Gianenrico Senna
Unità Operativa di Allergologia
Azienda Universitaria-Ospedaliera
Istituti Ospitalieri di Verona
Allergia : una
malattia
sistemica con
localizzazione
d’organo
Ospedale Civile Maggiore di Verona
The early phase
IgE
Legame
allergene
B
Mastcell
istamina
Recettore H1
Contrazione m. liscio
Permeabilità
Vasodilatazione
Stimolazione term.nervose
Broncospasmo, starnuti,
prurito, pomfi, tosse, eritema.
lacrimazione, anafilassi…
JACI 2011
JACI 2011
Stone et al. JACI 2009
Stone et al. JACI 2009
Th1
II-12
CD4
IL-4
ITS
Th2
ALLERGEN
ADJUVANTS
APC
iNOS
IL-5
ECP
EDX
MBP
B
IgE
Y
Y
Y
ALLERGEN
YYY
MAST
IL-13
Fibro
MEDIATORS
Eos
LATE PHASE
INFLAMMATION
The allergic reaction:
today
Histamine
LTs
REMODELLING
EARLY
PHASE
ENDOTHELINS
CELL
RECRUITMENT
Neu
ADHESION
MOLECULES
Eosinophils
Kinetics of the allergic reaction after nasal challenge
symptoms
eosinophils
30’
0
challenge
1h
6h
12h
24h
Rhinitis
Controls
Bronchial hyperresponsiveness and airway inflammation
markers in nonasthmatics with allergic rhinitis.
Polosa R et al. ERJ 2000
Exhaled nitric oxide as diagnostic test for asthma in
rhinitics patients with asthmatic symptoms
Heffler, 2006
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
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
Induce infiammazione nasale
La stimolazione bronchiale
segmentale endoscopica con allergene
Allergia: malattia sistemica
Progenitori
midollari
allergene
Fattori
chemotattici
Progenitori
IL-5R+
Rhinitis and onset of asthma : a longitudinal population
based study
Shaaban et al. Lancet 2008; 372 : 1049
29 centres (14 countries) : 6.461 partecipants
Frequency and impact of allergic rhinitis in
asthma patients in everyday general medical
practice : a French observational crosssectional study
Magnan et al Allergy 2008; 63 : 292
OTITE
ALTERAZIONI
DEL SONNO
CONGIUNTIVITE
RINITE
ALTERAZIONI
SCHELETRICHE
FACCIALI
ASMA
SINUSITE
POLIPOSI
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.
Influence of comorbid conditions on asthma
Boulet LP, ERJ 2009; 33 : 897
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%
Clinical aspects of the link between chronic
sinonasal diseases and asthma.
Dursun et al. Allergy Asthma Proc 2006; 27 : 510
Risk factors of frequent exacerbation in
difficult-to-treat asthma
Ten Brinke A et al Eur Resp J 2005; 26 : 812
51
Risk factors of frequent exacerbation in difficultto-treat asthma
Ten Brinke A et al Eur Resp J 2005; 26 : 812
51
> 3 exacerbation/yr
< 1 exacerbation/yr
Influence of comorbid conditions on asthma
Boulet LP ERJ 2009; 33 : 897
Predictors of habitual snoring and obstructive
sleep apnea risk in patients with asthma
Teodorescu et al Chest 2009;135: 132
Dose dependent relationship
between habitual snoring and
ICS dose
Dose dependent relationship
between high OSAS and ICS
dose
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
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
Pollen and eosinophilic
esophagitis
Fogg et al. JACI 2003; 112 : 796
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
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%
Hallmarks of Remodelling in asthma
Bas. Membrane
Submucosa
Smooth muscle
Thickening
Collagen Deposition
Hypertrophy
Remodelling of the upper airways in allergic rhinitis : is it a feature of
the disease ?
Salib & Howarth Clin Exp Allergy 2003 ; 33 : 1629
JACI, 2007
Jyonouchi et al Immunol Allergol Clin N Am 2009
CEA, 2010
Benedetto et al.JACI 2011
Van den Oord, 2010
Marenholtz et al JACI, 2009
Corrigan, JACI 2006
Benedetto et al, J Invest Dermatol 2008
CEA, 2010
CEA, 2010
CEA, 2010
2010
Rondon et al JACI 2011
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
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
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
Allergy 2011
Allergy 2011
ASTHMA
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
G. Senna
P. Bonadonna
A. Dama
M. Schiappoli
S. Dal Ponte
E. Conte
E. Olivieri
N. Contro
P. Lavarini
C. Melotti
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)