Carlo Capristo pdf

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Best practice nell’asma cronico

Dipartimento

Dipartimento di di Pediatria Pediatria Seconda

Seconda Università Università di di Napoli Napoli

Carlo Capristo

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2011

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JACI 2010

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TUCSON CHILDREN’S RESPIRATORY STUDY:

1980 TO PRESENT Taussig JACI 2003

HYPOTHETICAL PEAK PREVALENCE BY AGE FOR THE 3 DIFFERENT WHEEZING PHENOTYPES.

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Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airwayresponsiveness in mid-childhood J Henderson Thorax

2008;63;974

6265 children in a longitudinal birth cohort (the ALSPAC)

from birth to 7 yrs

phenotypes based on patterns of wheezing

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Grave wheezing intermittente

Episodi acuti non frequenti di wheezing associati con:

FENOTIPI DI ASMA DEL BAMBINO

Bacharier LB et al - JACI 2007;119:604–610

• Minima morbidità al di fuori del periodo di interessamento dell’apparato respiratorio

• Caratteristiche atopiche, incluso eczema, sensibilizzazione

allergica ed eosinofilia ematica periferica

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Fattori di rischio per asma (2-4 anni)

Guilbert - J Allergy Clin Immunol 2004; 114: 1282

PIÙ

> 3 episodi di wheezing nell’ultimo anno

1 criterio maggiore 2 criteri minori

OPPURE

1 criterio maggiore

•

un genitore con asma

•

dermatite atopica

•

sensibiliz. aeroallergeni

2 criteri minori

•

sensibiliz. alimenti

•

wheezing al di fuori di episodi infettivi

•

eosinofilia (>4%)

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WHEEZING IN PRE-SCHOOL CHILDREN

Episodic (viral) wheeze

Multiple trigger wheeze

Children who wheeze intermittently and are well between episodes Triggers: viruses

Wheeze both during and between exacerbations Triggers: virus, smoke, allergenes, exercise

wheeze wheeze

Brand 2008

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p=0.03 p=0.003

In soggetti con multi-trigger wheezing le alterazioni

infiammatorie e strutturali sono simili indipendentemente dall’atopia

Perdita epiteliale

Vasi

Turato AJRCCM 2008

Spessore MB Eosinofili

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?

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2003

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Transient early wheezers

Non-atopic wheezers

IgE-associated wheeze/asthma

Wheezing prevalence

0 3 6 11

Age (years)

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253 cohort members

VmaxFRC at 1 month of age

Individuals with bronchiolitis were prospectively

identified

At 11 years of age lung function was

repeated

Box and whisker plot for z scores for % V’maxFRC at 1 month

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253 cohort members

VmaxFRC at 1 month of age

Individuals with bronchiolitis were prospectively

identified

At 11 years of age lung function was repeated

Box and whisker plot for z scores for % FEF_25-75 at 11 years

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Am J Respir Crit Care Med 2011

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Transient early wheezers

Non-atopic wheezers

IgE-associated wheeze/asthma

Wheezing prevalence

0 3 6 11

Age (years)

Important changes in ariway

physiology start very early in life!

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L. Grainge

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1. Transient wheezing,

Reduced lung development is a premorbid predisposing factor for:

C. Calogero, P.D. Sly Eur Respir Mon 2010

1. Transient wheezing, 2. Bronchiolitis,

3. Persistent atopic wheezing,

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Bronchial development complete by the 18°week

True alveoli begin to develop Windows of susceptibility

True alveoli begin to develop at 28 weeks and increase in number, size and complexity during the first 3-4 years of life.

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2007

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Genetics of allergic disease

John W. Holloway JACI 2010

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Bouzigon E.

Ordered-Subset Regression Analysis of Asthma with Two Single-Nucleotide Polymorphisms (SNPs)

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Bouzigon E.

Ordered-Subset Regression Analysis of Asthma with Two Single-Nucleotide Polymorphisms (SNPs)

ORMDL3 Associated Gene Variants are Associated with Asthma and Exacerbations but not Atopy in Early Childhood

Hans Bisgaard AJRCCM 2009

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Patrick M.A. Sleiman NEJM 2010

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Fattori che influiscono sulla patogenesi dell’asma

da infezioni respiratorie

Busse et al. Lancet 2010

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How Viral Infections Cause Exacerbation of Airway Diseases

Mallia P, Johnston SP - CHEST 2006

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259 bambini seguiti dalla nascita fino all’età di 6 anni

Lavaggi nasali, colture e PCR durante gli episodi di wheezing

Wheezing Rhinovirus Illnesses in Early Life Predict Asthma Development in High-Risk Children

Episodi di wheezing tra 0 a 3 anni indotti da RSV (OR: 2,6), RV (OR: 9,8) o entrambi (OR:

10) sono correlati ad un maggiore rischio di asma a 6 anni

Dall’ età di 3 anni, il wheezing indotto da RV è maggiormente correlato (OR 25,6) ad asma all’età di 6 anni rispetto alla sensibilizzazione verso pneumo allergeni (OR 3.4).

Jackson Am J Respir Crit Care Med Vol 2008

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2011

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PERENNIAL ALLERGEN SENSITISATION EARLY IN LIFE AND CHRONIC ASTHMA IN CHILDREN: A BIRTH COHORT STUDY

Illi Lancet 2006; 368: 763

1314 children from birth to 13 years of age (MAS study)

% of children symptom free at school age and normal lung function at puberty

90 – 80 – 70 – 100 –

age (MAS study)

Allergen exposure at age 6 months, 18 months, and at 3, 4, and 5 yrs

Lung function at 7, 10, and 13 yrs

children with wheeze but not atopy

90%

70 – 60 – 50 – 40 – 30 – 20 – 10 –

0

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FEV

₁

/FVC

94 – 93 – 92 – 91 – 90 –

95 –

92.6%

p<0.001

PERENNIAL ALLERGEN SENSITISATION EARLY IN LIFE AND CHRONIC ASTHMA IN CHILDREN: A BIRTH COHORT STUDY

Illi Lancet 2006; 368: 763

1314 children from birth to 13 years of age (MAS study)

Sensitized to mite and exposed early in life to high dose of with allergen

87.4%

90 – 89 – 88 – 87 – 86 – 85 – 80

p<0.001

Not sensitized

age (MAS study)

Allergen exposure at age 6 months, 18 months, and at 3, 4, and 5 yrs

Lung function

at 7, 10, and 13 yrs

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Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein

The main house-dust-mite

allergen, Der p 2, has structuralstructural homology

homology with MD-2 (also known as LY96), the

lipopolysaccharide

lipopolysaccharide (LPS)(LPS)-- binding

binding componentcomponent ofof the the TollToll-- like

like receptorreceptor (TLR) 4 signalling

≈

like

like receptorreceptor (TLR) 4 signalling complex.

Here we show that Der p 2 also has functionalfunctional homologyhomology,

facilitating signalling through

direct interactions with the TLR4 complex, and reconstituting

LPS-driven TLR4 TLR4 signallingsignalling in the absence of MD-2.

Trompette, Nature 2009

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C

Childhood hildhood disadvantage disadvantage factors

factors

Thorax 2010

European Community Respiratory Health Survey

participants aged 20–45 years randomly selected from general populations.

Spirometry in 1991–3 (n=13,359) and 9 years later (n=7,738).

••Maternal asthma, Maternal asthma,

••Paternal asthma, Paternal asthma,

••Childhood asthma, Childhood asthma,

••Maternal smoking and Maternal smoking and

••Childhood respiratory infections Childhood respiratory infections

factors

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Thorax 2010

OR for FEV₁/FVC ≤ 70%

7.2

8 – 7 –

1.7

6.3

1 1

7.2

≥3

1.6

≥3

n°FACTORS IN MEN n°FACTORS IN WOMEN

6 – 5 – 4 – 3 – 2 – 1 – 0

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Carlo Capristo

Dipartimento di Pediatria S.U.N.

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Progetto Mondiale ASMA 2010

• Anamnesi ed insieme dei sintomi

• Esame obiettivo

• Prove di funzionalità respiratoria – Spirometria

– Test di reversibilità

– Test di provocazione bronchiale aspecifico

Diagnosi di asma

– Test di provocazione bronchiale aspecifico

• Indagini per identificare i fattori di rischio

• Altre indagini

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