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ชมุรมุโรคระบับัหายใจและเวัชบั'าบั�ดวั�กฤติใน้เด กชมุรมุโรคระบับัหายใจและเวัชบั'าบั�ดวั�กฤติใน้เด กแห�งประเทศ์ไทยแห�งประเทศ์ไทย

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Clinical Asthma Control (GINA 2006)

• No (twice or less/week) daytime symptoms • No limitation of daily activities, including

exercise• No nocturnal symptoms or awakening because

of asthma• No (twice or less/week) need for reliever

treatment• Normal or near-normal lung function results• No exacerbations

Asthma management program

Component 1. Develop patient/doctor partnership

Component 2. Identify and reduce exposure to risk

factors

Component 3. Assess, treat, and monitor asthma

Component 4. Manage asthma exacerbations

Component 5. Special Considerations

Levels of Asthma Control (GINA 2006)Characteristic Controlled

(All of the followings)

Partly Controlled(Any measure present in

any week)

Uncontrolled

Daytime symptoms None

(twice or less / week)

More than twice/week

Three or more

features of partly

controlled asthma present in any week

Limitations of activities

None Any

Nocturnal symptoms/awakening

None Any

Need for reliever/ rescue treatment

None

(twice or less / week)

More than twice/week

Lung function

(PEF or FEV1)***

Normal <80% predicted or personal best (if known)

Exacerbations None One or more/year* One in any week**

* Any exacerbation should prompt review of maintenance treatment to ensure that it is adequate

** By definition, an exacerbation in any week makes that an uncontrolled asthma week

*** Lung function is not a reliable test for children 5 years and younger

Asthma Control Test

Activities all the time most of the time

some of the time

little of the time

none of the time

Shortness of breath > 1/day 1/day 3-6/wk 1-2/wk not at all

Symptoms

at night / morning

> 4/wk 2-3/wk 1/wk 1-2/wk not at all

Use of beta-2

agonists> 3/day 1-2/day 2-3/wk < 1/wk not at all

Control rate

not controlled

poorly controlled

somewhat controlled

well controlled

completely controlled

Score 1 Score 2 Score 3 Score 4 Score 5

Asthma Control Test

Score 25 Total control

Score 20-24 Well controlled

Score <20 Not be controlled

Childhood Asthma Control Test

How is your asthma?

Very bad Bad Good Very good

Playing / exercises

Can’t do Don’t like A little problem

No problem

Cough All the time Most of the time

Some of the time

None of the time

Wake up at night

All the time Most of the time

Some of the time

None of the time

Score 0 Score 1 Score 2 Score 3

Children Asthma Control Test

Daytime symptoms

everyday 19-24 11-18 4-10 1-3 0

Daytime wheeze

everyday 19-24 11-18 4-10 1-3 0

Wake up at night

everyday 19-24 11-18 4-10 1-3 0

Score 0 Score 1 Score 2 Score 3 Score 4 Score 5

Childhood Asthma Score

Score < 19 Not well controlled

Score > 20 Under controlled

Management Approach Based On ControlFor Children Older Than 5 Years, Adolescents and Adults

(GINA 2006)

Control Maintain and find lowest controlling step

Partly controlled Consider stepping up to gain control

Uncontrolled Step up until controlled

Exacerbation Treat as exacerbation

Level Control Treatment Action

Increase

Red

uce

ReduceTreatment Steps Increase

Asthma education & Environment controlAs needed

rapid acting

β2-agonist

As needed rapid acting β2-agonist

Controller

options

Select one Select one Add one or more Add one or both

Low- dose

inhaled ICS*

Low-dose ICS

plus long-acting β2-agonist

Medium or high-dose ICS plus long-

acting β2-agonist

Oral glucocorticosteroid

(lowest dose)

Leukotriene

modifier**

Medium or

high dose ICS

Leukotriene

modifier Anti-IgE treatment

Low dose ICS plus

Leukotriene modifier

Sustained release

theophylline

Low dose ICS plus

sustained- release theophylline

Step 1 Step 2 Step 3 Step 4 Step 5

*ICS = Inhaled glucocorticosteroids

** = Receptor antagonist or synthesis inhibitors

The first 3 drugs used for asthma controlThe first 3 drugs used for asthma control (N = 171)(N = 171)

1 LB2

LL39/882

3783 LL2

76171 - 099 052189 0973. ( . . ) . (4 4 .3 2 ) 4458( . ) 4444( . )

2 3 488 LL 3183 6 5171 - 106 054205 0862. ( . . ) . 3864( . ) 3735( . ) 3801( . )

3 8 88 LLLL 1383 LLLL 21171 - 054 019149 0191. ( . . ) . 909( . ) 1566( . ) 1228( . )

Drug N (%) Drug N (%) Drug N (%) L LL / SH Total OR (95% CI) P

RH = Regional hospital

PH = Provincial hospital

SH = Small hospitalVangveeravong M.Thai Pediatr J 2005; 12(1);25-32.

The first The first 33 drugs used for asthma control drugs used for asthma control by different kinds of doctorsby different kinds of doctors

((NN = 172)= 172)

1 1320IS / LL2

4395 LL2

2757 - 029 007097 0027. ( . . ) . LB2

650( . ) 4526( . ) 4737( . ) 2 LB

2 420 LL 3695 1 857 - 337 1161002 0011. ( . . ) . IS

200( . ) 3789( . ) 3157( . ) 3 320KETO / LLLL 1095 LLLL 1257 - 000 000131 0068. ( . . ) . THEO

150( . ) 1053( . ) 2105( . )

Drug N (%) Drug N (%) Drug N (%) OR (95% CI) P Drug

LLL NG Others (O) Ped : NG + O

Ped = PediatriciansPed = Pediatricians

NG = Newly graduated doctorsNG = Newly graduated doctors

LLLL0 .0 0 0

Vangveeravong M.Thai Pediatr J 2005; 12(1);25-32.

NN

N

N

O H

H

O

H

N

NN

N

O H

O

H3C

CH3

O

N

N

N

N

O

O

O

CH2

H3C

CH3

XANTHINE

THEOPHYLLINE

DOXOPHYLLINE

Methylxanthinespostulated mechanism of action

Increased cyclic AMP levelby inhibiting phosphodiesterase-4 (PDE-4)

ACAC PDE-4

c’APM c’APM ATPATP 5’AMP5’AMP

Bronchodilatation

(+) (-)

β2-agonistsβ2-agonists XanthinesXanthines

Bronchodilating actions

• Inhibit C’ nucleotide phosphodiesterase (PDEs)

• Antagonize receptor-mediated actions of adenosine

Adenosine - bronchoconstriction

- potentiate immunologically induced mediator release from human lung mast cells

Bronchoprotective actions

• Reduction of airway responsiveness to “specific” challenges with allergen

Hendeles et al. J Allergy Clin Immuno 1995; 95:505.

• Against non-specific stimuli - exercise Pollock et al. Pediatrics 1977;60:840.

- fog Allegra. Eur J Respir Dis 1980;61(S),106:41.

- SO2 Koenig et al. J Allergy Clin Immunol 1992; 89:789.

Anti-inflammatory actions

• Inhibition of LTs release from the airways Rabe et al. Am J Crit Care Med 1995;151(S):338 abstract

• Attenuation of the effects of LTD4 at its receptors

Howell. J Pharmacol ExpTher 1990; 225:1108

• Blockade of adenosine-induced mediator release in mast cells

Welton&Simko. Biochem Pharmacol 1980; 29:1085

• Attenuation of late phase airway obstruction in airway response to histamine, in allergics

Hendeles. JACI 1995; 95 :505.

Anti-inflammatory actions

• Decrease of the allergen induced migration of eosinophils into the airway mucosa

Sullivan et al. Lancet 1994;343: 1006.

• Restoration of corticosteroid responsiveness by activation of histone deacetylase (HDAC) and consequent suppression of inflammation

Cosio et al. J Exp Med 2004.

• Decrease of microvascular leakage of plasma into the airway

Erjefalt & Persson. Acta Physiol Scand 1986; 128:653

• Decrease of neutrophils and LTB4 at nights in asthmatics

Kraft et al. Am J Crit Care Med 1996; 154 :1505.

Pulmonary system• Relax airway smooth muscles Rabe et al. Am Rev Respir Dis 1993; 147(S):A 184, abstract.

• Relax smooth musles in pulmonary arteries

Hendeles & Weinberger. New Engl J Med 1996; 334:1380.

• Reduce decrease in lung function at night in asthmatics

Kraft et al. Am J Crit Care Med 1996; 154:1505.

Pulmonary system

• Decrease fatigue in diaphragmatic muscles

Merciano et al. New Engl J Med 1984 ; 311:349.

• Increase mucociliary clearance Cotromanes et al. Chest 1985; 88:194.

• Block (centrally-acting) decrease in ventilation during hypoxia

Easton & Anthonisen. J Appl Physio1998; 64:1445.

Preventive Bronchodilatation Anti-inflammatory

Cromoglycate +++Nedocromil ++Ketotifen ++β2-agonists + +++Anticholinergics + +++Corticosteroids +++Antileukotrienes + ++Methylxanthines ++ +++ ++