INFECCIONES VIRALES BRONQUIOLITIS NEUMONITIS NEUMONIA VIRAL

1. H1N1 INFECCIONES VIRALES BRONQUIOLITIS NEUMONITIS NEUMONIA VIRAL OSELTAMIVIR INFECCIONES BACTERIANAS NEUMONIA BRONQUITIS ATB ¿¿ATIPICAS?? COQUELUCHE VRS OTRAS VACUNAS PALIMIZUMAB NEUMOCOCO VACUNA 13 VALENTE

2. De 100 niños menores de 1 año, 70 se infectan con VRS, 22 desarrollan síntomas 3 ingresarán Para nuestro país serían 1500 niños que ingresarían De ellos pasarían a CTI 3% (50) Un estudio de cohortes (Swingler, 2000), concluyen que la duración de los síntomas de BQL es de unos 12 días. SIGN se incluye la información de un trabajo sobre el daño ciliar que dura, entre 13 y 17 semanas.

4. Taussig: Pediatric Respiratory Medicine, 2nd Edition

5. SINDROME POSTBRONQUIOLITIS ¿DE QUE HABLAMOS? ¿EXISTE? ¿ES ASMA? ¿SON VARIAS INFECCIONES SEGUIDAS? ¿ES UNA INFECCIÓN PROLONGADA? ¿EXISTE UN TERRENO ESPECIAL? ¿TODO JUNTO?

7. Cinco preguntas básicas en la evaluación de un niño con infecciones respiratorias recurrentes ¿1. Este niño tiene infecciones recurrentes del tracto respiratorio? (tenía síntomas respiratorios recurrentes causados por otra condición respiratoria?) 2. ¿Son las infecciones respiratorias recurrentes localizadas en las vías respiratorias superiores o inferiores? 3. ¿Existe alguna participación de otros sistemas u órganos? 4. ¿Son la frecuencia y severidad de infecciones recurrentes de las vías respiratorias inferiores suficientes para justificar las investigaciones adicionales? 5. En cada episodio en que zona del pulmón(s) asienta la pato-logía, ¿cómo esto ayuda a planificar nuevas investigaciones? P.L.P. Brandetal./PaediatricRespiratoryReviewsxxx(2011)xxx–xxx

8. Sibilancias que persisten post BQL Korppi M et al. Am J Dis Child 1993;146:628-631 • De 83 niños <2 años hospitalizados con BQL, un alto porcentaje mantiene sibilancias 100 76% 80 58% 60 % niños con sibilancias 40 20 0 1-2 (n=83) 2-3 (n=76) Edad (años) 8

9. Allergy. 2009 Sep;64(9):1359-65. Epub 2009 Mar 23. Recurrentwheezingafterrespiratorysyncytial virus or non-respiratorysyncytial virus bronchiolitis in infancy: a 3-year follow-up. Valkonen H, Waris M, Ruohola A, Ruuskanen O, Heikkinen T. SourceDepartment of Pediatrics, Turku University Hospital, Finland Within the first year after hospitalization, 36 of 217 (16.6%) children with non-RSV bronchiolitis developed recurrent wheezing, compared with five of 199 (2.5%) children with RSV bronchiolitis [relative risk (RR) 6.6; 95% confidence interval (CI) 2.6-16.5]. The rates of recurrent wheezing were significantly increased in the non-RSV group also within 2 years (RR 2.9; 95% CI 1.7-5.1) and 3 years (RR 3.4; 95% CI 2.0-5.7) after hospitalization. The increased risk of recurrent wheezing in children with non-RSV-associated bronchiolitis was observed both in boys and girls at all time points of the 3-year follow-up, and it was not explained by the age difference between the RSV and non-RSV groups or any confounding seasonal factors. CONCLUSION: Children hospitalized with bronchiolitis caused by other viruses than RSV develop recurrent wheezing at substantially higher rates during a 3-year follow-up period than do children with RSV-induced bronchiolitis. Los niños hospitalizados con bronquiolitis causada por otros virus diferente al RSV desarrollan sibilancias recurrentes con una tasa mayor durante un período de 3 años de seguimiento que los niños con bronquiolitis inducida por RSV

10. 35 30% 30 25 20 15 10 3% 5 0 RSV (n=47) Control (n=93) VRS-Bronquiolitis: ¿Asociación con asma? n= 140, incidencia de asma a los 7.5 años en niños con infección por VRS comparado con controles Niños con asma a la edad de 7,5 años (%) 10 Sigurs N et al. Am J Respir Crit Care Med 2000;161:1501-1507

11. Sintomas respiratorios recurrentes según los años de evolución, luego de infección inicial por VRS Henry et al. 1985 Arch Dis Child Webb et al. 1985 Arch Dis Child Hall et al. 1984 J Pediatr

12. Patogenesis • Predisposición genética (atopia es la propensión a la producción de IgE) • Combinado con exposición ambiental contribuye al desarrollo de la enfermedad Cole-Johnson et al., 2002Sept 15, 2007Stockholm

13. Immunologic cascade of allergy 1. Persorption of Allergen 2. Sensitization to allergen IL-10 TGF-beta Treg 3. Inflammation TNF-, eosinophilic proteins DCr Stockholm Romagnani, 1996 Hansen 2001, Mc Quirk 2002

14. New immune pathways from chronic post-viral lung disease Loralyn A. Benoit1 and Michael J. Holtzman Department of Medicine - Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, USA Ann N Y Acad Sci. 2010 January ; 1183: 195–210. doi:10.1111/j.1749-6632.2009.05136.x.

15. Javascript is required to show this page properly. Click on image to magnify. Restos virales activan células presentadoras de antígeno (CPAs) y facilitan así la activación de presentación y el consecuente de antígeno CD1d-dependiente de invariables CD4− naturales células killer T (NKT). Las células NKT luego interactúan directamente con los macrófagos pulmonares a través de la producción de IL-13 y enlace con el receptor de IL-13 (IL-13R virus -cél. epiteliales v/a (AEC) –cél. dendríticas (pDC) - cél- tipo I interferón (IFN).

16. For Discussion

17. ZhonghuaShiYan He LinChuang Bing Du XueZaZhi. 2009 Oct;23(5):371-4. [Thecorrelation factor aboutrespiratorysyncytial virus bronchiolitis and post-bronchiolitiswheezing in infant]. [Article in Chinese] Tian M, Zhao DY, Wen GY, Shi SY. Source Department of Respiratory Medicine, theAffiliated Nanjing Children's Hospital of NJMU, Nanjing 210008, China Not breast feeding, exposure to cigarette smoke and the deficiency of VitA, D were the significant risk factors contributed to the RSV bronchiolitis.Exposure to cigarette smoke, the deficiency of VitA, D, the personal history of atopy and the family history of atopy were the significant risk factors contributed to the post-bronchiolitis wheezing in children Exposición al humo de cigarro, la deficiencia de Vit A, D, la historia personal de atopia y la historia familiar de atopia fueron los factores significativos de riesgo que contribuyeron a la sibilancias post-bronquiolitis

18. M E S A R E D O N D A : I N F E C C I Ó N Y A S M A ( M o d e r a d o r : A . B l a n c o Q u i r ó s ) Infecciónvírica y asma: mecanismos inmunológicos F. Lorente*, E. Laffond**, E. Moreno** e I. Dávila** *Unidad de Alergia Infantil, **Unidad de Alergia. Hospital Clínico Universitario. Salamanca Allergol et Immunopathol 2001; 29 (3): 126-151. Stein et al (1999)efectuaron un seguimiento de 888 niños que padecieron bronquiolitis VRS, hasta los 13 años observando que a los 3-5 años padecían asma el 69 %, a los 4-5 años el 55 % y a los 6-8 años el 31 %. RSV in early life and risk of wheeze and allergy by age 13 years Diferentes tipo de infecciones víricas, incluyendo infecciones víricas experimentales con diversas cepas de rinovirus (RV 16), influenza, y VRS pueden causar cambios en la respuesta de la vía aérea frente a histamina, metacolina o alergenos . La infección experimental con rinovirusincrementa la respuesta a histamina, metacolina y alergenos e incrementa la posibilidad de desarrollar una respuesta inflamatoria alérgica retardada después de la inhalación de antígeno. Folkerts G, Busse WW, Nijkan FP, Srokness R, Gern JE, State of the art: virus-induced airway hiperresponsivennes and asthma. Am J Respir Crit Care Med 1998; 157: 1708-20

19. Episodic Viral Wheeze and Multiple Trigger Wheeze in preschool children: A useful distinction for clinicians? Andre´ Schultz , Paul L.P. BrandA./ Paediatric Respiratory Reviews 12 (2011) 160–164

20. VIRUS Y ASMA Persistencia viral y Infección resp. baja Retraso curación epitelial Alergenos, rinitis, Tabaco, polución Sensibilización y síntomas de asma

21. (Human rhinovirus) Factors linked to more-severe HRV or common cold infections

22. MINIREVIEW The ABCs of Rhinoviruses, Wheezing, and Asthma James E. Gern Efectos propuestos de integridad epitelial sobre la gravedad de las infecciones HRV y exacerbaciones de asma. (A) epitelio de las vías respiratorias intacto es resistente a la infección HRV. Si el epitelio es saludable, exposición a HRV es menos probable que iniciar una infección, y si se producen infecciones, la replicación está en un nivel bajo y la gravedad de la enfermedad es leve. (B) alergias y contaminantes pueden dañar el epitelio a través de una variedad de mecanismos; alergia se asocia con inflamación crónica de celular que puede interrumpir las células epiteliales, mientras que los contaminantes pueden tener efectos tóxicos directos sobre las células epiteliales. Cuando se lesiona la capa epitelial, exposición a HRV conduce a replicación viral mejorada y una enfermedad más grave. En los pacientes con asma, resfriados graves tienen más probabilidades que las infecciones leves o asintomáticas provocar exacerbaciones agudas del asma. JOURNAL OF VIROLOGY, Aug. 2010, p. 7418–7426

23. VRS-Induce Bronquiolitis QUIZAS TENGA DIFERENTES FASES Fase II Fase III Largo tiempo Fase I Sibilante persistente Fase Aguda Sibilancias y asma Infección Viral Días Semanas Meses Otros virus -Inducen Bronquiolitis QUIZAS TENGAN DIFERENTES FASES (No se respetan escalas) 23

24. Evolución con sibilancias postbronquiolitis 1ª INFECCIÓN VRS • Eliminador lento VRS • Reinfección por VRS u otro virus • ¿Alergenos? Lesión Tto??? Daño persistente o/y HRB DAÑO INICIAL

25. Evolución con sibilancias postbronquiolitis VRS INFECCIÓN VRS Pulmon patologico previo Evolución cronicidad Insuficiencia respiratoria crónica Tto??? BOOP Agrava daño preexistente

26. Evolución con sibilancias postbronquiolitis Factores predisponentes INFECCIÓN POR VRS Reinfección Descartar otras patologías Tto?? Daño pulmonar-HRB AUMENTA SUCEPTIBILIDAD NUEVAS INFECCIONES

27. CLINICAL MICROBIOLOGY REVIEWS, Jan. 2010, p. 74–98 Vol. 23, No. 1 Respiratory Viral Infections in Infants: Causes, ClinicalSymptoms, Virology, and Immunology John S. Tregoning and JürgenSchwarze Centre for Infection, Department of Cellular and Molecular Medicine, St. George’s University of London, London SW17 0RE, United Kingdom,and Child Life and Health and Centre for Inflammation Research, the University of Edinburgh, the Queen’s Medical Research Institute, Edinburgh, United Kingdom

28. ¿Es un único virus “VRS” que lesiona el pulmón?

29. 1º ¿Cuánto dura la eliminación del VRS? Regamey describe que el 20% de los pacientes presentan test virológicos positivos a las 3 semanas del inicio de una infección respiratoria. Regamey N, Kaiser L, Roiha HL, Deffernez C, Kuehni CE, Latzin P, et al; Swiss Paediatric Respiratory Research Group. Viral etiology of acute respiratory infections with cough in infancy: a community-based birth cohort study. Pediatr Infect Dis J. 2008 Feb;27(2):100-5.

30. Es mas de 1 virus

32. Abreviaturas: AV, adenovirus; BoV, bocavirus; CoV, coronavirus; EV, enterovirus; Echo, echovirus; hMPV, metaneumovirus humano; IV, virus de la gripe; PIV, parainfluenza virus; RV, rhinovirus; RSV, virus sincitial respiratorio; CMV, citomegalovirus;

33. ¿Es el huésped el que condiciona la lesión pulmonar?

36. Acta Paediatr. 2011 Jul 18. doi: 10.1111/j.1651-2227.2011.02414.x. [Epubahead of print] WeightGain in Infancy and Post-BronchiolitisWheezing. Nuolivirta K, Koponen P, Helminen M, Korppi M. Source Seinäjoki Central Hospital, Seinäjoki, FinlandPaediatricResearch Centre, TampereUniversity and University Hospital, Tampere, Finland Both occurrence and recurrence of post-bronchiolitis wheezing were associated with birth weight >4000 g and the recurrence of post-bronchiolitis wheezing with WFL >110% at age 1.5 years. The associations were robust to adjustments with gender and allergy. Higher weight gain from birth to hospitalization at age <6 months was associated with wheezing in the subgroup of children with birth weight >4000 g. Ocurrencia y recurrencia de sibilancias post-bronquiolitis se asociaron con peso al nacer > 4000 g y la recurrencia de las sibilancias post-bronquiolitis con WFL > 110% a los 1,5 años. Las asociaciones fueron sólidas a los ajustes con el género y la alergia. Mayor aumento de peso desde el nacimiento a hospitalización a edad < 6 meses se asoció con sibilancias en el subgrupo de niños con peso al nacer > 4000 g.

37. BRONQUIOLITIS Polución ambiental Polimorfismos en los genes de la respuesta inmune innata LA EDAD INFECCIÓN LACTANCIA PESO ASOCIACIÓN OTROS VIRUS N.I. ALTERACIONES EN EL SURFACTANTE Malformaciones CARGA VIRAL ASMA FQ DBP FUMADOR PASIVO Regulador transcripcional Jun, interferón alfa (IFN-), óxido nítrico sintasa receptor de vitamina D No se respetan porcentajes

38. Opciones Terapéuticas de las sibilancias inducidas post BQL 38

39. Optiones • Antibioticos – por infección asociada o por un efecto antiinflamatorio • Broncodilatadores • B2 agonistas inhalados • Corticoides inhalados • Antagonistas Leukotrienos • Immunoglobulinas

40. SALBUTAMOL -SI RESPONDE ¿ES ASMA? (VER FACTORES PREDISPONENTES) PARA BQL NO HAY TIEMPOS. SOLO LA EVOLUCIÓN EN EL TIEMPO Y MANTENIENDO RESPUESTA ANTIBIOTICOS MACRÓLIDOS -NO HAY EVIDENCIA CIENTIFICA SUFICIENTE

41. Efecto del Montelukast en Bronchiolitis Inducida por VRS • A RDBPC trial studied the effects of the LTRA montelukast on the post-infectious course of RSV-induced bronchiolitis • 130 infants aged 3-36 months were randomized to receive montelukast or placebo • Study treatment was montelukast 5 mg chewable tablets or matching placebo taken in the evening for 28 days • Symptoms were recorded by the caretakers on diary cards Bisgaard H. Am J Respir Crit Care Med 2003;167:379-383 41

42. 30 Montelukast (n=61) Placebo (n=55) 20 p=0.015 10 0 28 0 7 14 21 Montelukast Improved the Symptoms of RSV-Induced Bronchiolitis • Montelukast significantly improved symptom-free days &nights (daily median) Median symptom-free days and nights (%) Days Missing data were considered to be symptomatic days. Bisgaard H. Am J Respir Crit Care Med 2003;167:379-383 42

43. Montelukast : Reduced Exacerbations - Post RSV Bronchiolitis 25 18.2% 20 Patients with exacerbations (%) 15 10 6.6% 5 0 Montelukast Placebo * Withdrawal due to symptom severity, or attending emergency department or hospitalisation due to lung symptoms Bisgaard H. Am J Respir Crit Care Med 2003;167:379-383 43

44. Medicina basada en la evidencia • Evidencias en Pediatria Editorial Montelukast en la bronquiolitis: historia y enseñanzas de una decepción • Antonio Martinez-Gimeno. Medico adjunto y Profesor Asociado. Seccion de Neumologia y Alergia Pediatricas. • Hospital Universitario 12 de Octubre.Departamento de Pediatria. Facultad de Medicina de la Universidad Complutense de Madrid. Madrid (Espana). • Fecha de publicacion en Internet: 24 de febrero de 2009 - http://www.aepap.org/EvidPediatr/etoc.htm

45. A Double-Blind, Placebo-Controlled, Randomized Trial of Montelukast for Acute Bronchiolitis Israel Amirav, MDa,b, Anthony S. Luder, MB, BSa,b, Natalie Kruger, MDa, Yael Borovitch, MDc, Ilan Babai, PhDc,d, Dan Miron, MDa,b, Miriam Zuker, BSc, MT, ASCPa, Gay Tal, MDe, Avigdor Mandelberg, MDc,d A placebo-controlled, double-blind, randomized trial was conducted in 53 infants with acute bronchiolitis. Montelukast had no effect on hospital LOS, clinical course, or cytokines’ response when given in the early acute phase. Montelukast no mejora el curso clínico de la bronquiolitis aguda. Ningún efecto significativo de montelukast en la proporción de citocina 1 2/T-helper T-helper cuando en la primera fase aguda puede demostrarse. Pediatría 2008; 122: e1249–e1255 J Pediatr. 2010 May;156(5):749-54. Epub 2010 Feb 20. A randomizedintervention of montelukastfor post-bronchiolitis: effectoneosinophildegranulation. Kim CK, Choi J, Kim HB, Callaway Z, Shin BM, Kim JT, Fujisawa T, Koh YY. Source Department of Pediatrics and Asthma and Allergy Center, InjeUniversitySanggyePaik Hospital, Seoul, Korea. CONCLUSION: Montelukast treatment reduces eosinophil degranulation and is associated with a decrease in recurrent wheezing episodes in post-RSV bronchiolitis

46. Study of Montelukast for the Treatment of Respiratory Symptoms of Post–Respiratory Syncytial Virus Bronchiolitis in Children Hans Bisgaard1, Alejandro Flores-Nunez2, Anne Goh3, Parvin Azimi4, Andrew Halkas5, Marie-Pierre Malice6, Jean-Louis Marchal6, S. Balachandra Dass6, Theodore F. Reiss6, and Barbara A. Knorr6* Conclusions: In this study, montelukast did not improve respiratory symptoms of post-RSV bronchiolitis in children. Am J Respir Crit Care Med Vol 178. pp 854–860, 2008 AT A GLANCE COMMENTARY Scientific Knowledge on the Subject A previous pilot study (n = 130) reported the significant efficacy ofmontelukast in post-RSV bronchiolitic respiratory symptoms. What This Study Adds to the Field In this study, montelukast did not improve respiratory symptoms of post-RSV bronchiolitis in children.

47. Acta Paediatr. 2009 Nov;98(11):1830-4. Epub 2009 Jul 31. Montelukastdoesnotprevent reactive airwaydisease in youngchildrenhospitalizedfor RSV bronchiolitis. Proesmans M, Sauer K, Govaere E, Raes M, De Bilderling G, De Boeck K. Source Department of Pediatrics, PediatricPulmonologyUniversity Hospital of Leuven, Leuven, Belgium. marijke.proesmans@uz.kuleuven.ac.be CONCLUSION: Treatment with montelukast after hospital admission for RSV bronchiolitis in children younger than 2 years of age did not reduce symptoms of cough and wheeze. We cannot exclude that a subgroup of children may, however, benefit from this treatment.

48. An Esp Pediatr. 2000 Apr;52(4):351-5. [Inhaled corticosteroids and wheezing post-bronchiolitis]. [Article in Spanish] Callén Blecua M, Aizpurua Galdeano P, Ozcoidi Erro I, Mancisidor Aguinagalde L, Guedea Adiego C, Busselo Ortega E, Ibarrondo Uriarte I. Source CAP de Amara Centro, Beraun, Andoain e Irún Inhaled beclomethasone given for 3 months does not significantly modify the occurrence of wheezing episodes during the treatment period or during the following 12 months

49. Cochrane Database Syst Rev. 2000;(2):CD001107. Inhaled steroids for episodic viral wheeze of childhood. McKean M, Ducharme F. Source Department of Child Health, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Royal Infirmary P.O. Box 65, Leicester, UK, LE2 7LX. mcm5@leicester.ac.uk Abstract BACKGROUND: Recurrent episodic wheeze in association with viral upper respiratory tract infection (URTI) is a specific clinical illness distinct from persistent atopic asthma. OBJECTIVES: The objective of this review was to identify whether corticosteroid treatment, given episodically or daily, is beneficial to children with viral episodic wheeze. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) of corticosteroid treatment versus placebo in children under 17 years of age who suffer from 'episodic viral wheeze', which is defined by wheeze in association with coryzal symptoms with minimal or no intercurrent lower respiratory tract symptoms. DATA COLLECTION AND ANALYSIS: Trial quality was assessed independently by two reviewers. Study authors were contacted for missing information. Studies were categorised according to whether treatment was given episodically or daily (maintenance). The primary outcome was episodes requiring oral corticosteroids. Secondary outcomes addressed episode severity, frequency and duration and parental treatment preference. MAIN RESULTS: Five randomised controlled trials in children with a history of mild episodic viral wheeze were identified. Most of the children had previously required no or infrequent oral corticosteroids and had very infrequent hospital admissions. There were three studies of preschool children given episodic high dose inhaled corticosteroid (1.6 - 2.25 mg per day), two using a crossover and one a parallel design. The two studies of maintenance corticosteroid (400 micrograms per day) were parallel in design, one of pre-school children the other of children aged 7 -9 years. Results from the two cross-over studies of episodic high dose inhaled corticosteroids showed a reduced requirement for oral corticosteroids (Relative risk (RR)=0.53, 95% CI: 0.27, 1.04). In these 2 double blind studies, this treatment was preferred by the children's parents over placebo (RR=0.64, 95% CI: 0.48,0.87). Maintenance low dose inhaled corticosteroids did not show any clear reduction over placebo in the proportion of episodes requiring oral corticosteroids (N=2 trials, RR=0.82, 95%CI: 0.23,2.90) or in those requiring hospital admission (N=1 trial, RR=0.21, 95% CI: 0.01,4.11). REVIEWER'S CONCLUSIONS: Episodic high dose inhaled corticosteroids provide a partially effective strategy for the treatment of mild episodic viral wheeze of childhood. There is no current evidence to favour maintenance low dose inhaled corticosteroids in the prevention and management of episodic mild viral induced wheeze. Inhalación episódica de dosis alta de corticosteroides proporcionan una estrategia parcialmente eficaz para el tratamiento de la sibilancia episódica leve viral de la infancia. No hay ninguna evidencia actual a favor de la inhalación de dosis bajas de mantenimiento de corticosteroides en la prevención y gestión de sibilancias episódicas leve inducidas por virus

50. BMJ. 2009 Mar 31;338:b897. doi: 10.1136/bmj.b897. The effect of high dose inhaled corticosteroids on wheeze in infants after respiratory syncytial virus infection: randomised double blind placebo controlled trial. Ermers MJ, Rovers MM, van Woensel JB, Kimpen JL, Bont LJ; RSV Corticosteroid Study Group. Source Department of Paediatric Infectious Diseases, Wilhelmina Children's Hospital, University Medical Centre Utrecht, PO Box 85090, 3508 AB Utrecht, Netherlands. Abstract OBJECTIVE: To determine whether early initiated anti-inflammatory therapy with prolonged high dose inhaled glucocorticoids influences the occurrence and severity of recurrent wheeze after respiratory syncytial virus related lower respiratory tract infections. DESIGN: Randomised double blind placebo controlled trial. PARTICIPANTS: 243 previously healthy infants (126 boys, 117 girls) aged less than 13 months and admitted to hospital with respiratory syncytial virus infection. INTERVENTIONS: 200 mug extra fine hydrofluoroalkane (HFA) beclometasone dipropionate twice daily or matched placebo administered by a pressurised metered dose inhaler and a spacer during the first three months after hospital admission. MAIN OUTCOME MEASURE: The primary outcome was the number of days with wheeze in the year after the three month intervention period. RESULTS: Of the 243 eligible infants, 119 were randomised to receive beclometasone and 124 to receive placebo. No significant difference was found in the number of days with wheeze between the two groups (total days, 1761/33 568 in the beclometasone group v 2301/36 556 in the placebo group, P=0.31) and the proportion of infants with wheeze did not differ between the groups (61% in the beclometasone group v 62% in the placebo group, P=0.90). In the predefined subgroup of infants who did not need mechanical ventilation (n=221), beclometasone reduced the number of days with wheeze by 32% (relative reduction in total days, 1315/30 405 in the beclometasone group v 2120/33 149 in the placebo group, P=0.046). This reduction was most pronounced during the first six months of the follow-up year after intervention. The proportion of infants with wheeze did not differ between the groups (59% in the beclometasone group v 60% in the placebo group, P=0.89). CONCLUSIONS: Early initiated high dose extra fine HFA beclometasone to infants during the first three months after hospital admission for respiratory syncytial virus infection has no major effect on recurrent wheeze. The general use of such treatment during lower respiratory tract infection with respiratory syncytial virus should not be advocated. CONCLUSIONES: Inició temprano de dosis altas de HFA beclometasone extra fino a los lactantes durante los primeros tres meses después de hospitalización de infección por virus sincitial respiratorio no tiene ningún efecto importante sobre sibilancias recurrentes. El uso general de ese tratamiento durante la infección de las vías respiratorias inferiores con virus sincitial respiratorio no debe ser recomendado