, Tanupattarachai S, Limwattananon S, Teeratakulpisarn S, Kosalaraksa P. Efficacy of dexamethasone injection for acute bronchiolitis in hospitalized children: a randomized, double-blind, placebo-controlled trial. Pediatr Pulmonol 2007; 42: 433–439.
- 129Corneli HM, Zorc JJ, Majahan P, Shaw KN, Holubkov R, Reeves SD, Ruddy RM, Malik B, Nelson KA, Bregstein JS, Brown KM, Denenberg MN, Lillis KA, Cimpello LB, Tsung JW, Borgialli DA, Baskin MN, Teshome G, Goldstein MA, Monroe D, Dean JM, Kuppermann N. A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis. N Engl J Med 2007; 357: 331–339.
- 130Chao LC, Lin YZ, Wu WF, Huang FY. Efficacy of nebulized budesonide in hospitalized infants and children younger than 24 months with bronchiolitis. Acta Paediatr Taiwan 2003; 44: 332–335.
- 131de Blic J. Use of corticoids in acute bronchiolitis in infants. Arch Pediatr 2001; 8: 49S–54S.
- 132Blom D, Ermers M, Bont L, van Aalderen WM, van Woensel JB. Inhaled corticosteroids during acute bronchiolitis in the prevention of post-bronchiolitic wheezing. Cochrane Database Syst Rev 2007; (1): CD004881.
- 133Ermers MJ, Rovers MM, van Woensel JB, Kimpen JL, Bont LJ. The effect of high dose inhaled corticosteroids on wheeze in infants after respiratory syncytial virus infection: randomised double blind placebo controlled trial. BMJ 2009; 338: b897.
- 134Bentur L, Shoseyov D, Feigenbaum D, Gorichovsky Y, Bibi H. Dexamethasone inhalations in RSV bronchiolitis: a double-blind, placebo-controlled study. Acta Paediatr 2005; 94: 866–871.
- 135Plint AC, Johnson DW, Patel H, Wiebe N, Correll R, Brant R, Mitton C, Gouin S, Bhatt M, Joubert G, Black KJ, Turner T, Whitehouse S, Klassen TP. Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med 2009; 360: 2079–2089.
- 136Hall CB, McBride JT, Walsh EE, Bell DM, Gala CL, Hildreth S, Ten Eyck LG, Hall WJ. Aerosolized ribavirin treatment of infants with respiratory syncytial viral infection. A randomized double-blind study. N Engl J Med 1983; 308: 1443–1447.
- 137Rodriguez WJ, Kim HW, Brandt CD, Fink RJ, Getson PR, Arrobio J, Murphy TM, McCarthy V, Parrott RH. Aerosolized ribavirin in the treatment of patients with respiratory syncytial virus disease. Pediatr Infect Dis J 1987; 6: 159–163.
- 138Smith DW, Frankel LR, Mathers LH, Tang AT, Ariagno RL, Prober CG. A controlled trial of aerosolized ribavirin in infants receiving mechanical ventilation for severe respiratory syncytial virus infection. N Engl J Med 1991; 325: 24–29.
- 139Guerguerian AM, Gauthier M, Lebel MH, Farrell CA, Lacroix J. Ribavirin in ventilated respiratory syncytial virus bronchiolitis. A randomized, placebo-controlled trial. Am J Respir Crit Care Med 1999; 160: 829–834.
- 140Meert KL, Sarnaik AP, Gelmini MJ, Lieh-Lai MW. Aerosolized ribavirin in mechanically ventilated children with respiratory syncytial virus lower respiratory tract disease: a prospective, double-blind, randomized trial. Crit Care Med 1994; 22: 566–572.
- 141Taber LH, Knight V, Gilbert BE, McClung HW, Wilson SZ, Norton HJ, Thurson JM, Gordon WH, Atmar RL, Schlaudt WR. Ribavirin aerosol treatment of bronchiolitis associated with respiratory syncytial virus infection in infants. Pediatrics 1983; 72: 613–618.
- 142Everard ML, Swarbrick A, Rigby AS, Milner AD. The effect of ribavirin to treat previously healthy infants admitted with acute bronchiolitis on acute and chronic respiratory morbidity. Respir Med 2001; 95: 275–280.
- 143Ventre K, Randolph A. Ribavirin for respiratory syncytial virus infection of the lower respiratory tract in infants and young children. Cochrane Database Syst Rev 2007; (1): CD000181.
- 144Kabir ML, Haq N, Hoque M, Ahmed F, Amin R, Hossain A, Khatoon S, Akhter S, Shilpi T, Haq R, Anisuzzaman S, Khan MH, Ahamed S, Khashru A. Evaluation of hospitalized infants and young children with bronchiolitis—a multi centre study. Mymensingh Med J 2003; 12: 128–133.
- 145Vogel AM, Lennon DR, Harding JE, Pinnock RE, Graham DA, Grimwood K, Pattemore PK. Variations in bronchiolitis management between five New Zealand hospitals: can we do better? J Paediatr Child Health 2003; 39: 40–45.
- 146Putto A, Ruuskanen O, Meurman O. Fever in respiratory virus infections. Am J Dis Child 1986; 140: 1159–1163.
- 147Greenes DS, Harper MB. Low risk of bacteremia in febrile children with recognizable viral syndromes. Pediatr Infect Dis J 1999; 18: 258–261.
- 148Titus MO, Wright SW. Prevalence of serious bacterial infections in febrile infants with respiratory syncytial virus infection. Pediatrics 2003; 112: 282–284.
- 149Kneyber MC, Blusse van Oud-Alblas H, van Vliet M, Uiterwaal CS, Kimpen JL, van Vught AJ. Concurrent bacterial infection and prolonged mechanical ventilation in infants with respiratory syncytial virus lower respiratory tract disease. Intensive Care Med 2005; 31: 680–685.
- 150Thorburn K, Harigopal S, Reddy V, Taylor N, van Saene HK. High incidence of pulmonary bacterial co-infection in children with severe respiratory syncytial virus (RSV) bronchiolitis. Thorax 2006; 61: 611–615.
- 151Purcell K, Fergie J. Driscoll Children's Hospital respiratory syncytial virus database: risk factors, treatment and hospital course in 3308 infants and young children, 1991 to 2002. Pediatr Infect Dis J 2004; 23: 418–423.
- 152Andrade MA, Hoberman A, Glustein J, Paradise JL, Wald ER. Acute otitis media in children with bronchiolitis. Pediatrics 1998; 101: 617–619.
- 153Purcell K, Fergie J. Concurrent serious bacterial infections in 912 infants and children hospitalized for treatment of respiratory syncytial virus lower respiratory tract infection. Pediatr Infect Dis J 2004; 23: 267–269.
- 154Shazberg G, Revel-Vilk S, Shoseyov D, Ben-Ami A, Klar A, Hurvitz H. The clinical course of bronchiolitis associated with acute otitis media. Arch Dis Child 2000; 83: 317–319.
- 155 Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics 2004; 113: 1451–1465.
- 156Field CM, Connolly JH, Murtagh G, Slattery CM, Turkington EE. Antibiotic treatment of epidemic bronchiolitis—a double-blind trial. Br Med J 1966; 1: 83–85.
- 157Friis B, Andersen P, Brenoe E, Hornsleth A, Jensen A, Knudsen FU, Krasilnikoff PA, Mordhorst CH, Nielsen S, Uldall P. Antibiotic treatment of pneumonia and bronchiolitis. A prospective randomised study. Arch Dis Child 1984; 59: 1038–1045.
- 158Boogaard R, Hulsmann AR, van Veen L, Vaessen-Verberne AA, Yap YN, Sprij AJ, Brinkhorst G, Sibbles B, Hendriks T, Feith SW, Lincke CR, Brandsma AE, Brand PL, Hop WC, de Hoog M, Merkus PJ. Recombinant human deoxyribonuclease in infants with respiratory syncytial virus bronchiolitis. Chest 2007; 131: 788–795.
- 159Nasr SZ, Strouse PJ, Soskolne E, Maxvold NJ, Garver KA, Rubin BK, Moler FW. Efficacy of recombinant human deoxyribonuclease I in the hospital management of respiratory syncytial virus bronchiolitis. Chest 2001; 120: 203–208.
- 160Daviskas E, Anderson SD, Gonda I, Eberl S, Meikle S, Seale JP, Bautovich G. Inhalation of hypertonic saline aerosol enhances mucociliary clearance in asthmatic and healthy subjects. Eur Respir J 1996; 9: 725–732.
- 161Wark P, McDonald VM. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev 2009; (2): CD001506.
- 162Zhang L, Mendoza-Sassi RA, Wainwright C, Klassen TP. Nebulized hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev 2008; (4): CD006458.
- 163LeVine AM, Bruno MD, Huelsman KM, Ross GF, Whitsett JA, Korfhagen TR. Surfactant protein A-deficient mice are susceptible to group B streptococcal infection. J Immunol 1997; 158: 4336–4340.
- 164Wright JR. Immunomodulatory functions of surfactant. Physiol Rev 1997; 77: 931–962.
- 165Wright JR. Pulmonary surfactant: a front line of lung host defense. J Clin Invest 2003; 111: 1453–1455.
- 166Wu H, Kuzmenko A, Wan S, Schaffer L, Weiss A, Fisher JH, Kim KS, McCormack FX. Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability. J Clin Invest 2003; 111: 1589–1602.
- 167LeVine AM, Elliott J, Whitsett JA, Srikiatkhachorn A, Crouch E, DeSilva N, Korfhagen T. Surfactant protein-d enhances phagocytosis and pulmonary clearance of respiratory syncytial virus. Am J Respir Cell Mol Biol 2004; 31: 193–199.
- 168Dargaville PA, South M, McDougall PN. Surfactant abnormalities in infants with severe viral bronchiolitis. Arch Dis Child 1996; 75: 133–136.
10.1136/adc.75.2.133 Google Scholar
- 169Ventre K, Haroon M, Davison C. Surfactant therapy for bronchiolitis in critically ill infants. Cochrane Database Syst Rev 2006; (3): CD005150.
- 170Barach AL, Eckman M. The effects of inhalation of helium mixed with oxygen on the mechanics of respiration. J Clin Invest 1936; 15: 47–61.
- 171Hollman G, Shen G, Zeng L, Yngsdal-Krenz R, Perloff W, Zimmerman J, Strauss R. Helium–oxygen improves Clinical Asthma Scores in children with acute bronchiolitis. Crit Care Med 1998; 26: 1731–1736.
- 172Cambonie G, Milesi C, Fournier-Favre S, Counil F, Jaber S, Picaud JC, Matecki S. Clinical effects of heliox administration for acute bronchiolitis in young infants. Chest 2006; 129: 676–682.
- 173Martinon-Torres F, Rodriguez-Nunez A, Martinon-Sanchez JM. Heliox therapy in infants with acute bronchiolitis. Pediatrics 2002; 109: 68–73.
- 174Liet JM, Millotte B, Tucci M, Laflammme S, Hutchison J, Creery D, Ducruet T, Lacroix J. Noninvasive therapy with helium–oxygen for severe bronchiolitis. J Pediatr 2005; 147: 812–817.
- 175Gross MF, Spear RM, Peterson BM. Helium–oxygen mixture does not improve gas exchange in mechanically ventilated children with bronchiolitis. Crit Care 2000; 4: 188–192.
- 176Bisgaard B. Montelukast in RSV bronchiolitis. Am J Respir Crit Care Med 2004; 169: 542–543.
- 177Bisgaard H, Flores-Nunez A, Goh A, Azimi P, Halkas A, Malice M-P, Marchal J-L, Dass SB, Reiss TF, Knorr BA. Study of montelukast for the treatment of respiratory symptoms of post-respiratory syncytial virus bronchiolitis in children. Am J Respir Crit Care Med 2008; 178: 854–860.
- 178Koetz A, Nilsson P, Linden M, van der Hoek L, Ripa T. Detection of human coronavirus NL63, human metapneumovirus and respiratory syncytial virus in children with respiratory tract infections in south-west Sweden. Clin Microbiol Infect 2006; 12: 1089–1096.
- 179Hall CB, Douglas RG, Jr. Nosocomial respiratory syncytial viral infections. Should gowns and masks be used? Am J Dis Child 1981; 135: 512–515.
- 180Agah R, Cherry JD, Garakian AJ, Chapin M. Respiratory syncytial virus (RSV) infection rate in personnel caring for children with RSV infections. Routine isolation procedure vs routine procedure supplemented by use of masks and goggles. Am J Dis Child 1987; 141: 695–697.
- 181Thorburn K, Kerr S, Taylor N, van Saene HK. RSV outbreak in a paediatric intensive care unit. J Hosp Infect 2004; 57: 194–201.
- 182Gala CL, Hall CB, Schnabel KC, Pincus PH, Blossom P, Hildreth SW, Betts RF, Douglas RG, Jr. The use of eye–nose goggles to control nosocomial respiratory syncytial virus infection. JAMA 1986; 256: 2706–2708.
- 183Leclair JM, Freeman J, Sullivan BF, Crowley CM, Goldmann DA. Prevention of nosocomial respiratory syncytial virus infections through compliance with glove and gown isolation precautions. N Engl J Med 1987; 317: 329–334.
- 184Krasinski K, LaCouture R, Holzman RS, Waithe E, Bonk S, Hanna B. Screening for respiratory syncytial virus and assignment to a cohort at admission to reduce nosocomial transmission. J Pediatr 1990; 116: 894–898.
- 185 Committee on Infectious Diseases and Committee on Fetus and Newborn. Revised indications for the use of palivizumab and respiratory syncytial virus immune globulin intravenous for the prevention of respiratory syncytial virus infections. Pediatrics 2003; 112: 1442–1446.
- 186Groothuis JR, Simoes EA, Levin MJ, Hall CB, Long CE, Rodriguez WJ, Arrobio J, Meissner HC, Fulton DR, Welliver RC. Prophylactic administration of respiratory syncytial virus immune globulin to high-risk infants and young children. The Respiratory Syncytial Virus Immune Globulin Study Group. N Engl J Med 1993; 329: 1524–1530.
- 187Simoes EA, Sondheimer HM, Top FH, Jr., Meissner HC, Welliver RC, Kramer AA, Groothuis JR. Respiratory syncytial virus immune globulin for prophylaxis against respiratory syncytial virus disease in infants and children with congenital heart disease. The Cardiac Study Group. J Pediatr 1998; 133: 492–499.
- 188O'Shea TM, Sevick MA, Givner LB. Costs and benefits of respiratory syncytial virus immunoglobulin to prevent hospitalization for lower respiratory tract illness in very low birth weight infants. Pediatr Infect Dis J 1998; 17: 587–593.
- 189Johnson S, Oliver C, Prince GA, Hemming VG, Pfarr DS, Wang SC, Dormitzer M, O'Grady J, Koenig S, Tamura JK, Woods R, Bansal G, Couchenour D, Tsao E, Hall WC, Young JF. Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus. J Infect Dis 1997; 176: 1215–1224.
- 190Sekul EA, Cupler EJ, Dalakas MC. Aseptic meningitis associated with high-dose intravenous immunoglobulin therapy: frequency and risk factors. Ann Intern Med 1994; 121: 259–262.
- 191Subramanian KN, Weisman LE, Rhodes T, Ariagno R, Sanchez PJ, Steichen J, Givner LB, Jennings TL, Top FH, Jr., Carlin D, Connor E. Safety, tolerance and pharmacokinetics of a humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. MEDI-493 Study Group. Pediatr Infect Dis J 1998; 17: 110–115.
- 192Cardenas S, Auais A, Piedimonte G. Palivizumab in the prophylaxis of respiratory syncytial virus infection. Expert Rev Anti Infect Ther 2005; 3: 719–726.
- 193Piedimonte G, Rodriguez MM, King KA, McLean S, Jiang X. Respiratory syncytial virus upregulates expression of the substance P receptor in rat lungs. Am J Physiol Lung Cell Mol Physiol 1999; 277: L831–L840.
- 194King KA, Hu C, Rodriguez MM, Romaguera R, Jiang X, Piedimonte G. Exaggerated neurogenic inflammation and substance P receptor upregulation in RSV-infected weanling rats. Am J Respir Cell Mol Biol 2001; 24: 101–107.
- 195Piedimonte G, King KA, Holmgren NL, Bertrand PJ, Rodriguez MM, Hirsch RL. A humanized monoclonal antibody against respiratory syncytial virus (palivizumab) inhibits RSV-induced neurogenic-mediated inflammation in rat airways. Pediatr Res 2000; 47: 351–356.
- 196Piedimonte G. Neural mechanisms of respiratory syncytial virus-induced inflammation and prevention of respiratory syncytial virus sequelae. Am J Respir Crit Care Med 2001; 163: S18–S21.
- 197 IMPACT-RSV. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. The IMpact-RSV Study Group. Pediatrics 1998; 102: 531–537.
- 198Feltes TF, Cabalka AK, Meissner HC, Piazza FM, Carlin DA, Top FH, Jr., Connor EM, Sondheimer HM. Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr 2003; 143: 532–540.
- 199 American Academy of Pediatrics. Respiratory syncytial virus. In: LK Pickering, CJ Baker, DW Kimberlin, SS Long editors. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th edition. Elk Grove Village, IL: American Academy of Pediatrics; 2009. pp. 560–569.
- 200 Synagis Product Information. MedImmune, Inc, 2009. Available at: http://www.synagis.com.
- 201Groothuis JR. Safety of palivizumab in preterm infants 29 to 32 weeks' gestational age without chronic lung disease to prevent serious respiratory syncytial virus infection. Eur J Clin Microbiol Infect Dis 2003; 22: 414–417.
- 202Lacaze-Masmonteil T, Seidenberg J, Mitchell I, Cossey V, Cihar M, Csader M, Baarsma R, Valido M, Pollack PF, Groothuis JR. Evaluation of the safety of palivizumab in the second season of exposure in young children at risk for severe respiratory syncytial virus infection. Drug Saf 2003; 26: 283–291.
- 203Simoes EA, Groothuis JR, Carbonell-Estrany X, Rieger CH, Mitchell I, Fredrick LM, Kimpen JL. Palivizumab prophylaxis, respiratory syncytial virus, and subsequent recurrent wheezing. J Pediatr 2007; 151: 34–42.
- 204Wu H, Pfarr DS, Tang Y, An LL, Patel NK, Watkins JD, Huse WD, Kiener PA, Young JF. Ultra-potent antibodies against respiratory syncytial virus: effects of binding kinetics and binding valence on viral neutralization. J Mol Biol 2005; 350: 126–144.
- 205Wu H, Pfarr DS, Johnson S, Brewah YA, Woods RM, Patel NK, White WI, Young JF, Kiener PA. Development of motavizumab, an ultra-potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract. J Mol Biol 2007; 368: 652–665.
- 206Abarca K, Jung E, Fernandez P, Zhao L, Harris B, Connor EM, Losonsky GA. Safety, tolerability, pharmacokinetics, and immunogenicity of motavizumab, a humanized, enhanced-potency monoclonal antibody for the prevention of respiratory syncytial virus infection in at-risk children. Pediatr Infect Dis J 2009; 28: 267–272.
- 207Losonsky GA, Fernandez P, Abarca K, Jung E, Gerdes J, Hultquist M, Connor E. Phase I/II trial in high risk infants of Medi-524, an enhanced potency respiratory syncytial virus specific monoclonal antibody. Pediatric Academic Societies Annual Meeting 2005; Abstract 715.
- 208Simoes E, Carbonell Estrany X, Losonsky GA, Hultquist M, Harris B, Connor E. Phase III trial of motavizumab, an enhanced potency respiratory syncytial virus (RSV)-specific monoclonal antibody for the prevention of serious RSV disease in high risk infants. Pediatric Academic Societies Annual Meeting 2007; Abstract 8220.9.
- 209Hall CB, Hall WJ, Gala CL, MaGill FB, Leddy JP. Long-term prospective study in children after respiratory syncytial virus infection. J Pediatr 1984; 105: 358–364.
- 210Henry RL, Hodges IG, Milner AD, Stokes GM. Respiratory problems 2 years after acute bronchiolitis in infancy. Arch Dis Child 1983; 58: 713–716.
- 211Webb MS, Henry RL, Milner AD, Stokes GM, Swarbrick AS. Continuing respiratory problems three and a half years after acute viral bronchiolitis. Arch Dis Child 1985; 60: 1064–1067.
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