Proceeding to the Future of Asthma Therapy Terry Wu 吳中隆 AstraZeneca Taiwan

氣喘定義 氣喘乃是一種呼吸道持續性的慢性發炎反應，且支氣管對於各種刺激，會產生過度反應 (遺傳體質加上外來過敏原)。 2. 反覆發作的氣流阻滯、會自行緩解或經適當治療而恢復。(可逆性的肺功能障礙) 3. 依嚴重程度，可出現：呼吸困難、哮嗚音、胸悶和咳嗽，尤其是在夜間或清晨，症狀更明顯、有些人會出現多痰。

Current golden standard treatment manages the two components of asthma separately* Inflammation Bronchoconstriction `Rescue Inhaler Rapid symptom relief Does not address underlying inflammation Maintenance Inhaler Daily use Prevention * Canadian Asthma Consensus Report., CMAJ; 1999 SMART: Symbicort Maintenance And Reliever Therapry

Happy life ??? SMART: Symbicort Maintenance And Reliever Therapry

Asthma is characterized by its variability and unpredictability SUSCEPTIBILITY ENVIRONMENT ASTHMA WHERE ??? Changes in home environment Dirt Insect slough-off Pet Drugs Changes in outdoor environment Pollen Pollutants Temperature changes Air humidity Genetic Factors Changes in diet Maternal smoking Breast Feeding Less early life infections WHEN ??? SMART: Symbicort Maintenance And Reliever Therapry

Patients over-rely on SABAs vs. ICS; irrespective of asthma severity Rabe KF at al, Eur Respir J 2000; 16: 802-807 SMART: Symbicort Maintenance And Reliever Therapry

Despite ICS or ICS/LABA maintenance, 74% of patients used rescue therapy each day Base: all patients (n=2,406) Partridge MR at al, BMC Pulmonary Medicine 2006; 6:13 SMART: Symbicort Maintenance And Reliever Therapry

氣喘之嚴重度分類 只要符合症狀或尖峰呼氣流速值任一項，就可以納入分級。 病情分級 白天出現症狀 夜間出現症狀 尖峰呼氣 流速值 第四級 嚴重持續性 連續發生， 日常生活受限。 經常發生 低於預測值的60% 變異度大於30% 第三級 中度持續性 每天都有， 活動氣喘發作。 每週一次以上 介於預測值的60%~80% 第二級 輕微持續性 每週都有， 但少於每天一次。 每月二次以上 大於預測值的80% 變異度介於20%~30% 第一級 輕微間歇性 少於每週一次，發作之 無症狀。 少於每月二次 變異度小於20% 只要符合症狀或尖峰呼氣流速值任一項，就可以納入分級。 SMART: Symbicort Maintenance And Reliever Therapry

SMART: Symbicort Maintenance And Reliever Therapry

SMART: Symbicort Maintenance And Reliever Therapry

Your suggestion is??? SMART: Symbicort Maintenance And Reliever Therapry

Symbicort SMART Symbicort Maintenance And Reliever Therapy Inflammation and Bronchoconstriction It provides rapid symptom relief and improved control Patients do not require a separate SABA SMART: Symbicort Maintenance And Reliever Therapry

Total daily medication use (maintenance and relief) Symbicort SMART has better efficacy over fixed-dose combination at lower dose Total daily medication use (maintenance and relief) Fixed Symbicort Fixed Symbicort + prn SABA + prn Symbicort (Symbicort SMART) If a combination inhaler containing formoterol and budesonide is selected, it may be used for both rescue and maintenance. This approach has been shown to result in reductions in exacerbations and improvements in asthma control in adults and adolescents at relatively low doses of treatment (Evidence A) … page60 SMART: Symbicort Maintenance And Reliever Therapry

So what??? SMART: Symbicort Maintenance And Reliever Therapry

Symbicort SMART reduces asthma exacerbation rates more effectively than fixed combination -39% * ** * P<0.001 vs. Seretide + SABA ** P<0.01 vs. 2x Symbicort + SABA Seretide 50/250 µg bid + SABA Symbicort 320/9 µg bid + SABA Symbicort SMART 160/4.5 µg bid + as needed A six month double-blind study including 3,335 patients COMPASS: Kuna P et al, Int J Clin Prac. 2007; 61: 725-736 SMART: Symbicort Maintenance And Reliever Therapry

Symbicort SMART reduces the use of daily reliever -38% * * P<0.001 Seretide + SABA Symbicort SMART Maintenance dose of Seretide titrated on clinicians’ judgment to be either 2x50/100 µg; 2x50/250 µg or 2x50/500 µg Maintenance dose of Symbicort 160/4.5 µg; 1 or 2 puffs bid based on clinicians’ judgment One year randomized real life study including 2,143 patients COSMOS: Vogelmeier C et al, Eur Respir J. 2005; 26: 819-828 SMART: Symbicort Maintenance And Reliever Therapry

Symbicort SMART reduces numbers of hospitalizations and ER treatments -39% * P<0.01 vs. Seretide + SABA * Seretide 50/250 µg bid + SABA Symbicort 320/9 µg bid + SABA Symbicort SMART 160/4.5 µg bid + as needed A six month double-blind study including 3,335 patients COMPASS: Kuna P et al, Int J Clin Prac. 2007; 61: 725-736 SMART: Symbicort Maintenance And Reliever Therapry

Symbicort SMART reduces drug load of oral corticosteroids -45% Seretide 50/250 µg bid + SABA Symbicort 320/9 µg bid + SABA Symbicort SMART 160/4.5 µg bid + as needed A six month double-blind study including 3,335 patients COMPASS: Kuna P et al, Int J Clin Prac. 2007; 61: 725-736 SMART: Symbicort Maintenance And Reliever Therapry

Why??? SMART: Symbicort Maintenance And Reliever Therapry

Time after drug administration (minutes) Formoterol provides not only rapid symptom relief but also anti-inflammatory benefits rapid symptom relief 500 1000 1500 2000 2500 Formoterol P<0.01 Neutrophil count (x103/mm3) P<0.005 P<0.5 Placebo Budesonide Baseline 4 weeks Maneechotesuwan et al, CHEST 2005; 128(4): 1936-1942 Time after drug administration (minutes) 5 10 15 20 25 30 FEV1 at 3 minutes after inhalation: p<0.001 for all active treatments compared with placebo Mean FEV1 (% change from baseline) Formoterol 9 µg Formoterol 4.5 µg Salbutamol 200 µg Salbutamol 450 µg Placebo Seberova E et al, Respiratory Medicine 2000; 94(6): 607 - 611 In a double-blind randomized crossover study, the effects of 4 weeks’ treatment with formoterol 24 µg bid (F; Turbuhaler) compared with placebo (PLC) on sputum neutrophil numbers and interleukin (IL)-8 levels in asthmatic patients was evaluated.1 Therapy with budesonide 400 µg bid (BD; Turbuhaler) for 4 weeks was added at the end as the "gold standard" anti-inflammatory effect comparison. Formoterol significantly reduced neutrophil count compared with placebo. There was a significant correlation between the reduction in sputum IL-8 levels and the number of neutrophils, indicating that formoterol may attenuate neutrophilic airway inflammation by inhibiting IL-8 production. These data suggest that formoterol reduces neutrophilic airway inflammation in patients with mild asthma and that this might be beneficial in preventing asthma exacerbations. SMART: Symbicort Maintenance And Reliever Therapry

Single dose of budesonide (2,400 µg) within 6 hours Budesonide has anti-inflammatory effect much faster than we thought it’d be rapid symptom relief Single dose of budesonide (2,400 µg) within 6 hours Placebo Budesonide 800 µg Time (hours) FEV1 (L) -2 -1 1 2 3 4 5 6 7 8 9 10 * Treatment at the start of the late response * p<0.05 60 Eosinophils 50 Placebo 40 Budesonide p<0.05 30 Sputum eosinophils (%) 20 10 The effect of budesonide used in the relief of allergen symptoms has shown no effect on the immediate asthmatic response, however budesonide significantly reduces the late phase allergic reaction – an event that is thought to develop as a result of the increased inflammation. This highlights one aspect of the value of budesonide given in response to symptoms. Paggiaro PL et al, Am J Crit Care Med 1994;149:1447–51. Gibson P et al: Am J Respir Crit Care Med 2001; 163: 32-36 SMART: Symbicort Maintenance And Reliever Therapry

Balanag V.M et al, Pulm Pharm Thera 2006; 19(2): 139-147 prn Symbicort Given that formoterol and budesonide each has its own rapid onset and anti-inflammatory effects, they together do work better than they do separately; which is why Symbicort can be used as reliever SMART: Symbicort Maintenance And Reliever Therapry

Symbicort is as effective and well tolerated as salbutamol in treating acute asthma prn Symbicort Balanag VM et al, Pulm Pharm Thera 2006; 19(2): 139-147 SMART: Symbicort Maintenance And Reliever Therapry

Timing is more important than overall dosage Number of days using oral steroids over 6 months 20 40 60 80 100 120 p<0.001 Foresi A et al, CHEST 2000; 117(2): 440-446 Budesonide 100 µg bid + placebo qd Budesonide 100µg bid +budesonide 200µg qd Budesonide 800 µg bid + placebo qd It is the timing of the increase in ICS dose, resulting from as-needed use of budesonide/formoterol to treat symptoms, rather than the total inhaled dose of ICS that improves efficacy. O’Byrne PM et al, J Allergy Clin Immuno 2007; 119: 1332-1336 Prof. O’Byrne is the member of GINA scientific committee This was the first study to show that in patients receiving a low maintenance dose of budesonide (200 µg/day) + a temporary (7-day) increase in budesonide dose (+ 200 µg 4 times a day) at the first sign of worsening asthma effectively manages an exacerbation as well as regular higher doses of budesonide (800 µg/day). This study showed that once asthma was under control, a low dose of budesonide was as effective as a fixed moderate-dose for maintaining asthma control, provided this dose was increased (both total dose and frequency) at the first sign of a worsening in asthma control. This study was the first to show that adjustable dosing with budesonide provides similar asthma control with a lower overall steroid dose compared with fixed moderate-dose treatment. SMART: Symbicort Maintenance And Reliever Therapry

Symbicort Maintenance And Reliever Therapy Symbicort SMART license has been received on Sep 26th, 2007 Symbicort® Turbuhaler® 160/4.5μg/dose (Budesonide/formoterol) 衛署藥輸字第023265號 ….. B. 以吸必擴®作為氣喘症之維持和緩解療法 成人和青少年（12歲及以上）：一般維持劑量是每天1次，每次吸入2劑；或每天2次，每次吸入1劑。有些病人可能需要使用每天2次，每次吸入2劑的維持劑量。病患應視症狀需求而增加吸入劑量，但單次使用不得吸入超過6劑。每日可在短時間內使用最高可至共12劑之總劑量。 一般原則 為緩解症狀而增加吸入劑數的病人，如果在2週內，氣喘控制情況仍未見改善，應考慮重新評估氣喘的治療。成人和青少年每日通常不需要吸入8劑以上。特殊情況下，成人和青少年每日可在短時間內最高吸入12劑。 SMART: Symbicort Maintenance And Reliever Therapry

Q: 如何區分氣喘跟一般感冒? 常見問題 與 衛教重點 氣喘的特徵: 1.氣道發炎反應。 2.氣道敏感度增加。 3.氣道變形。 4.可逆性的氣道阻塞現象。 一般的感冒通常是急性發作，大約在 1~2 週內痊癒， 若是時常感冒，或感冒一兩個月都不會好，尤其是 久咳不癒，都有可能是氣喘。 最好找專科醫師仔細的問診和檢查，以免延誤治療。 SMART: Symbicort Maintenance And Reliever Therapry

氣喘 氣喘 無 氣喘 80-100%氣喘 25-30%氣喘 氣 喘 會 不 會 遺 傳 ? 父親 母親 父親 母親 SMART: Symbicort Maintenance And Reliever Therapry

Q: 氣喘患者可以運動嗎 ? 常見問題 與 衛教重點 若因運動而引發氣喘則表示氣喘控制不良，運動可增 加肺活量，清除蓄積氣道內的痰液，反而有利於呼 吸功能。 氣喘患者平時應加強吸入性類固醇藥物的使用以控制 炎性反應，若規則持續使用3-6週後，可有效減少 50% 氣喘發作的機率。 儘可能避免在乾冷空氣中運動，並延長暖身運動的時 間，運動前使用支氣管擴張劑預防，均可有效避免 運動誘發型氣喘。 SMART: Symbicort Maintenance And Reliever Therapry

43歲女性設計師，抽煙史10年，近來無症狀要求想停藥。 Q: 我的氣喘病沒再發作可以自行停藥嗎﹖ A:1.氣喘用藥是屬於長期保養藥物。 Case Sharing - 2 43歲女性設計師，抽煙史10年，近來無症狀要求想停藥。 Q: 我的氣喘病沒再發作可以自行停藥嗎﹖ A:1.氣喘用藥是屬於長期保養藥物。 2.抽煙很容易誘發氣喘發作，應鼓勵患者積 極戒煙。 SMART: Symbicort Maintenance And Reliever Therapry

未按醫師指示用藥 是造成氣喘無法良好控制的最重要原因 未按醫師指示用藥 是造成氣喘無法良好控制的最重要原因 擔心藥物副作用 97% 擔心藥物用久會失效 78% 藥物沒有立即藥效 78% 不知道用藥的重要性 72% 沒有症狀就不用藥 68% SMART: Symbicort Maintenance And Reliever Therapry

30歲女性患者，從小氣喘病史，無規則用藥，常依賴急 性緩解藥物，現因急性發作住院治療中。 Q: 不了解急性緩解藥物與控制藥物使用時機。 Case Sharing - 4 30歲女性患者，從小氣喘病史，無規則用藥，常依賴急 性緩解藥物，現因急性發作住院治療中。 Q: 不了解急性緩解藥物與控制藥物使用時機。 A:1.急性緩解藥物是擴張支氣管的藥物，過度依 賴會有潛在的危機。 2.適當投與預防性抗發炎藥物治療使呼吸道變 得乾淨，呼吸順暢，氣喘自然可控制良好。 SMART: Symbicort Maintenance And Reliever Therapry

Q: 氣喘用藥分為幾種？ 常見問題 與 衛教重點 控制藥物（治本藥物） 減輕呼吸道發炎與腫脹並預防氣喘發作 緩解藥物（治標藥物） 使用後可迅速讓呼吸道平滑肌舒張， 以消除氣喘的症狀 SMART: Symbicort Maintenance And Reliever Therapry

Q: 如何有效控制氣喘的過敏原？ 常見問題 與 衛教重點 控制塵螨，簡化居家佈置 減少動物皮屑，盡量不要飼養有毛的寵物 每天清除食物和飲料殘渣，避免蟑螂滋生 避免接觸花粉和黴菌，最好把室內濕度減至50%以下 減少菸害、油煙及空氣污染 SMART: Symbicort Maintenance And Reliever Therapry

常見問題 與 衛教重點 ~ 類固醇恐懼症 ~ 經常有病人或家屬，聽到類固醇(俗稱美國仙丹)， 就好像遇到蛇蠍，避之唯恐不及，以至於哮喘控制 不良。事實上如能按原則使用，注意減量步驟及規 則的追蹤複診，類固醇是相當安全且可靠的抗哮喘 藥物。何況目前吸入型類固醇種類多，效果如同口 服者，依照一般建議劑量的使用，副作用甚少，不 必多慮。 SMART: Symbicort Maintenance And Reliever Therapry

Q:吸入性類固醇和口服類固醇有何不同？ 常見問題 與 衛教重點 口服劑型會直接被腸胃道吸收至血液中，其藥效會作 用於全身各系統，造成全身性副作用比較大。例如： 下視丘-腦下垂體-腎上腺的抑制作用、成長的抑制 、 體重增加、高血壓、胃潰瘍、水牛肩或月亮臉等。 吸入性類固醇則直接作用於肺部呼吸道，沒有經過消 化道吸收和血液循環，所以副作用幾乎沒有。除此 之外，吸入性類固醇劑量遠比口服劑型低很多，吸 入性類固醇劑量 100μg 約相當於一顆口服類固醇 的 1/50 。 SMART: Symbicort Maintenance And Reliever Therapry

Q:使用吸入性類固醇之後，發現口腔內有白斑，聲音沙 啞的現象，偶有喉嚨不適或疼痛的情形應該要怎麼 辦？ 常見問題 與 衛教重點 Q:使用吸入性類固醇之後，發現口腔內有白斑，聲音沙 啞的現象，偶有喉嚨不適或疼痛的情形應該要怎麼 辦？ 吸入性類固醇是局部作用的藥物，副作用少，經口腔、 喉嚨而達到下呼吸道，藥物在吸入過程中會有部分 沉積在喉嚨 。 可採取在吸藥後多漱口，然後將水吐掉或將定量噴霧 吸入劑加延伸管的方式避免其副作用的發生。 SMART: Symbicort Maintenance And Reliever Therapry

Symbicort Clinical Story: Turbuhaler 37

How to use Turbuhaler® 不要忘了 漱口 1.旋轉並移 去瓶蓋 2. 一手拿直 瓶身,另一手 推底盤,先向 右再向左轉 到底,聽到“ 卡嚓”一聲, 即填藥完成 3. 先請吐氣, 含住吸嘴後深 深快速地吸飽 一口氣,閉氣5 秒後,輕輕且慢 慢的吐氣,即完 成一次吸入動 作 勿對著藥瓶 吐氣 4. 將瓶蓋旋 轉歸位 不要忘了 漱口 Slide 4 • Turbuhaler® is easy for patients to use • Use of Turbuhaler® is easy for nurses and doctors to teach 1 - Remove the protective cover. A rattling sound may be heard when you unscrew the cover 2 - Holding the inhaler in an upright position, turn the grip on the bottom of the inhaler as far as it will go and then back again to the starting point. This results in an audible click. 3 - After breathing out (but not through the Turbuhaler®), place the mouthpiece between the teeth and close the lips around it to form a tight seal - Inhale forcefully and deeply 4 - Remove Turbuhaler® from the mouth before breathing out and replace the protective cover • If more than one inhalation has been prescribed, repeat these steps • Once finished, rinse the mouth with water (do not swallow the water)‏ 38

Turbuhaler® – checking dose Patients can easily check that they are using Turbuhaler correctly by inhaling through a piece of dark cloth. If the device is used correctly, drug will be deposited on the fabric. Note that the amount of drug depicted on this figure is not that large as in reality. 39

謝 謝 聆 聽 SMART: Symbicort Maintenance And Reliever Therapry