Gianenrico Senna Unit Operativa di Allergologia Azienda UniversitariaOspedaliera

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 Ig. E Legame allergene B Mastcell istamina Recettore H 1 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

Th 1 II-12 CD 4 ITS Th 2 ALLERGEN ADJUVANTS APC i. NOS IL-5 ECP EDX MBP Eos LATE PHASE INFLAMMATION The allergic reaction: today B IL-4 Ig. E Y Y Y ALLERGEN IL-13 Fibro YYY MAST MEDIATORS Histamine LTs REMODELLING EARLY PHASE ENDOTHELINS CELL RECRUITMENT Neu ADHESION MOLECULES

Eosinophils

Kinetics of the allergic reaction after nasal challenge symptoms eosinophils 0 30’ challenge 1 h 6 h 12 h 24 h

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 i. NOS 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-5 R+

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 Inflammation Congestion in Upper Respiratory Diseases Inflammation 1 -4 Allergic Rhinitis Nasal Polyposis Rhinosinusitis Congestion 4 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 A correlation between asthma severity and a CT scan score has been confimed

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 : üAllergen sensitization on the skin induced localized dermatitis and airway eosinophilia üAirway 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 : üAllergen exposure in the asthmatic airway induced eosinophilia not only in the local airway, but distally in bone marrow with increased IL 5 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 Ig. E 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 ü Nasal polyps are characterized by Th 2 dominated cytokine pattern üCytokine environment is decisive regarding the impact of S. Aureus enteroxins, as superantigens üS. Aureus enteroxins B further shifts the cytokine pattern in nasal polyps toward Th 2 cytokines (IL 4 - IL 5) üFurthermore S. Aureus enteroxins influence local immunoglobulin syntesis and induce polyclonal Ig. E production, which may contribute to severe inflammation through a mastcell activation

Van Zele et al. JACI 2004; 114 : 983 87% 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)