XIX CONGRESSO NAZIONALE

Società Italiana di Pediatria Preventiva e Sociale

Torino 26-28 ottobre 2007

Wheezing e Asma: Linee Guida, Luci ed Ombre

NICOLA OGGIANO

Il Bambino con Disturbi Respiratoridalla flogosi all’infezione: prevenzione, diagnosi e terapia

Istituto di Scienze Materno-InfantiliUniversità Politecnica delle Marche

ANCONA

GINA

lobal

itiative for

sthma

http://www.ginasthma.org

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

Revised 2006Revised 2006

The influence of variation in type and pattern of symptoms on assessment in pediatric asthma

• The goals of therapy for asthma, based on the NationalAsthma Education and Prevention Program guidelines,have not been achieved for the majority of children

• In addition, parents and children overstimate the child’sasthma control and commonly restrict activities to controlasthma symptomps

• Deficiencies in the control of asthma may be related tothe underestimation of the burden of disease

AL Fuhlbrigge Pediatrics 2006;118:619

(801 interviews were completed by parents of children aged 4 to 15 years and by children themselves aged 16 to 18 years)

> 80% predetto< 2 volte / mese<1volta /settimanaSTEP 1intermittente

> 80% predetto> 2 volte / mese>1volta /settimana<1 volta /giorno

STEP 2 lieve persistente

60 - 80% predetto>1 volta/settimanaquotidiani

attacchi limitantil’attività fisica

STEP 3 Mod. persistente

< 60% predettofrequenticontinui

att. fisica limitataSTEP 4grave persistente

FEV1 o PEFSintomi notturnisintomiSTEP

La presenza di almeno uno dei criteri di gravità è sufficiente per classificare un paziente in un determinato livello di gravità

Classificazione di gravità in assenza di terapia

GINA 2005

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

AL Fuhlbrigge Pediatrics 2006;118:619PM Gustafsson Int. Clin Pract 2006; 60:321

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

AT Luskin J Allergy CIin Immunol 2005;115:S539SW Stoloff J Allergy Clin Immunol 2006;117:544

Levels of Asthma Control

3 or more features of partly controlled asthma present in any week

< 80% predicted or personal best (if

known) on any dayNormalLung function

(PEF or FEV1)

One or more / year 1 in any weekNoneExacerbation

More than twice / week

None (2 or less / week)

Need for rescue / “reliever” treatment

AnyNoneNocturnal

symptoms / awakening

AnyNoneLimitations of activities

More than twice / week

None (2 or less / week)Daytime symptoms

Uncontrolled Partly controlled(Any present in any week)

Controlled(All of the following)

Characteristic

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

< 19 punti scarso controllo > 20 punti buon controllo

MOLTO SENSIBILE NEL BAMBINOridotto 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;170:426JD Spahn J Pediatr 2006;148:11AL Fuhlbrigge Pediatrics 2006;118:e347

B > 83-85%(GINA ’06) >90% A > 70-75%

FEV1/FVC(I. Tiffeneau)

Riflette la pervietà nei bronchi di piccolo calibro (> 2 mm di diametro)Si riduce precocemente nell’asma(in fase preclinica)

> 70%FEF 25-75

significato nellabroncostruzione asmatica

v.n. (% pr.)parametro

Riflette la pervietà nei bronchi di grosso e medio calibroNormale nelle fasi ostruttive precoci

> 80%FEV1

Si riduce nell’asma grave, dove èindice indiretto di intenso air trapping

> 80%FVC

>1250750-1250500-750Flunisolide

>400200-400100-200FP

>600200-600100-200BUD (d.p.i.)

>500250-50050-200BDP (h.f.a.)

Alto dosaggioMedio dosaggio

Basso dosaggio

Farmaco

Dosaggio giornaliero (µg/die) comparativo stimatodegli steroidi inalatori in età pediatrica*

*I dosaggi comparativi devono essere valutati anche in considerazione dei diversi sistemi di erogazione disponibili per ciascun composto (MDI, DPI, nebulizzatore)

GINA 2005

>1250750-1250500-750Flunisolide

>400200-400100-200FP

>600200-600100-200BUD (d.p.i.)

>500250-50050-200BDP (h.f.a.)

Alto dosaggioMedio dosaggio

Basso dosaggio

Farmaco

Dosaggio giornaliero (µg/die) comparativo stimatodegli steroidi inalatori in età pediatrica*

*I dosaggi comparativi devono essere valutati anche in considerazione dei diversi sistemi di erogazione disponibili per ciascun composto (MDI, DPI, nebulizzatore)

GINA 2005

nebulizzatore

Estimate Comparative Daily Dosages for Inhaled Glucocorticosteroids by AgeEstimate Comparative Daily Dosages for Inhaled Glucocorticosteroids by Age

Drug 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

Drug 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>500-1000250-500Budesonide-Neb Inhalation Suspension

>1000 >400600-1000 >200-400200-600 100-200Budesonide

>800-1200 >400> 400-800 >200-400200-400 100-200Mometasone furoate

>2000 >1200>1000-2000 >800-1200400-1000 400-800Triamcinolone acetonide

>500 >500>250-500 >200-500100-250 100-200Fluticasone

>2000 >1250>1000-2000 >750-1250500-1000 500-750Flunisolide

>320-1280 >320>160-320 >160-320 80 – 160 80-160Ciclesonide

>1000 >400>500-1000 >200-400200-500 100-200 Beclomethasone

GINA 2006

Asthma Management and Prevention Program

Component 3: Assess, Treat and Monitor Asthma

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

controlled

partly controlled

uncontrolled

exacerbation

LEVEL OF CONTROLLEVEL OF CONTROL

maintain and find lowest controlling step

consider stepping up to gain control

step up until controlled

treat as exacerbation

TREATMENT OF ACTIONTREATMENT OF ACTION

TREATMENT STEPSREDUCE INCREASE

STEP

1STEP

2STEP

3STEP

4STEP

5

RED

UC

EIN

CR

EASE

medium-dose ICS

SHORT–COURSE MONTELUKAST FOR INTERMITTENT ASTHMA IN CHILDREN. A Randomized Controlled Trial

(220 children 2-14 years with intermittent asthma. Follow-up 12 months)

• 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

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

medium-dose ICS

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

Treating to Achieve Asthma Control

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

Montelukast, compared with fluticasone, for control of asthma among 6 to 14 year old patients with mild asthma: the MOSAIC study

Attacchi di Asma

Fluticasone Montelukast(25,6%) (32,%)

Steroidi Sistemici

Fluticasone Montelukast(10,5%) (17,8%)

ML Garcia Garcia Pediatrics 2005; 116: 360

RFD (rescue-free days)

Studio munticentrico controllato e randomizzato a gruppi paralleli; 12 mesi di trattamento

For children older than 5 years, adolescents and adults

* Autorizzazione LABA: Salmeterolo > 4 anni; Formoterolo > 6 anni

medium-dose ICS

**

For children 5 years and younger

* Autorizzazione LABA: Salmeterolo > 4 anni; Formoterolo > 6 anni

Medium

dose ICS

Low-dose ICS+ LABA **

Step 3

Treating to Achieve Asthma Control

PM O’Byrne et al AJRCCM 2005;171:129

Budesonide/formoterol combination therapy as bothmaintenance and reliever medication in asthma

Budesonide/formoterol maintenance plus reliever therapy: a new stategy in pediatric asthma

341 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

The SMART regimen using budesonide/formoterol forboth 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;130:1733

Additional Step 3 Options

Low-dose inhaled glucocorticosteroid combined with leukotriene modifiers (Evidence A*)

Low-dose sustained-release theophylline (Evidence B*)

Treating to Achieve Asthma Control

*only for children older than 5 years

Formoterol, montelukast, and budesonide in asthmaticchildren: Effect on lung function and exhaled nitric oxide

This study has demonstratedthat 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

M Miraglia del Giudice Respir Med 2007;101:1809

48 children 7-11 years of age

bud 200µg bidstop montelukastadd formoterol

bud 200µg bidstop formoteroladd montelukast

S.I. a dosaggio adeguato

STEP 3 bambini in età scolare

β2-Long Acting

Antileucotrienici

?

oppure

associare

Steroide Inalatorio + beta-2 Long Acting

• Bassi valori spirometrici

• EIA

GP Currie CHEST 2005;128:2954

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

Leukotriene modifier therapy for mildsleep-disordered breathing in children

• Oral therapy with a leukotriene modifier appears to beassociated with improved breathing during sleep

• The use of LT receptor antagonist emerges as a potentialtherapeutic consideration in children with mild SDB

24 children with SDB 2-10 years; montelukast fro 16 weeks

AD Goldbart AJRCCM 2005;172:364

medium-dose ICS

**

ICS + LABA + leukotriene modifier

* Autorizzazione LABA: Salmeterolo > 4 anni; Formoterolo > 6 anni

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!

Persistent asthmatic using 400-800 ug/day of inhaled corticosteroid (beclomethasone equivalent)

• 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? Symptoms controlled?

Add a LABA Add a LTRAarrange further review

yes

no no

GP Currie CHEST 2005;128:2954

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)

Treating to Achieve Asthma Control

Monitoring

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

Is childhood asthma beingunderdiagnosed and undertreated ?

Prevalence of asthma-like symptoms in young children

ANP Speight BMJ 1978;2:331

H Bisgaard Pediatr Pulmonol 2007;42:723

Wheezing Infant: luci ed ombre

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

Wheezing Infant e Remodeling

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

Basement membrane thickening has been know tobe present in children with asthma. In addition, wereport an association between BM thicness and sex, FEV1/FVC, total IgE, and the presence of IgE specificto D. pteronyssinus

S Saglani AJRCCM 2007;176:858

ES Kim Allergy 2007;62:635

Long-term inhaled corticosteroids in preschool children at high risk for asthma (PEAK study)

Our data show that the natural course of asthma in young children at hig risk forsubsequent asthma is notmodified by two years of treatment with inhaledcorticosteroids. The treament, however, didreduce the burden of illness

285 children 2-3 years old with a positive asthma predictive Index; fluticasonepropionate 100 µg x 2 or placebo for 2 years; 1 year follow-up without medication

TW Guilbert N Engl J Med 2006;354:1985

Inhaled corticosteroids do notprevent the development of asthma

Despite these findings, it is important topoint out that the evidence remains strong that ICS therapy improves control of asthma symptoms in preschool children

CN Lumeng J Pediatr 2007;150:114

Inhaled corticosteroids do notprevent the development of asthma

Therefore, judicious use of ICS in earlychildhood is still warranted in those withchronic wheezing in accordance withestablished guidelines for the treatment of childhood asthma

CN Lumeng J Pediatr 2007;150:114

XIX CONGRESSO NAZIONALE

Società Italiana di Pediatria Preventiva e Sociale

Torino 26-28 ottobre 2007

GRAZIE PER L’ATTENZIONE!

NICOLA OGGIANO

Il Bambino con Disturbi Respiratoridalla flogosi all’infezione: prevenzione, diagnosi e terapia

Istituto di Scienze Materno-InfantiliUniversità Politecnica delle Marche

ANCONA