INFECCIONES BACTERIANAS

Presentación del tema: "INFECCIONES BACTERIANAS"— Transcripción de la presentación:

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

3

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?

6

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: 100 76% 80 58% % niños con sibilancias 60 40 Slide 8 Out of 83 children aged <2 years who were hospitalised for wheezing and who completed a follow-up until the age of 3 years, 76% (61/83) had subsequent wheezing at age 1-2 years and 58% (44/76) at age 2-3 years.10 In a study of 888 children followed prospectively up to age 13 years, in which the children were assessed by their paediatrician whenever they had signs or symptoms of lower-respiratory tract disease, 472 had at least one lower-respiratory tract illness and recorded test for viruses and other agents. Of these, 43.9% (207/427) had been infected with RSV lower-respiratory tract illness before the age of 3 years.14 Those who had suffered from RSV infections before the age of 3 years were 3.2 times more likely to have infrequent wheeze and 4.3 times more likely to have frequent wheeze at age 6 years compared with those children who had not had lower-respiratory tract disease before the age of 3 years. The risk for both frequent and infrequent wheeze decreased with age, and became non-significant at age 13 years. The results were adjusted for sex, maternal education, family history of asthma, allergy skin tests at age 6 years, birth weight, and maternal smoking.14 20 1-2 (n=83) Edad (años) 2-3 (n=76) De 83 niños <2 años hospitalizados con BQL, un alto porcentaje mantiene sibilancias 8

9 Sibilancias al año de la BQL
Allergy. 2009 Sep;64(9): Epub 2009 Mar 23. Recurrent wheezing after respiratory syncytial virus or non-respiratory syncytial virus bronchiolitis in infancy: a 3-year follow-up. Valkonen H, Waris M, Ruohola A, Ruuskanen O, Heikkinen T. Source Department of Pediatrics, Turku University Hospital, Finland Nº pacientes Sibilancias al año de la BQL A los 3 años % BQL no VRS 217 36 16,6 BQL a VRS 199 5 2,5 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) ]. The rates of recurrent wheezing were significantly increased in the non-RSV group also within 2 years (RR 2.9; 95% CI ) and 3 years (RR 3.4; 95% CI ) 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 VRS-Bronquiolitis: ¿Asociación con asma?
n= 140, incidencia de asma a los 7.5 años en niños con infección por VRS comparado con controles 3% 30% 5 10 15 20 25 30 35 RSV (n=47) Control (n=93) Niños con asma a la edad de 7,5 años (%) Slide 9 Airway hyperreactivity develops in some children after a lower-respiratory tract viral infection.2 In a study of 140 children, 47 of whom were hospitalised with RSV in infancy, 30% of the RSV group had developed asthma compared with 3% in the control group at age 7.5 years (p<0.0001). For “any wheezing,” the cumulative prevalence was 68% and 34%, respectively (p<0.001).12 In the same study, RSV showed the highest independent risk ratio for asthma out of all of the potential risk factors (hereditary and environmental) studied, with an odds ratio (OR) of 12.7 (95% confidence interval (CI) 3.4 to 47.2).12 10 Sigurs N et al. Am J Respir Crit Care Med 2000;161:

11 Sintomas respiratorios recurrentes según los años de evolución, luego de infección inicial por VRS
Henry et al Arch Dis Child Webb et al Arch Dis Child Hall et al 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., 2002 Sept 15, Stockholm

13 Immunologic cascade of allergy
Treg IL-10 TGF-beta 1. Persorption of Allergen 2. Sensitization to allergen TNF-, eosinophilic proteins 3. Inflammation DCr Sept 15, 2007 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 January ; 1183: 195–210. doi: /j 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 Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2009 Oct;23(5):371-4.
[The correlation factor about respiratory syncytial virus bronchiolitis and post-bronchiolitis wheezing in infant]. [Article in Chinese] Tian M, Zhao DY, Wen GY, Shi SY. Source Department of Respiratory Medicine, the Affiliated Nanjing Children's Hospital of NJMU, Nanjing , 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 ) Infección vírica 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): 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 rinovirus incrementa 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:

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

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

22 The ABCs of Rhinoviruses, Wheezing, and Asthma

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 Fase Aguda Sibilante persistente Sibilancias y asma Infección Viral Días Semanas Meses Slide 6 RSV-induced bronchiolitis may consist of several phases: Phase 1: Infection with RSV in children usually begins in the nasopharynx with coryza and congestion, often associated with low-grade fever.7 Phase 2: Acute phase. During a period of 2-5 days, the infection may progress to the lower respiratory tract, with subsequent development of cough, dyspnoea, and wheeze.7 This phase lasts for several days and symptoms are usually mild to moderate in severity; however, 1-2% of infants will require hospitalisation.8 Phase 3: Persistent or recurrent episodes of wheezing. A study held in a private paediatric clinic in North Carolina, in which 6,165 cases of lower respiratory illnesses were seen, 52.9% of patients aged 2 years had an occurrence of wheezing with RSV infection.5 Longer term: Children who develop RSV-induced bronchiolitis can be at risk of recurrent episodes of wheezing as well as the development of asthma. A summary of available retrospective and prospective studies of children with mild to moderate or severe RSV lower-respiratory tract infection shows that infection in infancy may be associated with an increased risk of bronchial obstructive symptoms years after the infection, and lung function may be affected for several years. The mechanisms that underlie this connection are not clear.9 A prospective study followed 127 children aged <2 years, who were hospitalised due to wheezing (n=83) or pneumonia (n=44) during 12 months in A total of 108 children were followed up until 3 years of age. Recurrent wheezing was more common in the children originally admitted for wheeze compared with pneumonia. From the patients admitted due to wheeze, subsequent wheezing was seen in 76% (61/80) of children aged 1-2 years and in 58% (44/76) aged 2-3 years. The respective values in the pneumonia group were 9% (3/33) and 15% (5/32). Subsequent wheezing was seen in 52% (15/29) of children with wheezing-associated RSV infection, compared with 14% (2/14) of patients with pneumonia as the initial infection. The findings suggested that bronchial hyper reactivity was the host factor most conducive to recurrent wheezing.10 In a prospective follow-up study of 54 children aged <2 years hospitalized for RSV bronchiolitis, 51% (24/47) had late-onset or persistent wheezing at age 5 years. “Persistent wheezing” included children who wheezed during the first year of life and had asthma or asthma attacks at age 5 years; “late-onset wheezing” was defined as no wheeze during the first year of life and the presence of asthma or asthma attacks at age 5 years.11 In another prospective follow-up study, 47 children initially hospitalized with RSV bronchiolitis were assessed at a mean age of 7.5 years. A matched control group of 89 children were also followed over the same period. The cumulative incidence of asthma was 30% (14/47) in the RSV group vs. 3% (3/93) in the control group.12 Otros virus -Inducen Bronquiolitis QUIZAS TENGAN DIFERENTES FASES 23 (No se respetan escalas)

24 Daño persistente o/y HRB
Evolución con sibilancias postbronquiolitis 1ª INFECCIÓN VRS Eliminador lento VRS Reinfección por VRS u otro virus ¿Alergenos? Lesión Tto??? El concepto Control refleja no solamente la severidad de los sintomas, sino la respuesta al tratamiento, y que la severidad no es una caracteristica invariable del paciente, sino que va cambiando con los meses o anos. Es un enfoque dinamico e individual. Daño persistente o/y HRB DAÑO INICIAL 24 24

25 Insuficiencia respiratoria crónica Agrava daño preexistente
Evolución con sibilancias postbronquiolitis VRS INFECCIÓN VRS Pulmon patologico previo Evolución cronicidad Insuficiencia respiratoria crónica Tto??? El concepto Control refleja no solamente la severidad de los sintomas, sino la respuesta al tratamiento, y que la severidad no es una caracteristica invariable del paciente, sino que va cambiando con los meses o anos. Es un enfoque dinamico e individual. BOOP Agrava daño preexistente 25 25

26 Descartar otras patologías AUMENTA SUCEPTIBILIDAD NUEVAS INFECCIONES
Evolución con sibilancias postbronquiolitis Factores predisponentes INFECCIÓN POR VRS Reinfección Descartar otras patologías Tto?? El concepto Control refleja no solamente la severidad de los sintomas, sino la respuesta al tratamiento, y que la severidad no es una caracteristica invariable del paciente, sino que va cambiando con los meses o anos. Es un enfoque dinamico e individual. Daño pulmonar-HRB AUMENTA SUCEPTIBILIDAD NUEVAS INFECCIONES 26 26

27 CLINICAL MICROBIOLOGY REVIEWS,
Jan. 2010, p. 74–98 Vol. 23, No. 1 Respiratory Viral Infections in Infants: Causes, Clinical Symptoms, Virology, and Immunology John S. Tregoning and Jürgen Schwarze 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 Feb;27(2):100-5.

30 Es mas de 1 virus

31

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?

34

35

36 Acta Paediatr. 2011 Jul 18. doi: 10. 1111/j. 1651-2227. 2011. 02414. x
Acta Paediatr Jul 18. doi: /j x. [Epub ahead of print] Weight Gain in Infancy and Post-Bronchiolitis Wheezing. Nuolivirta K, Koponen P, Helminen M, Korppi M. Source Seinäjoki Central Hospital, Seinäjoki, Finland Paediatric Research Centre, Tampere University 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 No se respetan porcentajes
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
Slide 20 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 Slide 29 This randomised study assessed the effect of the LTRA montelukast on the post-infectious course of RSV-induced bronchiolitis.33 One hundred and thirty infants aged 3-36 months were enrolled and randomised to receive either montelukast 5 mg chewable tablets (n=65) or matching placebo (n=65) in the evenings, once daily, for 28 days. Treatment started within 7 days of the appearance of symptoms.33 Symptoms were recorded on diary cards during the 4-week treatment period and for a further 4 weeks following the end of treatment.33 Symptoms recorded by the caretaker were: Night-time cough Daytime cough Wheeze Dyspnoea Limitation of activity (on a 5-point scale, from 0=no symptoms to 4=very severe symptoms) Daytime and night-time ß2-agonist rescue medication use, and attendance at emergency clinics or a hospital for lung symptoms, was also noted.33 SINGULAIRTM is not currently indicated to treat RSV infection. Please refer to the full prescribing information on approved indications and dosage. 41 Bisgaard H. Am J Respir Crit Care Med 2003;167:

42 Montelukast Improved the Symptoms of RSV-Induced Bronchiolitis
Montelukast significantly improved symptom-free days &nights (daily median) 30 20 10 7 14 21 28 Montelukast (n=61) Placebo (n=55) p=0.015 Median symptom-free days and nights (%) Slide 30 Treatment with oral montelukast was associated with a significant improvement in the primary endpoint, symptom-free days and nights. Infants on montelukast were free from daytime and night-time symptoms on 6 of 28 days (22% of the treatment period) compared with 1 of 28 days (4% of the treatment period) in the placebo group (p=0.015).33 Daytime cough (one component of a symptom-free day) was improved significantly with montelukast (p=0.04); improvements in other components of the symptom-free day, night-time cough, wheeze, shortness of breath, and limitation of activity, were all numerically in favour of montelukast but did not reach statistical significance.33 SINGULAIRTM is not currently indicated to treat RSV infection. Please refer to the full prescribing information on approved indications and dosage. Days Missing data were considered to be symptomatic days. Bisgaard H. Am J Respir Crit Care Med 2003;167: 42

43 Montelukast : Reduced Exacerbations - Post RSV Bronchiolitis
25 20 18.2% Patients with exacerbations (%) 15 10 6.6% Slide 31 Montelukast reduced the incidence of exacerbations and significantly increased the time to occurrence of the first exacerbation, compared with placebo.33 An exacerbation was defined as study withdrawal due to symptom severity, visit to an emergency department, or hospitalization due to lung symptoms. Exacerbations occurred in 4/61 (6.6%) patients on montelukast and 10/55 (18.2%) patients on placebo (p=0.08).33 The time to first exacerbation was 8 days on placebo and 23 days on montelukast (p=0.044).33 SINGULAIRTM is not currently indicated to treat RSV infection. Please refer to the full prescribing information on approved indications and dosage. 5 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: 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

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 May;156(5): Epub 2010 Feb 20. A randomized intervention of montelukast for post-bronchiolitis: effect on eosinophil degranulation. 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, Inje University Sanggye Paik 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.
Montelukast does not prevent reactive airway disease in young children hospitalized for RSV bronchiolitis. Proesmans M, Sauer K, Govaere E, Raes M, De Bilderling G, De Boeck K. Source Department of Pediatrics, Pediatric Pulmonology University Hospital of Leuven, Leuven, Belgium. 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. 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 ( 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 Mar 31;338:b897. doi: /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/ in the beclometasone group v 2301/ 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/ in the beclometasone group v 2120/ 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

51 Cochrane Database Syst Rev. 2011 Jan 19;(1):CD004881.
WITHDRAWN: Inhaled corticosteroids during acute bronchiolitis in the prevention of post-bronchiolitic wheezing. Blom DJ, Ermers M, Bont L, van Woensel JB, Van Aalderen WM. Source Department of Pediatrics, Zaans Medisch Centrum, Koningin Julianaplein 58, Amsterdam, Netherlands, 1500 EE Zaandam. This review does not demonstrate an effect of inhaled corticosteroids given during the acute phase of bronchiolitis in the prevention of post-bronchiolitic wheezing. The small number of included participants and the inability to pool all clinical outcomes precludes us from making strong recommendations.

52 EVOLUCIÓN A ASMA DE LOS SIBILANTES
Infant wheeze with atopic parent (s) Infant wheeze + atopic eczema and/or other food allergies atopic parent + positive skin prick test + raised sIL-2R 20% 40% 50% 90%

53 Interacción de factores causantes de enfermedades después de la infección viral respiratoria y el impacto de la infancia. La causa última de la enfermedad después de la infección viral respiratoria es la oclusión de las vías respiratorias, lo que conduce a una reducción en el intercambio de gas, dificultad respiratoria. Esta oclusión de las vías respiratorias puede ser inmune o mediada por los virus y probablemente es una combinación de ambos. En los primeros años de vida hay una gran interrelación entre el daño mediado por virus e inmunidad. El sistema inmunológico infantil es sesgado a un fenotipo de pobre respuesta, con una menor respuesta de interferón, conduce a una mayor carga viral de tipo I. La respuesta inmune adaptativa también es sesgada y limitada en su efecto. Estos factores actúan en combinación con tamaño de cuerpo pequeño y pequeños vías aéreas lo que aumentan aún mas la severidad de la enfermedad

54 Riesgo sibilancia-asma
Bajo peso nacer Gesta fumadora Sexo femenino Eczema Atopía Madre adolescente (1ª gesta) Niño sibilante Solo con infección viral Con varios precipitantes Remisión en 80% Asma persistente (con o sin evidencia de atopía) % ?? COPD in adults

55 En suma Individualizar el paciente Tratamiento personalizado Seguido por un solo profesional Sin respuesta por 2 meses suspender tto

56 PERSONALIZADO CLARAMENTE IDENTIFICADO DINÁMICO PACIENCIA-PARA ACOMPAÑAR ESTA FAMILIA Y ESTOS NIÑOS

57 QUE HAY DE LOS INMUNO MODULADORES