Orapan poachanukoon, MDA/P of Allergy and Immunology

Thammasat Universsity

ASTHMA TREATMENT IN CHILDREN AND

ADULTS

Outline of my talk:

²Children and adults: what’s difference?²How to measure of asthma control?²What’s new in asthma guideline? ²Variability response to medications

(asthma phenotype)

93.66 98.69 104.23 109.41 105.76 104.61

201.34

247.89 239.31 239.14

226.64

260.65

0

50

100

150

200

250

300

ป ี 2548 ป ี 2549 ป ี 2550 ป ี 2551 ป ี 2552 ป ี 2553

อ ัตรา

ต อ

1000

00 ปชก

UC

หอบห ืดในผ ู ใหญ

หอบห ืดในเด ็ก

อัตราการรับไวรักษาในรพ.ตอ 100,000 ปชก.UC : ป 2548 – 2553 ของผูปวยโรคหืดในผูใหญและเด็ก

ที่มา : แหลงขอมูล ฐานขอมูลผูปวยในรายบุคคล (IP individual records) ป 2548-2553

adults

children

อัตราตอ

100,

000

อัตราปวยตายของผูปวยที่รับไวรักษาในโรงพยาบาลดวยโรคหืดในผูใหญและเด็กป 2548 – 2553

ที่มา : แหลงขอมูล ฐานขอมูลผูปวยในรายบุคคล (IP individual records) ป 2548-2552 ขอมูลป 2553

ผลการประเมินคุณภาพการดูแลผูปวยโรคหืด ป 2549 - 2550

• การรักษาตามมาตรฐานการดูแลผูปวย

• การประเมินความรุนแรงของโรคโดยการวัด PEF นอย

• มีการรักษาดวยยา inhale corticosteroid นอย

• ขาดการใหความรูเรื่องโรค

• ขาดการประเมินการใชยาพนอยางถูกวิธี

• หนวยบริการรับภาระคาใชจายการใหบริการผูปวยนอกเพ่ิมข้ึน

ป 2549 ป 2550

มีการประเมินสมรรถภาพปอด 2.43% 1.08%

มีการรักษาดวยยาพนสเตียรอยด 27.21% 10.92%

การใหคําแนะนําเรื่องการใชยาพนอยางถูกวิธ ี 14.70% 10.08%

การสนับสนุน ของ สปสช.

1. การอบรม ฟนฟู ความรูการดูแลผูปวยโรคหืด

2. การจัดต้ังคลินิกโรคหืด Easy asthma clinic

3. การชดเชยคายาสูดสเตียรอยด

4. การสนับสนุนงบประมาณตามคุณภาพผลงานบริการ

• 2549-2550 ประเมินคุณภาพการดูแลผูปวยโ รคหืด (audit)

• 2551 สนับสนุนการจัดทําและเผยแพร guideline

• 2551-2552 นํารองการจัดต้ัง EAC เขตพ้ืนท่ีขอนแกน• 2551-2554 สนับสนุนงบประมาณ• 2553 -2554 ขยาย EAC คลอบคลุมหนวยบริการประจําทุกแหง และ จายชดเชยคายา ICS

การพัฒนาระบบการดูแลผูปวยโรคหืด โดย สปสช.

โ รคหืดเปนโ รคท่ีพบบอยในเด็กมากกวาผูใหญ

Haahtela et al. Thorax 2006

0

1

2

3

4

5

6

7

Inci

denc

e (/1

000)

0–45–9

10–1415–19

20–2425–29

30–3435–39

40–4445–49

50–5455–59

60–6465–69

70–7475–79

80–8485+

Age group

ขอแตกตางระหวางโ รคหืดในเด็กและผูใหญ

²Diagnosis: WARI , COPD

²Natural history

²Management: asthma control, medications

Challenges in Diagnosing and Managing Pediatric Asthma

1. GINA 2010. 2. Wardlaw AJ et al. Clin Exp Allergy. 2005 3. Henderson J et al. Thorax. 2008. 4. Bacharier LB et al. Allergy. 2008. 5. Guilbert TW et al. N Engl J Med. 2006. 6. Castro-Rodríguez JA et al. Am J Respir Crit Care Med. 2000. 7. Henderson J et al. Arch Dis Child. 2009. 8. Bloomberg GR et al. Pediatrics. 2009. 9. LemanskeRF Jr et al. N Engl J Med. 2010. 10. Langmack EL et al. Curr Opin Pulm Med. 2010. 11. Lima JJ et al. Curr OpinPulm Med. 2009.

diagnosis difficult.1,2

Measuring lung function can

pose problems.1,7

Difficult to predict which wheeze will

continue to be symptomatic when

they are older.5,6

Difficult to predict respond to

medication.9–11

Compliance with prescribed

therapy8

Symptoms may

change with age.3,4

Presentation of Asthma May Overlap With Other Airway Disorders

1. Wardlaw AJ et al. Clin Exp Allergy. 2005;35:1254–1262.

Asthma COPD

Viral wheeze

(children) Emphysema

Hyperventilationsyndrome Infective

(bacterial)asthma ABPA

Bronchiectasis

Nonsmokingfixed obstruction

Obliterativebronchiolitis

EosinophilicbronchitisChronic

cough

Taussig et al J Allergy Clin Immunol 2003; 111: 661-75

Phenotypes wheezing in childhood..

Asthma Predictive Index (API) Developed and Modified to Help Predict Asthma1–4

1. History of ≥4 wheezing episodes with ≥1 physician diagnosis2. Must meet ≥1 major criteria or ≥2 minor criteria:1. Major Criteria 1. Minor Criteria1. Parental history of asthma2. Physician-diagnosed atopic dermatitis3. Allergic sensitization to ≥1

aeroallergen

1. Allergic sensitization to milk, egg, or peanuts

2. Wheezing unrelated to colds3. Eosinophilia >4%

1. Castro-Rodríguez JA et al. Am J Respir Crit Care Med. 2000;162:1403–1406. 2. Guilbert TW et al. J Allergy Clin Immunol. 2004;114:1282–1287. 3. Guilbert TW et al. N Engl J Med. 2006;354(19):1985–1997. 4. Thai guideline 2008

Modified API for Use in Young Children With Wheeze

Outcomes with original API (Tucson Study)1

• Negative predictive value: 91.6% at Year 6; 84.2% at Year 13• Positive predictive value: 47.5% at Year 6; 51.5% at Year 13

Atopic dermatitis

Allergy TestingSkin prick test / positive result

25372540

2547 2548

• GINA guideline definition of control – a gold standard

GINA 2009

Characteristic Controlled (all of the following)

Daytime symptoms Twice or less per week

Limitations on activities None

Nocturnal symptoms or awakenings None

Need for reliever/‘rescue’ treatment Twice or less per week

Lung function Normal

Ideal Tool for Assessing Asthma Control

Frequency of different asthma outcomes

50-80

30045050

????

1

Soren Pedersen. Primary Care Respiratory Journal 2009.

Assessing Asthma Control: PEF

• Use for objective evaluation in• acute asthma• chronic home monitoring

• Normal values• 5 x Ht (cm) – 400

• Blow in sitting/standing position• Techniques• Best of 3 blows

Assessing Asthma Control: Symptoms

www.asthmacontroltest.com

Assessing Asthma Control: HRQL

• Generic: SF-36, EQ-5D, CHQ (lack of responsiveness)

• Specific: AQLQ, MiniAQLQ, PAQLQ, MiniPAQLQ, C-PAQLQ, CAQ• Need cultural adaptation and modification

Poachanukoon et al. Pediatr Allergy Immunol 2006; 17: 207-212.

Lertsinudom S et al. J Med Assoc Thai 2010; 93(3): 373-7.

Development and Validation of MiniPAQLQ in Thai Asthmatic Children

Poachanukoon O 2010.

• 15 items: activities (4 items), emotions (3 items), symptoms (5 items), environment (3 items)

Domains Validity Reliability

Controlled Asthma

Uncontrolled Cronbach’salpha

SymptomsActivitiesEmotionsEnvironmentsOverall

6.6 + 0.546.7 + 0.576.4 + 0.915.3 + 1.106.3 + 0.51

4.7 + 1.14*5.0 + 1.36*4.6 + 1.67*4.1 + 1.24*4.6 + 0.96*

0.8550.8860.7650.6160.910

Lertsinudom S et al. J Med Assoc Thai 2010; 93(3): 373-7.

Correlation between QoL score and asthma parameters

Juniper EF1 Poachanukoon O2, 3

PPEFR morningPEFR eveningFEV1Asthma controlAsthma severitySalbutamol use

0.50.40.38

--

0.4

0.30.3

0.370.4

P < 0.05-

1. Am J Respir Crit Care Med 199.52. Pediatr Allergy Immunolgy 2006 3. Thai Journal of Pediatrics 2005

QoL questionnaire Summary

²There are only weak to moderate correlations between asthma quality of life and conventional clinical measures of asthma control²To evaluate the effect of interventions, QoL assessments should included in clinical studies in conjunction with conventional clinical measures.²Limitation: not available for all age groups, need validation and cultural adaptation

Assessing asthma control: Inflammation

•Which indicator of inflammation should we measure?- sputum eosinophils- exhaled NO- BHR

§How practical is the measurement?

Inflammation can also be present during symptom-free periods

Adapted from Woolcock A. Clin Exp Allergy Rev 2001; 1: 62–64.

AHR is a marker of inflammation

AHR

Rescue medication useImpaired am PEFImpaired FEV1

Start of treatment (months)

% R

educ

tion

2 4 6 18

Rate of response of different measures of asthma control over 18 months of ICS treatment

Nightsymptoms

Green RH et al. Lancet 2002; 360: 1715-21.

§If eosinophil < 1% -step down§If eosinophil 1-3% -no change§If eosinophil > 3% -step up§Results:

-sputum eosinophil and FeNO in sputum management group lower than BTS (P < 0.05)

-PC20 better (P < 0.05)

6 asthma admission

1 asthma admission

Exhaled NO: Non-invasive marker of inflammation

The Cochrane Library 2009

§ Randomized controlled comparisons of adjustment of asthma therapybased on FeNO compared to traditional methods§ 6 studies (4 children/adults, 2 adults), 1053 participants § No significant difference between groups

(asthma exacerbation, symptoms, spirometry)

“The role of utility FeNO to tailor the dose of ICS can’t routinely recommended for clinical practice”

Conclusions of 2 parts

§Asthma in adult and children are difference in diagnosis and measuring of asthma control.§Asthma control is a key goal in asthma management and

should be monitored on a regular basis§Clinical Asthma Score and QoL questionnaire may easy

to asssess§Monitoring airway inflammation may better reflect asthma

control but is not readily available at this time-helpful in research, not clinically applicable

§There is no instrument. Each one has been developed for a different purpose and has different measurement properties.

Asthma guideline and response to medications

Step 1 Step 2 Step 3 Step 4 Step 5

Low-dose ICS plus sustained-release

theophyline

Sustained release theophyline

Low-dose ICS plus leukotriene modifier

Anti-IgE treatmentLeukotriene modifierMedium- or

high-dose ICSLeukotriene modifier

Oral glucocorticosteroid

(lowest dose)

Medium- or high-dose ICS

plus long-acting ß2-agonist

Low-dose ICS plus long-acting ß2-agonist

Low-dose inhaled ICS

Add one or moreAdd one or moreSelect oneSelect one

Controlleroptions

As needed rapid-acting ß2-agonistAs needed rapid-acting ß2-agonist

Asthma educationEnvironmental control

Management approach based on control (Adults and children> 5 years)

GINA and Thai Guideline 2011.

1-5%

Thai Guideline for children < 5 years

Thai Guideline

ICS 200 μg or LTRA

ICS 400 or ICS+LTRA

ICS 800 or ICS+LTRA or ICS+LABA

Theophylline or oral steroids

เด็กหญิงอาย ุ20 ปมีประวัติหอบบอยตอนกลางคืน ไ อเวลาออกกําลังกาย เคยนอนรพ. ดวยเรื่องหอบกําเริบทุกป เขา ICU 1 ครั้งเม่ือ 2 เดือนท่ีผานมาจงใหการรักษา

ก. Medium dose ICSข. ICS +LABAข. LTRAค. ICS+theophyllineง. RABA prn

• เด็กชายอายุ 2 ป มีอาการหอบงายชวงเปนหวัด พนยาขยายหลอดลมแลวอาการดีขึ้น บางครั้งเลนแลวเหน่ือย ชวงน้ีอากาศเย็นมีอาการจาม นํ้ามูก คัดจมูกเปนๆหายๆ

• ไ ดรับยา ICS 200 g

จงใหการรักษาก. ICS+LABAข . Add LTRAค. Add theophyllineง. Double dose ICS

Regularly assess:-Control-Triggers-Compliance-Inhaler technique-Comorbidity

Environmental controlEducation, Written action plan and Follow-up

Fast-acting bronchodilator on demand

Inhaled corticosteroids

Low Moderate High

Add-on therapy

Pred

Anti IgE

Modify maintenance therapy

Verymild

Mild Moderate Moderatelysevere

Severe

The dose response curve of ICS

Kankaanranta H et al. Respiratory Research 2004.

Dose-response study with ICS

Kankaanranta H et al. Respiratory Research 2004.

Doses of ICS for children

Drug Low dose (μg) Medium dose(μg)

High dose(μg)

BDPBudesonide*Budesonide neb.Ciclesonide*FluticasoneMometasone*Triamcinolone

100-200100-200250-50080-160

100-200100-200400-800

> 200-400> 200-400> 500-1000> 160-320> 200-500> 200-400> 800-1200

>400>400>1000>320>500>400>1200

*Approved for once-daily dosing in mild patients

GINA 2009

Drug Low dose (μg)

Medium dose(μg)

High dose(μg)

BDPBudesonideCiclesonideFluticasoneMometasone

200-500200-40080-160

100-250200-400

> 500-1000> 400-800> 160-320> 250-500> 400-800

>1000-1200>800-1600>320-1280>500-1000>500-1200

Doses of ICS for adult

GINA 2009

Pharmacologic factors that promote efficacy and safety of ICS

Efficacy

Lung depositionDeviceParticle size

TechniqueProdrug

Pum. RetentionLipophilicitySlow distribution

safety

- low oral bioa.- fast systemic

clearance-Increased PPB-lung deposition-activation prodrug

PK/PD properties of ICSs

CS RRA Oral bioavailability

(%)

Clearance(L/hr)

VD(L)

Mometasone FFluticasone PBDPCiclesonideBudesonideTriamcinolone

23001800

5312

935233

< 1< 1

15-20121123

5466-901501528437

-318-859

20207

183-301103

Clinical Asthma 2008.

HOW TO CHOOSE ADD-ON MEDICATION?

Seretide evohaler (Non-CFC MDI)25/50, 25/125, 25/250Acculaher (DPI)50/100, 50/250, 50/500

Choice of ICS+LABA in Thailand

Symbicort Turbuhaler (DPI)4.5/80, 4.5/160, 4.5/320

β2-Agonist Basics: Are They All the Same?

Fast

Fast onset, short duration

Inhaled terbutalineInhaled albuterol

Fast onset, long duration

Inhaled formoterol

Slow

Slow onset, short duration

Oral terbutalineOral albuterol

Oral formoterol

Slow onset, long duration

Inhaled salmeterolOral bambuterol

Short Long

Speed of Onset

Duration of Action

The addition of LABA to ICS in asthma

•Safety concerns regarding LABA (FDA)•Should LABA+ICS be used as initial therapy?•Should ICS+LABA be used in children?•Can LABA be withdrawn once asthma is controlled?

Sears MR. Current Opinion in Pulmonary Medicine 2011, 17: 23-28.

Additional of LABA to ICS vs. same dose of ICS for asthma in adults and children

Cochrane Review 2010

• Inclusion criteria: RCTs in children aged > 2 years, and adults• Results:

- 77 studies, 21,248 pts. (4625 children, 16623 adults) - LABA reduced risk of exacerbation (RR 0.77, 28 studies), improve FEV1, symptoms free days, reduced use of RABA

- In children, superior to ICS alone but NS (RR 0.89)- No serious S/E with LABA (RR 1.09)

• Conclusions: - In Adults: effects and no serious S/E- In Children: effects are much more uncertain

The addition of LABA to ICS in asthma

• Should LABA+ICS be used as initial therapy?-cochrane reviewin 27 trials: ICS+LABA did not reduce exacerbation, admissions compared with ICS alone-In steroid-naïve patients, dose of ICS should sufficient to control is critical requirement before adding LABA

- Conclusion: combination should not be considered as first-line therapy without prior trial of ICS

Sears MR. Current Opinion in Pulmonary Medicine 2011, 17: 23-28.

Variability in Treatment Response: Distribution of Individual Responses for FEV1

Patie

nts,

%

<–30 –30 to<–20

–20 to<–10

–10 to<0

0 to<10

10 to<20

20 to<30

30 to<40

40 to<50

≥50

Change in FEV1 From Baseline, %

Montelukast sodium 10 mg qdb (n=387)Beclomethasone 200 mcg (4 puffs) bidc (n=251)

Malmstrom K et al. Ann Intern Med .1999;130:487–495.

0

30

20

10

a

Variability in Response to ICS Treatment:Distribution of Responses Recorded in 3 Studies

ICS=inhaled corticosteroid; CAMP=Childhood Asthma Management Program; ACRN=Asthma Clinical Research Network.

Tantisira KG et al. Hum Mol Genet. 2004;13:1353–1359.

0

5

10

15

20

25

30

35

40

Patie

nts,

%

Change in FEV1 From Baseline, %

Adult StudyCAMPACRN

>4030 to 0

20 to30

10 to20

0 to10

–10 to 0

–20 to –10

<–20

CLIC Primary Outcome: FEV1 Response1

FEV1 Change With Fluticasone Propionate30

Bothmedicationsn=22(17%)

Montelukast sodium alone

n=6 (5%)

Line o

f iden

tity

Neither medicationn=69 (55%)

Fluticasonepropionate alone

n=29 (23%)

Concordance Correlation 0.55 (0.43, 0.65)

–50 –40 –30 –20 –10 0 10 20 40–50

–40

–30

–20

–10

0

10

20

30

40

FEV 1

Cha

nge

With

Mon

telu

kast

Sod

ium

CLIC=Characterizing Response to a Leukotriene Receptor Antagonist and an Inhaled Corticosteroid. Szefler SJ et al. J Allergy Clin Immunol. 2005;115:233–242,

≥7.5% FP response

CLIC: Difference in Asthma Control(Days-per-Week Response)1,a

Better responseto montelukast sodium (n=15)

Better response to fluticasone

propionate(n=36)

Part

icip

ants

–7 –6 –5 –4 –3 –2 –1 0 1 2 3 4 5 6 7

Zeiger RS et al. J Allergy Clin Immunol. 2006;117:45–52,

Good response:Younger age < 10 yFemaleMild asthma

BADGER – study design

• 182 children (6–17 years of age) with uncontrolled asthma while on ICS 100 μg bd randomised to each of three blinded step-up therapies in random order for 16 weeks (triple cross-over design):

• ICS 250 μg bd (ICS step-up),

• ICS 100 μg plus LABA 50 μg bd (LABA step-up)

• ICS 100 μg bd plus 5 or 10 mg daily (LTRA step-up)

• Primary endpoint: composite of exacerbations, asthma-control days and FEV1 to assess whether differential response to step-up regimens >25%

Lemanske RF et al. N Engl J Med 2010

LABA step-up significantly more likely to provide best response compared with ICS or LTRA step-up

Lemanske et al. N Engl J Med 2010

p=0.004

p=0.02

p=NS

0 10 20 30 40 50 60

% Patients

LABA vs ICS

LABA betterNeutralICS better

LABA vs LTRA

ICS vs LTRA

LABA betterNeutralLTRA better

ICS betterNeutralLTRA better

Possible Predictors of Responsiveness to Asthma Therapy in Clinical Trials

1. Szefler SJ et al. J Allergy Clin Immunol. 2005;115:223–242. 2. Zeiger RS et al. J Allergy Clin Immunol. 2006;117:45–52. 3. Bacharier LB et al. Allergy. 2008;63(1):5–34. 4. Knuffman JE et al. J Allergy Clin Immunol. 2009;123(2):411–416.

Therapy Some Possible Predictors of ResponseICS1-5 ↓ Lung function

↑ Bronchodilator use↑ Inflammation, spumtum eosinophiliaPositive skin test responseParental history of asthma

Montelukast1-3, 6 Young age (<10 years)Shorter asthma durationLess severe asthma↑ Levels of urinary leukotrienesETS, aspirin induced asthma

6. Scadding et al. Cur Opinion in Allergy and Clinical Immunology 2010 5. Current Opinion in Pulmonary Medicine 2011, 17: 16-22.

Asthma Phenotype: Clinical applications

•Variable response to controller therapies•One treatment plan cannot be expected to be efficacious for all different asthma

•Asthma phenotype is still important!!!

Role of Phenotypes in Management of Asthma

Asthma: A Result of Complex Interactions1,2

Slide 65

Genes Environmentalfactors

1. Drake KA et al. Pharmacogenomics. 2008;9(4):453–462. 2. Papadopoulos NG et al. Pediatr Allergy Immunol. 2008:19(suppl 19):51–59.

Demographicfactors

Social factors

Gene–environment interactions

Gene–gene interactions

Geneticancestry

Multiple clinical manifestations(phenotypes)

Asthma syndrome

Our Understanding of Asthma Continues to Increase Over Time1–6

1. Kiley J et al. Curr Opin Pulm Med. 2007;13:19–23. 2. Tang EA et al. In: Adkinson NF Jr. Middleton’s Allergy. Principles & Practice. 7th ed. Mosby Elsevier; 2009:715–767. 3. Vignola AM et al. J Allergy Clin Immunol. 2000;105:1041–1053. 4. Bousquet J et al. Allergy. 1992:47:3–11. 5. Henderson J et al. Arch Dis Child. 2009;94(5):333–336. 6. Postma DS et al. Proc Am Thorac Soc. 2009;6:283–287.

Airway Hyperresponsiveness

Inflammation and Remodeling

Phenotypes and Genetics

Bronchoconstriction IMPO

RTA

NT

CO

NC

EPTS

IN A

STH

MA

Measure response:-clinical outcomes-pulmonary function-inflammation marker

Associate response:-patient charac.-biomarkers-genetics

Monitor response:-asthma control day-need rescue Rx-FEV1-eNO-sputum

Characteristics associated with drug responses

Szefler SJ. J Allergy Clin Immunol 2011; 127: 102-15.

Identification of Asthma Phenotypes Is Critical

Modified from Bacharier LB et al. Allergy. 2008;63(1):5–34.

Trigger-Based Pediatric Phenotypes: Virus-Induced Asthma

1. Papadopoulos NG et al. Allergy. 2007;62:457–470.

Pathophysiology of Virus-Induced Asthma Exacerbations1

Viral infection

Cellular damageIrritant and allergen

penetration

Mediators

Chemotaxis Immune response Neural effects

Virus-Induced Asthma: Management Approaches

• Nonpharmacologic measures• Avoidance of infections as much as possible1 (eg, by frequent hand

washing, avoiding contact with sick people)2

• Pharmacologic therapy• Use of controller medication may be especially important before

virus season when exacerbation rate would be high.3

• ICSs have shown a limited role in treating asthma triggered by the common cold.4

• LTRAs may reduce exacerbations.3

1. Bacharier LB et al. Allergy. 2008;63:5–34. 2. Mayo Clinic. mayoclinic.com/health/asthma/as00024/method=print. Accessed 23 April 2010.3. Bisgaard H et al. Am J Respir Crit Care Med. 2005;171:315–322. 4. McKean MC et al. Cochrane Database Syst Rev. 2000;(1):CD001107.

Prevention of Viral Induced Asthma (PREVIA)

2.34

1.60

0

1

2

3

Montelukast 4 mg (n=265)

Placebo (n=257)

Exacerbationepisoderate / year 32%

p≤0.001

Bisgaard H et al. Am J Respir Crit Care Med 2005.

Trigger-Based Pediatric Phenotypes: Exercise-Induced Asthma

Slide 72

Model of the Pathophysiology of Exercise-Induced Bronchoconstriction1

1. Hallstrand TS et al. Curr Allergy Asthma Rep. 2009;9:18–25.

Exercise-induced water lossCooling dehydrationMucin release

Epithelialcells

Basementmembrane

Sensory nerve

Airwaysmoothmuscle

Neurokinin A

EosinophilsMast cell

PGD2

cysLTs15-LO-1

5-LOCOX

15S-HETECOX

PGE2

cPLA2

sPLA2-X

MUC5AC

Gobletcell

PL AA

Trigger-Based Pediatric Phenotypes: Exercise-Induced Asthma

•Exercise: a common trigger of symptoms1

•Affects up to 90% of children with asthma2

•May occur with other triggers2

• Loss of water and heat from airway appears to initiate pathologic/proinflammatory response to exercise.3,4

1. Parsons JP et al. Curr Opin Pulm Med. 2009;15:25–28. 2. Stempel DA. In: Leung DYM. Pediatric Asthma: Principles and Practice. Mosby; 2003:435–443. 3. Hallstrand TS et al. Curr Allergy Asthma Rep. 2009;9:18–25. 4. Schwartz LB et al. Allergy. 2008:63:953–961.

Exercise-Induced Asthma: Management Approaches• Nonpharmacologic measures1–4

• Participation in sports encouraged• Warmup and cooldown periods• Nose breathing• Avoidance of known allergens

• Pharmacologic• Long-term control medications: Antiinflammatory therapy (eg, ICS and

LTRAs), associated with reduced frequency and severity of EIB5

• Pretreatment before exercise: SABAs preferred therapy;LABAs, although frequent/chronic use not recommended;LTRAs; cromolyn5,6

ICS=inhaled corticosteroids; LTRA=leukotriene receptor antagonist; LABA=long-acting β-agonist; SABA=short-acting β-agonist.1. Bacharier LB et al. Allergy. 2008;63:5–34. 2. Global Initiative for Asthma. ginasthma.org/guidelineitem.asp??i1=2&i2=1&intid=1689. Accessed 9 April 2010. 3. Schwartz LB et al. Alergy. 2008:63:953–961. 4. Billen A et al. Postgrad Med J. 2008;84:512–517. 5. Expert Panel Report 3. Summary Report 2007. J Allergy Clin Immunol. 2007;120:S94–S138. 6. National Asthma Education and Prevention Program, National Heart, Lung, and Blood Institute, National Institutes of Health. The Expert Panel Report 3 (EPR-3) Full Report 2007. National Institutes of Health; 2007.

Trigger-Based Pediatric Phenotypes: Allergen-Induced Asthma

1. Gern JE et al. Nat Rev Immunol. 2002;2:132–138.

Pathophysiology of Allergen-Induced Asthma1

A. Acute phase B. Chronic phase

Allergen

Mast cell

IL-4

IL-5

HistamineLeukotrienes

IgE

IL-4 IL-5 IL-13Eosinophil

Leukocyterecruitment

Degranulation

MucusMacrophage

TNF-α

Goblet cell

Epithelial cell

Airway damage/

inflammation

Th2

Predictors of response to ICSs

• Corticosteroids better response in atopic or severe AS• Biomarkers such as -BHR-eosinophilic inflammation-eNO-severe asthma-older age at onset of asthma

Clinical Asthma 2008.

สิ่งสําคัญในการเลือกใช ยา controller

²ความรุนแรงของโ รค²ลักษณะผูปวย (asthma phenotype)²ความรวมมือในการรักษา²การมียาในโ รงพยาบาล การเบิกจาย²ประสิท ธิภาพและราคายา

Adherence

Disease Control

↓ Morbidity

↓ Economic Burden

↓ Mortality

Achieve Goals

Environmental Modification

Irritant Occupational Trigger

Allergen

Monitoring Asthma Control

Disease Variability

Appropriate Pharmacotherapy

Manage Comorbidities

AR

GERD

CRSCost-effectivenessEvidence-based Decision-making

Pharmacogenetics

Asthma Management Paradigm

Components of Asthma Education

• Understand what is asthma

• Recognize and avoid triggers

• Understand when and why to use each medication

• Understand how to monitor asthma

• Use inhalers and peak flow meters properly

• Develop an asthma “Action Plan”

• Recognize acute severe asthma

Level of knowledge about disease and treatment in asthmatic patients

Poachanukoon O et al. Thai J Ped 2011.

Asthma control and compliance from different sites and age of patients

Children Elderly patients

Compliance < 50% Compliance > 80%

Asthma Action Plan

• รูสึกวาสบายดี• อาการกําเริบ• มีอาการมาก/อาการแยมาก

-หายใจแรงและเร็ว-หอบจนอกบุม กระสับกระสาย-ปลายนิ้วหรือริมฝปากเขียว-ไมมีแรง ใชยาขยายหลอดลมแลวไมดีข้ึน

บัตรประจําตัวและแผนปฏิบัติตัวเมื่อมีอาการ

Important factors if uncontrolled with ICS

1. Poor compliance in patients with ICS is very common for treatment failure (compliance with ICS < 50%)

2. Problems with inhalation techniques are very common, especially in children and elderly

3. Environmental factors

Conclusions

•Asthma is a chronic inflammatory disorder of the airways

•The phenotype of asthma and its progression varies

•It is important to consistently monitor patients in order to achieve maximum control

•The new asthma guidelines will provide an excellent framework for clinical practice