Inter-society consensus document on treatment and prevention of bronchiolitis in newborns and infants

Italian Journal of Pediatrics

Giovanni Corsello⁵  Susanna Esposito^1,15  Filippo Festini²  Giuseppe Di Mauro³  Francesco Paravati⁹  Carlo Minetti^2,20  Gianpaolo Donzelli^1,11  Luigi Memo⁴  Antonio Francesco Urbino^1,18  Carlo Catassi^1,16  Giuseppe Magazzù^1,19  Marco Cappa^1,13  Marina Picca⁸  Roberto Bernardini^1,17  Giampietro Chiamenti^1,12  Paolo Biban^1,10  Andrea Biondi¹  Pierluigi Colonna⁶  Costantino Romagnoli⁷  Alessandro Rimini⁶  Silvia Vandini⁷  Giovanni A Rossi^1,14  Paolo Manzoni⁷  Marcello Lanari⁷  Eugenio Baraldi^2,21 

[1] AIEOP - Società Italiana di Ematologia e Oncologia Pediatrica, Italy;SISIP - Società Italiana di Scienze Infermieristiche Pediatriche, Italy;SIPPS - Società Italiana di Pediatria Preventiva e Sociale, Italy;SIMGePeD - Società Italiana Malattie Genetiche Pediatriche e Disabilità Congenite, Italy;SIP-Società Italiana di Pediatria, Italy;SICP-Società Italiana di Cardiologia Pediatrica, Italy;SIN-Società Italiana di Neonatologia, Italy;SICuPP - Società Italiana delle Cure Primarie Pediatriche, Italy;SIPO - Società Italiana Pediatria Ospedaliera, Italy;AMIETIP - Accademia Medica Infermieristica di Emergenza e Terapia Intensiva Pediatrica, Italy;SIMP - Società Italiana di Medicina Perinatale, Italy;FIMP - Federazione Italiana Medici Pediatri, Italy;SIEDP - Società Italiana di Endocrinologia e Diabetologia Pediatrica, Italy;SIMRI-Società Italiana per le Malattie Respiratorie Infantili, Italy;SITIP - Società Italiana di Infettivologia Pediatrica, Italy;SIGENP - Società Italiana Gastroenterologia Epatologia e Nutrizione Pediatrica, Italy;SIAIP - Società Italiana di Allergologia e Immunologia Pediatrica, Italy;SIMEUP - Società Italiana di Medicina di Emergenza ed Urgenza Pediatrica, Italy;SIFC - Società Italiana per lo studio della Fibrosi Cistica, Italy;SINP - Società Italiana di Neurologia Pediatrica, Italy;Women’s and Children’s Health Department, Unit of Pediatric Respiratory Medicine and Allergy, University of Padova, Via Giustiniani 3, 35128 Padova, Italy

关键词: Prophylaxis;    Prevention;    Oxygen therapy;    Immunodeficiency;    Congenital heart diseases;    Bronchopulmonary dysplasia;    Prematurity;    Respiratory syncytial virus;    Bronchiolitis;   

Others  :  1146362
DOI  :  10.1186/1824-7288-40-65

 received in 2014-04-17, accepted in 2014-04-18,  发布年份 2014

【 摘 要 】

Acute bronchiolitis is the leading cause of lower respiratory tract infection and hospitalization in children less than 1 year of age worldwide. It is usually a mild disease, but some children may develop severe symptoms, requiring hospital admission and ventilatory support in the ICU. Infants with pre-existing risk factors (prematurity, bronchopulmonary dysplasia, congenital heart diseases and immunodeficiency) may be predisposed to a severe form of the disease.

Clinical diagnosis of bronchiolitis is manly based on medical history and physical examination (rhinorrhea, cough, crackles, wheezing and signs of respiratory distress). Etiological diagnosis, with antigen or genome detection to identify viruses involved, may have a role in reducing hospital transmission of the infection.

Criteria for hospitalization include low oxygen saturation (<90-92%), moderate-to-severe respiratory distress, dehydration and presence of apnea. Children with pre-existing risk factors should be carefully assessed.

To date, there is no specific treatment for viral bronchiolitis, and the mainstay of therapy is supportive care. This consists of nasal suctioning and nebulized 3% hypertonic saline, assisted feeding and hydration, humidified O₂ delivery. The possible role of any pharmacological approach is still debated, and till now there is no evidence to support the use of bronchodilators, corticosteroids, chest physiotherapy, antibiotics or antivirals. Nebulized adrenaline may be sometimes useful in the emergency room. Nebulized adrenaline can be useful in the hospital setting for treatment as needed. Lacking a specific etiological treatment, prophylaxis and prevention, especially in children at high risk of severe infection, have a fundamental role. Environmental preventive measures minimize viral transmission in hospital, in the outpatient setting and at home. Pharmacological prophylaxis with palivizumab for RSV bronchiolitis is indicated in specific categories of children at risk during the epidemic period.

Viral bronchiolitis, especially in the case of severe form, may correlate with an increased incidence of recurrent wheezing in pre-schooled children and with asthma at school age.

The aim of this document is to provide a multidisciplinary update on the current recommendations for the management and prevention of bronchiolitis, in order to share useful indications, identify gaps in knowledge and drive future research.

【 授权许可】

   
2014 Baraldi et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, Auinger P, Griffin MR, Poehling KA, Erdman D, Grijalva CG, Zhu Y, Szilagyi P: The burden of respiratory syncytial virus infection in young children. N Engl J Med 2009, 360(6):588-598.
• [2]American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis: Diagnosis and management of bronchiolitis. Pediatrics 2006, 118(4):1774-1793.
• [3]Zorc JJ, Hall CB: Bronchiolitis: Recent evidence on diagnosis and management. Pediatrics 2010, 125(2):342-349.
• [4]Bosis S, Esposito S, Niesters HG, Zuccotti GV, Marseglia G, Lanari M, Zuin G, Pelucchi C, Osterhaus AD, Principi N: Role of respiratory pathogens in infants hospitalized for a first episode of wheezing and their impact on recurrences. Clin Microbiol Infect 2008, 14(7):677-684.
• [5]Paranhos-Baccala G, Komurian-Pradel F, Richard N, Vernet G, Lina B, Floret D: Mixed respiratory virus infections. J Clin Virol 2008, 43(4):407-410.
• [6]Thompson 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(2):179-186.
• [7]Manzoni P, Paes B, Resch B, Carbonell-Estrany X, Bont L: High risk for RSV bronchiolitis in late preterms and selected infants affected by rare disorders: a dilemma of specific prevention. Early Hum Dev 2012, 88(Suppl 2):S34-S41.
• [8]Lanari M, Giovannini M, Giuffré L, Marini A, Rondini G, Rossi GA, Merolla R, Zuccotti GV, Salvioli GP, Investigators RADAR: Study Group. Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity. Pediatr Pulmonol 2002, 33(6):458-465.
• [9]Sigurs N, Aljassim F, Kjellman B, Robinson PD, Sigurbergsson F, Bjarnason R, Gustafsson PM: Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life. Thorax 2010, 65(12):1045-1052.
• [10]Stein 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.
• [11]Lenney W, Boner AL, Bont L, Bush A, Carlsen KH, Eber E, Fauroux B, Götz M, Greenough A, Grigg J, Hull J, Kimpen J, Sánchez Luna M, De Benedictis FM: Medicines used in respiratory diseases only seen in children. Eur Respir J 2009, 34(3):531-551.
• [12]Da Dalt L, Bressan S, Martinolli F, Perilongo G, Baraldi E: Treatment of bronchiolitis: state of the art. Early Hum Dev 2013, 89(Suppl 1):S31-S36.
• [13]Bronchiolitis Guideline Team, Cincinnati Children’s Hospital Medical Center: Evidence Based Clinical Practice Guideline for Medical Management of Bronchiolitis in Infants 1 Year of Age or Less Presenting with a First Time Episode. Cincinnati: Cincinnati Children’s Hospital Medical Center; 2010.
• [14]Management of Bronchiolitis in Infants: The Hospital for Sick Children, Clinical Practice Guideline. 2011. [Last Modified]
• [15]Waris M, Meurman O, Mufson MA, Ruuskanen O, Halonen P: Shedding of infectious virus and virus antigen during acute infection with respiratory syncytial virus. J Med Virol 1992, 38(2):111-116.
• [16]Principi N, Esposito S: Antigen-based assays for the identification of influenza virus and respiratory syncytial virus: why and how to use them in pediatric practice. Clin Lab Med 2009, 29(4):649-660.
• [17]Meerhoff TJ, Houben ML, Coenjaerts FE, Kimpen JL, Hofland RW, Schellevis F, Bont LJ: Detection of multiple respiratory pathogens during primary respiratory infection: nasal swab versus nasopharyngeal aspirate using real-time polymerase chain reaction. Eur J Clin Microbiol Infect Dis 2010, 29(4):365-371.
• [18]Princess Margaret Hospital for Children, Melbourne. 2010. http://www.pmh.health.wa.gov.au/development/manuals/clinical_practice_guidelines/documents/bronchiolitis_cpg.pdf webcite
• [19]Scottish Intercollegiate Guidelines Network (SIGN): Bronchiolitis in Children. 2006. [Guideline no. 91]
• [20]Milési C, Baleine J, Matecki S, Durand S, Combes C, Novais AR, Cambonie G: Is treatment with a high flow nasal cannula effective in acute viral bronchiolitis? A physiologic study. Intensive Care Med 2013, 39(6):1088-1094.
• [21]Arora B, Mahajan P, Zidan MA, Sethuraman U: Nasopharyngeal airway pressures in bronchiolitis patients treated with high-flow nasal cannula oxygen therapy. Pediatr Emerg Care 2012, 28(11):1179-1184.
• [22]Hilliard TN, Archer N, Laura H, Heraghty J, Cottis H, Mills K, Ball S, Davis P: Pilot study of vapotherm oxygen delivery in moderately severe bronchiolitis. Arch Dis Child 2012, 97(2):182-183.
• [23]Bressan S, Balzani M, Krauss B, Pettenazzo A, Zanconato S, Baraldi E: High-flow nasal cannula oxygen for bronchiolitis in a pediatric ward: a pilot study. Eur J Pediatr 2013, 172:1649-1656.
• [24]Zhang L, Mendoza-Sassi RA, Wainwright C, Klassen TP: Nebulised hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev 2013, 7:CD006458.
• [25]Morawetz D, Cheah E, Barton R, Standish J, Connell TG: Is nebulised hypertonic saline useful as an adjunctive treatment for acute bronchiolitis in infants and children less than 24 months of age? J Paediatr Child Health 2011, 47(12):922-926.
• [26]Ralston S: Repeated dosing of nebulised 5% saline improves respiratory scores in inpatients with mild to moderate bronchiolitis at 48 h. Evid Based Med 2011, 16(3):82-83.
• [27]Kuzik BA, Al-Qadhi SA, Kent S, Flavin MP, Hopman W, Hotte S, Gander S: Nebulized hypertonic saline in the treatment of viral bronchiolitis in infants. J Pediatr 2007, 151(3):266-270. 270.e1
• [28]Mandelberg A, Amirav I: Hypertonic saline or high volume normal saline for viral bronchiolitis: mechanisms and rationale. Pediatr Pulmonol 2010, 45(1):36-40.
• [29]Ralston S, Hill V, Martinez M: Nebulized hypertonic saline without adjunctive bronchodilators for children with bronchiolitis. Pediatrics 2010, 126(3):e520-e525.
• [30]Turner T, Wilkinson F, Harris C, Mazza D, Health for Kids Guideline Development Group: Evidence based guideline for the management of bronchiolitis. Aust Fam Physician 2008, 37(6):6-13.
• [31]Mussman GM, Parker MW, Statile A, Sucharew H, Brady PW: Suctioning and length of stay in infants hospitalized with bronchiolitis. JAMA Pediatr 2013, 167(5):414-421.
• [32]Babl FE, Sheriff N, Neutze J, Borland M, Oakley E: Bronchiolitis management in pediatric emergency departments in Australia and New Zealand: a PREDICT study. Pediatr Emerg Care 2008, 24(10):656-658.
• [33]Oakley E, Babl FE, Acworth J, Borland M, Kreiser D, Neutze J, Theophilos T, Donath S, South M, Davidson A, Paediatric Research in Emergency Departments International Collaborative: A prospective randomised trial comparing nasogastric with intravenous hydration in children with bronchiolitis (protocol): the comparative rehydration in bronchiolitis study (CRIB). BMC Pediatr 2010, 1:10-37.
• [34]Luu R, Dewitt PE, Reiter PD, Dobyns EL, Kaufman J: Hyponatremia in Children with Bronchiolitis Admitted to the Pediatric Intensive Care Unit Is Associated with Worse Outcomes. J Pediatr 2013, 163:1652-1656.
• [35]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.
• [36]Roque I, Figuls M, Giné-Garriga M, Granados Rugeles C, Perrotta C: Chest physiotherapy for acute bronchiolitis in paediatric patients between 0 and 24 months old. Cochrane Database Syst Rev 2012, 15:2. CD004873
• [37]Gadomski AM, Brower M: Bronchodilators for bronchiolitis. Cochrane Database Syst Rev 2010, 12:CD001266.
• [38]Hartling L, Bialy LM, Vandermeer B, Tjosvold L, Johnson DW, Plint AC, Klassen TP, Patel H, Fernandes RM: Epinephrine for bronchiolitis. Cochrane Database Syst Rev 2011, 6:CD003123.
• [39]Skjerven HO, Hunderi JO, Brügmann-Pieper SK, Brun AC, Engen H, Eskedal L, Haavaldsen M, Kvenshagen B, Lunde J, Rolfsjord LB, Siva C, Vikin T, Mowinckel P, Carlsen KH, Lødrup Carlsen KC: Racemic adrenaline and inhalation strategies in acute bronchiolitis. N Engl J Med 2013, 368(24):2286-2293.
• [40]Blom 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 Jan 24;(1):CD004881. Review. Update in. Cochrane Database Syst Rev 2011, 1:CD004881.
• [41]Fernandes RM, Bialy LM, Vandermeer B, Tjosvold L, Plint AC, Patel H, Johnson DW, Klassen TP, Hartling L: Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database Syst Rev 2013, 6:CD004878.
• [42]Corneli HM, Zorc JJ, Mahajan 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: Bronchiolitis study group of the pediatric emergency care applied research network (pecarn). a multicenter, randomized, controlled trial of dexamethasone for bronchiolitis. N Engl J Med 2007, 357(4):331-339.
• [43]Plint 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: Pediatric emergency research canada (PERC) epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med 2009, 360(20):2079-2089.
• [44]Spurling GK, Doust J, Del Mar CB, Eriksson L: Antibiotics for bronchiolitis in children. Cochrane Database Syst Rev 2011, 6:CD005189.
• [45]Pinto LA, Pitrez PM, Luisi F, De Mello PP, Gerhardt M, Ferlini R, Barbosa DC, Daros I, Jones MH, Stein RT, Marostica PJ: Azithromycin therapy in hospitalized infants with acute bronchiolitis is not associated with better clinical outcomes:a randomized, double-blinded, and placebo-controlled clinical trial. J Pediatr 2012, 161(6):1104-1108.
• [46]Ventre K, Randolph A, WITHDRAWN: Ribavirin for respiratory syncytial virus infection of the lower respiratory tract in infants and young children. Cochrane Database Syst Rev 2010, 5:CD000181.
• [47]Zedan M, Gamil N, El-Assmy M, Fayez E, Nasef N, Fouda A, Settin A: Montelukast as an episodic modifier for acute viral bronchiolitis: a randomized trial. Allergy Asthma Proc 2010, 31(2):147-153.
• [48]Amirav I, Luder AS, Kruger N, Borovitch Y, Babai I, Miron D, Zuker M, Tal G, Mandelberg A: A double-blind, placebo-controlled, randomized trial of montelukast for acute bronchiolitis. Pediatrics 2008, 122(6):e1249-e1255.
• [49]Bisgaard H, Flores-Nunez A, Goh A, Azimi P, Halkas A, Malice MP, Marchal JL, 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(8):854-860.
• [50]Bisgaard H: Study group on montelukast and respiratory syncytial virus. a randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am J Respir Crit Care Med 2003, 167(3):379-383.
• [51]Proesmans M, Sauer K, Govaere E, Raes M, De Bilderling G, De Boeck K: Montelukast does not prevent reactive airway disease in young children hospitalized for RSV bronchiolitis. Acta Paediatr 2009, 98(11):1830-1834.
• [52]Kim CK, Choi J, Kim HB, Callaway Z, Shin BM, Kim JT, Fujisawa T, Koh YY: A randomized intervention of montelukast for post-bronchiolitis: effect on eosinophil degranulation. J Pediatr 2010, 156(5):749-754.
• [53]Enriquez A, Chu IW, Mellis C, Lin WY: Nebulised deoxyribonuclease for viral bronchiolitis in children younger than 24 months. Cochrane Database Syst Rev 2012, 11:CD008395.
• [54]Ramesh P, Samuels M: Are methylxanthines effective in preventing or reducing apnoeic spells in infants with bronchiolitis? Arch Dis Child 2005, 90(3):321-322.
• [55]Sajit NT, Steggall M, Padmakumar B: Apnoeas in bronchiolitis: is there a role for caffeine? Arch Dis Child 2005, 90(4):438.
• [56]Ralston S, Hill V: Incidence of apnea in infants hospitalized with respiratory syncytial virus bronchiolitis: a systematic review. J Pediatr 2009, 155(5):728-733.
• [57]Hall CB: Nosocomial respiratory syncytial virus infections: the "Cold War" has not ended. Clin Infect Dis 2000, 31(2):590-596.
• [58]Sattar SA, Springthorpe VS, Tetro J, Vashon R, Keswick B: Hygienic hand antiseptics: should they not have activity and label claims against viruses? Am J Infect Control 2002, 30(6):355-372.
• [59]Isaacs D, Dickson H, O'Callaghan C, Sheaves R, Winter A, Moxon ER: Handwashing and cohorting in prevention of hospital acquired infections with respiratory syncytial virus. Arch Dis Child 1991, 66(2):227-231.
• [60]Centers for Disease Control and Prevention (CDC): Respiratory Syncytial Virus, Transmission and Prevention. 2010.
• [61]Groothuis J, Bauman J, Malinoski F, Eggleston M: Strategies for prevention of RSV nosocomial infection. J Perinato 2008, 28(5):319-323.
• [62]Bont L: Nosocomial RSV, infection control and outbreak management. Paediatr Respir Rev 2009, 10(Suppl 1):16-17.
• [63]Karanfil LV, Conlon M, Lykens K, Masters CF, Forman M, Griffith ME, Townsend TR, Perl TM: Reducing the rate of nosocomially transmitted respiratory syncytial virus. Am J Infect Control 1999, 27(2):91-96.
• [64]Macartney KK, Gorelick MH, Manning ML, Hodinka RL, Bell LM: Nosocomial respiratory syncytial virus infections: the cost-effectiveness and cost-benefit of infection control. Pediatrics 2000, 106(3):520-526.
• [65]Subramanian KN, Weisman LE, Rhodes T, Ariagno R, Sánchez 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(2):110-115.
• [66]Sáez-Llorens X, Castaño E, Null D, Steichen J, Sánchez PJ, Ramilo O, Top FH Jr, Connor E: Safety and pharmacokinetics of an intramuscular humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. The MEDI-493 Study Group. Pediatr Infect Dis J 1998, 17(9):787-791.
• [67]American Academy of Pediatrics: Policy statement – modified recommendations for use of palivizumab for prevention of respiratory syncytial virus infections. Pediatrics 2009, 124(6):1694-1701.
• [68]Null D Jr, Pollara B, Dennehy PH, Steichen J, Sánchez PJ, Givner LB, Carlin D, Landry B, Top FH Jr, Connor E: Safety and immunogenicity of palivizumab (Synagis) administered for two seasons. Pediatr Infect Dis J 2005, 24(11):1021-1023.
• [69]Feltes TF, Cabalka AK, Meissner HC, Piazza FM, Carlin DA, Top FH Jr, Connor EM, Sondheimer HM, Cardiac Synagis Study Group: Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr 2003, 143(4):532-540.
• [70]Figueras Aloy J, Quero J, Doménech E, López Herrera MC, Izquierdo I, Losada A, Perapch J, Sánchez-Luna M: Comité de estándares de la sociedad española de neonatología. [recommendations for the prevention of respiratory syncytial virus infection]. An Pediatr (Barc) 2005, 63(4):357-362.
• [71]Robinson J: Preventing respiratory syncytial virus infections. Paediatr Child Health 2011, 16(8):487-490.
• [72]Raccomandazioni della Società Italiana di Neonatologia per la prevenzione delle malattie da virus respiratorio sinciziale (VRS) Acta Neonatologica Pediatrica 2004, 18:19-30.
• [73]Lanari M, Prinelli F, Adorni F, Di Santo S, Faldella G, Silvestri M, Musico M: Collaborators, on behalf of the ‘italian neonatology study group on rsv infections’. maternal milk protects infants against bronchiolitis during the first year of life. results from an italian cohort of newborns. Early Hum Dev 2013, 89(1):S51-S57.
• [74]Belderbos ME, Houben ML, Wilbrink B, Lentjes E, Bloemen EM, Kimpen JL, Rovers M, Bont L: Cord blood vitamin D deficiency is associated with respiratory syncytial virus bronchiolitis. Pediatrics 2011, 127(6):e1513-e1520.
• [75]Camargo CA Jr, Rifas-Shiman SL, Litonjua AA, Rich-Edwards JW, Weiss ST, Gold DR, Kleinman K, Gillman MW: Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J Clin Nutr 2007, 85(3):788-795.
• [76]Midulla F, Pierangeli A, Cangiano G, Bonci E, Salvadei S, Scagnolari C, Moretti C, Antonelli G, Ferro V, Papoff P: Rhinovirus bronchiolitis and recurrent wheezing: 1-year follow-up. Eur Respir J 2012, 39(2):396-402.
• [77]Backman K, Piippo-Savolainen E, Ollikainen H, Koskela H, Korppi M: Increased asthma risk and impaired quality of life after bronchiolitis or pneumonia in infancy. Pediatr Pulmonol 2014, 49:318-325.
• [78]Blanken MO, Rovers MM, Molenaar JM, Winkler-Seinstra PL, Meijer A, Kimpen JL, Bont L, Dutch RSV: Neonatal Network Respiratory syncytial virus and recurrent wheeze in healthy preterm infants. N Engl J Med 2013, 368(19):1791-1799.
• [79]Resch B, Manzoni P, Lanari M: Severe respiratory syncytial virus (RSV) infection in infants with neuromuscular diseases and immune deficiency syndromes. Paediatr Resp Rev 2009, 10:148-153.
• [80]Afghani B, Ngo T: Severe respiratory syncytial virus infection in term infants with genetic or other underlying disorders. Pediatrics 2008, 121:868-869.
• [81]Mori M, Kawashima H, Nakamura H, Nakagawa M, Kusuda S, Saji T, Tsutsumi H, Yokota S, Itoh S, Surveillance Committee for Severe RSV Infection: Surveillance committee for severe rsv infection. nationwide survey of severe respiratory syncytial virus infection in children who do not meet indications for palivizumab in japan. J Infect Chemother 2011, 17:254-263.
• [82]Wilkesmann A, Ammann RA, Schildgen O, Eis-Hübinger AM, Müller A, Seidenberg J, Stephan V, Rieger C, Herting E, Wygold T, Hornschuh F, Groothuis JR, Simon A, DSM RSV Ped Study Group: Hospitalized children with respiratory syncytial virus infection and neuromuscular impairment face an increased risk of a complicated course. Pediatr Infect Dis J 2007, 26:485-491.
• [83]Giebels K, Marcotte JE, Podoba J, Rousseau C, Denis MH, Fauvel V, Laberge S: Prophylaxis against respiratory syncytial virus in young children with cystic fibrosis. Pediatr Pulmonol 2008, 43:169-174.
• [84]Winterstein AG, Eworuke E, Dandan X, Schuler P: Palivizumab immunoprophylaxis effectiveness in children with cystic fibrosis. Pediatr Pulmonol 2013, 48:874-884.
• [85]Bloemers BL, Van Furth AM, Weijerman ME, Gemke RJ, Broers CJ, van den Ende K, Kimpen JL, Strengers JL, Bont LJ: Down syndrome: a novel risk factor for respiratory syncytial virus bronchiolitis – a prospective birth-cohort study. Pediatrics 2007, 120:e1076-e1081.
• [86]Zachariah P, Ruttenber M, Simoes EA: Down syndrome and hospitalizations due to respiratory syncytial virus: a population-based study. J Pediatr 2012, 160:827-831.
• [87]Van Beek D, Paes B, Bont L: Increased risk of RSV infection in children with down's syndrome: clinical implementation of prophylaxis in the european union. Clin Dev Immunol 2013, 801581. doi:10.1155/2013/801581. Epub 2013 Jun 25
• [88]Hall 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.
• [89]El Saleeby CM, Somes GW, DeVincenzo JP, Gaur AH: Risk factors for severe RSV disease in children with cancer: the importance of lymphopenia and young age. Pediatrics 2008, 121:235-243.
• [90]Sung L, Alonzo TA, Gerbing RB, Aplenc R, Lange BJ, Woods WG: Children’s oncology group. respiratory syncytial virus infections in children with acute myeloid leukemia: a report from the children’s oncology group. Pediatr Blood Cancer 2008, 51:784.
• [91]Simon A, Muller A, Khurana K, Engelhart S, Exner M, Schildgen O, Eis-Hübinger AM, Kamin W, Schaible T, Wadas K, Ammann RA, Wilkesmann A, DSM RSV Paed Study Group: Nosocomial infection: a risk factor for a complicated course in children with respiratory syncytial virus infection – results from a prospective multicenter German surveillance study. Int J Hyg Environ Health 2008, 211:241-250.
• [92]Thorburn K: Pre-existing disease is associated with a significantly higher risk of death in severe respiratory syncytial virus infection. Arch Dis Child 2009, 94:99-103.
• [93]Kristensen K, Stensballe LG, Bjerre J, Roth D, Fisker N, Kongstad T, Svendsen AL, Nielsen BW: Risk factors for respiratory syncytial virus hospitalisation in children with heart disease. Arch Dis Child 2009, 94:785-789.
• [94]Lanari M, Rossi GA, Merolla R, Di Luzio Paparatti U: High risk of nosocomial-acquired RSV infection in children with congenital heart disease. J Pediatr 2004, 145(1):140. author reply 140-1
• [95]Cabalka AK: “Physiologic risk factors for respiratory viral infections and immunoprophylaxis for RSV in young children with CHD”. Pediatr Infect Dis J 2004, 23:S41-S45.
• [96]Khongphatthanayothin A, Wong PC, Samara Y, Newth CJ, Wells WJ, Starnes VA, Chang AC: Impact of respiratory syncytial virus infection on surgery for congenital heart disease: postoperative course and outcome. Crit Care Med 1999, 27:1974-1981.
• [97]Willson DF, Landrigan CP, Horn SD, Smout RJ: Complications in infants hospitalized for bronchiolitis or respiratory syncytial virus pneumonia. J Pediatr 2003, 143(5 Suppl):S142-S149.
• [98]Bollettino della Società Italiana di Cardiologia Pediatrica Anno 13: La Prevenzione Della Malattia Da Virus Respiratorio Sinciziale Nei Bambini Con Cardiopatia Congenita O Acquisita Nell’infanzia. 2006. [Raccomandazioni della Società Italiana di Cardiologia Pediatrica (SICP)]