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Gianenrico SennaGianenrico SennaUnità Operativa di Allergologia
Azienda Universitaria-Ospedaliera
Istituti Ospitalieri di Verona
Ospedale Civile Maggiore di VeronaAllergia : una malattia
sistemica con localizzazione
d’organo
Legame allergene
Mastcell
istamina
B
IgE
Contrazione m. liscioPermeabilitàVasodilatazioneStimolazione term.nervose
Recettore H1
The early phase
Broncospasmo, starnuti, prurito, pomfi, tosse, eritema.lacrimazione, anafilassi…
APC
ALLERGEN
Th1
Th2
Eos
IL-5
BIL-4Y
Y Y Y
Y Y IgE
MASTFibro
IL-13
MEDIATORS
ALLERGEN
ECPEDXMBP
CD4 ITSII-12
EARLYPHASE
HistamineLTs
ADHESIONMOLECULES
LATE PHASEINFLAMMATION
REMODELLING
ADJUVANTS
RECRUITMENT
ENDOTHELINSiNOS
Neu
CELL
The allergic reaction:today
Eosinophils
0 30’ 1h 6h 12h 24h
challenge
Kinetics of the allergic reaction after nasal challenge
symptomseosinophils
Bronchial hyperresponsiveness and airway inflammationmarkers in nonasthmatics with allergic rhinitis.Polosa R et al. ERJ 2000
RhinitisControls
Exhaled nitric oxide as diagnostic test for asthma in rhinitics patients with asthmatic symptoms
Heffler, 2006
Increased expression of iNOS might have a role in the development of allergic inflammation in upper airways and in comorbidity of AR and asthma
Ann Allergy Asthma Immunol 2008: 100 : 12
La stimolazione nasale con allergene
Aumenta la reattività bronchialeInduce infiammazione bronchiale
Littell NT, Changes in airways resistance following nasal provocation. Am Rev Respir Dis 1990Corren 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
La stimolazione bronchiale segmentale endoscopica con allergene
Induce infiammazione nasale
allergene Fattori chemotattici
Progenitorimidollari
ProgenitoriIL-5R+
Allergia: malattia sistemica
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 cross-sectional study
Magnan et al Allergy 2008; 63 : 292
RINITE
ALTERAZIONIDEL SONNO
CONGIUNTIVITE
OTITE
SINUSITEPOLIPOSI
ALTERAZIONISCHELETRICHE
FACCIALI ASMA
InflammationInflammation is the Major Underlying Cause of Mucosal Congestion in Upper Respiratory Diseases
Image of congested nasal passage in rhinosinusitis courtesy of Professor J.-M. Klossek.Image of congested nasal passage in rhinosinusitis courtesy of Professor J.-M. Klossek.1. Minshall et al. 1. Minshall et al. Otolaryngol Head Neck SurgOtolaryngol Head Neck Surg. 1998;118:648; 2. Bachert et al. . 1998;118:648; 2. Bachert et al. J Allergy Clin Immunol.J Allergy Clin Immunol. 1997;99:837; 1997;99:837;3. Bachert et al. 3. Bachert et al. AllergyAllergy. 1998;53:2; 4. van Drunen et al. . 1998;53:2; 4. van Drunen et al. Allergy.Allergy. 2005;60(suppl 80):5. 2005;60(suppl 80):5.
Allergic RhinitisAllergic Rhinitis RhinosinusitisRhinosinusitisInflammationInflammation1-41-4
Nasal PolyposisNasal Polyposis
CongestionCongestion44
Influence of comorbid conditions on asthma
Boulet LP, ERJ 2009; 33 : 897
Rhinosinusitis in severe asthmaBresciani et al. JACI 2001; 107 .73
88% 100%
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
Clinical aspects of the link between chronic sinonasal diseases and asthma.
Dursun et al. Allergy Asthma Proc 2006; 27 : 510
Ten Brinke A et al Eur Resp J 2005; 26 : 812
51
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 difficult-to-treat asthma
> 3 exacerbation/yr
< 1 exacerbation/yr
Influence of comorbid conditions on asthmaBoulet LP ERJ 2009; 33 : 897
Predictors of habitual snoring and obstructive sleep apnea risk in patients with asthmaTeodorescu 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 eosinophiliaAirway 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 allergyMagnusson 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
Prevalence : 4.3 cases per 10.000 individualsMales/female 3:1Age : 30-40 yrsSymptoms : dysphagia (93%), food impaction(61%), hearthburn (23%) others : chest pain, odynophagia, vomitingAllergic history 51%Peripheral eosinophilia 31%Increase of IgE 55%
Sgouros et al. 2006; 18 : 211
Bas. Membrane
Thickening Collagen Deposition Hypertrophy
Hallmarks of Remodelling in asthma
Submucosa Smooth muscle
Remodelling of the upper airways in allergic rhinitis : is it a feature of the disease ?Salib & Howarth Clin Exp Allergy 2003 ; 33 : 1629
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
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
63%
67%
87%
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
ASTHMA
Allergy 2011
G. SennaP. BonadonnaA. DamaM. SchiappoliS. Dal PonteE. ConteE. Olivieri
N. ControP. LavariniC. Melotti
Collaborations
A. BonerB.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)
Centro di riferimento regionale per la Centro di riferimento regionale per la prevenzione, la diagnosi e la terapia delle prevenzione, la diagnosi e la terapia delle
malattie allergichemalattie allergiche
Unità Operativa di AllergologiaUnità Operativa di Allergologia
Ospedale Civile Maggiore di VeronaOspedale Civile Maggiore di Verona
Azienda Ospedaliera di VeronaAzienda Ospedaliera di Verona
Aknowledgement