Wheezing e Asma: Linee Guida, Luci ed Ombre

Transcript

1 XIX CONGRESSO NAZIONALE Società Italiana di Pediatria Preventiva e Sociale Torino ottobre 2007 Il Bambino con Disturbi Respiratori dalla flogosi all infezione: prevenzione, diagnosi e terapia Wheezing e Asma: Linee Guida, Luci ed Ombre NICOLA OGGIANO Istituto di Scienze Materno-Infantili Università Politecnica delle Marche ANCONA

2 G IN lobal itiative for A sthma

3 Global Strategy for Asthma Management and Prevention (2006) Revised 2006

4 The influence of variation in type and pattern of symptoms on assessment in pediatric asthma (801 interviews were completed by parents of children aged 4 to 15 years and by children themselves aged 16 to 18 years) The goals of therapy for asthma, based on the National Asthma Education and Prevention Program guidelines, have not been achieved for the majority of children In addition, parents and children overstimate the child s asthma control and commonly restrict activities to control asthma symptomps Deficiencies in the control of asthma may be related to the underestimation of the burden of disease AL Fuhlbrigge Pediatrics 2006;118:619

5 Classificazione di gravità in assenza di terapia STEP sintomi Sintomi notturni FEV1 o PEF STEP 4 grave persistente continui att. fisica limitata frequenti < 60% predetto STEP 3 Mod. persistente quotidiani attacchi limitanti l attività fisica >1 volta/settimana 60-80% predetto STEP 2 lieve persistente >1volta /settimana <1 volta /giorno > 2 volte / mese > 80% predetto STEP 1 intermittente <1volta /settimana < 2 volte / mese > 80% predetto La presenza di almeno uno dei criteri di gravità è sufficiente per classificare un paziente in un determinato livello di gravità

6 Le limitazioni di una classificazione basata sulla gravità Difficoltà applicative nella pratica clinica Formule complicate, difficili da ricordare Eccessivo schematismo Non considera la variabilità della storia naturale dell asma Non predice necessariamente la risposta al trattamento PM Gustafsson Int. Clin Pract 2006; 60:321 AL Fuhlbrigge Pediatrics 2006;118:619

7 Controllo dell asma Il controllo è un parametro molto più dinamico, più idoneo alla variabilità della malattia asmatica Tiene in considerazione non solo la gravità, ma anche la risposta al trattamento, molto spesso imprevedibile La risposta può risultare soddisfacente con trattamenti di breve durata e bassi dosaggi di S.I. anche in pazienti con grado inizialmente elevato di gravità SW Stoloff J Allergy Clin Immunol 2006;117:544 AT Luskin J Allergy CIin Immunol 2005;115:S539

8 Levels of Asthma Control Characteristic Controlled (All of the following) Partly controlled (Any present in any week) Uncontrolled Daytime symptoms None (2 or less / week) More than twice / week Limitations of activities Nocturnal symptoms / awakening Need for rescue / reliever treatment None None None (2 or less / week) Any Any More than twice / week 3 or more features of partly controlled asthma present in any week Lung function (PEF or FEV 1 ) Normal < 80% predicted or personal best (if known) on any day Exacerbation None One or more / year 1 in any week

9 Childhood Asthma Control Test (C-ACT) AH Liu J Allergy Clin Immunol 2007;119:817

10 parametro FVC FEV1/FVC (I. Tiffeneau) v.n. (% pr.) > 80% B > 83-85% (GINA 06) >90% A > 70-75% significato nella broncostruzione asmatica Si riduce nell asma grave, dove è indice indiretto di intenso air trapping MOLTO SENSIBILE NEL BAMBINO ridotto nelle forme ostruttive medio-gravi indice molto affidabile di elevato rischio di riacutizzazione asmatica severa CD Ramsey Pediatr Pulmonol 2005;39:268 LB Bacharier AJRCCM 2004;170:426 JD Spahn J Pediatr 2006;148:11 AL Fuhlbrigge Pediatrics 2006;118:e347 FEV1 FEF > 80% > 70% Riflette la pervietà nei bronchi di grosso e medio calibro Normale nelle fasi ostruttive precoci Riflette la pervietà nei bronchi di piccolo calibro (> 2 mm di diametro) Si riduce precocemente nell asma

11 Dosaggio giornaliero (µg/die) comparativo stimato degli steroidi inalatori in età pediatrica* Farmaco Basso dosaggio Medio dosaggio Alto dosaggio BDP (h.f.a.) >500 BUD (d.p.i.) >600 FP >400 Flunisolide >1250 *I dosaggi comparativi devono essere valutati anche in considerazione dei diversi sistemi di erogazione disponibili per ciascun composto (MDI, DPI, nebulizzatore) GINA 2005

12 Dosaggio giornaliero (µg/die) comparativo stimato degli steroidi inalatori in età pediatrica* Farmaco Basso dosaggio Medio dosaggio Alto dosaggio BDP (h.f.a.) >500 BUD (d.p.i.) >600 FP >400 Flunisolide nebulizzatore >1250 *I dosaggi comparativi devono essere valutati anche in considerazione dei diversi sistemi di erogazione disponibili per ciascun composto (MDI, DPI, nebulizzatore) GINA 2005

13 Estimate Comparative Daily Dosages for Inhaled Glucocorticosteroids by Age Drug Beclomethasone Low Daily Dose (µg) Medium Daily Dose (µg) High Daily Dose (µg) > 5 y Age < 5 y > 5 y Age < 5 y > 5 y Age < 5 y > > >1000 >400 Budesonide > >1000 >400 Budesonide-Neb Inhalation Suspension > >1000 Ciclesonide > > > >320 Flunisolide > > >2000 >1250 Fluticasone > > >500 >500 Mometasone furoate > > > >400 Triamcinolone acetonide > > >2000 >1200

14 Asthma Management and Prevention Program Component 3: Assess, Treat and Monitor Asthma Depending on level of asthma control, the patient is assigned to one of five treatment steps Treatment is adjusted in a continuous cycle driven by changes in asthma control status. The cycle involves: - Assessing Asthma Control - Treating to Achieve Control - Monitoring to Maintain Control

15 LEVEL OF CONTROL controlled partly controlled uncontrolled exacerbation REDUCE INCREASE TREATMENT OF ACTION maintain and find lowest controlling step consider stepping up to gain control step up until controlled treat as exacerbation REDUCE STEP 1 STEP 2 TREATMENT STEPS STEP 3 STEP 4 INCREASE STEP 5

16 medium-dose ICS

17 SHORT COURSE MONTELUKAST FOR INTERMITTENT ASTHMA IN CHILDREN. A Randomized Controlled Trial (220 children 2-14 years with intermittent asthma. Follow-up 12 months) Short course of Montelukast (4 mg or 5 mg) introduced at the onset of each URTI or asthma symptoms and continued for a minimum of 7 days or until symptoms had resolved for 48 hours Nonsignificant reduction in specialist attendances and hospitalizations, duration of episode, and β-agonist and prednisolone use Modest reduction in acute health care resource utilization, symptoms, time off from school, and parental time off from work CH Robertson AJRCCM 2007; 175:323

18 medium-dose ICS

19 Treating to Achieve Asthma Control Step 2 Reliever medication plus a single controller A low-dose inhaled glucocorticosteroid is recommended as the initial controller treatment for patients of all ages (Evidence A) Alternative controller medications include leukotriene modifiers (Evidence A) appropriate for patients unable/unwilling to use inhaled glucocorticosteroids

20 all interno dello step 2 in caso di mancato controllo prima di un eventuale step up è prevista una variazione Montelukast vs Steroidi Inalatori ma non il contrario

21 Montelukast, compared with fluticasone, for control of asthma among 6 to 14 year old patients with mild asthma: the MOSAIC study Studio munticentrico controllato e randomizzato a gruppi paralleli; 12 mesi di trattamento Attacchi di Asma RFD (rescue-free days) Fluticasone Montelukast (25,6%) (32,%) Steroidi Sistemici Fluticasone Montelukast (10,5%) (17,8%) ML Garcia Garcia Pediatrics 2005; 116: 360

22 For children older than 5 years, adolescents and adults * medium-dose ICS * Autorizzazione LABA: Salmeterolo > 4 anni; Formoterolo > 6 anni

23 For children 5 years and younger Medium dose ICS Low-dose ICS + LABA * * Autorizzazione LABA: Salmeterolo > 4 anni; Formoterolo > 6 anni

24 Step 3 Treating to Achieve Asthma Control

25

26 Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma PM O Byrne et al AJRCCM 2005;171:129

27 Budesonide/formoterol maintenance plus reliever therapy: a new stategy in pediatric asthma The SMART regimen using budesonide/formoterol for both maintenance and as needed symptom relief reduce the exacerbation rate compared with both fixed dose combination and higer fixed dose ICS alone in children with asthma H Bisgaard Chest 2006;130: children (4 11 years) with asthma uncontrolled on ICS; 12 month, double-blind, study budesonide/formoterol 80/4,5 µg (symbicort maintenance and relief therapy, SMART) budesonide/formoterol 80/4,5 µg (fixed combination) plus terbutaline budesonide 320 µg (fixed dose budesonide) plus terbutaline

28 Treating to Achieve Asthma Control Additional Step 3 Options Low-dose inhaled glucocorticosteroid combined with leukotriene modifiers (Evidence A*) Low-dose sustained-release theophylline (Evidence B*) *only for children older than 5 years

29 Formoterol, montelukast, and budesonide in asthmatic children: Effect on lung function and exhaled nitric oxide 48 children 7-11 years of age This study has demonstrated that add-on therapy with montelukast to low dosage of budesonide is more effective than the addition of LABA or doubling the dose of budesonide in controlling airway inflammation measured as FEno in asthmatic children bud 200µg bid stop formoterol add montelukast M Miraglia del Giudice Respir Med 2007;101:1809 bud 200µg bid stop montelukast

30 STEP 3 bambini in età scolare S.I. a dosaggio adeguato associare β 2 -Long Acting oppure Antileucotrienici?

31 Steroide Inalatorio + beta-2 Long Acting Bassi valori spirometrici EIA GP Currie CHEST 2005;128:2954

32 Steroide Inalatorio + Antileucotrienico Rinosinusite allergica Dermatite atopica Malattia allergica sistemica Allergia alimentare EIA Previsione di scarsa compliance? Da GP Currie CHEST 2005;128:2954 mod

33 Leukotriene modifier therapy for mild sleep-disordered breathing in children 24 children with SDB 2-10 years; montelukast fro 16 weeks Oral therapy with a leukotriene modifier appears to be associated with improved breathing during sleep The use of LT receptor antagonist emerges as a potential therapeutic consideration in children with mild SDB AD Goldbart AJRCCM 2005;172:364

34 ICS + LABA + leukotriene modifier * medium-dose ICS * Autorizzazione LABA: Salmeterolo > 4 anni; Formoterolo > 6 anni

35 Asma grave (difficile) non risponde ai livelli alti di terapia Fattori interferenti (inf. da germi atipici, sinusite, RGE, obesità, nuove sensibilizzazioni, turbe di ritmo e conduzione) Farmaci interferenti (ad es. β-bloccanti) Diagnosi erronea (ad es. FC, DCP, corpo estraneo) Bassa compliance per la terapia inalatoria!

36 Persistent asthmatic using ug/day of inhaled corticosteroid (beclomethasone equivalent) GP Currie CHEST 2005;128:2954 Assess inhaler technique and improve delivery device where necessary Check compliance Exclude avoidable trigger factors Exclude concomitant diseases Persistent asthmatic with preserved airway calibre or with symptomatic allergic rhinitis Persistent asthmatic with impaired airway calibre Add a LTRA Add a LABA Symptoms controlled? no Add a LABA yes arrange further review Symptoms controlled? no Add a LTRA

37 Treating to Achieve Asthma Control Monitoring Patients are seen 1 to 3 months after the initial visit and every 3 months thereafter (Evidence D) After an exacerbation follow-up should be offered within 2 weeks to 1 month (Evidence D)

38 Treating to Maintain Asthma Control When control as been achieved, ongoing monitoring is essential to: - maintain control (for at least 3 months) - establish lowest step/dose treatment Asthma control should be monitored by the health care professional and by the patient

39 Wheezing Infant: luci ed ombre Is childhood asthma being underdiagnosed and undertreated? ANP Speight BMJ 1978;2:331 Prevalence of asthma-like symptoms in young children H Bisgaard Pediatr Pulmonol 2007;42:723

40 L M Taussig, F Martinez et al J Allergy Clin Immunol 2003;111:661

41 Wheezing Infant e Remodeling Basement membrane thickening has been know to be present in children with asthma. In addition, we report an association between BM thicness and sex, FEV 1 /FVC, total IgE, and the presence of IgE specific to D. pteronyssinus ES Kim Allergy 2007;62:635 The characteristic pathological features of asthma in adults and school-aged children develop in preschool children with confirmed wheeze between the age of one and three years, a time when intervention may modify the natural history of asthma S Saglani AJRCCM 2007;176:858

42 Long-term inhaled corticosteroids in preschool children at high risk for asthma (PEAK study) 285 children 2-3 years old with a positive asthma predictive Index; fluticasone propionate 100 µg x 2 or placebo for 2 years; 1 year follow-up without medication Our data show that the natural course of asthma in young children at hig risk for subsequent asthma is not modified by two years of treatment with inhaled corticosteroids. The treament, however, did reduce the burden of illness TW Guilbert N Engl J Med 2006;354:1985

43 Inhaled corticosteroids do not prevent the development of asthma Despite these findings, it is important to point out that the evidence remains strong that ICS therapy improves control of asthma symptoms in preschool children CN Lumeng J Pediatr 2007;150:114

44 Inhaled corticosteroids do not prevent the development of asthma Therefore, judicious use of ICS in early childhood is still warranted in those with chronic wheezing in accordance with established guidelines for the treatment of childhood asthma CN Lumeng J Pediatr 2007;150:114

45 XIX CONGRESSO NAZIONALE Società Italiana di Pediatria Preventiva e Sociale Torino ottobre 2007 Il Bambino con Disturbi Respiratori dalla flogosi all infezione: prevenzione, diagnosi e terapia GRAZIE PER L ATTENZIONE! NICOLA OGGIANO Istituto di Scienze Materno-Infantili Università Politecnica delle Marche ANCONA