Term
Asthma
common chronic disease in children
1.5 death/100000 in US
1/4 children have asthma in UK and Australia
IgE isotype is corelated with asthma
SES is related |
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Microbial esposure
children growing up in rural areas is related to low asthma rate |
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Signs:
Bronchoconstriction, bronchospasm
Vascular leakage of plasma
Vasodilation
Airway inflammation
Obstruction 3rd-7th bronchial generations |
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Symptoms:
Wheezing
Coughing
Tightness of chest
SOB
Death due to asphyxiation and general body hypoxia follow by respiratory collapse follwing anaphylactic shock |
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Term
Clinical Triad
Intermittent and reversible airway obstruction is our prime target for pharm treatment with the use of Bronchodilators
Chronic bronchial inflammation is another target using Anti-inflammatories
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Cellular and Molecular Mech of Allergy
allergen+APC Dendritic, then immediate release of chemokines...
In asthma pt, you get more Th2 cell
IL-4,5,10,12,13 are the important interleukins in Th2.
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Term
IL-4 autoregulate the Th2, promotes IgE switching, recruits eosinophils
IL-4 & IL-5 cause B-cell proliferation and maturation and switch to IgE secretion
IL-10 inhibitsd IL-2, IFN and TNF
IL-12, growth and differentiation of ThO cells
IL-13 promotes IgE
Activation of recruitment of Eosinophil cause all damage in late phase of asthma |
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Lack of exposure to bac and virus increases incidence of
asthma
Because
When you're exposed to lots of Bac or virus, you're secreating lots of IL-12 which favors Th1 cells, Th1 cells will secrets lots of IFN-γ. IFN-γ inhibits Th2. inc |
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Early phase: Narrowing of lumen caused by mast cell basophil
Late phase: accumulation of inflammatory cells by Eosinophil.
Eosinophil is an effector cell, it is activated and has cytotoxic effect against epithelium.
Repeated asthma attack cause permanent damage to the airway lining. (airway remodeling) |
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Eosinophil
derived from CD34 precursor cells, it elicits response against helminthic infections
The major protein it secrets: MBP (major basic protein)
ECP (eosinophilic cationic protein)
Both cause reversible and irreversible damage to the lungs |
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Anti-inflammatories:
Cromolyn Sodium
been used in many years, known to reduce asthma like symptom.
Mast-cell stabilizer. Used as prophylactic.
Prevents pulmonary mast cell degranulation and release of histamine and leukotrienes. |
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Nedocromil sodium
similar to Cromolyn sodium, it stabilize mast cell, has other lesser known fxns
Prevents prostaglandin and leukotriene production. |
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Corticosteroids/Glucocorticoids
potent anti-inflammatory, act on late phase
suppress cell-mediated and humoral immunity
inhibit production of PG, LT, and cyclooxygenase
act as a ligant on GR (nuclear transcription factors TFs)
protein in the cell acts on DNA to upregulate or down-regulate gene expression |
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Dimers trans-activate gene transcription
Monomers trans-repress gene transcripton
eg: Flusone, GC inhaler
side effects: candiditis, yeast infection on the tongue
long term effect: osteoprosis, cataract in the eye |
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Mechanism of GC
GR dimer: binding to DNA and trans-activating gene expression of anti-inflammatory proteins
Side effects: metabolic endocrine
GR monomer: inhibit transcription factors such as NF-κB to decrease inflammatory proteins |
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