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Gianenrico Senna Unità Operativa di Allergologia Azienda Universitaria-Ospedaliera Istituti Ospitalieri di Verona Ospedale Civile Maggiore di Verona. Allergia : una malattia sistemica con localizzazione d’organo. Broncospasmo, starnuti, prurito, pomfi, tosse, eritema.

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Gianenrico Senna Unità Operativa di Allergologia Azienda Universitaria-Ospedaliera


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slide1

Gianenrico Senna

Unità Operativa di Allergologia

Azienda Universitaria-Ospedaliera

Istituti Ospitalieri di Verona

Ospedale Civile Maggiore di Verona

Allergia : una malattia sistemica con localizzazione d’organo

slide2

Broncospasmo, starnuti,

prurito, pomfi, tosse, eritema.

lacrimazione, anafilassi…

The early phase

Legame

allergene

IgE

B

Mastcell

istamina

Recettore H1

Contrazione m. liscio

Permeabilità

Vasodilatazione

Stimolazione term.nervose

slide9

Th1

B

II-12

IL-4

IgE

CD4

Y Y

ITS

Y

Th2

ALLERGEN

Y Y Y

IL-13

ALLERGEN

MAST

ADJUVANTS

IL-5

Fibro

MEDIATORS

Eos

ECP

EDX

MBP

APC

Histamine

LTs

REMODELLING

EARLY

PHASE

iNOS

ENDOTHELINS

LATE PHASE

CELL

INFLAMMATION

RECRUITMENT

ADHESION

MOLECULES

The allergic reaction:

today

Neu

slide11

symptoms

eosinophils

Kinetics of the allergic reaction after nasal challenge

0

30’

1h

6h

12h

24h

challenge

slide12

Rhinitis

Controls

Bronchial hyperresponsiveness and airway inflammation

markers in nonasthmatics with allergic rhinitis.

Polosa R et al. ERJ 2000

slide13

Exhaled nitric oxide as diagnostic test for asthma in rhinitics patients with asthmatic symptoms

Heffler, 2006

slide14

Ann Allergy Asthma Immunol 2008: 100 : 12

Increased expression of iNOS might have a role in the development of allergic inflammation in upper airways and in comorbidity of AR and asthma

slide15

La stimolazione nasale con allergene

Aumenta la reattività bronchiale

Induce infiammazione bronchiale

Littell NT, Changes in airways resistance following nasal provocation. Am Rev Respir Dis 1990

Corren J Changes in bronchial responsiveness following nasal provocation with allergens. JACI 1992

Small P ET AL The effects of allergen-induced nasal provocation on pulmonary function in patients with perennial allergic rhinitis. Am J Rhinol 1989

slide16

Induce infiammazione nasale

La stimolazione bronchiale

segmentale endoscopica con allergene

slide17

Allergia: malattia sistemica

Progenitori

midollari

allergene

Fattori

chemotattici

Progenitori

IL-5R+

slide18

Rhinitis and onset of asthma : a longitudinal population based study

Shaaban et al. Lancet 2008; 372 : 1049

29 centres (14 countries) : 6.461 partecipants

slide19

Frequency and impact of allergic rhinitis in asthma patients in everyday general medical practice : a French observational cross-sectional study

Magnan et al Allergy 2008; 63 : 292

slide20

ALTERAZIONI

DEL SONNO

CONGIUNTIVITE

OTITE

RINITE

SINUSITE

POLIPOSI

ALTERAZIONI

SCHELETRICHE

FACCIALI

ASMA

inflammation is the major underlying cause of mucosal congestion in upper respiratory diseases
Inflammation is the Major Underlying Cause of Mucosal Congestion in Upper Respiratory Diseases

Inflammation1-4

Allergic Rhinitis

Nasal Polyposis

Rhinosinusitis

Congestion4

Image of congested nasal passage in rhinosinusitis courtesy of Professor J.-M. Klossek.

1. Minshall et al. Otolaryngol Head Neck Surg. 1998;118:648; 2. Bachert et al. J Allergy Clin Immunol. 1997;99:837;

3. Bachert et al. Allergy. 1998;53:2; 4. van Drunen et al. Allergy. 2005;60(suppl 80):5.

slide22

Influence of comorbid conditions on asthma

Boulet LP, ERJ 2009; 33 : 897

slide23

Rhinosinusitis in severe asthma

Bresciani et al. JACI 2001; 107 .73

CT scan abnormality was common to both groups, but the clinical (p<0.05) and the CT scan severity scores (p<.0005) were higher in the subjects with severe steroid-dependent asthma

88%

100%

slide24

Clinical aspects of the link between chronic sinonasal diseases and asthma.

Dursun et al. Allergy Asthma Proc 2006; 27 : 510

A correlationbetweenasthmaseverity and a CT scan score hasbeenconfimed

slide25

Risk factors of frequent exacerbation in difficult-to-treat asthma

Ten Brinke A et al Eur Resp J 2005; 26 : 812

51

slide26

Risk factors of frequent exacerbation in difficult-to-treat asthma

Ten Brinke A et al Eur Resp J 2005; 26 : 812

51

> 3 exacerbation/yr

< 1 exacerbation/yr

slide27

Influence of comorbid conditions on asthma

Boulet LP ERJ 2009; 33 : 897

slide28

Predictors of habitual snoring and obstructive sleep apnea risk in patients with asthma

Teodorescu et al Chest 2009;135: 132

Dose dependent relationship between high OSAS and ICS dose

Dose dependent relationship between habitual snoring and ICS dose

slide29

Systemic aspects

Allergen sensititization is not just a local event, but also a systemic event

  • In animal models :
  • Allergen sensitization on the skin induced localized dermatitis and airway eosinophilia
  • Airway sensitization not only caused eosinophilic esophagitis, but also skin eosinophilia, accelerated bone marrow eosinophilopoiesis and blood eosinophilia

Spergel JM. Clin Exp Allergy 2005; 35 : 1421

slide30

Systemic aspects

Allergen sensitization is not just a local event, but also a systemic event

  • In human models :
  • Allergen exposure in the asthmatic airway induced eosinophilia not only in the local airway, but distally in bone marrow with increased IL5 expression

Wood et al. Am J Resp Crit Care Med 2002; 166: 883

slide31

Pollen and eosinophilic esophagitis

Fogg et al. JACI 2003; 112 : 796

slide32

Seasonal intestinal inflammation in patients with birch pollen allergy

Magnusson et al. JACI 2003; 112 : 45

Marked increase of MBP-stained eosinophils in patients during the pollen season

MBP-stained eosinophils in healthy control subjects

eosinophilic esophagitis
Eosinophilic esophagitis

Sgouros et al. 2006; 18 : 211

Prevalence : 4.3 cases per 10.000 individuals

Males/female 3:1

Age : 30-40 yrs

Symptoms : dysphagia (93%),

food impaction(61%),

hearthburn (23%)

others : chest pain, odynophagia, vomiting

Allergic history 51%

Peripheral eosinophilia 31%

Increase of IgE 55%

slide35

Hallmarks of Remodelling in asthma

Bas. Membrane

Submucosa

Smooth muscle

Thickening

Collagen Deposition

Hypertrophy

slide36

Remodelling of the upper airways in allergic rhinitis : is it a feature of the disease ?

Salib & Howarth Clin Exp Allergy 2003 ; 33 : 1629

slide50

Role of staphylococcal superantigens in upper airway disease

Bachert et al Curr Opin Allergy Clin Immunol 2008; 8 : 34

  • Nasal polyps are characterized by Th2 dominated cytokine pattern
  • Cytokine environment is decisive regarding the impact of S.Aureus enteroxins, as superantigens
  • S.Aureus enteroxins B further shifts the cytokine pattern in nasal polyps toward Th2 cytokines (IL4- IL5)
  • Furthermore S.Aureus enteroxins influence local immunoglobulin syntesis and induce polyclonal IgE production, which may contribute to severe inflammation through a mastcell activation
slide51

Van Zele et al. JACI 2004; 114 : 983

87%

67%

63%

Colonization rates in controls and subjects with CRS were 33.3% and 27.3%, whereas 63% in patients with nasal polyposis and 87.5% in subgroups with asthma and aspirin hypersensitivity

slide52

The role of sinus disease in asthma

Bachert et al Curr Opin Allergy Clin Immunol 2006; 6 : 29

Hypotheses explaining the link between sinus disease and asthma

slide55

Unità Operativa di Allergologia

Ospedale Civile Maggiore di Verona

Azienda Ospedaliera di Verona

Centro di riferimento regionale per la prevenzione, la diagnosi e la terapia delle malattie allergiche

Aknowledgement

Collaborations

A. Boner

B.Caruso (Verona)

C. Le Pera (Verona)

R. Zanotti (Verona)

P. Gisondi (Verona)

L. Castellani (Trento)

M. Crivellaro (Padova)

M. Pagani (Mantova)

C. Lombardi (Brescia)

GW Canonica (Genova)

G. Passalacqua (Genova)

L. Antonicelli (Ancona)

S: Durham (Londra)

M. Calderon (Londra)

A. Romano (Roma)

G. Senna

P. Bonadonna

A. Dama

M. Schiappoli

S. Dal Ponte

E. Conte

E. Olivieri

N. Contro

P. Lavarini

C. Melotti