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IMPACT OF ASTHMA AND ALLERGIC RHINITIS ON EACH

IMPACT OF ASTHMA AND ALLERGIC RHINITIS ON EACH. Arzu Yorgancıoğlu. Epidemiologic Anatomic Physiologic Immunopathologic Therapeutic. EMBRYOLOGIC DEVELOPMENT. Begins during the 4th week of gestation and continues after birth Nasal placode and prominences ; Nose

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IMPACT OF ASTHMA AND ALLERGIC RHINITIS ON EACH

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  1. IMPACT OF ASTHMA AND ALLERGIC RHINITIS ON EACH Arzu Yorgancıoğlu

  2. Epidemiologic • Anatomic • Physiologic • Immunopathologic • Therapeutic

  3. EMBRYOLOGIC DEVELOPMENT • Begins during the 4th week of gestation and continues after birth • Nasal placode and prominences ; Nose • Laryngotracheal groove in the ventral wall of primitive pharynx ; Larynx,trachea and bronchi

  4. Bousquet J JACI 2004;113

  5. SIMILARITIES Chronology in embryology Respiratory epithelium DIFFERENCES Subepithelial capillaries, arterial system, venous,cavernous sinosoids Cartilage (nasal fossa-bronchi) No muscle in nasal cavity, Lower airways SMOOTH MUSCLE ANATOMY

  6. VASCULAR ENGORGEMENT BRONCHOCONSTRICTION Bousquet J JACI 2004;113

  7. Chronic Allergic Inflammatory Airway Syndrome Allergic Rhinitis Allergic rhinitis + Bronchial Hyperreactivity Allergic Rhinitis + Asthma

  8. Vertical and Horizontal Relationship Togias A JACI 2003;111

  9. VERTICAL RELATIONSHIP Aspiration of Inflammatory Material Oral breathing Systemic Propagation of Nasal Inflammation Nasopharyngo-bronchial reflex Togias A Allergy 1999;54(suppl 57):94..

  10. ASPIRATION OF INFLAMMATORY MATERIAL • First contact for inhaled allergens, contact with nasal secretions, allergenity and biologic activity • Insufficient invivo data,rabbit study + • No deposition of nasal secretions in lung (Tc99m enj) Bardin P J Allergy Clin Immunol 1990;86:82

  11. ORAL BREATHING • Bypassing the nose • Deprivation of lower airways from protective mechanisms (Nasal air conditioning, humidifying, filtering • Possible detrimental consequences

  12. NAZOBRONCHIAL REFLEX Healthy Indıvıdual • Nasal provocation with dry cold air bronchoconstruction • With oral breathing , warming , local anesthesia or antikcholinergic no response

  13. NAZOBRONCHIAL REFLEX AR +, Asthma - • Provocation with natural or metacholine , histamin BHR + • Sensorineural apparatus of the inflamed nose is upregulated nasobronchial reflex is upregulated as well. Simons Clin Exp All Rev 2003;3

  14. Nasal allergen provocation increases bronchial hyperresponsiveness Change in PC20 after nasal provocation Plasebo (n=10)Allergen (n=10) 3 2 0 Geometricmean PC20(methacholine,mg/ml) *** ** 1600 Postchallenge Time 0800 Baseline 1200 Postchallenge Corren J et al J Allergy Clin Immunol 1992;89:611-618.

  15. Patients with allergic rhinitis develops bronchial hyperresponsivess in polen season Prevalance of Bronchial hyperresponsiveness 60 50 40 30 20 10 0 (n=27) p<0.02 % of patients 48 11 Off season Season Madonini E et al J Allergy Clin Immunol 1987;79:358-363.

  16. seasonal perennial seasonal rhinitis rhinitis + perennial rhinitis 80 Bronchial hyperresponsiveness - 821 adult - 20-44 y - PC20 methacholine ≤4mg 60 40 % subjects 20 0 controls asthma non-asthmatic without wheeze

  17. Nasal mucosa of rhinitic patients with asthma responds more vigorously to nasal cold dry air than the ones without asthma • Nasal response to natural cat allergen exposure is greater with rhinitis and asthma than in patients with rhinitis alone • The presence of asthma and rhinitis signifies a higher degree of functional abnormality of the entire airway Hanes LS Clinical and Experimental Allergy 2006;36:26 Corren J J Allergy Clin Immunol 2005 ;

  18. BHR Asymptomatic in rhinitic patients Close connection between BHR and allergen exposure • A relationship between the degree of BHR And FEF 25-75 Ciprandi G Respiratory medicine 2004;98:826

  19. SYSTEMIC INFLAMMATION CLINICAL DATA

  20. Common Immunologıcal mechanism Preformed mediators Histamine IgE Mastcell Acute allergikreaction Newly synthesized mediatorsCysLT, PG, PAF Eosinophills Allergen T cell Chronic allergikreaction Cytokines Casale TB, Amin BV Clin Rev Allergy Immunol 2001;21 Kay AB N Engl J Med 2001;344

  21. Eosinophilic Infiltration Allergic rhinitis Astma Eosinophil infiltration Bousquet J et al J Allergy Clin Immunol Suppl 2001;108(5):S148-S149.

  22. Similarities in early and late response 100 FEV1(% change) 50 0 0 1 2 3 4 5 6 7 8 9 10 24 Time (h) AsthmaAllergic rhinitis Late Phase Early phase Symptom score Antigenprovocation 1 3–4 8–12 24 Time(h) Varner AE, Lemanske RF Jr. In: Asthma and Rhinitis. 2nd ed. Oxford: Blackwell Science, 2000:1172-1185 Togias A. J Allergy Clin Immunol 2000;105(6 pt 2):S599-S604.

  23. NASAL PROVOCATION SYSTEMIC RESPONSE • Nasal allergen provocation peripheric eosinophilia Togias A J Allergy Clin Immunol 2000:106. • Nasal provocation spontaneus cytokine decharge from peripheric leucocysts Togias A J Allergy Clin Immunol 2002:109.

  24. NASAL PROVOCATION SYSTEMIC RESPONSE P=0.004 Eosinophils /mm3 Togias JACI 2000; 106: 247 - 50

  25. Increase in eosinophils in bronchial epithelium after allergen provocation 1600 1200 800 400 0 ** +cell/mm2 ** BMK13 bronchial subepithelium * T0 A B C T24 Braunstahl, Am J Respir Crit Care Med 2000; 161:2051-57.

  26. Increase in Eosinophils in Bronchial Epithelium Braunstahl, Am J Respir Crit Care Med 2000; 161:2051-57.

  27. NASAL PROVOCATION SYSTEMIC RESPONSE • 9 AR , 9 controls ( nasal provocation) • Symptom scores, PFT, Peripheric Blood, nasal and bronchial biopsy • ½ ve 12h ; pulmonary and nasal symptom scores, functions • 24h; Peripheric eosinophil and IL-5 Nasal + bronchial eosinophil and IL-5 Endothelial adhesion molecules in Nasal and bronchial mucosa Braunstahl GJ J Allergy Clin Immunol 2001:107

  28. Braunstahl GJ JACI 2001:107.

  29. Systemic Inflammatory Response to Allergen Provocation ICAM-1/CD31 VCAM-1/CD31 ELAM-1/CD31 % Braunstahl GJ et al. JACI 2001; 107: 469-76

  30. Nasal biopsy(ICAM-1,VCAM-1,E-Selectin,CD31 24s Braunstahl GJ JACI 2001:107

  31. Bronchial biopsy(ICAM-1,VCAM-1,E-Selectin,CD31 24s Braunstahl GJ JACI 2001:107

  32. Inhalation study with 99mTc • No deposition in lung after nasal exposition Corren J J Allergy Clin Immunol 1992:89.

  33. BRONCHIAL PROVOCATION SYSTEMIC RESPONSE • Segmental bronchial provocation in AR patients • Eosinophilia after 24 h • Nasal and bronchial mucosa ; eosinophilia IL-5 eotaksin + cell Braunstahl AJRCCM 2000:161.

  34. BRONCHIAL PROVOCATION SYSTEMIC RESPONSE • Segmental bronchial provocation in AR • 24 s; Nasal mucosal mast c.(degranulation) and basophil Peripheric basophilia (migration) Lower and upper airways; eosinophil , IL 5 and eotaksin positive cells Braunstahl AJRCCM 2001:164.

  35. 9 atopic asthmatics9 AR, Asthma –Segmental bronchial provocation • BAL; cell count, histamine, MMP, IL-5, IFN-  , IL-10 • Cell,mediatör and cytokine profile similar • PD causing airway response change 5 times lower in asthmatics • Preexisting airway sensitivity, injury, remodeling?? Kelly E J Allergy Clin Immunol 2003;111:79.

  36. Nasal mucosal inflammation in Asthma in the absence of rhinitis (n=9) (n=8) (n=10) 18 16 14 12 10 8 6 4 2 0 Eosinophils p<0.001 p<0.001 Rhinitis No Rhinitis Control Asthma Gaga M et al Clin Exp Allergy 2000;20:663-669.

  37. Bronchial mucosa Nasal mucosa Bousquet J et al. N Engl J Med 1990 Chanez P et al. Am J Respir Crit Care Med 1999 Eosinophils in asthmatics

  38. Similar airway findings in patients with rhinitis without asthma Bavbek S, J Invest Allergol Clin Immunol 1996; 6(3): 172-182

  39. RESULT • AR-Asthma relationship BIDIRECTIONAL • Local allergen exposure causes generalized airway inflammation • SYSTEMIC RESPONSE due to IL-5

  40. DIFFERENCES • Pathogenetic mechanisms and the resultant inflammation ; not different • Difference due to TARGET ORGAN characteristics (intrinsic features)

  41. Immunopathologic Differences between Rhinitis and Asthma • Epithelial injury – Specific for asthma • Remodelling – Specific for asthma • Mechanism in hyprereactivity - ? sensorineural in nose Multifaceted in lung

  42. Epithelial Shedding Nasal patient Nasal control Bronchial kcntrol Bronchial patient Chanez P AJRCCM 1999;159

  43. EPITHELIAL SHEDDING • Epithelial sheeding more prominent in bronchus (correlating with disease severity) • The less severe eosinophilic inflammation ? • A reason other than eosinophils (Episialin ?) Polosa R J Allergy Clin Immunol 2000;106:1124 Shaida A J Allergy Clin Immunol 2001;108:791

  44. EPITHELIAL SHEDDING • The characteristics of nasal mucosa • Higher clearance rate • More resistance to injury • Higher regeneration capacity • Protection against MMP

  45. Basal Membrane in Rhinitis • Thickness of the nasal epithelium in patients with PAR is greater than that of patients with SAR and controls Calderon et al. JACI 1994; 93: 635-43 • Thickness of BM is greater in patients with SAR than controls Limet al. Am J Respir Crit Care Med 1995; 151: 136-44

  46. Thickness of Nasal and Bronchial Basal Membrane in Steroid -dependant asthmatics Control Asthma p<0.001 14 12 10 8 6 4 2 0 14 12 10 8 6 4 2 0 Basal membrane Thickness (mm) p<0.004 Nose Bronchus Nose Bronchus Chanez P et al. Am J Respir Cit Care Med 1999; 159: 588-95

  47. BM thickening more prominent in bronchus • Episialine (antiadhesion molecule secreted by epithelium)s ignificantly more in bronchus Chanez P AJRCCM 1999;159

  48. Episialine immunoreactivity NASAL BRONCHIAL Chanez P AJRCCM 1999;159

  49. Upper airway response leads to less remodeling??

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