Respiratory Syncytial Virus is the Most Common Causative Agent of Viral
Bronchiolitis in Young Children: An Updated Review

Kam   L.   Hon; Alexander   K. C.   Leung; Alex   H.C.   Wong; Amrita      Dudi; Karen   K.Y.   Leung
Abstract

Background: Viral bronchiolitis is a common condition and a leading cause of hospitalization in young children.
Objective: This article provides readers with an update on the evaluation, diagnosis, and treatment of viral bronchiolitis, primarily due to RSV.
Methods: A PubMed search was conducted in December 2021 in Clinical Queries using the key terms "acute bronchiolitis" OR “respiratory syncytial virus infection”. The search included clinical trials, randomized controlled trials, case control studies, cohort studies, meta-analyses, observational studies, clinical guidelines, case reports, case series, and reviews. The search was restricted to children and English literature. The information retrieved from the above search was used in the compilation of this article.
Results: Respiratory syncytial virus (RSV) is the most common viral bronchiolitis in young children. Other viruses such as human rhinovirus and coronavirus could be etiological agents. Diagnosis is based on clinical manifestation. Viral testing is useful only for cohort and quarantine purposes. Cochrane evidence-based reviews have been performed on most treatment modalities for RSV and viral bronchiolitis. Treatment for viral bronchiolitis is mainly symptomatic support. Beta-agonists are frequently used despite the lack of evidence that they reduce hospital admissions or length of stay. Nebulized racemic epinephrine, hypertonic saline and corticosteroids are generally not effective. Passive immunoprophylaxis with a monoclonal antibody against RSV, when given intramuscularly and monthly during winter, is effective in preventing severe RSV bronchiolitis in high-risk children who are born prematurely and in children under 2 years with chronic lung disease or hemodynamically significant congenital heart disease. Vaccines for RSV bronchiolitis are being developed. Children with viral bronchiolitis in early life are at increased risk of developing asthma later in childhood.
Conclusion: Viral bronchiolitis is common. No current pharmacologic treatment or novel therapy has been proven to improve outcomes compared to supportive treatment. Viral bronchiolitis in early life predisposes asthma development later in childhood.
Keywords: Bronchiolitis, viral, respiratory syncytial virus, RSV, wheezing, beta-agonists, nebulized racemic epinephrine, hypertonic saline, corticosteroids.
Graphical Abstract

[1]
Ngai P, Bye MR. Bronchiolitis. Pediatr Ann  2002; 31(2): 90-7.
 [http://dx.doi.org/10.3928/0090-4481-20020201-06] [PMID: 11862728]

[2]
Leung AKC, Kellner JD, Davies HD. Respiratory syncytial virus bronchiolitis. J Natl Med Assoc  2005; 97(12): 1708-13.
 [PMID: 16396064]

[3]
Alharbi AS, Alqwaiee M, Al-Hindi MY, et al. Bronchiolitis in children: The Saudi initiative of bronchiolitis diagnosis, management, and prevention (SIBRO). Ann Thorac Med  2018; 13(3): 127-43.
 [http://dx.doi.org/10.4103/atm.ATM_60_18] [PMID: 30123331]

[4]
Fitzgerald DA, Kilham HA. Bronchiolitis: Assessment and evidence-based management. Med J Aust  2004; 180(8): 399-404.
 [http://dx.doi.org/10.5694/j.1326-5377.2004.tb05993.x] [PMID: 15089730]

[5]
Panitch HB. Bronchiolitis in infants. Curr Opin Pediatr  2001; 13(3): 256-60.
 [http://dx.doi.org/10.1097/00008480-200106000-00008] [PMID: 11389361]

[6]
Panitch HB, Callahan CW Jr, Schidlow DV. Bronchiolitis in children. Clin Chest Med  1993; 14(4): 715-31.
 [http://dx.doi.org/10.1016/S0272-5231(21)00934-5] [PMID: 8313675]

[7]
Perlstein PH, Kotagal UR, Bolling C, et al. Evaluation of an evidence-based guideline for bronchiolitis. Pediatrics  1999; 104(6): 1334-41.
 [http://dx.doi.org/10.1542/peds.104.6.1334] [PMID: 10585985]

[8]
Chávez-Bueno S, Mejías A, Jafri HS, Ramilo O. Respiratory syncytial virus: Old challenges and new approaches. Pediatr Ann  2005; 34(1): 62-8.
 [http://dx.doi.org/10.3928/0090-4481-20050101-14] [PMID: 15693217]

[9]
Holman RC, Shay DK, Curns AT, Lingappa JR, Anderson LJ. Risk factors for bronchiolitis-associated deaths among infants in the United States. Pediatr Infect Dis J  2003; 22(6): 483-90.
 [http://dx.doi.org/10.1097/01.inf.0000069765.43405.3b] [PMID: 12799502]

[10]
Davies HD, Matlow A, Petric M, Glazier R, Wang EE. Prospective comparative study of viral, bacterial and atypical organisms identified in pneumonia and bronchiolitis in hospitalized Canadian infants. Pediatr Infect Dis J  1996; 15(4): 371-5.
 [http://dx.doi.org/10.1097/00006454-199604000-00017] [PMID: 8866810]

[11]
Straliotto SM, Siqueira MM, Machado V, Maia TMR. Respiratory viruses in the pediatric intensive care unit: Prevalence and clinical aspects. Mem Inst Oswaldo Cruz  2004; 99(8): 883-7.
 [http://dx.doi.org/10.1590/s0074-02762004000800017] [PMID: 15761607]

[12]
Hon KL, Leung TF, Cheng WY, et al. Respiratory syncytial virus morbidity, premorbid factors, seasonality, and implications for prophylaxis. J Crit Care  2012; 27(5): 464-8.
 [http://dx.doi.org/10.1016/j.jcrc.2011.12.001] [PMID: 22227087]

[13]
Tong AS, Hon KL, Tsang YC, et al. Paramyxovirus infection: Mortality and morbidity in a pediatric intensive care unit. J Trop Pediatr  2016; 62(5): 352-60.
 [http://dx.doi.org/10.1093/tropej/fmw016] [PMID: 27037248]

[14]
Willson DF, Landrigan CP, Horn SD, Smout RJ. Complications in infants hospitalized for bronchiolitis or respiratory syncytial virus pneumonia. J Pediatr  2003; 143(5): S142-9.
 [http://dx.doi.org/10.1067/S0022-3476(03)00514-6] [PMID: 14615713]

[15]
Jhawar S. Severe bronchiolitis in children. Clin Rev Allergy Immunol  2003; 25(3): 249-57.
 [http://dx.doi.org/10.1385/CRIAI:25:3:249] [PMID: 14716070]

[16]
Maggon K, Barik S. New drugs and treatment for respiratory syncytial virus. Rev Med Virol  2004; 14(3): 149-68.
 [http://dx.doi.org/10.1002/rmv.423] [PMID: 15124232]

[17]
Smyth RL, Mobbs KJ, O’Hea U, Ashby D, Hart CA. Respiratory syncytial virus bronchiolitis: Disease severity, interleukin-8, and virus genotype. Pediatr Pulmonol  2002; 33(5): 339-46.
 [http://dx.doi.org/10.1002/ppul.10080] [PMID: 11948978]

[18]
Sharland M, Bedford-Russell A. Preventing respiratory syncitial virus bronchiolitis. BMJ  2001; 322(7278): 62-3.
 [http://dx.doi.org/10.1136/bmj.322.7278.62] [PMID: 11154604]

[19]
Ralston SL, Lieberthal AS, Meissner HC, et al. Clinical practice guideline: The diagnosis, management, and prevention of bronchiolitis. Pediatrics  2014; 134(5): e1474-502.
 [http://dx.doi.org/10.1542/peds.2014-2742] [PMID: 25349312]

[20]
Bordley WC, Viswanathan M, King VJ, et al. Diagnosis and testing in bronchiolitis: A systematic review. Arch Pediatr Adolesc Med  2004; 158(2): 119-26.
 [http://dx.doi.org/10.1001/archpedi.158.2.119] [PMID: 14757603]

[21]
Kirolos A, Manti S, Blacow R, et al. A systematic review of clinical practice guidelines for the diagnosis and management of bronchiolitis. J Infect Dis  2020; 222 (Suppl. 7): S672-9.
 [http://dx.doi.org/10.1093/infdis/jiz240] [PMID: 31541233]

[22]
Carbonell-Estrany X, Figueras-Aloy J, Law BJ. Identifying risk factors for severe respiratory syncytial virus among infants born after 33 through 35 completed weeks of gestation: Different methodologies yield consistent findings. Pediatr Infect Dis J  2004; 23(11): S193-201.
 [http://dx.doi.org/10.1097/01.inf.0000144664.31888.53] [PMID: 15577573]

[23]
Lozano JM. Bronchiolitis. Clin Evid  2005; (14): 285-97.
 [PMID: 16620408]

[24]
Schuh S. Update on management of bronchiolitis. Curr Opin Pediatr  2011; 23(1): 110-4.
 [http://dx.doi.org/10.1097/MOP.0b013e3283425442] [PMID: 21157348]

[25]
Meissner HC. Selected populations at increased risk from respiratory syncytial virus infection. Pediatr Infect Dis J  2003; 22(2): S40-4.
 [http://dx.doi.org/10.1097/00006454-200302001-00006] [PMID: 12671451]

[26]
Welliver RC, Willison DF, Scott CA. Review of epidemiology and clinical risk factors for severe respiratory syncytial virus (RSV) infection. J Pediatr  2003; 143(5) (Suppl.): S112-7.
 [http://dx.doi.org/10.1067/S0022-3476(03)00508-0] [PMID: 14615709]

[27]
Leung AKC, Sauve RS. Breast is best for babies. J Natl Med Assoc  2005; 97(7): 1010-9.
 [PMID: 16080672]

[28]
Collins PL, Fearns R, Graham BS. Respiratory syncytial virus: Virology, reverse genetics, and pathogenesis of disease. Curr Top Microbiol Immunol  2013; 372: 3-38.
 [http://dx.doi.org/10.1007/978-3-642-38919-1_1] [PMID: 24362682]

[29]
Smyth RL, Openshaw PJ. Bronchiolitis. Lancet  2006; 368(9532): 312-22.
 [http://dx.doi.org/10.1016/S0140-6736(06)69077-6] [PMID: 16860701]

[30]
Bourke T, Shields M. Bronchiolitis. BMJ Clin Evid  2011; 2011: 0308.

[31]
Milani GP, Bollati V, Ruggiero L, et al. Bronchiolitis and SARS-CoV-2. Arch Dis Child  2021; 106(10): 999-1001.
 [http://dx.doi.org/10.1136/archdischild-2020-321108] [PMID: 33707224]

[32]
Falahi S, Sayyadi H, Abdoli A, Kenarkoohi A, Mohammadi S. The prevalence of human bocavirus in <2-year-old children with acute bronchiolitis. New Microbes New Infect  2020; 37: 100736.
 [http://dx.doi.org/10.1016/j.nmni.2020.100736] [PMID: 32983545]

[33]
Erickson EN, Bhakta RT, Mendez MD. Pediatric bronchiolitis. Treasure Island, (FL): StatPearls Publishing 2022.
 [PMID: 30137791]

[34]
Schroeder AR, Mansbach JM. Recent evidence on the management of bronchiolitis. Curr Opin Pediatr  2014; 26(3): 328-33.
 [http://dx.doi.org/10.1097/MOP.0000000000000090] [PMID: 24739493]

[35]
Mansbach JM, Hasegawa K, Piedra PA, Sullivan AF, Camargo CA Jr. Severe coronavirus bronchiolitis in the pre-covid-19 era. Pediatrics  2020; 146(3): e20201267.
 [http://dx.doi.org/10.1542/peds.2020-1267] [PMID: 32522783]

[36]
Andina-Martinez D, Alonso-Cadenas JA, Cobos-Carrascosa E, et al. SARS-CoV-2 acute bronchiolitis in hospitalized children: Neither frequent nor more severe. Pediatr Pulmonol  2022; 57(1): 57-65.
 [http://dx.doi.org/10.1002/ppul.25731] [PMID: 34664782]

[37]
Barrezueta LB, Zamorano MG, Casillas PL, Raposo MB, Fernández IS, Vázquez AP. Influence of the covid-19 pandemic on the epidemiology of acute bronchiolitis. Enferm Infecc Microbiol Clin 2021. [Epub ahead of print].
 [http://dx.doi.org/10.1016/j.eimc.2021.11.014] [PMID: 34955579]

[38]
McNamara PS, Flanagan BF, Baldwin LM, Newland P, Hart CA, Smyth RL. Interleukin 9 production in the lungs of infants with severe respiratory syncytial virus bronchiolitis. Lancet  2004; 363(9414): 1031-7.
 [http://dx.doi.org/10.1016/S0140-6736(04)15838-8] [PMID: 15051283]

[39]
McNamara PS, Flanagan BF, Hart CA, Smyth RL. Production of chemokines in the lungs of infants with severe respiratory syncytial virus bronchiolitis. J Infect Dis  2005; 191(8): 1225-32.
 [http://dx.doi.org/10.1086/428855] [PMID: 15776367]

[40]
Cooper AC, Banasiak NC, Allen PJ. Management and prevention strategies for respiratory syncytial virus (RSV) bronchiolitis in infants and young children: A review of evidence-based practice interventions. Pediatr Nurs  2003; 29(6): 452-6.
 [PMID: 14743842]

[41]
Friedman JN, Rieder MJ, Walton JM, et al. Bronchiolitis: Recommendations for diagnosis, monitoring and management of children one to 24 months of age. Paediatr Child Health  2014; 19(9): 485-98.
 [http://dx.doi.org/10.1093/pch/19.9.485] [PMID: 25414585]

[42]
Hall CB, Powell KR, Schnabel KC, Gala CL, Pincus PH. Risk of secondary bacterial infection in infants hospitalized with respiratory syncytial viral infection. J Pediatr  1988; 113(2): 266-71.
 [PMID: 3397789]

[43]
Ralston S, Hill V, Waters A. Occult serious bacterial infection in infants younger than 60 to 90 days with bronchiolitis: A systematic review. Arch Pediatr Adolesc Med  2011; 165(10): 951-6.
 [http://dx.doi.org/10.1001/archpediatrics.2011.155] [PMID: 21969396]

[44]
McDaniel CE, Ralston S, Lucas B, Schroeder AR. Association of diagnostic criteria with urinary tract infection prevalence in bronchiolitis: A systematic review and meta-analysis. JAMA Pediatr  2019; 173(3): 269-77.
 [http://dx.doi.org/10.1001/jamapediatrics.2018.5091] [PMID: 30688987]

[45]
Laham JL, Breheny PJ, Gardner BM, Bada H. Procalcitonin to predict bacterial coinfection in infants with acute bronchiolitis: A preliminary analysis. Pediatr Emerg Care  2014; 30(1): 11-5.
 [http://dx.doi.org/10.1097/PEC.0000000000000026] [PMID: 24365727]

[46]
Duttweiler L, Nadal D, Frey B. Pulmonary and systemic bacterial co-infections in severe RSV bronchiolitis. Arch Dis Child  2004; 89(12): 1155-7.
 [http://dx.doi.org/10.1136/adc.2004.049551] [PMID: 15557055]

[47]
Al-Balkhi A, Klonin H, Marinaki K, et al. Review of treatment of bronchiolitis related apnoea in two centres. Arch Dis Child  2005; 90(3): 288-91.
 [http://dx.doi.org/10.1136/adc.2003.039404] [PMID: 15723920]

[48]
Sreeram N, Watson JG, Hunter S. Cardiovascular effects of acute bronchiolitis. Acta Paediatr Scand  1991; 80(1): 133-6.
 [http://dx.doi.org/10.1111/j.1651-2227.1991.tb11747.x] [PMID: 1851367]

[49]
Panitch HB. Respiratory syncytial virus bronchiolitis: Supportive care and therapies designed to overcome airway obstruction. Pediatr Infect Dis J  2003; 22(2) (Suppl.): S83-7.
 [http://dx.doi.org/10.1097/00006454-200302001-00012] [PMID: 12671457]

[50]
Khoshoo V, Edell D. Previously healthy infants may have increased risk of aspiration during respiratory syncytial viral bronchiolitis. Pediatrics  1999; 104(6): 1389-90.
 [http://dx.doi.org/10.1542/peds.104.6.1389] [PMID: 10585993]

[51]
Pinnington LL, Smith CM, Ellis RE, Morton RE. Feeding efficiency and respiratory integration in infants with acute viral bronchiolitis. J Pediatr  2000; 137(4): 523-6.
 [http://dx.doi.org/10.1067/mpd.2000.108396] [PMID: 11035832]

[52]
Friedman JN, Davis T, Somaskanthan A, Ma A. Avoid doing chest x rays in infants with typical bronchiolitis. BMJ  2021; 375: e064132.
 [http://dx.doi.org/10.1136/bmj-2021-064132] [PMID: 34686495]

[53]
Zorc JJ, Hall CB. Bronchiolitis: Recent evidence on diagnosis and management. Pediatrics  2010; 125(2): 342-9.
 [http://dx.doi.org/10.1542/peds.2009-2092] [PMID: 20100768]

[54]
Caballero MT, Polack FP, Stein RT. Viral bronchiolitis in young infants: New perspectives for management and treatment. J Pediatr (Rio J)  2017; 93 (Suppl. 1): 75-83.
 [http://dx.doi.org/10.1016/j.jped.2017.07.003] [PMID: 28859915]

[55]
Ghazaly M, Nadel S. Overview of prevention and management of acute bronchiolitis due to respiratory syncytial virus. Expert Rev Anti Infect Ther  2018; 16(12): 913-28.
 [http://dx.doi.org/10.1080/14787210.2018.1543589] [PMID: 30381972]

[56]
Davies HD, Wang EE, Manson D, Babyn P, Shuckett B. Reliability of the chest radiograph in the diagnosis of lower respiratory infections in young children. Pediatr Infect Dis J  1996; 15(7): 600-4.
 [http://dx.doi.org/10.1097/00006454-199607000-00008] [PMID: 8823854]

[57]
McCarthy CA, Hall CB. Respiratory syncytial virus: Concerns and control. Pediatr Rev  2003; 24(9): 301-9.
 [http://dx.doi.org/10.1542/pir.24.9.301] [PMID: 12949266]

[58]
Meissner HC, Long SS. 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((6 Pt 1)): 1442-6.
 [http://dx.doi.org/10.1542/peds.112.6.1447] [PMID: 14654628]

[59]
Henrickson KJ, Hall CB. Diagnostic assays for respiratory syncytial virus disease. Pediatr Infect Dis J  2007; 26(11): S36-40.
 [http://dx.doi.org/10.1097/INF.0b013e318157da6f] [PMID: 18090198]

[60]
Eiland LS. Respiratory syncytial virus: Diagnosis, treatment and prevention. J Pediatr Pharmacol Ther  2009; 14(2): 75-85.
 [http://dx.doi.org/10.5863/1551-6776-14.2.75] [PMID: 23055894]

[61]
NICE Guideline Bronchiolitis in children: diagnosis and management;. London: National Institute for Health and Care Excellence (NICE) 2021.
 [PMID: 34464037]

[62]
Surveillance report 2019 surveillance of bronchiolitis in children: Diagnosis and management (NICE guideline NG9);. London: National Institute for Health and Care Excellence (NICE) 2019.
 [PMID: 34464039]

[63]
Scarfone RJ. Bronchiolitis--or is it? Pediatr Ann  2000; 29(2): 89-92.
 [http://dx.doi.org/10.3928/0090-4481-20000201-07] [PMID: 10693208]

[64]
Ricci V, Delgado Nunes V, Murphy MS, Cunningham S. Bronchiolitis in children: Summary of NICE guidance. BMJ  2015; 350: h2305.
 [http://dx.doi.org/10.1136/bmj.h2305] [PMID: 26037525]

[65]
Wright M, Mullett CJ, Piedimonte G. Pharmacological management of acute bronchiolitis. Ther Clin Risk Manag  2008; 4(5): 895-903.
 [http://dx.doi.org/10.2147/tcrm.s1556] [PMID: 19209271]

[66]
Hancock DG, Charles-Britton B, Dixon DL, Forsyth KD. The heterogeneity of viral bronchiolitis: A lack of universal consensus definitions. Pediatr Pulmonol  2017; 52(9): 1234-40.
 [http://dx.doi.org/10.1002/ppul.23750] [PMID: 28672069]

[67]
Zhang L, Mendoza-Sassi RA, Wainwright C, Klassen TP. Nebulised hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev  2017; 12(12): CD006458.
 [http://dx.doi.org/10.1002/14651858.CD006458.pub4] [PMID: 29265171]

[68]
Mallory MD, Shay DK, Garrett J, Bordley WC. Bronchiolitis management preferences and the influence of pulse oximetry and respiratory rate on the decision to admit. Pediatrics  2003; 111(1): e45-51.
 [http://dx.doi.org/10.1542/peds.111.1.e45] [PMID: 12509594]

[69]
Gern JE. Viral respiratory infection and the link to asthma. Pediatr Infect Dis J  2004; 23(1): S78-86.
 [http://dx.doi.org/10.1097/01.inf.0000108196.46134.a6] [PMID: 14730274]

[70]
Martinón-Torres F. Current treatment for acute viral bronchiolitis in infants. Expert Opin Pharmacother  2003; 4(8): 1355-71.
 [http://dx.doi.org/10.1517/14656566.4.8.1355] [PMID: 12877643]

[71]
Brooks CG, Harrison WN, Ralston SL. Association between hypertonic saline and hospital length of stay in acute viral bronchiolitis: A reanalysis of 2 meta-analyses. JAMA Pediatr  2016; 170(6): 577-84.
 [http://dx.doi.org/10.1001/jamapediatrics.2016.0079] [PMID: 27088767]

[72]
Redant S, Nehar-Stern N, Honoré PM, et al. Acute bronchiolitis: Why put an iv line? J Transl Intern Med  2021; 9(3): 185-9.
 [http://dx.doi.org/10.2478/jtim-2021-0013] [PMID: 34900629]

[73]
Gill PJ, Anwar MR, Kornelsen E, Parkin P, Mahood Q, Mahant S. Parenteral versus enteral fluid therapy for children hospitalised with bronchiolitis. Cochrane Database Syst Rev  2021; 12(12): CD013552.
 [http://dx.doi.org/10.1002/14651858.CD013552.pub2] [PMID: 34852398]

[74]
Kua KP, Lee SW. Complementary and alternative medicine for the treatment of bronchiolitis in infants: A systematic review. PLoS One  2017; 12(2): e0172289.
 [http://dx.doi.org/10.1371/journal.pone.0172289] [PMID: 28212381]

[75]
Lin J, Zhang Y, Xiong L, Liu S, Gong C, Dai J. High-flow nasal cannula therapy for children with bronchiolitis: A systematic review and meta-analysis. Arch Dis Child  2019; 104(6): 564-76.
 [http://dx.doi.org/10.1136/archdischild-2018-315846] [PMID: 30655267]

[76]
Beggs S, Wong ZH, Kaul S, Ogden KJ, Walters JAE. High-flow nasal cannula therapy for infants with bronchiolitis. Cochrane Database Syst Rev  2014; 2014(1): CD009609.
 [http://dx.doi.org/10.1002/14651858.CD009609.pub2] [PMID: 24442856]

[77]
Combret Y, Prieur GLE, Roux P, Médrinal C. Non-invasive ventilation improves respiratory distress in children with acute viral bronchiolitis: A systematic review. Minerva Anestesiol  2017; 83(6): 624-37.
 [http://dx.doi.org/10.23736/S0375-9393.17.11708-6] [PMID: 28192893]

[78]
Jat KR, Mathew JL. Continuous positive airway pressure (CPAP) for acute bronchiolitis in children. Cochrane Database Syst Rev  2019; 1(1): CD010473.
 [http://dx.doi.org/10.1002/14651858.CD010473.pub3] [PMID: 30701528]

[79]
Gadomski AM, Scribani MB. Bronchodilators for bronchiolitis. Cochrane Database Syst Rev  2014; 2014(6): CD001266.
 [http://dx.doi.org/10.1002/14651858.CD001266.pub4] [PMID: 24937099]

[80]
Chavasse RJPG, Seddon P, Bara A, McKean MC. Short acting beta agonists for recurrent wheeze in children under 2 years of age. Cochrane Database Syst Rev  2002; 2002(3): CD002873.
 [http://dx.doi.org/10.1002/14651858.CD002873] [PMID: 12137663]

[81]
Kellner JD, Ohlsson A, Gadomski AM, Wang EE. Efficacy of bronchodilator therapy in bronchiolitis. A meta-analysis. Arch Pediatr Adolesc Med  1996; 150(11): 1166-72.
 [http://dx.doi.org/10.1001/archpedi.1996.02170360056009] [PMID: 8904857]

[82]
Kellner JD, Ohlsson A, Gadomski AM, Wang EE. Bronchodilators for bronchiolitis. Cochrane Database Syst Rev  2000; (2): CD001266.
 [PMID: 10796626]

[83]
Abul-Ainine A, Luyt D. Short term effects of adrenaline in bronchiolitis: A randomised controlled trial. Arch Dis Child  2002; 86(4): 276-9.
 [http://dx.doi.org/10.1136/adc.86.4.276] [PMID: 11919104]

[84]
Hartling L, Russell KF, Patel H, Klassen TP, Liang Y. Epinephrine for bronchiolitis. Cochrane database Syst Rev  2004; (1): CD003123.
 [http://dx.doi.org/10.1002/14651858.CD003123.pub2] [PMID: 14974006]

[85]
Bjornson C, Russell K, Vandermeer B, Klassen TP, Johnson DW. Nebulized epinephrine for croup in children. Cochrane Database Syst Rev  2013; 2013(10): CD006619.
 [http://dx.doi.org/10.1002/14651858.CD006619.pub3] [PMID: 24114291]

[86]
Hartling L, Fernandes RM, Bialy L, et al. Steroids and bronchodilators for acute bronchiolitis in the first two years of life: Systematic review and meta-analysis. BMJ  2011; 342(7801): d1714.
 [http://dx.doi.org/10.1136/bmj.d1714] [PMID: 21471175]

[87]
Hartling L, Bialy LM, Vandermeer B, et al. Epinephrine for bronchiolitis. Cochrane database Syst Rev  2011; 61(6): 289-90.
 [http://dx.doi.org/10.1002/14651858.CD003123.pub3] [PMID: 21678340]

[88]
Kua KP, Lee SWH. Systematic review and meta-analysis of the efficacy and safety of combined epinephrine and corticosteroid therapy for acute bronchiolitis in infants. Front Pharmacol  2017; 8: 396.
 [http://dx.doi.org/10.3389/fphar.2017.00396] [PMID: 28690542]

[89]
Everard M, Bara A, Kurian M, N’Diaye T, Ducharme F, Mayowe V. Anticholinergic drugs for wheeze in children under the age of two years. Cochrane Database Syst Rev  2005; 2005(3): CD001279.
 [http://dx.doi.org/10.1002/14651858.CD001279.pub2] [PMID: 16034861]

[90]
Zhang L, Mendoza-Sassi RA, Klassen TP, Wainwright C. Nebulized hypertonic saline for acute bronchiolitis: A systematic review. Pediatrics  2015; 136(4): 687-701.
 [http://dx.doi.org/10.1542/peds.2015-1914] [PMID: 26416925]

[91]
Zhang L, Gunther CB, Franco OS, Klassen TP. Impact of hypertonic saline on hospitalization rate in infants with acute bronchiolitis: A meta-analysis. Pediatr Pulmonol  2018; 53(8): 1089-95.
 [http://dx.doi.org/10.1002/ppul.24066] [PMID: 29893029]

[92]
Jafri HS. Treatment of respiratory syncytial virus: Antiviral therapies. Pediatr Infect Dis J  2003; 22(2): S89-92.
 [http://dx.doi.org/10.1097/00006454-200302001-00013] [PMID: 12671458]

[93]
Randolph AG, Wang EE. Ribavirin for respiratory syncytial virus lower respiratory tract infection. A systematic overview. Arch Pediatr Adolesc Med  1996; 150(9): 942-7.
 [http://dx.doi.org/10.1001/archpedi.1996.02170340056011] [PMID: 8790125]

[94]
King VJ, Viswanathan M, Bordley WC, et al. Pharmacologic treatment of bronchiolitis in infants and children: A systematic review. Arch Pediatr Adolesc Med  2004; 158(2): 127-37.
 [http://dx.doi.org/10.1001/archpedi.158.2.127] [PMID: 14757604]

[95]
Lauwers E, Ides K, Van Hoorenbeeck K, Verhulst S. The effect of intrapulmonary percussive ventilation in pediatric patients: A systematic review. Pediatr Pulmonol  2018; 53(11): 1463-74.
 [http://dx.doi.org/10.1002/ppul.24135] [PMID: 30019451]

[96]
Alarcón-Andrade G, Cifuentes L. Should systemic corticosteroids be used for bronchiolitis? Medwave  2018; 18(3): e7207.
 [http://dx.doi.org/10.5867/medwave.2018.03.7206] [PMID: 29750779]

[97]
Alarcón-Andrade G, Cifuentes L. Do inhaled corticosteroids have a role for bronchiolitis? Medwave  2018; 18(2): e7183.
 [http://dx.doi.org/10.5867/medwave.2018.02.7182] [PMID: 29677180]

[98]
Fernandes RM, Wingert A, Vandermeer B, et al. Safety of corticosteroids in young children with acute respiratory conditions: A systematic review and meta-analysis. BMJ Open  2019; 9(8): e028511.
 [http://dx.doi.org/10.1136/bmjopen-2018-028511] [PMID: 31375615]

[99]
Goebel J, Estrada B, Quinonez J, Nagji N, Sanford D, Boerth RC. Prednisolone plus albuterol versus albuterol alone in mild to moderate bronchiolitis. Clin Pediatr (Phila)  2000; 39(4): 213-20.
 [http://dx.doi.org/10.1177/000992280003900404] [PMID: 10791133]

[100]
Schuh S, Coates AL, Binnie R, et al. Efficacy of oral dexamethasone in outpatients with acute bronchiolitis. J Pediatr  2002; 140(1): 27-32.
 [http://dx.doi.org/10.1067/mpd.2002.120271] [PMID: 11815760]

[101]
Pérez-Gutiérrez F, Otárola-Escobar I, Arenas D. Are leukotriene inhibitors useful for bronchiolitis? Medwave  2016; 16 (Suppl. 5): e6799.
 [http://dx.doi.org/10.5867/medwave.2016.6799] [PMID: 28032855]

[102]
Peng WS, Chen X, Yang XY, Liu EM. Systematic review of montelukast’s efficacy for preventing post-bronchiolitis wheezing. Pediatr Allergy Immunol  2014; 25(2): 143-50.
 [http://dx.doi.org/10.1111/pai.12124] [PMID: 24118637]

[103]
Liu F, Ouyang J, Sharma AN, et al. Leukotriene inhibitors for bronchiolitis in infants and young children. Cochrane Database Syst Rev  2015; 2015(3): CD010636.
 [http://dx.doi.org/10.1002/14651858.CD010636.pub2] [PMID: 25773054]

[104]
Bisgaard H. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am J Respir Crit Care Med  2003; 167(3): 379-83.
 [http://dx.doi.org/10.1164/rccm.200207-747OC] [PMID: 12406832]

[105]
Farley R, Spurling GK, Eriksson L, DelMar CB. Antibiotics for bronchiolitis in children under two years of age. Cochrane Database Syst Rev  2014; 2014(10): CD005189.
 [http://dx.doi.org/10.1002/14651858.CD005189.pub4] [PMID: 25300167]

[106]
McCallum GB, Plumb EJ, Morris PS, Chang AB. Antibiotics for persistent cough or wheeze following acute bronchiolitis in children. Cochrane Database Syst Rev  2017; 8(8): CD009834.
 [http://dx.doi.org/10.1002/14651858.CD009834.pub3] [PMID: 28828759]

[107]
Hon KL, Leung E, Tang J, et al. Premorbid factors and outcome associated with respiratory virus infections in a pediatric intensive care unit. Pediatr Pulmonol  2008; 43(3): 275-80.
 [http://dx.doi.org/10.1002/ppul.20768] [PMID: 18219695]

[108]
Che SY, He H, Deng Y, Liu EM. Clinical effect of azithromycin adjuvant therapy in children with bronchiolitis: A systematic review and Meta analysis. Zhongguo Dang Dai Er Ke Za Zhi  2019; 21(8): 812-9.
 [http://dx.doi.org/10.7499/j.issn.1008-8830.2019.08.014] [PMID: 31416508]

[109]
Enriquez A, Chu I-W, Mellis C, Lin W-Y. Nebulised deoxyribonuclease for viral bronchiolitis in children younger than 24 months. Cochrane Database Syst Rev  2012; 11(11): CD008395.
 [http://dx.doi.org/10.1002/14651858.CD008395.pub2] [PMID: 23152257]

[110]
Jat KR, Chawla D. Surfactant therapy for bronchiolitis in critically ill infants. Cochrane Database Syst Rev  2015; 2015(8): CD009194.
 [http://dx.doi.org/10.1002/14651858.CD009194.pub3] [PMID: 26299681]

[111]
Liet JM, Ducruet T, Gupta V, Cambonie G. Heliox inhalation therapy for bronchiolitis in infants. Cochrane Database Syst Rev  2015; 2015(9): CD006915.
 [http://dx.doi.org/10.1002/14651858.CD006915.pub3] [PMID: 26384333]

[112]
Hon K-L, Leung TF, Hung CWE, Cheung KL, Leung AKC. Ingestion--associated adverse events necessitating pediatric ICU admissions. Indian J Pediatr  2009; 76(3): 283-6.
 [http://dx.doi.org/10.1007/s12098-009-0054-9] [PMID: 19347668]

[113]
Poon WT, Ho CH, Yip KL, et al. Grayanotoxin poisoning from Rhododendron simsii in an infant. Hong Kong Med J  2008; 14(5): 405-7.
 [PMID: 18840915]

[114]
Sanders SL, Agwan S, Hassan M, vanDriel ML, DelMar CB. Immunoglobulin treatment for hospitalised infants and young children with respiratory syncytial virus infection. Cochrane Database Syst Rev  2019; 8(8): CD009417.
 [http://dx.doi.org/10.1002/14651858.CD009417.pub2] [PMID: 31446622]

[115]
Fernandes RM, Bialy LM, Vandermeer B, et al. Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database Syst Rev  2013; 2013(6): CD004878.
 [http://dx.doi.org/10.1002/14651858.CD004878.pub4] [PMID: 23733383]

[116]
Perrotta C, Ortiz Z, Roque M. Chest physiotherapy for acute bronchiolitis in paediatric patients between 0 and 24 months old. Cochrane Database Syst Rev  2005; (2): CD004873.
 [PMID: 15846736]

[117]
Roquéi Figuls M, Giné-Garriga M, Granados Rugeles C, Perrotta C, Vilaró J. Chest physiotherapy for acute bronchiolitis in paediatric patients between 0 and 24 months old. Cochrane Database Syst Rev  2016; 2(2): CD004873.
 [http://dx.doi.org/10.1002/14651858.CD004873.pub5] [PMID: 26833493]

[118]
Umoren R, Odey F, Meremikwu MM. Steam inhalation or humidified oxygen for acute bronchiolitis in children up to three years of age. Cochrane database Syst Rev  2011; (1): CD006435.
 [http://dx.doi.org/10.1002/14651858.CD006435.pub2] [PMID: 21249676]

[119]
Belderbos ME, Houben ML, vanBleek GM, et al. Breastfeeding modulates neonatal innate immune responses: A prospective birth cohort study. Pediatr Allergy Immunol  2012; 23(1): 65-74.
 [http://dx.doi.org/10.1111/j.1399-3038.2011.01230.x] [PMID: 22103307]

[120]
Feltes TF, Cabalka AK, Meissner HC, et al. Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr  2003; 143(4): 532-40.
 [http://dx.doi.org/10.1067/S0022-3476(03)00454-2] [PMID: 14571236]

[121]
Wegner S, Vann JJ, Liu G, et al. Direct cost analyses of palivizumab treatment in a cohort of at-risk children: Evidence from the North Carolina Medicaid Program. Pediatrics  2004; 114(6): 1612-9.
 [http://dx.doi.org/10.1542/peds.2004-0959] [PMID: 15574623]

[122]
Madhi SA, Simões EAF. Single-dose nirsevimab prevents RSV infection. J Pediatr  2021; 228: 310-3.
 [http://dx.doi.org/10.1016/j.jpeds.2020.10.066] [PMID: 33342497]

[123]
Piedra PA. Clinical experience with respiratory syncytial virus vaccines. Pediatr Infect Dis J  2003; 22(2): S94-9.
 [http://dx.doi.org/10.1097/00006454-200302001-00014] [PMID: 12671459]

[124]
Polack FP, Karron RA. The future of respiratory syncytial virus vaccine development. Pediatr Infect Dis J  2004; 23(1): S65-73.
 [http://dx.doi.org/10.1097/01.inf.0000108194.71892.95] [PMID: 14730272]

[125]
Thompson M, Vodicka TA, Blair PS, Buckley DI, Heneghan C, Hay AD. Duration of symptoms of respiratory tract infections in children: Systematic review. BMJ  2013; 347: f7027.
 [http://dx.doi.org/10.1136/bmj.f7027] [PMID: 24335668]

[126]
Openshaw PJ, Dean GS, Culley FJ. Links between respiratory syncytial virus bronchiolitis and childhood asthma: Clinical and research approaches. Pediatr Infect Dis J  2003; 22(2): S58-64.
 [http://dx.doi.org/10.1097/00006454-200302001-00009] [PMID: 12671454]

[127]
Kneyber MCJ, Steyerberg EW, de Groot R, Moll HA. Long-term effects of respiratory syncytial virus (RSV) bronchiolitis in infants and young children: A quantitative review. Acta Paediatr  2000; 89(6): 654-60.
 [http://dx.doi.org/10.1080/080352500750043945] [PMID: 10914957]

[128]
Bradley JP, Bacharier LB, Bonfiglio JA, Schechtman KB. Strun kR, Storch G. Severity of respiratory syncytial virus bronchiolitis is affected by cigarette smoke exposure and atopy. Pediatrics  2005; 115(1): e7-e14.
 [http://dx.doi.org/10.1542/peds.2004-0059] [PMID: 15629968]

[129]
Martinez FD. Respiratory syncytial virus bronchiolitis and the pathogenesis of childhood asthma. Pediatr Infect Dis J  2003; 22(2): S76-82.
 [http://dx.doi.org/10.1097/00006454-200302001-00011] [PMID: 12671456]

[130]
Chang JC, Chiou JY, Ko JL, Huang JY, Lue KH. Early bronchiolitis contributes to preschool asthma. Children (Basel)  2021; 8(12): 1176.
 [http://dx.doi.org/10.3390/children8121176] [PMID: 34943372]

[131]
Wang G, Han D, Jiang Z, Li M, Yang S, Liu L. Association between early bronchiolitis and the development of childhood asthma: A meta-analysis. BMJ Open  2021; 11(5): e043956.
 [http://dx.doi.org/10.1136/bmjopen-2020-043956] [PMID: 34049905]
Cite As
Current Pediatric Reviews

Respiratory Syncytial Virus is the Most Common Causative Agent of Viral Bronchiolitis in Young Children: An Updated Review

Abstract

Graphical Abstract
