guideline asthma 2008
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26(8)
50(1) (3) ..2545
( )
2551
: : .. 2551
1 2552
5,000
National Library of Thailand Cataloging in Publication Data
.. 2551. : .. 2551.--
: , 2552118 .
1. ----. 2. ----. I. .
616.238ISBN 978-611-7197-01-7
:
(.)120 3 2-4 . 10210 0-2141-4000 0-2143-9730www.nhso.go.th
: 0-2214-4660 0-2612-4509
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Chronic inflammation chronic inflammation airway remodeling airway remodeling (airway hyper-responsiveness)
(irreversible airway obstruction)
( ) ( )
()
( )
( )
( )
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3 3.1 (descriptive studies) 3.2 (fair-designed, controlled
clinical trial) 4
4.1 (consensus)
4.2
2 (anecdotal report)
(Quality of Evidence) 1
1.1 (systematic review)
- (randomize-controlled, clinicaltrials)
1.2 - 1 (a well-designed, randomize-controlled,clinical trial)
2
2.1 (non-randomized-controlled, clinical trials)
2.2 (well-designed, non-randomized-controlled, clinical trial)
2.3 (cohort) (casecontrol analytic studies) (case control analytic studies) /
2.4 (multiple time series)
.. 2480
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.. 2551 .. 2551
.. 2551
3
3 4 5
5
6 6
8 8 9
10
11
11
AIA Aspirin-induced asthmaDPI Dry powder inhalerFVC Forced vital capacityHEPA High efficiency particulate air filterICS Inhaled corticosteroid
LABA Long-acting !2-agonistMax MaximumMin MinimumMDI Metered-dose inhalerNB Nebulized solution (respiratory solution, respules)NSAIDs Non-steroidal anti-inflammatory drugs
PEF Peak expiratory flowSABA Short-acting !
2- agonist
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56 57 57
57 58 58
61 61 61
61
62 65
65
65 66 66 73 74 allergen immunotherapy 79
80 asthma exacerbation 82 asthma exacerbation 85 87
88
89 89
13 14 14
17 20 21
29 30 33
33 34
34 35 35 35
36 37 38
PEF variability 38 PEF
38Asthma Control Test (ACT)
41 52
.. 2551 55
56
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.. 2551
25441
( 12,219 20 44 6.8 4.0 - -
2)25452
( 3,454 20 44 16.4 3.25 3.31 2.91
2)
(bronchial hyper-responsiveness, BHR)
1
1
..
(%)
()
()
(%)
(%)
BHR
(%)
3 .. 2551
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8 9 .. 2551 .. 2551
FEV1 methacholine
(methacholine challenge test)12 ( 2, ++)
corticosteroid ( ++) ( ++) airway remodeling ( ++)
1. 2.
3. 4. 5.
1.
2.
3.
4.
5. (asthmaexacerbation)
6. 7.
1.
1.
2. 3.
( ++)
4. peak flow meter
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10 11 .. 2551 .. 2551
5.
( ++)
2.
(++)
1. (allergen)
2.
3.
4. NSAID aspirin !-blocker5.
6. 7.
8.
indoorpollutant ( +/-) allergic rhinitis ( ++)
3.
3.1 10, 13
corticosteroid intermittent persistent asthma 2
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12 13 .. 2551 .. 2551
> 80 %< 20 %
> 80 %
< 20 -30 %
60 - 80 %> 30 %
< 60 %
> 30 %
2 10, 13
PEF or FEV1
PEF variability
1
Intermittent
2
Mild persistent
3
Moderate persistent
4
Severe persistent
- 1
-
- PEF
-
1 1
-
- -
-
-
-
2
-
2
-
1
-
3.2
(controller)
Asthma Control Test (ACT)14( 1, ++) Asthma Control Questionnaire (ACQ)15 ( 1, ++)
3 (3) (controlled)
(relievers) 16(partly controlled) (uncontrolled)
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14 15 .. 2551 .. 2551
( 2
2 ) partly controlled
3
reliever/ ( 2
rescue treatment 2 )
80%
predicted or personal
(PEF or FEV1) best (if known)
1 1 (Exacerbation)*
3
*
Controlled Partly Controlled
( ( 1 Uncontrolled
) )
4.
4.1 (controller) (reliever) 4
4 13
CONTROLLER
MEDICATIONS1. Corticosteroid
2. Long-acting
!2-agonist*(LABA)
beclomethasone budesonide fluticasone prednisolone( ) hydrocortisone dexamethasone methylprednisolone
salmeterol** formoterol***
ANTI-INFLAMMATORYAGENT
inflammatory cell inflammatorycell17(1, ++)
mucus
!
2-agonist
18( 2, ++)
corticosteroid
neutrophilic airwayinflammation 19-20( 1, ++)
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16 17 .. 2551 .. 2551
2. Methylxanthine
3. Anticholinergic
!
2-agonist
terbutaline
salbutamol terbutaline procaterol aminophylline
ipratropium bromide+ fenoterol salbutamol
3. ICS LABA
4. Leukotriene
modifier
5. Xanthine(sustained release)
6. Anti-IgE
RELIEVERMEDICATION1. Short-acting!
2-agonist
microvascular
leakage
ICS LABA
leukotriene corticosteroid
IgE IgE mast cells basophils
salmeterol fluticasone
formoterol budesonide
montelukast
theophylline doxofylline
(omalizumab)
salbutamol terbutaline procaterol fenoterol salbutamol
* long-acting !2-agonist
inhaled corticosteroid ( ++)** acute asthma
( -)*** short-acting
!2-agonist
4.1.1 (controller)
1. Corticosteroid
Corticosteroid ( ++) glucocorticoid receptor inflammatory cell
cytokine
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22 23 .. 2551 .. 2551
controlled uncontrolled controlled !2-agonist (
++) !2-agonist ICS controller ( ++)
6 *
* Global Initiative Asthma 2006
Reduce Treatment Steps Increase
Step 1 Step 2 Step 3 Step 4
Asthma educationEnvironmental control
As neededrapid-acting
!2-agonist
As needed rapid- acting !2-agonist
Leukotrienemodifier
Medium-or-high-dose ICSLow-dose ICSplus leukotriene
modifierLow-dose ICSplus sustained
releasetheophylline
LeukotrienemodifierSustainedrelease
theophylline
Controlleroptions
Select one Select oneAdd one or
more
Low-doseinhaled
ICS*
Low-dose ICSplus
long-acting!
2-agonist
Medium-or-high-dose ICS
plus
long-acting!
2-agonist
* ICS-inhaled glucocorticosteroid
Step 5
Add one orboth
Oral glucocor-ticosteroid
(lowest dose)
Anti-lgEtreatment
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26 27 .. 2551 .. 2551
5 ( 4 1 2)
5
4 !2-agonist
controller 4 corticosteroid 51(
4, +) anti-IgE allergic
asthma 52-57
( 1, ++)4 5
4.2.2
controller
3 - 4 16, 58
4.2.3 10, 13
(assessing asthma control) (1) (treating to achieve control) (monitoring tomaintain control) ( ++)
1
Assessing asthma control
Treating toachieve control
Monitoring tomaintain control
(Stepping down treatment)
1. corticosteroid
3 corticosteroid 50% 3 59-61( 1,
++) corticosteroid corticosteroid ( 1, ++)62-63
2. corticosteroid long-acting!
2-agonist 3
- corticosteroid 50%
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30 31 .. 2551 .. 2551
1. oxygen oxygen nasal cannula mask O
2
saturation > 90%
69
( 1, ++)2. (PEF > 50%
) rapid onset !2-agonist nebulizer70-72(
1, ++) MDI spacer73
( 1, ++) nebulizer
0.5 1 . (salbutamol 2.5 5 .) MDI spacer 2 puff 15 30 16puff 4 6 nebulizer 15 30 4 6 ( ++)
2
2
National Asthma Education and Prevention Program. Expertpanel report 2: Guideline for the diagnosis and management of asthma.
Bethesda, MD: National Institutes of Health, 1997; .55: 4051
Reassessment in 1 hr
Reassessment in 12 hr
PEFR > 50%O
2to achieve SaO
2> 90%
!2-agonist MDI (spacer) q 10 min
or nebulize q 20 min in 1 hrSystemic corticosteroid
PEFR < 50%O
2to achieve SaO
2> 90%
!2-agonist +anticholinergic
nebulize q 20 min in 1 hrSystemic corticosteroid
PEFR 5080%!2-agonist + anticholinergic
nebulize q 60 min for 13 hrSystemic corticosteroid
PEFR < 50%!2-agonist + anticholinergic
Consider IV aminophylline, MgSO4Systemic corticosteroid
Good response(PEFR > 70%)
Discharge
Incomplete response(PEFR 5070%)Admit ward
Initial assessment (History, Physical exam & PEFR)
Poor response(PEFR < 50%)Admit ICU
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36 37 .. 2551 .. 2551
( ++)
7.3
bronchial hyper-responsiveness
FEV
1 80
systemic corticosteroid systemiccorticosteroid 6 corticosteroid
24 (+)
bronchial hyper-responsiveness
corticosteroid airway hyper-responsiveness airway remodeling
peak flow meter ACT
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38 39 .. 2551 .. 2551
1. PEF variability PEF 11
morning pre-bronchodilator PEF 1 PEF (3)
3 morning pre-bronchoditator PEF
PEF variability
2. Asthma Control Test (ACT).14
PEF min x 100PEF max
Nathan Asthma Control Test (ACT) (4)
4 1 5 ( = 5 = 1) Nathan ACT ACT sensitivity specificity (uncontrolled) 19 25 20 24
4 Asthma Control Test (ACT)
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40 41 .. 2551 .. 2551
(partly controlled) 19 (uncontrolled) sensitivity specificity ACT (uncontrolled) score 20 ACT 25 21 24 controlled partly controlled 20 uncontrolled (5)
5 Asthma Control Test(ACT)
1. Boonsawat W, Charoenphan P, Kiatboonsri S et al. Survey ofasthma control in Thailand. Respirology 2004; 9:373-378.2. Dejsomritrutai W, Nana A, Chierakul N, et al. Prevalence of bron-
chial hyper-responsiveness and Asthma in the adult populationin Thailand. Chest 2006; 129:602-609.
3. . . . . 2537.
4. . (). . 2540.
5. . (). . 2547; 19:179-193.
6. Larche M, Robinson DS and Kay AB. The role of T lymphocytes
in the pathogenesis of asthma. J Allergy Clin Immunol 2003;111:450-463; quiz 64.
7. Maneechotesuwan K, Xin Y, Ito K, et al. Regulation of Th2 cytokinegenes by p38 MAPK-mediated phosphorylation of GATA-3.J Immunol 2007; 178:2491-2498.
8. Jatakanon A, Lim S and Barnes PJ. Changes in sputum eosino-
phils predict loss of asthma control. Am J Respir Crit Care Med2000; 161:64-72.
9. Busse WW and Lemanske RF, Jr. Asthma. N Engl J Med 2001;344:350-362.
10. Global Initiative for Asthma. Asthma management and preventionprogram. Global strategy for asthma management and prevention(updated 2006). Bethesda, MD US Department of Health and
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76 Lanes SF Garrett JE Wentworth CE 3rd Fitzgerald JM and randomized study Intern Med 2000; 39:794-797
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50 51 .. 2551 .. 2551
76. Lanes SF, Garrett JE, Wentworth CE, 3rd, Fitzgerald JM andKarpel JP. The effect of adding ipratropium bromide to salbutamolin the treatment of acute asthma: a pooled analysis of threetrials. Chest 1998; 114:365-372.
77. Rodrigo GJand Rodrigo C. First-line therapy for adult patientswith acute asthma receiving a multiple-dose protocol ofipratropium bromide plus albuterol in the emergency department.Am J Respir Crit Care Med 2000; 161:1862-1868.
78. Parameswaran K, Belda Jand Rowe BH. Addition of intravenous
aminophylline to beta2-agonists in adults with acute asthma.Cochrane Database Syst Rev 2000:CD002742.79. Rowe BH, Bota GW, Fabris L, Therrien SA, Milner RAand Jacono
J. Inhaled budesonide in addition to oral corticosteroids toprevent asthma relapse following discharge from the emergencydepartment: a randomized controlled trial. JAMA 1999; 281:
2119-2126.80. Manser R, Reid Dand Abramson M. Corticosteroids for acute
severe asthma in hospitalised patients. Cochrane Database SystRev 2001:CD001740.
81. Harrison BD, Stokes TC, Hart GJ, Vaughan DA, Ali NJ andRobinson AA. Need for intravenous hydrocortisone in addition
to oral prednisolone in patients admitted to hospital with severeasthma without ventilatory failure. Lancet 1986; 1:181-184.
82. Ratto D, Alfaro C, Sipsey J, Glovsky MMand Sharma OP. Areintravenous corticosteroids required in status asthmaticus? JAMA1988; 260:527-529.
83. Hasegawa T, Ishihara K, Takakura S, et al. Duration of systemic
corticosteroids in the treatment of asthma exacerbation; a
randomized study. Intern Med 2000; 39:794-797.84. Watchara Boonsawat, Uraiwan Zaeoui, Sunee Lerdsinudomand
Chanee Samosorn. Implementation of GINA guidelines througheasy asthma clinic. Respirology (2007)12, (suppl 4) A147.
85. (Easy Asthma Clinic). In: , , eds. 5th BGH Annual academicmeeting:From the basic to the top in medicine. : .; 2548:83-87.
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.. 2551
:
:
:
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1. Airway inflammation
2. Structural changes in the airways (airway remodeling)3. Bronchial hyper-responsiveness4. Variable and partially reversible airway obstruction
/
1. ( ++)
1.1
1.2
1.3 atopic dermatitis,allergic rhinitis
1.4
Cough-variant asthma
peak expiratory flow bronchialhyper-responsiveness
.. 2551
4.5 (.
.. 2530) 12.7 (. .. 2538) 9.05 (.. 2538) 10.06 ( .. 2542) 4.0 .. 2529-2533 (anti-inflammatory drugs) 1.9 .. 2540-2544
(bronchial hyper-responsiveness) (variable airflow obstruction) (wheeze)
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58 59 .. 2551 .. 2551
- PEF variability > 20%- PEF variability = PEF max PEF min
1/2
(PEF max + PEF min)3.2
1) allergy skin test, serumspecific IgE
2) bronchial hyper-responsiveness methacholine, histamine, mannitol exercise challengetest
3) airway inflammation non-invasive sputum eosinophil, exhaled nitric oxide, exhaledcarbon monoxide
< 5
1. (> 1 )2.
3. 4. 3
x 100%
1. 2. 3. 4.
5.
(> 10 )6.
2. 2.1 (wheeze)
2.2
2.3 2.4
allergic rhinitis, allergic conjunctivitis atopic dermatitis3.
3.1 5
( +)1) Spirometry FEV1 FVC
- FEV1 > 12 % > 200 . (pre andpost bronchodilator)
- FEV1/FVC ratio < 0.752) Peak expiratory flow (PEF)
- PEF > 20 % (pre and post bronchodilator)
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60 61 .. 2551 .. 2551
1. 2. 3. 4.
5.
6.
5
1.
2. 3.
4. 5.
1.
3
1. (Atopic dermatitis)
2. 2 2.1 allergic rhinitis2.2 2.3 CBC eosinophilia (> 4%)
(Therapeutic trial) ( +):
short acting !2-agonist
inhaled corticosteroids
recurrent wheezing
(< 5 ) 1. Chronic rhinosinusitis2. Gastroesophageal reflux3. Recurrent lower respiratory tract infections4. Congenital heart diseases5. Bronchopulmonary dysplasia
6. Tuberculosis7. Congenital malformation causing narrowing of the
intrathoracic airways8. Foreign body aspiration9. Immune deficiency10. Primary ciliary dyskinesia syndrome11. Cystic fibrosis
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step
leukotriene modifier ( +)
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68 69 .. 2551 .. 2551
difficult-to-treat asthma
medium-dose ICS
LABA ( ++) leukotriene modifier sustained-release theophyllinehigh-dose ICS LABA 3 6 corticosteroids 2
5 (4 1 2)
step 4 oral corticosteroids step 4
corticosteroids anti-IgE oral corticosteroids
ICS ICS
sustained-release theophylline ( +) cromone (sodium cromoglycate)
3 ( )
low-dose ICS long-acting !2-agonist (LABA) (
++) low-dose inhaled ICS 3 - 4 ICS uncontrolled partly controlled
formoterol LABA
formoterol reliever controller step 3 medium-doseICS ( ++) MDI spacer
low-dose ICS leukotriene modifier ( +) low-dose ICS
sustained-release theophylline ( +) 2 (< 5 )
4 ( ICS LABA )
(
+)
2 < 5 1 > 5
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70 71 .. 2551 .. 2551
* leukotriene modifier may be particularly useful if the patient has concomitant rhinitis** Check compliance, allergen avoidance and re-evaluate diagnosis*** Check compliance and consider referring to specialist
S
tep
up
therapy
to
gain
control
Stepdownifappro
priate
Stepdownifapp
ropriate ICS or leukotriene modifier*
(200 mcg BDP equivalent) (dose depend on age)
Insufficient control**
Increase ICS or Add ICS to(400 mcg BDP equivalent) leukotriene modifier
Insufficient control**
Increase ICS dose (800 mcg BDP equivalent)or
Add ICS to leukotriene modifieror
Add LABA
Insufficient control***
Consider other options- Theophylline
- Oral corticosteroids
Level of Control
Controlled
Partly controlledUncontrolledExacerbation
Maintain and find lowest controlling step
Consider stepping up to gain controlStep up until controlledTreat as exacerbation
Treatment Steps
Asthma educationEnvironmental control
As needed short
acting !2-agonist
Controller
options
As needed short acting !2-agonist
Select one
Low-dose inhaled
ICS*
Leukotriene
modifier**
Select one
Low-dose ICS
plus Long acting!
2-agonist
Medium-or
high-dose ICS
Low-dose ICS plus
Leukotriene modifier
Low-dose ICS plus
sustained release
theophylline
Add one or more
Medium-or high-
dose ICS pluslong acting
!2-agonist
Leukotriene
modifier
Sustained release
theophylline
Treatment ActionR
ed
uce
Increase
Reduce Increase
Step 1 Step 2 Step 3 Step 4
Add one or both
Oral
glucocorticosteroid(lowest dose)
Anti-IgE
treatment
* ICS = inhaled glucocorticosteroids** = Receptor antagonist or synthesis inhibitors
Step 5
:
4.2 (monitoring to maintain control)
8 inhaled corticosteroids
(equivalent dose)
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72 73 .. 2551 .. 2551
1 3 3 controlled 6
step down controlled
1. controlled medium-to highdoseICS 3 50%
2. controlled low-dose ICS
3. controlled ICS LABA ICS 50% 3 low-dose ICS LABA < 5 LABA ICS
4. controlled ICS ICS 50% 3 low-dose ICS
5. controlled 1
Drug Low Daily Medium Daily High Daily
Dose (mcg) Dose (mcg) Dose (mcg)Beclomethasone dipropionate 100 200 > 200 400 > 400- MDI (50, 100, 200, 250 mcg)- DPI (Easyhaler; 200 mcg)Budesonide 100 200 > 200 400 > 400- MDI (100, 200 mcg)
- DPI (Easyhaler, Turbuhaler,Swinghaler; 100, 200 mcg)
- Nebulized solution (500,1000 mcg)
Ciclesonide 80 160 > 160 320 > 320- MDI (80, 160 mcg)
Fluticasone propionate 100 200 > 200 500 > 500- MDI (50, 125, 250 mcg)- DPI (Accuhaler; 100,
250 mcg)- Nebulized solution (500,
2000 mcg)Mometasone furoate 100 200 > 200 400 > 400- DPI (220 mcg)
(equivalent dose)
: combination of salmeterol + fluticasone: .. 2551 4
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10
10
< 4 MDI plus spacer with face mask Nebulizer with face mask
4 - 6 MDI plus spacer with mouthpiece Nebulizer with mouthpiece
> 6 DPI Nebulizer with mouthpiece
MDI plus spacer with mouthpiece
: DPI accuhaler, easyhaler, turbuhaler
swinghaler Spacer corticosteroid spacer valve
valve spacer mouth piece
allergen immunotherapy
Allergen immunotherapy allergic asthma
1. 2. 3. 4.
/
4.Sustained-release
theophylline
5.Anti-IgE
/tab
-Theophylline
-Omalizumab
-5-6mg/kg/dose1
2
,600mg/day
-
IgE
-
-anaphylacticreaction
2
-
-
-12
inhaledcorticosteroid
s
Mild Moderate Severe
respiratory
5. asthma exacerbation
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80 81 .. 2551 .. 2551
2 - 12 < 160 /1 2 < 120 /2 8 < 110 /
PEF
(% predicted
personal best)
PaO2(on air)
/
PaCO2
(on air)
SaO2% (on air)
> 80 %
< 45 mm Hg
> 95 %
60 80%
> 60 mm Hg
< 45 mm Hg
91 95 %
< 60%
< 60 mm Hg
(cyanosis)
> 45 mm Hg
< 90 %
respiratoryarrest
(/) < 100 100 120 > 120
asthma exacerbation 1111 asthma exacerbation
Mild Moderate Severe
30 /
< 2 < 60 /2 12 < 50 /1 5 < 40 /6 8 < 30 /
suprasternal
retraction
wheeze
end expiratory
respiratoryarrest
Paradoxicalthoraco-
abdominal
movement
wheeze
* MDI with spacer DPI
5.1 asthma exacerbation 3
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1
(1)
(2) inhaled short acting!2-agonist
(3) (4)
3 asthma exacerbation
,
4
PEF > 80%predicted personal
best
- inhaled SABA 2 4
puffs 3 4
24 48
12
Inhaled SABA* 2 4 puffs/dose3 20
3 PEF 60-80%
predicted personal
best
- inhaled SABA
6 10 puffs 1 2
PEF
< 60% predicted personal best
- inhaled SABA
6 10 puffs 1 2
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(6) -
(4) systemic corticosteroids
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- (mucolytic)
-
- asthma exacerbation
5.3
(1) (2) 1 - 3
(PEF < 70%predicted personal best oxygen saturation < 95%)
(3) (high risk)
- near fatal asthma ventilator-
- prednisolone
- !2-agonists ( 1 )-
3 - 4 prednisolone 0.5 - 1 ././ 40 ./ 3 - 5
hydro-cortisone 5 ././ 6 100 ./ methylprednisolone 1 ././ 6 40 ./ hydrocor tisone methylprednisolone systemic corticosteroid prednisolone 3 - 5 taper off steroid
nebulized ICS acuteexacerbation ICS ICS
(5) - Epinephrine 1:1000 (adrenaline) 0.01 ./.
0.3 .
- SABA NB MDI
- anaphylaxis angioedema - Aminophylline 5 ./. loading dose IV drip 1 ././. loading dose 5 - 15 ./.
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3. (tertiary prevention)
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96 97 .. 2551 .. 2551
1. , , ,
. .. 2543 . 2543; 39:172-197.
2. . .. 2548.
3. American Academy of Pediatrics, Subcommittee on Managementof Sinusitis and Committee on Quality Improvement. Clinicalpractice guideline: management of sinusitis. Pediatrics 2001;108:798-808.
4. British guideline on the management of asthma. Thorax 2003; 58
(Suppl 1):i1-94.5. Boonyarittipong P, Tuchinda M, Balangkura K, Visitsunthorn Nand Vanaprapar N. Prevalence of allergic diseases in Thaichildren. J Pediatr Soc Thai 1990; 29:24-32.
6. Bousquet J, Van Cauwenberge P and Khaltaev N, ARIA WorkshopGroup, World Health Organization. Allergic rhinitis and its
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