氣喘 : 風雲再起Asthma: an old disease, a new Asthma: an old disease, a new

challenge of futurechallenge of future王圳華 醫師

Chun-Hua Wang, MD

Schematic representation of a) pro-asthmatic epithelium with a close relationship between altered epithelial cell transcription factors, goblet cell metaplasia and T-helper cell (Th) type 2 inflammation. b) The altered

epithelium also interacts with the underlying mesenchyme in a chronic wound response to contribute towards airway wall remodelling and ongoing inflammation

Clinical phenotypes of asthmaClinical phenotypes of asthma

Haldar P et al, AJRCCM 2008

Adult Asthma

GINA Guideline

Well controlledWell controlled

Step down

SucceedSucceed

Self ManagementWith minimal medications

Self ManagementWith minimal medications

FailFail

Not Well controlledNot Well controlled

Compliance

Identify triggering factors

YesYes

Avoid / TreatAvoid / Treat

NONO

Severe AsthmaSevere Asthma

Low dose or high doseLow dose or high dose

Not Well Controll Asthma

Not Well Controll Asthma

Bad compliance

Bad compliance Good compliance

Compliance monitor

Compliance monitor

No identified causesGERD

RhinitisSinusitis

EmotionalOccupationalDrug induced

ExerciseMenstruation

GERDRhinitisSinusitis

EmotionalOccupationalDrug induced

ExerciseMenstruation

History Therapeutic trial

History Therapeutic trial

Severe Asthma

Eosi

noph

ilic

Eosi

noph

ilic

Neu

trop

hilic

Neu

trop

hilic

Alle

rgic

(IgE

)Al

lerg

ic (I

gE)

Airw

ay

rem

odel

ing

Airw

ay

rem

odel

ing

Induced SputumBlood

Breath condensate FeNO

Bronchial biopsy

Induced SputumBlood

Breath condensate FeNO

Bronchial biopsy

Severe Asthma

High collapsibility of airways

Lung hyperinflation

High airway hyper-responsiveness

Inflammation(steroid insensitive)

Structural Changes

Environmental FactorsEnvironmental Factors Host FactorsHost Factors

GenomicsGenomics

EpigeneticsEpigenetics

Allergen, virus, or oxidant stress induced injury

Allergen, virus, or oxidant stress induced injury

Epithelial sheddingSubmucosal inflammation

Epithelial sheddingSubmucosal inflammation

Recruit bone-marrow-derived fibrocytes

Recruit bone-marrow-derived fibrocytes

Recruit fibrocytes to submucosa, ASM

Recruit fibrocytes to submucosa, ASM

FibroblastproliferationFibroblastproliferation

Myofibroblast

EGF, TGF-CTGF

Chronic stimulation

Airway remodelingAirway remodeling ASMASM

?

Acute inflammationAcute inflammation

CXCR4CXCR4

FibroblastFibroblast

CXCL12

Higher level of IL-13, TGF-1Higher level of IL-13, TGF-1

CCL19

CCR7CCR7 EGFREGFR

MyofibroblastMyofibroblast Tissue repairing

Anti-IgE antibodies

(Omalizumab)Omalizumab)

Anti-IgE antibodies

(Omalizumab)Omalizumab)

NeutrophilNeutrophilNeutrophilNeutrophil EosinophilsEosinophilsEosinophilsEosinophils AirwayAirwayremodelingremodeling

AirwayAirwayremodelingremodeling

AllergyAllergyEnviromentaEnviromenta

ll

AllergyAllergyEnviromentaEnviromenta

ll

PDE4 PDE4 inhibitorsinhibitors

PDE4 PDE4 inhibitorsinhibitors

Anti-IL5 Anti-IL5 antibodiesantibodies

Anti-IL5 Anti-IL5 antibodiesantibodies

??Anti-elastaseAnti-elastaseThermoplastyThermoplasty

??Anti-elastaseAnti-elastaseThermoplastyThermoplasty

??Anti-IgE AbAnti-IgE Ab

??Anti-IgE AbAnti-IgE Ab

FibrocytesFibrocytesOxidative stressOxidative stressMast cellsMast cells

Progressive remodelingProgressive remodelingPoorly controlPoorly controlProgressive remodelingProgressive remodelingPoorly controlPoorly control