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 Respiratori
dalla flogosi all’infezione: prevenzione, diagnosi e terapia
Istituto di Scienze Materno-Infantili Università Politecnica delle Marche
ANCONA
G IN A
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 2006 Revised 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 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
(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 /settimana STEP 1
intermittente
> 80% predetto
> 2 volte / mese
>1volta /settimana
<1 volta /giorno STEP 2
lieve persistente
60 - 80% predetto
>1 volta/settimana quotidiani
attacchi limitanti l’attività fisica STEP 3
Mod. persistente
< 60% predetto frequenti
continui
att. fisica limitata STEP 4
grave persistente
FEV1 o PEF Sintomi notturni
sintomi STEP
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;118:619 PM 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:S539 SW 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 day Normal
Lung function (PEF or FEV1)
One or more / year 1 in any week None
Exacerbation
More than twice / week None (2 or less /
week) Need for rescue /
“reliever” treatment
Any None
Nocturnal symptoms /
awakening
Any Limitations of None
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 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
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 nella
broncostruzione asmatica v.n. (% pr.)
parametro
Riflette la pervietà nei bronchi di grosso e medio calibro
Normale nelle fasi ostruttive precoci
> 80%
FEV1
Si riduce nell’asma grave, dove è indice indiretto di intenso air trapping
> 80%
FVC
>1250 750-1250
500-750 Flunisolide
>400 200-400
100-200 FP
>600 200-600
100-200 BUD (d.p.i.)
>500 250-500
50-200 BDP (h.f.a.)
Alto dosaggio Medio
dosaggio Basso
dosaggio Farmaco
Dosaggio giornaliero (µg/die) comparativo stimato degli 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
>1250 750-1250
500-750
Flunisolide
>400 200-400
100-200 FP
>600 200-600
100-200 BUD (d.p.i.)
>500 250-500
50-200 BDP (h.f.a.)
Alto dosaggio Medio
dosaggio Basso
dosaggio Farmaco
Dosaggio giornaliero (µg/die) comparativo stimato degli 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 Age
Estimate 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
>500-1000 250-500
Budesonide-Neb
Inhalation Suspension
>1000 >400 600-1000 >200-400
200-600 100-200 Budesonide
>800-1200 >400
> 400-800 >200-400 200-400 100-200
Mometasone furoate
>2000 >1200
>1000-2000 >800-1200 400-1000 400-800
Triamcinolone acetonide
>500 >500
>250-500 >200-500 100-250 100-200
Fluticasone
>2000 >1250
>1000-2000 >750-1250 500-1000 500-750
Flunisolide
>320-1280 >320
>160-320 >160-320 80 – 160 80-160
Ciclesonide
>1000 >400
>500-1000 >200-400 200-500 100-200
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 CONTROL LEVEL OF CONTROL
maintain and find lowest controlling step
consider stepping up to gain control
step up until controlled
treat as exacerbation
TREATMENT OF ACTION TREATMENT OF ACTION
TREATMENT STEPS
REDUCE INCREASE
STEP
1
STEP
2
STEP
3
STEP
4
STEP
5
REDUCEINCREASE
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 both
maintenance 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 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;130:1733
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 asthmatic children: Effect on lung function and exhaled nitric oxide
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
M Miraglia del Giudice Respir Med 2007;101:1809
48 children 7-11 years of age
bud 200µg bid stop montelukast add formoterol
bud 200µg bid stop formoterol add montelukast
S.I. a dosaggio adeguato
STEP 3 bambini in età scolare
β
2-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 mild sleep-disordered breathing in children
• 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
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 arrange further review Add a LTRA 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 being
underdiagnosed 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 to be present in children with asthma. In addition, we report an association between BM thicness and sex, FEV1/FVC, total IgE, and the presence of IgE specific to 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 for subsequent asthma is not modified by two years of treatment with inhaled corticosteroids.
The treament, however, did reduce the burden of illness
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
TW Guilbert N Engl J Med 2006;354:1985
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
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
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 Respiratori
dalla flogosi all’infezione: prevenzione, diagnosi e terapia
Istituto di Scienze Materno-Infantili Università Politecnica delle Marche
ANCONA
