asma longterm
TRANSCRIPT
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Definition: (ATS, 1962)
Respiratory disease
Tracheo-bronchial hyperreactive
Diffuse narrowing Reversible (disappear with or without
treatment)
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Definition (GINA, 2002) Asthma isa chronic inflammatorydisorder of the airway
in which many cells and cellular elements play a role, inparticular, mast cells, eosinophils, T lymphocytes,macrophages, neutrophils, and epithel cells. In susceptiblindividuals, this inflammation causes recurrent episodesof wheezing, breathless, chest tighness, and coughing,particularly at night or in the early morning. Theseepisodes are usually associated with widespread butvariable airflow obstruction that is often reversible eitherspontaneously or without treatment. The inflammation als
causes an associated increase in the exizting bronchialhyperresponsiveness to a variety of stimuli.
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Definition (National Guidelines)
Cough and/or wheeze that:
Episodic
Variable
Reversible
Atopic history
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Prevalence of asthma
Primary school children (6-13 year old) 4 17 %
Secondary school children (12-18 year old) 5.7 7.4 %
Hospitalized children 2.7% with asthma, usually with other diseases such
a pneumonia or ARI
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Triggers of asthma Respiratory infection (viral, mycoplasma)
Exercise
Allergens : - Inhaled
- Ingested (rare)
Irritants (cigarette smoke, air pollution) Weather changes
Medications (ASA)
Chemical (tartrazine, sulfites, menosodium
glutemate) Emotional stress
Gastroesophageal reflux
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Genetically predisposed individuals
Immune responseTh2, IgE, IgG4, IgG1
InflammationTh2, Mast cells, eosinophils
Wheezing
Inducers (I)
Indoor allergensAlternaria, etc
Enhancers (E)
RhinovirusOzone
2-agonist
Triggers
Exercise/cold airHistamine/methacholine
2-agonist
BHR
Avoidance
Anti- inflammatoriesImmunotherapy ?
? Avoidance
Platts-Mills et al. Ciba foundation 199
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Mechanisms of acute and chronic inflammation in asthma and
Remodeling processes
Inflammatory cellrecruitment Persistence of
Inflammatorycells
Activation offibroblasts ¯ophages
VascularPermeability
& oedema
InflammatoryCell
activation
decreasedapoptosis
TissueRepair
remodell
Epiteliel cellActivation &proliferation
Smooth muscle& mucous gland
proliferationRelease ofCytokines
And growth factors
IncreasedBronchial
hyperreactivity
Mucus secretion&
bronchoconstriction
InflammatoryMediatorrelease
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Airway
remodelling
ExacerbationNon-specific
hyperreactivity
Persistent airflowobstruction
Link between pathologic mechanism and clinical consequences in asth
Chronic
inflammation
Symptoms(Broncho-
constriction)
Acute
inflammation
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Clinical consequences of airway remodeling in asthma
Smoothmusclemass
increase
Mucousglands
increase
Inflammatorycells
persistence
Fibrogenicgrowthfactor
release
Elastolysis
Severebronchospasm
duringexacerbation
Importantmucous secretion
during exacerbation
On going
inflammation
Reduced elasticit
of airway wall
Colagen depositionon RBM and RCM
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Criteria of severity of childhoodasthma
Infrequent episodic symptoms Exacerbation 3-4 x/year, there is no sign and symptom in
between
Quality of lifegood
Frequent episodic symptoms Exacerbation 1 x/month, there is no sign and symptom in
between
Quality of lifegood, sometimes affected
Persistent symptoms Exacerbation > 1 x/month, there is sign and symptom in
between
Quality of lifelimited
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Risk factor for persistence of childhoodasthma
Sex Conflicting evidenceAge of onset Yes; early onset
Severity of asthma Yes; more severe
Eczema Yes
Family history of atopy Yes
Smoking (active/passive) Yes
Level of lung functionYes; impaired lung function at
age 7 predicts asthmatic symptoms
Treatment Not known
Paton J. Manual of asthma management, 2001
Do not over treat to avoid side effects
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DIAGNOSISCough and/or Wheeze
Clinical history
Physical examinationMantoux test
Suggestive of asthma: Episodic Nocturnal Seasonal Exertional Atopy
Indeterminate features or suggestivof alternative diagnosisNeonatal onset Failure to thrive Chronic infection Vomiting/choking Focal lung or CVS signs
If possible frequent peak flow
measurements :Reversibility (20%) Variability (20%)
Consider Chest and sinus x rays Lung function Bronchial challenge and/or Bronchodilator response
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.. Consider : Sweat test Immune function Ciliary & Reflux studies
Bronchodilator responseNo response
Response
WD/ Asthma
Assess severity and aetiology
Review diagnosis and complianceif poor response to treatment
+ ve- ve
Alternative diagnosis and treatmeChest x ray if more thanmild episodic disease
Trial of antiasthma treatmentConsider asthma as an
associated problemNot asthm
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Treatment
Treatment of attack : 2 agonist : inhaled, nebulized, oral
Ephinephrin : subcutan
Theophyllin/aminophyllin : oral, I.V.
Steroid : oral, I.M.
Prevention of attack : Avoidance : triggers (including enhancers, inducers)
especially improve indoor environment. Medicine : steroid, DSCG, antileukotrien, ketotifen,
cetirizine.
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Low dose steroid
Medium dose
steroid
Low dose
steroid + LABA
Low dose
steroid + ALTR
Low dose
steroid +TSR
High dose
steroid
Medium dose
steroid + LABA
Medium dose
steroid + ALTR
Medium dose
steroid + TSR
ORAL
STEROID
Longterm
management
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Interaction between LABA & Corticosteroids
Corticosteroid Increase b2-receptor
synthesis
Decrease b2-receptordownregulation
Attenuate inflammation-mediated b2- receptoruncoupling anddysfunction
LABA LABA increase GR
nuclear translocation
LABA prolong GR nuclearresidency time
LABA prime GR foractivation byMAPK-dependentphosphorylation Enhance antiinflammatory
activity of steroid
% Days Wh i
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Percentage of days (+ SE) on wich wheezing was noticed, medication was given, and abnorma
low peak expiratory flow rate (PEFR) was recorded during 4 week study period
% Days50
40
30
20
10
0
Wheezing
Medication
Low PEFR
Dust freeBedroom
ControlBedroom
PC20 Histamine
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Concentration of aerosolized histamine required to reduce the 1-secondforced expiratory volume (FEV1) by 20% (PC20 histamine) at start and end of trial perio
Initial
End of trial
20
ControlBedroom
Dust freeBedroom
Mg/ml
>8
84
2
1
0.50.25
0.12
0.06
0.03
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Conclusions
Asthma prevalence: increase
Classifications of childhood asthma:
infrequent episodic asthma, frequent episodic
asthma, and persistent asthma
Longterm management: Inhalation therapy
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