asthma phenotypes
DESCRIPTION
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. - PowerPoint PPT PresentationTRANSCRIPT
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Asthma phenotypesPawel Gorski
Medical UniversityLodz
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Asthma phenotypes-categories
• Clinical- mild/moderate, severe• Age of the onset- childhood, adulthood• IgE dependency- atopic(extrinsic),
nonatopic• Type of inflammation
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Inflammatory Phenotypes
Eosinophilic Neutrophilic
Paucigranulocytic
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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 granulocytarne Zapalenie eozynofilowe
w normie (<61%) Astma dobrze kontrolowana Typowa astma, często atopia,
Rozważ alternatywną diagnozę Rozważ dawkę kortykosteroidów
Liczba neutrofilów
>61% Zapalenie neutrofilowe Granulocytarne 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
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Non-Eosinophilic asthma
• Symptoms
• Increased Airway responsiveness
• Eosinophils within normal range
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Barnes, JACI, 2007
Neutrophilic inflammation in asthma
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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
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Clinical features of eosinophilic and non-eosinophilic asthma. Simpson et al.,
Respirology 2006
Eosinophilic
Neutrophilic
Pauci-granulocytic
Mixed
No. of subjects 38 19 29 7
Atopic, % 86% 92% 88% 100%
FEV1% predicted
78% 73% 79% 60%
ICS dose mg/day
1.5 2.0 1.5 2.0
PD15 (ml) 3.4 9.1 7.6 10
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Acquired and innate immune pathways leading to asthma (Douwes et al., Thorax 2002)
Paucigranulocytic ???
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IL-5
Eosinophils
ECPMBP
IL-8
Neutrophils
NE
Macrophages and Epithelial Cells
Allergens
Activated TH2 Cells
MMP-9
EosinophilicAsthma
NeutrophilicAsthma
Particulates, Pollutants, Virus, Endotoxin
Acquired Immunity
InnateImmunityTLRIgE
NF-kBOxidativestress
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Macrophages and Epithelial Cells
Allergens
Activated TH2 Cells
EosinophilicAsthma
NeutrophilicAsthma
Particulates, Pollutants, Virus,Endotoxin, Bacteria
Acquired Immunity
InnateImmunityTLRIgE
Inflammatory cell activation
hyperresponsiveness
ICS X X LABA
X LABA
Remodelling: ASM, mast cells
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Prospects for Cure of Neutrophilic Asthma
• Treatable exposure– Infection– non-infection
• Modify host response• Antagonise Neutrophils - LABA
– Chemokine/elastase inhibition
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Phenotypes of severe asthma
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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
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Does the Inflammatory Phenotype Predict
Response to Corticosteroids?
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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 LABA Jarayam L i wsp. Eur Respir J 2006, 27, 483-494
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