Carlo Capristo Montelukast, una molecola buona per tutte le stagioni?

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Carlo Capristo Montelukast, una molecola buona per tutte le stagioni?

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  • Carlo Capristo Montelukast, una molecola buona per tutte le stagioni?
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  • Leukotrienes M. Peter-Golden N Engl J Med 2007
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  • EXPRESSION OF THE CYSTEINYL LEUKOTRIENE 1 RECEPTOR IN NORMAL HUMAN LUNG AND PERIPHERAL BLOOD LEUKOCYTES CysLT 1 R CD34 + CD8 + CD4 + CCR3 T Cells Eosinophil Neutrophil Monocyte IL5R CD1 4 LTC 4 LTD 4 LTE 4 Macrophage LN5 M-CSF GM-CSF Basophil B lymphocyte CD19 M-CSF, GM-CSF, IL-3 LTC 4, LTD 4, LTE 4 Pluripotent Haemopoietic Stem Cell
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  • Partendo dalle linee guida, quali sono le nuove evidenze presenti in letteratura in tema di Asma bronchiale Asma da sforzo Wheezing prescolare
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  • Classification and pharmacological treatment of preschool wheezing: changes since 2008 Brand PLP, ERJ 2014;43:1172 significant new evidence 1)Since the publication of the European Respiratory Society Task Force report in 2008, significant new evidence has become available on the classification and management of preschool wheezing disorders. wheeze patterns in young children vary over time and with treatment distinction between episodic viral wheeze and multiple-trigger wheeze unclear in many patients. 2)The consensus group acknowledges that wheeze patterns in young children vary over time and with treatment, rendering the distinction between episodic viral wheeze and multiple-trigger wheeze unclear in many patients. 3)Inhaled corticosteroids remain first-line treatment for multiple-trigger wheeze, episodic viral wheeze with frequent or severe episodes 3)Inhaled corticosteroids remain first-line treatment for multiple-trigger wheeze, but may also be considered in patients with episodic viral wheeze with frequent or severe episodes, or when the clinician suspects that interval symptoms are being under reported.
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  • Classification and pharmacological treatment of preschool wheezing: changes since 2008 Brand PLP, ERJ 2014;43:1172 4)Any controller therapy should be viewed as a treatment trial 4)Any controller therapy should be viewed as a treatment trial, with scheduled close follow-up to monitor treatment effect. 5)The group recommends discontinuing treatment if there is no benefit and taking favourable natural history into account when making decisions about long-term therapy. 6)Oral corticosteroids are not indicated in mild-to- moderate acute wheeze episodes and should be reserved for severe exacerbations in hospitalised patients 6)Oral corticosteroids are not indicated in mild-to- moderate acute wheeze episodes and should be reserved for severe exacerbations in hospitalised patients.
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  • Classification and pharmacological treatment of preschool wheezing: changes since 2008 Brand PLP, ERJ 2014;43:1172 * * Brand PL, Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach. Eur Respir J 2008; 32: 10961110. *
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  • Classification and pharmacological treatment of preschool wheezing: changes since 2008 Brand PLP, ERJ 2014;43:1172 2013 consensus statement on classification and management of preschool wheezing disorders Distinction of preschool wheeze phenotypes distinction not clear in all patients The distinction between EVW and MTW is not clear in all patients Someconsistent pattern but symptom patterns change over time in many patients Some children retain a consistent pattern of EVW or MTW, but symptom patterns change over time in many patients and their airway pathology remains unclear Severity and frequency of episodes Severity and frequency of episodes seem to be at least as important to distinguish between children as the distinction between EVW and MTW
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  • Classification and pharmacological treatment of preschool wheezing: changes since 2008 Brand PLP, ERJ 2014;43:1172 2013 consensus statement on classification and management of preschool wheezing disorders Daily controller therapy In children with MTW, ICS are the first choice for daily controller therapy In children with EVW, daily therapy may be considered with either ICS or montelukast if: - the attacks are severe (requiring hospital admission or systemic corticosteroids); - or the attacks are frequent; - or the clinician suspects that interval symptoms are being under reported
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  • Classification and pharmacological treatment of preschool wheezing: changes since 2008 Brand PLP, ERJ 2014;43:1172 2013 consensus statement on classification and management of preschool wheezing disorders Daily controller therapy Any controller therapy should be viewed as a treatment trial, with scheduled follow-up Discontinue treatment if there has been no benefit Take favourable natural history into account: - taper down to lowest effective dose, and - discontinue treatment if the child has been symptom-free for 3 months on low-dose therapy
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  • Classification and pharmacological treatment of preschool wheezing: changes since 2008 Brand PLP, ERJ 2014;43:1172 2013 consensus statement on classification and management of preschool wheezing disorders Treatment of acute episodes Oral corticosteroids are not indicated in preschool children with an exacerbation of viral wheeze who do not need to be admitted to hospital Oral corticosteroids are indicated only in preschool children admitted to hospital with very severe wheeze; even in this group, evidence to support the use of prednisolone is not robust
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  • (PREVIA Study). Bisgaard ARCCM 2005;171:315 * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * placebo montelukast Percentage of patients with an exacerbation event
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  • 1.19 0.66 0.53 1.74 1.10 0.64 0.0 0.5 1.0 1.5 2.0 2.5 Totali (via inalatoria ed orale) Via InalatoriaVia Orale Montelukast 4 mg (n=265) Placebo (n=257) Cicli di trattamento con Corticosteroidi 32% 40% p=0.024 p=0.027 p=0.368 Montelukast Reduces Asthma Exacerbations in 2- to 5-Year-Old Children with Intermittent Asthma Bisgaard H et al. - Am J Respir Crit Care Med 2005; 171: 315322
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  • MONTELUKAST, confrontato con il fluticasone, nel controllo dellasma, in bambini dai 6 ai 14 anni con asma lieve: lo studio MOSAIC MOntelukast Study of Asthma In Children Garcia ML, et al Pediatrics 2005; 116(2): 360-369
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  • Studio MOSAIC Disegno Visite Mese Run-in placebo Montelukast 5 mg una volta al giorno* + placebo-fluticasone x2/die Fluticasone 100 g x2/die + placebo-montelukast una volta al giorno Periodo I Periodo II 6 12 8 5 4 4 0 321 -agonista o -agonista + 1 farmaco di controllo *I pazienti che compivano 15 anni di et, passavano al dosaggio di montelukast 10mg alla Visita 5 Garcia ML et al. Pediatrics 2005;116(2):360-369 N= 495 N= 499
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  • Studio MOSAIC Obiettivo Primario ENDPOINT PRIMARIO: Variazione dal basale della percentuale di giorni senza interventi di soccorso per asma (Rescue Free Days-RFD) (assunzione di - agonisti a breve durata dazione, CS per via sistemica, altri farmaci di soccorso o utilizzo di risorse sanitarie visite ambulatoriali, visite in PS, ricoveri ospedalieri) Garcia ML et al. Pediatrics 2005;116(2):360-369
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  • Studio MOSAIC Risultati 86.7 84.0 0 20 40 60 80 100 Montelukast 5 mg (n=482) Fluticasone 200 mcg (n=484) Analisi intention to treat modificata (MITT) Montelukast risultato NON INFERIORE al fluticasone sullendpoint primario nei 12 mesi di trattamento Giorni senza interventi di soccorso, media (%) Garcia ML et al. Pediatrics 2005;116(2):360-369
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  • Studio MOSAIC Risultati sulla velocit di crescita staturale 7.0 6.5 6.0 5.5 5.0 Mesi 4812 Montelukast 5 mg (n=481) Fluticasone 200 mcg (n=482) Velocit di crescita media (cm/anno) p=0.018 Garcia ML et al. Pediatrics 2005;116(2):360-369
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  • Montelukast As An Episode Modifier in the Treatment of Infrequent Episodic Asthma in Children TRATTAMENTO A BREVE TERMINE CON MONTELUKAST IN BAMBINI CON ASMA INTERMITTENTE: UNO STUDIO RANDOMIZZATO E CONTROLLATO Pre-Empt Robertson CF et al Am J Respir Crit Care Med 2007;175:323-329
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  • Studio PRE-EMPT Disegno 0 2 Settimane 52 settimane o 5 episodi trattati Montelukast 4 mg or 5 mg* una volta al giorno con episodi di URTI** o asma per un minimo di 1 settimana e un max di 20 giorni Placebo una volta al giorno con episodi di URTI** o asma per un minimo di 1 settimana e un max di 20 giorni Beta-agonisti al bisogno Periodo I Run-in Periodo II Trattamento attivo in doppio cieco *4 mg per I bambini di 2-5 anni di et, 5 mg per I bambini di 6-14 anni **URTI = Upper Respiratory Tract Infections generalmente seguite da asma n=107 n=113 Robertson CF et al. Am J Respir Crit Care Med 2007;175:323-329
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  • Studio PRE-EMPT Obiettivo Primario Obiettivo dello studio era valutare se un trattamento intermittente con montelukast, introdotto ai primi segni di un episodio acuto di asma o di infezione virale delle vie aeree superiori, potesse modificare la severit dellepisodio stesso Endpoint primario era lutilizzo non programmato di risorse sanitarie correlate al trattamento degli episodi asmatici acuti (visite mediche non programmate,visite pediatriche specialistiche, ricorso al pronto soccorso e ospedalizzazioni)(HRU*) Robertson CF et al. Am J Respir Crit Care Med 2007;175:323-329 *Healthcare Resource Utilization
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  • Il trattamento a breve termine con MONTELUKAST ha ridotto significativamente lutilizzo di risorse sanitarie correlate al trattamento degli episodi asmatici acuti 30.1 39.9 0 5 10 15 20 25 30 35 40 45 Montelukast (n=97)Placebo (n=105) p=0.008 -24% Episodi con HRU (%) Robertson CF et al. Am J Respir Crit Care Med 2007;175:323-329
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  • Il trattamento a breve termine con MONTELUKAST ha ridotto significativamente lHRU, i sintomi, i giorni di assenza da scuola dei bambini e quelli di assenza da lavoro dei genitori Nel gruppo trattato con MONTELUKAST confrontato con il gruppo placebo: -14% -28.5% -8.6% -37% -33% Robertson CF et al. Am J Respir Crit Care Med 2007;175:323-329 * p