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Gianenrico Senna Unità Operativa di Allergologia Azienda Universitaria-Ospedaliera

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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  1. 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

  2. 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

  3. JACI 2011

  4. JACI 2011

  5. Stone et al. JACI 2009

  6. Stone et al. JACI 2009

  7. 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

  8. Eosinophils

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

  10. Rhinitis Controls Bronchial hyperresponsiveness and airway inflammation markers in nonasthmatics with allergic rhinitis. Polosa R et al. ERJ 2000

  11. Exhaled nitric oxide as diagnostic test for asthma in rhinitics patients with asthmatic symptoms Heffler, 2006

  12. 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

  13. 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

  14. Induce infiammazione nasale La stimolazione bronchiale segmentale endoscopica con allergene

  15. Allergia: malattia sistemica Progenitori midollari allergene Fattori chemotattici Progenitori IL-5R+

  16. Rhinitis and onset of asthma : a longitudinal population based study Shaaban et al. Lancet 2008; 372 : 1049 29 centres (14 countries) : 6.461 partecipants

  17. 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

  18. ALTERAZIONI DEL SONNO CONGIUNTIVITE OTITE RINITE SINUSITE POLIPOSI ALTERAZIONI SCHELETRICHE FACCIALI ASMA

  19. 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.

  20. Influence of comorbid conditions on asthma Boulet LP, ERJ 2009; 33 : 897

  21. 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%

  22. 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

  23. Risk factors of frequent exacerbation in difficult-to-treat asthma Ten Brinke A et al Eur Resp J 2005; 26 : 812 51

  24. 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

  25. Influence of comorbid conditions on asthma Boulet LP ERJ 2009; 33 : 897

  26. 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

  27. 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

  28. 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

  29. Pollen and eosinophilic esophagitis Fogg et al. JACI 2003; 112 : 796

  30. 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

  31. 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%

  32. Hallmarks of Remodelling in asthma Bas. Membrane Submucosa Smooth muscle Thickening Collagen Deposition Hypertrophy

  33. Remodelling of the upper airways in allergic rhinitis : is it a feature of the disease ? Salib & Howarth Clin Exp Allergy 2003 ; 33 : 1629

  34. JACI, 2007

  35. Jyonouchi et al Immunol Allergol Clin N Am 2009

  36. CEA, 2010

  37. Benedetto et al.JACI 2011

  38. Van den Oord, 2010

  39. Marenholtz et al JACI, 2009

  40. Corrigan, JACI 2006

  41. Benedetto et al, J Invest Dermatol 2008

  42. CEA, 2010

  43. CEA, 2010

  44. CEA, 2010

  45. 2010

  46. Rondon et al JACI 2011

  47. 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

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