Transcript Slide 1

Therapeutic applications of
Immunology in Asthma
Prof.Yousser Mohammad
Meeting of the Syrian Thoracic Association
28- 7-2010
Generalities
Introduction
3000 Asthma patients world wide
5% in Syria?
 Understanding immunology& the resulting
inflammation and bronchoconsriction caused by
hyperresponsivness& leads to
Rational pharmaceutical treatment (‫)القرن العشرين‬
( Inhales corticosteroids), and to asthma control.
 Understanding Genetic polymorphism
implication (Single Nucleotide Polymorphism/
loci) in multiple chromosomes will lead
pharmacotherapy ( Pharmacogenetics ‫القرن‬
‫)الجادي والعشرين‬

Lymphocyte T H2 > TH1 in asthma
obstruction/inflammation needs long term
treatment to reverse( American Academy of
Asthma Allergy and Immunology)
pharmacogenetics
- 1990, the Human Genome Project (HGP) mapped
the locus of each of 30,000 to 35,000 genes on 23 chromosomes,
with an estimated 3 billion bases (adenine [A], guanine
[G], cytosine [C], and thymine [T]), and identified a number
of genetic variants or polymorphisms.1,2
- Recently, phase1 of the( Hap Map project) The Hap Map project
differs from the HGP in that the HGP is informative
about the invariance of the majority of bases across individuals,
while the Hap Map project focuses on differences in
DNA sequence among individuals. The aim of the Hap Map
Consortium was to create a public, genomewide database of
common (≥1% frequency) sequence variations. The human
genome has about 10 million common polymorphisms.
Genetic Polymorphism
- Cytokine gene cluster on the long arm of
chromosome 5 (5q31–33).
This chromosome region contains the genes
for many TH2
- Polymorphisms in this chromosome region
are more strongly
associated with allergy than asthma.
- Other polymorphism have been with the
common subunit of the IL4 and IL13
receptor are more associated with asthma
Mechanisms
Causal and triggers for asthma(Risk Factors)
Allergic Cascade
Early and Late phase of Allergy
1-Early
phase : 15
min
/exposure
After degranulation : Membrane
Phospholipids arachidonic acid( Late phase)
2-Late
phase :
attack
6h later
3-Irreversible Remodeling
Remoduling
Even mild persistent Asthma is
chronic inflammation
Patho-physiology
Airflow Limitation
Air way hyperresponsivness
Decrease of FEV1 over time
Reversibility
Genetic
Pharmacotherapy
Implication of Immunology and genetic
Genetically predetermined
response to B2 mimetics
Genetically predetermined response
to B2 mimetics
-Clinical studies demonstrate that patients
with polymorphisms, in the beta-adrenergic
receptor who are homozygous
at position 16 (Arg/Arg) do worse when
treated regularly with
beta-agonists. In contrast, patients treated
regularly with betaagonists
- who were homozygous for glycine at
position 16
(Gly/Gly) did not experience a change in their
peak flow,throughout the study
Genetic polymorphism in a single nucleotide lead response
to therapy
Genetically predetermined response
to Inhaled Cortic-osteroides
Genetically predetermined response
to Leukotrien modifiers
Xolair ( anti-IgE)
Immunotherapy
Why do asthma patient feel
shortness of breath??
Inflammation,
hypersecretion,
brochconstriction
Or Elephant on the
thorax??
I Feel breathless?????
How to use your Inhaler
Summary of acute and Chronic
Genetic Polymorphysme(SNP)of atopy
+
Environment(Allergenes, pollution, ETS)

Immuno – Inflammatory- BHR Phenotypes

Pharmacotherapy in the 21 st Century
References
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1- Clinical Immunology, edited by John Bradley: Sandoz, profeesor
and head of department of clinical immunology. Flinders University
and Flinders Medical Center. Adelaide, Ausralia.
Jame McClusky. Professor and director , clinical immunology,
Flander University and medical center, and transplant services,
blood transfusion service. Adelaide, Australia. Oxford, New York,
Melbourne. Oxford University Press 1997, printed in Hong Kong
Colour Atlas of immunology, S.R. Burmester MD, A.Pezzutto MD.
With contribution by T.Ulrichs and A.Aicher 2006. Thieme Stuttg
Art. New York . http://www.thieme.com
Nizar N. Jarjour, Elizabeth A.B Kelly; Pathogenesis of Asthma; in
Robert K.Bush. The Medical Clinics of North America. Sept 2002
vol 86, number 3 . W.B. Saunders Company The curtis center,
philadelphia Pensylvania ullen
Epigenetic
Epigenetics is defined as heritable changes
that affect gene expression without
altering the DNA sequence. Epigenetic
regulation of gene expression is facilitated
through different mechanisms such as
DNA methylation, histone modifications
and RNA-associated silencing by small
non-coding RNAs.
 Passive smoking : Asthma onset , pollution
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