氣喘合併慢性阻塞性肺病症候群 - Asthma and COPD Overlap Syndrome (ACOS) and case sharing -

時 間：民國 103年11月1日 地 點：臺北榮民總醫院致德樓第一會議廳 主 辦：台灣慢性阻塞性肺病學會、台灣氣喘學會 講 師：彰化基督教醫院林慶雄主任

E-mail : 47822@cch.org.tw

Differential diagnosis COPD

Chronic

bronchitis Emphysema

Asthma

Airflow

obstruction

COPD

Snider GL. Respiration 1995

Physiological characteristics

Thorax 2009;64:728–735.

Definition of ACOS

One of two clinical phenotypes:

• Asthma with partially reversible airflow obstruction, with or without emphysema or reduced DLco to <80% predicted; and

• COPD with emphysema accompanied by reversible or partially reversible airflow obstruction, with or without environmental allergies or reduced DLco

Zeki AA. J Allergy (Cairo) 2011;2011:861926

A nation-wide consensus of experts in COPD Diagnostic criteria of “Overlap Phenotype COPD–Asthma”:

<<2 major criteria >> or <<1 major + two minor criteria>> Major criteria:

• Very positive bronchodilator test (increase in FEV1 ≥15% and≥400 ml) • Eosinophilia in sputum • personal history of asthma.

Minor criteria: • High total IgE, • Personal history of atopy • positive bronchodilator test (increase in FEV1 ≥12% and ≥200 ml) on two or more

occasions.

Arch Bronconeumol. 2012;48(9):331–337

Criteria for ACOS

Major criteria

• A physician diagnosis of asthma and COPD in the same patient

• History or evidence of atopy, for example, hay fever

• Elevated total IgE

• Age 40 years or more

• Smoking >10 pack-years

• Post-BD FEV1 <80% and FEV1/FVC <70%

Minor criteria

• A 15% increase in FEV1 or 12% and 200 ml increase in FEV1 post-BD treatment with albuterol

Louir et al. Expert Rev. Clin. Pharmacol. 2013; 6(2), 197–219

This document has been developed by the Science Committees of both GINA and GOLD, based on a detailed review of available literature and consensus.

It provides an approach to distinguishing between asthma, COPD and the overlap of asthma and COPD, for which the term Asthma COPD Overlap Syndrome (ACOS) is proposed.

Rather than attempting a formal definition of ACOS, this document presents features that identify and characterize ACOS, ascribing equal weight to features of asthma and of COPD.

The primary objective of this approach is to inform clinical practice, based on current evidence.

PREFACE

宗旨

• 本文並未試圖制定 ACOS 的正式定義，而是列出一些可用於鑑定及描述 ACOS 的特定病徵，其中不論是氣喘或 COPD 的病徵皆同等重要，並附上 ACOS 的初步治療方案以供參考。

• 本文所提出的 ACOS 的敘述中包含一些疾病表現型，未來將可透過臨床診斷、病生理學分析、以及遺傳學等特徵而獲得更詳細的界定。

• 本文的主要目的在於根據現有的證據提供臨床處置的參考。

ACOS is associated with more impairment North Carolina 2007-2009

COPD, DO: 1-11, 2013

ACOS is associated with more comorbidities North Carolina 2007-2009

COPD, DO: 1-11, 2013

Clin Respir J 2013; 7: 342–346.

Increased healthcare utilization with ACOS 2009 Korean National Health Insurance Database

• COPD - a post-bronchodilator (BD) FEV1/FVC ratio of < 0.70

• Asthma - presence of wheezing in the last year and a minimum post-BD increase in FEV1 or FVC of 12% and 200 ml

• Overlap COPD-Asthma: the combination of the two

Design & definition : Analysis from PLATINO study

(5,044 subjects)

The prevalence for overlap among only the affected population was 11.6%

COPD prevalence: 11.7%

Asthma prevalence: 1.7%

Overlap prevalence: 1.8%

The prevalence for overlap among only the affected population was 11.6%

After adjusting for confounders, the COPD-Asthma overlap was associated with higher risks :

– Exacerbations (PR 2.11; 95%CI 1.08-4.12),

– Hospitalizations (PR 4.11; 95%CI 1.45-11.67)

– Worse GHS (PR 1.47; 95%CI 1.18-1.85), compared to those with COPD

AE, Hospitalization, and Health status

Step-wise approach to diagnosis of patients with respiratory symptoms

• Step 1: Does the patient have chronic airways disease?

• STEP 2. The syndromic diagnosis of asthma, COPD and ACOS in an adult patient

• STEP 3: Spirometry

• STEP 4: Commence initial therapy

• STEP 5: Referral for specialized investigations (if necessary)

較符合氣喘的特徵 較符合 COPD 的特徵 在 20 歲前發病。 在 40 歲後發病。 症狀可於幾天、幾小時甚至幾分鐘內出現變化。

症狀於夜晚或凌晨時較嚴重。 症狀因運動、情緒變化如大笑、吸入粉塵、或接觸過敏原後而誘發。

接受治療後，症狀仍持續存在。 每日的病情時好時壞，但症狀總是存在，且有運動性呼吸困難。

慢性咳嗽咳痰伴隨呼吸困難發作，不過咳嗽咳痰並不是呼吸困難的誘發因素。

紀錄顯示 (肺量計檢查、最大呼氣流量) 呼氣氣流受阻，且程度有所變化。

紀錄顯示持續性呼氣氣流受阻 (吸入支氣管擴張劑後之 FEV1/FVC <0.7)。

無症狀期的肺功能正常。 無症狀期的肺功能不正常。 曾被醫師診斷為氣喘。 有氣喘和其他過敏性疾病 (如過敏性鼻炎、濕疹) 的家族病史。

曾被醫師診斷為 COPD、慢性支氣管炎、或肺氣腫。

大量接觸危險因子，如吸菸、生物燃料等。

症狀未隨時間惡化，不過可能有季節性的變化；每年的症狀亦可能有所變化。

症狀自發性地改善，或持續數週對支氣管擴張劑或吸入型類固醇有立即性的反應。

症狀緩慢地惡化 (病情逐年進展)。 接受速效型支氣管擴張劑治療的效果有限。

檢查結果正常。 嚴重肺部過度充氣的影像學表現。

若某一側 (asthma or COPD)的勾選格數等於或大於另一側3格以上，則認為有較高可能性屬於asthma或COPD．若兩側勾選格數差異在3格內，則較有可能屬於ACOS

50-year-old woman

Height: 147 cm, Weight: 68 kg, BMI: 31.47 kg/m2

體脂肪: 40.3% (參考值女性: 19%~29%)

History of

Old pulmonary TB, hepatitis B, Allergic rhinitis

Smoking: no

Symptoms: episodic SOB and cough with sputum

HR: 87/min, RR: 20/min, BP: 96/65 mmHg

SpO2: 88% to 94 % (room air)

Case Discussion – basic data

2005/06/29

What is your diagnosis ?

1. Asthma

2. COPD, GOLD 3

3. Asthma COPD Overlap Syndrome

4. Neither Asthma nor COPD

Nature Medicine 2012;18:684-692

Follow up at Chest OPD

• FEV1\FVC = 56%, FEV1 = 23%, 0.54L (2005-12-12)

• FEV1\FVC = 58%, FEV1 = 37%, 0.79L (2007-08-22)

• FEV1\FVC = 55%, FEV1 = 33%, 0.71L (2008-01-23)

• Total IgE = 14.6 (2007-10-17)

• Total IgE = 21.1 (2008-04-16)

• Total IgE = 26.0 (2013-09-16)

• Specific IgE = non-reactive

Follow up at Chest OPD

ACT = 22 (2009-02-19)

ACT = 25 (2009-07-08)

ACT = 22 (2009-09-02)

ACT = 21 (2010-01-20)

ACT = 25 (2010-05-12)

ACT = 22 (2011-06-13)

• EXHALED NO = 21 (2009-02-19) SpO2 = 91% (room air)

• EXHALED NO = 19 (2009-03-18) SpO2 = 95% (room air)

• EXHALED NO = 18 (2009-04-15)

What is your therapy ?

1. LABA + PRN SABA

2. LAMA + PRN SABA

3. ICS + PRN SABA

4. LABA + LAMA + PRN SABA

5. LABA + ICS + PRN SABA

6. LAMA + ICS + PRN SABA

7. LABA + LAMA + ICS + PRN SABA

Clinical Practice

• 2000-04-20 Pulmicort (Budesonide) turbuhaler 2 puff BID Serevent (Salmeterol) inhaler 2 puff BID Oral prednisolone

• 2002-01-23 Pulmicort turbuhaler 2 puff BID Fomorterol turbuhaler 1 puff BID

• 2005-06-29 Symbicort 2 puff BID

• 2007-03-07 Seretide 2 puff BID Atrovent as needed

Clinical Practice

• 2009-09-30 Seretide 2 puff BID Spiriva 18μg 1 cap QD

• 2012-03-14 Onbrez 150μg 1 cap QD Spiriva handihaler 18μg 1 cap QD Spiriva Respimat 2.5μg 2 puff QD

• 2014-04-14 CAT=33

六分鐘走路試驗

六分鐘走路試驗

Clinical Practice

• 2014-04-14 CAT=33 Onbrez 150μg 1 cap QD Alvesco 2 puff QD

CCPC-COPD（2014-07-07）

• 身高: 147 cm, 體重: 66.2 kg, BMI: 30.64 kg/m2

• 血壓: 89/61 mmHg, 脈搏: 82 次/分, 呼吸速率: 20次/分 • 體脂肪: 40.1 (參考值 女性: 19%~29%) • 握力: 22.6 (normal) • SpO2 = 94 % • 膚色: 正常 • 口腔黏膜: 完整無破損 • FEV1 = 39.6% (GOLD 3) (2014-07-02) • CAT = 9 • mMRC scale: Grade 1 • GOLD Group D • BSRS-5 = 2 分, 身心適應良好 , 無自殺意念 • 目前居家肺復原

FEV1（% predicted）

FEV1（Liter）

0

0.2

0.4

0.6

0.8

1

1.2

2012/6

/1

2012/9

/1

2012/1

2/1

2013/3

/1

2013/6

/1

2013/9

/1

2013/1

2/1

2014/3

/1

2014/6

/1

2014/9

/1

Lit

er

CCPC

CCPC-COPD 照護系統【評估彙總表】

No data available so far

Treatment guidelines:

2014 ACOS guideline:

Asthma/ACOS feature: ICS (+ LABA), no LABA alone

COPD feature: bronchodilators (+ ICS), not ICS alone.

Adequate Dosage of ICS for ACOS

43

Asthma-COPD overlap syndrome is not uncommon (15-50%).

Patients of obstructive airway disease may present both features of asthma and COPD.

ICA/LABA is recommended as first choice for ACOS at this moment, yet, LAMA may also considered too.

There is no consensus so far, regarding the adequate dose and/or titration/tapering.

Conclusions