兒童氣喘治療新知 by ksdoctor

2014 GINA guideline for Pediatric Asthma

GINA Guideline for children < 5 yr

氣喘創議組織（GINA Global INiative for Asthma ) 成立於1993年由世界衛生組織（WHO) 和美國國家衛生院 (NIH)邀請世界各國氣喘專家所組成目前全球含台灣含台灣已有100多個國家積極推動氣喘防治計畫含台灣

Since 1993 1995 NHLBI/WHO Workshop report 2002 GINA guideline 2003 revised 2004 revised 2005 revised 2006 revised 2009 <5 Y/O children 2014 <5 /o children

(Diagnosis and Treatment Guidelines for Childhood Asthma in Taiwan)

GINA guideline-2009

02-25218926

感冒?還是過敏? (a heterogeneous disease)

variable expiratory airflow limitation.

(Diagnosis and Treatment Guidelines for Childhood Asthma in Taiwan)

transient wheezing 2 3 3

nonatopic wheezing 1 2

persistent asthma eosinophil

IgE

3 (Diagnosis and Treatment Guidelines for Childhood Asthma in Taiwan)

2015/9/18

Probability of asthma diagnosis or response to asthma treatment in children â&#x2030;¤5 years

GINA 2014, Box 6-1 (1/2)

ÂŠ Global Initiative for Asthma

王薇楊子毅 2004-3-13 12:51

2014 GINA guideline <5

Wheezing or cough that occurs exercise, laughing or crying without URI Past history of other allergic disease (AR or eczema) or parent history of asthma Clinical improvement during 2-3 months of controller treatment and worsening after cessation.

2011/04/24Li-Hsin Huang

(AD, AR)

aeroallergen, food allergen) ICS

IgE

x-ray: (>5yr) - eNO, exhaled breath condensates..

(Diagnosis and Treatment Guidelines for Childhood Asthma in Taiwan)

In Vitro (in vivo) 侵入性

侵入性

Skin prick test

Intradermal test

Skin patch test

(in vitro) 定量測試

Allergens microplate

ImmunoCAP

定性測試

MAST

定量/篩檢定量篩檢

BioIC

Is it Asthma?

http://www.ginasthma.com/

PAI (Predicted asthma index)

(aeroallergens)

(eosinophil) (wheezing)

(Diagnosis and Treatment Guidelines for Childhood Asthma in Taiwan)

(food allergen) J Allergy Clin Immunol 2004;114:1282-7

† ~

†

(Diagnosis and Treatment Guidelines for Childhood Asthma in Taiwan)

1. 建立病人/父母（照顧者）/醫師之間的合作關係 2. 找出及減少危險因子的暴露 3. 評估、治療及監測氣喘

2011/04/24

A. 評估、治療及監測氣喘治療的選擇必須考慮以下因素氣喘控制的程度目前的治療藥物的特性與取得的便利性經濟因素另外需考量不同文化的差異與不同的醫療體系

*缺lung function

GINA 2014, Box 6-5

Diagnosis and Classification Purpose

2005 GINA

2006 GINA

Diagnosis

氣喘病患分類依據 characterizing a group of patients with asthma

氣喘嚴重度分級 Asthma severity

Classification

治療選擇的依據 The basis for treatment decisions

氣喘嚴重度分級 Asthma severity

氣喘控制的程度 level of control

(診斷)

仍以“氣喘嚴重度分級” (Classification of Asthma Severity) 作為開始治療前將氣喘病患分類的依據 (臨床研究時)

(分類)

治療選擇的依據: 氣喘控制的程度 (Levels of Asthma Control ) 分為: 控制部分控制控制不佳

2006 GINA

Taiwan

11%

14%

18%

57%

The presence of one feature of severity is sufficient to place patient in that category.

Assessment of asthma 1.

Asthma control - two domains

Assess symptom control over the last 4 weeks Assess risk factors for poor outcomes

GINA 2014, Box 2-1

GINA assessment of asthma control [2014]

[GINA 2014]

每星期一次

GINA 2014, Box 2-2A

每星期二次或以上

B. Risk factors for poor asthma outcomes (≤5 years) Risk factors for exacerbations in the next few months • • • •

Uncontrolled asthma symptoms One or more severe exacerbation in previous year The start startof ofthe thechild’s child’s usual ‘flare-up’ season (especially if autumn/fall) usual ‘flare-up’ season (especially if autumn/fall) Exposures: tobacco smoke; indoor or outdoor air pollution; indoor allergens (e.g. house dust mite, cockroach, pets, mold), especially in combination with viral infection • Major psychological or socio-economic problems for child or family • Poor adherence with controller medication, or incorrect inhaler technique

Risk factors for fixed airflow limitation • Severe asthma with several hospitalizations several hospitalizations • History ofbronchiolitis bronchiolitis History of

Risk factors for medication side-effects • Systemic: Frequent courses of OCS; high-dose and/or potent ICS • Local: moderate/high-dose or potent ICS; incorrect inhaler technique; failure to protect skin or eyes when using ICS by nebulizer or spacer with face mask

GINA 2014, Box 6-4B

(nebulizer) 0 3 (MDI)

5 10

4 5 5 10 > 6 10

(DPI)

> 6

10 (Diagnosis and Treatment Guidelines for Childhood Asthma in Taiwan)

吸藥輔助器

D. ─

每天早晚各吹三次，記錄最高值特別是平時症狀不明顯的病人能夠幫助疾病嚴重度的診斷及監測藉由分區系統來做疾病的自主管理

27Huang 2011/04/24Li-Hsin

紅燈區(尖峰呼氣流速值為理想值的 ↓) 紅燈區尖峰呼氣流速值為理想值的60%↓ 尖峰呼氣流速值為理想值的表示危險表示危險，危險，應立即就醫

黃燈區(尖峰呼氣流速值為理想值的黃燈區尖峰呼氣流速值為理想值的60%~80%) 尖峰呼氣流速值為理想值的表示應小心表示應小心，應小心，最好一日內就醫 28Huang 2011/04/24Li-Hsin

綠燈區(尖峰呼氣流速值為理想值的綠燈區尖峰呼氣流速值為理想值的80%~100%) 尖峰呼氣流速值為理想值的表示安全表示安全

(C-ACTTM)

: 20 : 19

20 19

制 25(27)

制 20

≤ 1下

20-24 ≤19

The ACT can raise expectations for asthma management and facilitate the achievement of asthma control

病人自我處置計畫 (Written asthma action plan) 一、您每天要規則使用的藥物是： 1）____________________________________________________________ 2）____________________________________________________________ 3）____________________________________________________________

運動前可使用

二、增加治療藥物（升階治療）的時機您在過去一週的症狀： 1）白天出現氣喘症狀2 次以上是，否 2）會因為氣喘症狀而使行動（運動）受限是，否 3）會因為氣喘症狀而在夜間醒來是，否 4）會額外使用擴張劑2 次以上是，否 5）峰量計值低於公升/分是，否

如果上述問題回答「是」有3 題或3 題以上，則表示氣喘控制不佳，需要升階治療。

三、升階治療之用藥： 1）____________________________________________________________ 2）____________________________________________________________ 3）____________________________________________________________

維持此治療天

四、當有氣喘發作或急性惡化時要採取的步驟： 1）____________________________________________________________ 2）____________________________________________________________ 3）____________________________________________________________

五、有下列情況需要到醫院急診： 1）____________________________________________________________ 2）____________________________________________________________ 3）____________________________________________________________

醫師：______氣喘衛教師：______ 日期： __年 __月 __日

Assessment of asthma 1.

Asthma control - two domains

Assess symptom control over the last 4 weeks Assess risk factors for poor outcomes

Treatment issues

Check inhaler technique and adherence Ask about side-effects Does the patient have a written asthma action plan? What are the patientâ&#x20AC;&#x2122;s attitudes and goals for GINA 2014, Box 2-1 their asthma?

• • 140/90 mmHg

• • •

<100mg/dl

HbA1c LDL-

達成良好症狀控制及正常生活的影響 (symptom co良trol)

沒有緊急求診的記錄，不需要（或很少）使用乙二型交感神經興奮劑每日全無（或僅有輕微）慢性症狀日常活動（包括運動）不受限制沒有夜間相ou童管或試ake 尖峰呼氣流速值接近正常，早晚差異小於20％避免發生致命狀況

減輕風險(risk) 減輕風險

很少急性發作，若有也很輕微避免肺功能喪失沒有藥物引起的副作用或僅有輕微副作用

2011/04/24Li-Hsin Huang

36Huang 2011/04/24Li-Hsin

*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS **For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy

GINA 2014, Box 3-5, Step 3

ÂŠ Global Initiative for Asthma

GINA 2014, Box 6-5

2015/9/18

Initial controller treatment for adults, adolescents and children 6â&#x20AC;&#x201C;11 years

Start controller treatment early

Indications for regular low-dose ICS (step 2) - any of:

For best outcomes, initiate controller treatment as early as possible after making the diagnosis of asthma

Asthma symptoms more than twice a month Waking from asthma more than once a month Any asthma symptoms plus any risk factors for exacerbations

Consider starting at a higher step (â&#x2030;Ľ step 3) if:

Troublesome asthma symptoms on most days Waking from asthma once or more a week, especially if any risk factors for exacerbations

NEW! GINA 2014, Box 3-4 (1/2)

2015/9/18

Reliever medications (

Short-acting inhaled β2 agonists (SABAs) ( ) Other bronchodilators ( )

Controller medications (

) β2

)

ICS ( ) “和OCS (口服類固醇)不同” LTRA (  ) Long-acting b2 receptor agonists (ICS+LABAs) Sustained-release theophylline ( ) (≥ 12 y/o) Anti-IgE antibodies (≥ 6 y/o) ( IgE ) Cromolyn sodium

(Diagnosis and Treatment Guidelines for Childhood Asthma in Taiwan)

)

ICS (

(preferred options)

200

g BDP

-low daily dose)

ICS

1 2

ICS

LTRA

LABA (>5yr)

ICS (Diagnosis and Treatment Guidelines for Childhood Asthma in Taiwan)

‘ Fluticasone(Flixotide®)

Inhaled corticosteroid

Low daily dose (mcg)

Beclometasone dipropionate (HFA)

100

Budesonide (pMDI + spacer)

200

Budesonide (nebulizer)

500

Fluticasone propionate (HFA)

100

Ciclesonide

160

Mometasone furoate

Not studied below age 4 years

Not studied in this age group 至少使用三個月，以建立療效達到氣喘的控制。

Triamcinolone acetonide

GINA Box6-6 6-6 GINA 2014, 2014, Box

Ciclosonide (Alvesco®)

approved by the FDA in 2006 (台灣 in 2012)

® Ciclesonide/Alvesco

160

g/puff, 60 puffs /pack

NT 568 /pack :4

: :

, ,

2 puffs 1 puff

Pharmacology : 1. Conversion to an active metabolite 2. High pulmonary deposition and retention 3. High protein binding 4. Metabolized elsewhere in the body

2017-SL-11-09

Anti-IgE antibodies omalizumab (Xolair) -approved by the FDA in 2003

Taiwan Indication - 2010 4

Xolair( 1.

) add on therapy high dose ICS+LABA

severe persisted asthma )

2. (FEV1 < 80%) IgE

LTRA (

)

montelukast

< 10

leukotriene LTRA

ICS

ICS (add on)

ďź&#x152; 6 Adverse effect: irritable, GI upset..?

(granules)

(Diagnosis and Treatment Guidelines for Childhood Asthma in Taiwan)

Singulair Oral granule 6mon~5 y

Safety and tolerability in children

2751 patients, 6 months to 14 years

Pediatr Pulmonol. 2009;44:568–79 台灣兒童氣喘診療指引學術研討會

*每周一次以下每周一次以下

Step-up therapy in childhood asthma with ICS

Lancet 1994;344:219; Am J Respir Crit Care Med 1996; 153: 1481-8; N Engl J Med 1997;337:1405-11.

Step-up therapy in childhood asthma with ICS

N Engl J Med. 2010 Mar 3

Methods: triple-cross-over design

1. 2. 3.

182 children (6 -17 y/o) with uncontrolled asthma while receiving 100 μg

fluticasone (ICS) twice daily LABA step-up: 100 μg ICS + 50 μg of LABA bid daily ICS step-up: 250 μg ICS bid LTRA step-up: 100 μg ICS bid + plus 5/10 mg LTRA 3 outcomes: exacerbations, asthma-control days, and the FEV1 to determine whether the frequency of a differential response to the step-up regimens

LABA step-up led to the greatest likelihood of best response 52% vs. 32% P = 0.004 P = 0.002

54% vs. 34% P = 0.02

P = 0.004

However, many children had a best response to ICS or LTRA step-up therapy highlighting the need to monitor and adjust each childâ&#x20AC;&#x2122;s asthma therapy appropriately. (step 3 step 4) alternative step 3 treatment

N Engl J Med. 2010 Mar 3

Asthma management approach based on control (<5 歲)

控制不佳

ICS LT

ICS X2

ICS +LT

http://www.ginasthma.com/

1. 2. 3. 4. 5.

(RSV) (influenza virus) (parainfluenza virus) (rhinovirus) (adenovirus) (chlamydia)

(mycoplasma)

URI

(epithelial cells) (inflammatory mediators)

lgE

antibodies) ex. RSV lgE (histamine)

(specific IgE

Virus-Induced Asthma: Management Approaches

Nonpharmacologic measures 1 Avoidance of infections as much as possible 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 3 LTRAs may reduce exacerbations.

ICS=inhaled corticosteroids; LTRA=leukotriene-receptor antagonist. 1. Bacharier LB et al. Allergy. 2008;63:5â&#x20AC;&#x201C;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;171:315â&#x20AC;&#x201C;322. 4. McKean MC et al. Cochrane Database Syst Rev. 2000;(1):CD001107. doi:10.1002/14651858.CD001107. Slide 59

Management in Asthma Patients With AR

AR and asthma are “one airway disease” AR increases morbidity, therapeutic needs, and use of health-care resources in patients with asthma Montelukast has improved lung function, symptoms, and QoL in asthma patients with AR --Leukotrienes are mediators of both AR and asthma

Recommend leukotriene modifiers as an effective option in both conditions

Adapted from National Institutes of Health Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention: A Pocket Guide for Physicians and Nurses. Publication No. 95-3659B. Bethesda, MD: National Institutes of Health, 1998; Bousquet J et al. J Allergy Clin Immunol. 2001;108(suppl 5):S148–S149; Casale TB, Amin BV. Clin Rev Allergy Immunol. 2001;21:27–49; Philip G et al. Curr Med Res Opin. 2004;20:1549– 1558; Price DB et al. Allergy. 2006;61:737–742; Global Initiative for Asthma. Global strategy for asthma management and prevention. Available at htttp://www.ginaasthma.org. Accessed February 2007. Slide 60

長期持續“只”使用吸入型乙型交感神經興奮劑時會減少病患保護支氣管受刺激收縮的能力,停止使用後會引起反彈性氣管敏感度增加,故不建議每天規則性單獨使用,而建議在必要時使用

2011/04/24

61Huang Li-Hsin

Take home messages

(Diagnosis and Treatment Guidelines for Childhood Asthma in Taiwan)

Thanks a lot!

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