asma longterm

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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 &macrophages

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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