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Asthma phenotypes

Asthma phenotypes. Pawel Gorski Medical University Lodz. Asthma phenotypes-categories. Clinical- mild/moderate, severe Age of the onset- childhood, adulthood IgE dependency- atopic(extrinsic), nonatopic Type of inflammation. Inflammatory Phenotypes. Eosinophilic. Neutrophilic.

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Asthma phenotypes

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  1. Asthma phenotypes Pawel Gorski Medical University Lodz

  2. Asthma phenotypes-categories • Clinical- mild/moderate, severe • Age of the onset- childhood, adulthood • IgE dependency- atopic(extrinsic), nonatopic • Type of inflammation

  3. Inflammatory Phenotypes Eosinophilic Neutrophilic Paucigranulocytic

  4. Klasyfikacja astmy w oparciu o ocenę plwociny indukowanej Astma nieeozynofilowa Astma eozonofilowa Liczba eo w normie(<1,9%) Liczba eo > 1,9% Liczba neutrofilów Zapalenie ubogo granulocytarneZapalenie eozynofilowe w normie (<61%) Astma dobrze kontrolowana Typowa astma, często atopia, Rozważ alternatywną diagnozę Rozważ dawkę kortykosteroidów Liczba neutrofilów >61% Zapalenie neutrofiloweGranulocytarne mieszane • Ostra infekcja Ciężkie zaostrzenia astmy • -Infekcja przewlekła (Chlamydia, Astma oporna na leczenie • adenowirus) • -Palenie tytoniu • -Otyłość • -Ekspozycja na endotoksynę • -Antygeny zawodowe • - Zanieczyszczenia powietrza (ozon) Haldar P JACI 2007,119,1043-1052

  5. Non-Eosinophilic asthma • Symptoms • Increased Airway responsiveness • Eosinophils within normal range

  6. Neutrophilic inflammation in asthma Barnes, JACI, 2007

  7. Characteristics of Neutrophilic Asthma • Stable asthma: n=259 • Eosinophilic n=135, 52% • Neutrophilic alone n=60, 23% • Less atopy • Older • Later onset asthma Green RH et al Thorax 2002;57:875-9

  8. Clinical features of eosinophilic and non-eosinophilic asthma. Simpson et al., Respirology 2006

  9. Acquired and innate immune pathways leading to asthma (Douwes et al., Thorax 2002) ??? Paucigranulocytic

  10. Particulates, Pollutants, Virus, Endotoxin Allergens Acquired Immunity Innate Immunity IgE TLR Activated TH2 Cells Macrophages and Epithelial Cells NF-kB Oxidative stress IL-5 IL-8 Eosinophils Neutrophils MBP ECP MMP-9 NE Eosinophilic Asthma Neutrophilic Asthma

  11. Particulates, Pollutants, Virus, Endotoxin, Bacteria Allergens Acquired Immunity Innate Immunity IgE TLR Activated TH2 Cells Macrophages and Epithelial Cells ICS X X LABA Neutrophilic Asthma Eosinophilic Asthma Inflammatory cell activation Remodelling: ASM, mast cells X LABA hyperresponsiveness

  12. Prospects for Cure of Neutrophilic Asthma • Treatable exposure • Infection • non-infection • Modify host response • Antagonise Neutrophils - LABA • Chemokine/elastase inhibition

  13. Phenotypes of severe asthma

  14. Infiltrating cells in severe asthma • “No histologic criteria consistently differentiate severe from milder forms of asthma, perhaps because of confounding by the: - effects of therapy - difficulty in sampling distal lung compartments - variation with time” Chanez, Wenzel et al., JACI, 2007

  15. Does the Inflammatory Phenotype Predict Response to Corticosteroids?

  16. Odpowiedź na leki • Słabsza na ks jeśli liczba eo w plwocinie <3% 7 prac z lat 2000-2007 wg Haldar P JACI 2007,119,5, 1043-1052 • Ale…… Przecież są to chorzy na ogół otyli, wielu z nich pali papierosy, a u wielu stwierdza się inne choroby zapalne ( zapalenia jelit, hepatitis C, choroby autoimmunologiczne tarczycy, infekcje Helicobacter) • Czy zatem charakter zapalenia decyduje o odpowiedzi na ks? • Prawdopodobnie lepsza odpowiedź na etanercept Berry MA i wsp. NEJM 2006, 354, 697-708 • Dobra odpowiedź na LABAJarayam L i wsp. Eur Respir J 2006, 27, 483-494

  17. Thank you

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