医学交流课件：Asthma prevention and management strategy in Japan

1、Asthma prevention and management strategy in Japan Asthma death in Japan Japanese guidelines for adult asthma Asthma dilemma in Japan (Asthma-COPD overlap syndrome) Asthma prevention and management strategy in Japan Asthma deaths in Japan Japanese guidelines for adult asthma Asthma dilemma in Japan

2、Asthma as a variable disease Annual changes in asthma deaths Compiled under supervision of the Special Committee on Asthma Guidelines, General Incorporated Association of Japanese Society of Allergology; Asthma Prevention and Management Guideline 2015 2,000 8,000 16,000 18,000 4,000 Number of asthma

3、 deaths 0 6,000 12,000 14,000 10,000 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 1,550 deaths in 2014 Asthma deaths by age group in 2013 Number of asthma deaths (Deaths) (age groups) FemaleMale 500 250 50 0 350 150 450 300 400 200 100 0-4 5-9 15-19 30-34 20-24 25-29 35-39 40-44

4、45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90-94 95-99 100 10-14 Compiled under supervision of the Special Committee on Asthma Guidelines, General Incorporated Association of Japanese Society of Allergology; Asthma Prevention and Management Guideline 2015 Annual changes in asthma mortalit

5、y by age 1 100 10 0.1 (per 0.1 million population) 0 4 5 9 10 14 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 75 79 80 84 85 89 90 94 95 99 100(age) 200320082013 Compiled under supervision of the Special Committee on Asthma Guidelines, General Incorporated Association of J

6、apanese Society of Allergology; Asthma Prevention and Management Guideline 2015 Global changes in asthma mortality (population aged 5 to 34 years old) 19606570758085909520000510 (year) 4.50 0.00 4.00 3.50 3.00 2.50 2.00 1.50 1.00 0.50 Mortality from asthma (per 0.1 million population) Japan Hong Kon

7、g The U.S. Canada Sweden The U.K. France New Zealand Australia Compiled under the supervision of Special Committee on Asthma Guidelines, General Incorporated Association of Japanese Society of Allergology; Asthma Prevention and Management Guideline 2015 1) Copyright 2013 IMS Japan co Source: IMS JPM

8、 (MAT 2012 Dec) All rights reserved. 2) Ministry of Health, Labour and Welfare, Vital Statistics 2012 Ken Ohta: Mebio. 27: 27-33, 2010 3) MHLW Vital Statistics Japanese Guidelines for Asthma (million yen) （ （year） ） 1,000 2,000 3,000 8,000 0 4,000 6,000 7,000 5,000 Sales of inhaled corticosteroids N

9、umber of asthma deaths Inhaled corticosteroids + long-acting 2-agonist combinations1) Inhaled corticosteroids1) Number of asthma deaths2, 3) JGL 12 Asthma deaths and sales of inhaled corticosteroids JGL 93 JGL 95 JGL 98 JPGL 00 JPGL 02 JGL 03 JPGL 05 JGL 06 JPGL 08 JGL 09 JPGL 12 10,000 20,000 30,00

10、0 120,000 0 50,000 40,000 60,000 80,000 70,000 90,000 100,000 110,000 14 13 11 85 93 95 97 01 03 05 09 87 89 91 99 07 1,550 Asthma death in Japan Japanese guidelines for adult asthma Asthma dilemma in Japan (Asthma-COPD overlap syndrome) Asthma prevention and management strategy in Japan Asthma deat

11、hs in Japan Japanese guidelines for adult asthma Asthma dilemma in Japan Asthma as a variable disease Well-controlled (meets all criteria) Partly controlled (meets 1 or 2 criteria) Uncontrolled Asthma symptoms (in the daytime or night-time) NoneOnce or more a week Meets 3 or more of the partly contr

12、olled criteria Use of relieverNoneOnce or more a week Limitation of activities, including exercise Nonelimited Lung function (FEV1 and PEF) 80% of predicted or personal best value 80% of predicted or personal best value Diurnal (weekly) variation in PEF 20%*20% ExacerbationNoneOnce or more a year On

13、ce or more a month * Normal limit is 8% when measured twice a day. One or more exacerbations a month is assessed as uncontrolled, even if other criteria are not met. Assessment of asthma control Compiled under supervision of the Special Committee on Asthma Guidelines, General Incorporated Associatio

14、n of Japanese Society of Allergology; Asthma Prevention and Management Guideline 2015 Global Initiative for Asthma GINA assessment of asthma control GINA 2014, Box 2-2A Treatment step 1Treatment step 2Treatment step 3Treatment step 4 Symptoms （ （Mild intermittent） ） Less than once a week Mild and br

15、ief Occur at night less than twice a month （ （Mild persistent） ） Once or more a week, not every day Disturb everyday life or sleep once or more a month Occur at night twice or more a month （ （Moderate persistent） ） Every day Require short-acting inhaled 2 agonist almost every day Disturb everyday li

16、fe or sleep once or more a week Occur at night once or more a week （ （Severe persistent） ） Frequently exacerbated even under treatment Every day Everyday life limitation Frequently occur at night Symptoms and treatment steps for untreated patients Compiled under supervision of the Special Committee

17、on Asthma Guidelines, General Incorporated Association of Japanese Society of Allergology; Asthma Prevention and Management Guideline 2015 AgentProduct NameDevicePicture Dry powder Fluticasone propionate Flutide RotadiskDiskhaler Fluticasone propionate Flutide DiskusDiskus BudesonidePulmicortTurbuha

18、ler Mometasone furoate AsmanexTwisthaler pMDI Beclometasone propionate Qvar pMDI CiclesonideAlvescopMDI Fluticasone propionate Flutide AirpMDI Suspen- sion BudesonidePulmicort RespulesNebulizer ICS available in Japan Pharmaceutical companies official sites, Package inserts. AgentProduct NameDevicePi

19、cture pMDI Fluticasone propionate /Formoterol Fumarate Hydrate FlutiformpMDI Fluticasone propionate /Salmeterol xinafoate Adoair AIR pMDI Dry powder Fluticasone propionate /Salmeterol xinafoate Adoair DiskusDiskus Budesonide/ Formoterol Fumarate Hydrate SymbicortTurbuhaler Fluticasone Furoate /Vilan

20、terol Trifenatate Relvar Ellipta ICS/LABA combinations available in Japan Pharmaceutical companies official sites, Package inserts. Treatment step 1Treatment step 2Treatment step 3Treatment step 4 Long-term management agents Basic treatment ICS (low dose) ICS (low to medium dose) ICS (medium to high

21、 dose) ICS (high dose) If above cannot be used, use one of the following agents. LTRA Sustained-release theophylline (unnecessary for rare symptoms) If above is ineffective, concomitantly use one of the following agents. LABA (a combination agent can be used) LTRA Sustained-release theophylline Conc

22、omitantly use one or more of the following agents. LABA (a combination agent can be used) LTRA Sustained-release theophylline LAMA# # Concomitantly use multiple agents from the following. LABA (a combination agent can be used) LTRA Sustained-release theophylline LAMA# # If uncontrolled, add either o

23、r both of the below. Anti-IgE antibody Oral corticosteroids Additional treatment Antiallergics other than LTRA Antiallergics other than LTRA Antiallergics other than LTRA Antiallergics other than LTRA Exacerbation treatmentInhaled SABAInhaled SABAInhaled SABAInhaled SABA Treatment steps for asthma L

24、TRA, leukotriene receptor antagonists; LABA, long-acting 2 agonist; SABA, short-acting 2 agonist; LAMA, long-acting muscarinic antagonists Antiallergics refer to mediator antireleasers, histamine H1 antagonists, thromboxane A2 inhibitors, and Th2 cytokine inhibitors. Anti-IgE antibody is indicated f

25、or patients who are positive for perennial inhaled allergen with serum total IgE value of 30-1,500 IU/mL. Oral corticosteroids are intermittent administration for a short period. Keep the minimum maintenance dose if a patient cannot be controlled by enhanced treatment with other agents and short int

26、ermittent administration. # Tiotropium respimat only Management against mild exacerbations is shown. Compiled under supervision of the Special Committee on Asthma Guidelines, General Incorporated Association of Japanese Society of Allergology; Asthma Prevention and Management Guideline 2015 Global I

27、nitiative for Asthma GINA 2015 changes to Steps 4 and 5 Global Initiative for Asthma GINA 2015, Box 3-5, Steps 4 and 5 *For children 6-11 years, theophylline is not recommended, and the preferred Step 3 is medium dose ICS *For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reli

28、ever therapy # Tiotropium by soft-mist inhaler is indicated as add-on treatment for patients with a history of exacerbations; it is not indicated in children 18 years. Other controller options RELIEVER STEP 1STEP 2 STEP 3 STEP 4 STEP 5 Low dose ICS Consider low dose ICS Leukotriene receptor antagoni

29、sts (LTRA) Low dose theophylline* Med/high dose ICS Low dose ICS+LTRA (or + theoph*) As-needed short-acting beta2-agonist (SABA) Low dose ICS/LABA* Med/high ICS/LABA Refer for add-on treatment e.g. anti-IgE PREFERRED CONTROLLER CHOICE Add tiotropium# High dose ICS + LTRA (or + theoph*) Add tiotropiu

30、m# Add low dose OCS As-needed SABA or low dose ICS/formoterol* Asthma death in Japan Japanese guidelines for adult asthma Asthma dilemma in Japan (Asthma-COPD overlap syndrome) Asthma prevention and management strategy in Japan Asthma deaths in Japan Japanese guidelines for adult asthma Asthma dilem

31、ma in Japan Asthma as a variable disease DaytimeNighttimeDuring physical activity Any 0 Percentage of patients 45% 29% 27% 62% 70 (%) 60 50 40 30 10 20 Asthmatic symptoms in the previous month: 62% Mitsuru Adachi, et al., Allergology 19 (10), 1562-1570 Survey period: November 18 to December 26, 2011

32、 Subjects: Total 400 patients consisting of those previously diagnosed with asthma and who experienced asthmatic symptoms in the previous year as well as adult patients (aged 16 years or older) who used drugs for the treatment of asthma in the previous year Method of survey: A random telephone inter

33、view survey with Computer Assisted Telephone Interview (CATI) using the largest panel for offline investigation in Japan 34% 19% 24% 25% 39% 24% 18% 60% 0%10%20%30%40%50%60%70% Sports and recreation General body motion Vocational and career choices Social activities Sleep Lifestyle Household chores

34、Any Social activities limited by asthma (adults) Daily activity limitations: 60% Mitsuru Adachi, et al., Allergology 19 (10), 1562-1570 I sometimes forget inhalation therapy. I have once interrupted/discontinued inhalation therapy when I felt well. I have once forgotten to bring the inhalant with me

35、 when I was supposed to inhale it. I have once interrupted/discontinued inhalation therapy because of the expense. Inhalation therapy is sometimes interrupted because of the delay in visiting clinic/hospital. I have once interrupted/discontinued inhalation therapy because I thought the drug was inef

36、fective. I have experienced none of the above. Patients with high adherence 22.7% (n=127) Patients with low adherence 77.3% (n=432) 01020304070 (%) 22.7% 5060 4.8% 10.2% 12.5% 14.0% 35.1% 60.6% (n=559) *Patients who indicated “have experienced none of the above” were assumed to be patients with high

37、 adherence in the analysis. Forget or interrupt/discontinue inhalation: 77.3% Have you ever forgotten or interrupted/discontinued the use of inhalants? (Multiple answers allowed) Question to Patients Nagase H et al., Allergol Immunol 2013; 20 (9), 1332-1347 Changed the frequency? (n=559) YesNo Incre

38、ased the frequency255 (45.6%)304 (54.4%) Decreased the frequency301 (53.8%)258 (46.2%) (n=301) 33.6% 19.9% 9.3% 4.7% 4.0% 3.3% Because I take medicine only when I have symptoms. Because I am worried about prescription charge. Because I am worried about adverse drug reactions. Because the frequency o

39、f inhalation per day seems to be too often. Because the number of inhalations per dose seems to be too many. Because I am satisfied with the oral treatment. 0510152040 (%)30352545 Take medicine only when having symptoms: 33.6% Have you ever increased or decreased the frequency of the inhalation ther

40、apy at your discretion? Question to Patients Why did you increase or decrease the frequency of the inhalation therapy at your discretion? (Multiple answers allowed) Question to Patients Nagase H et al., Allergol Immunol 2013; 20 (9), 1332-1347 lQuestionnaires Asthma Control Test (ACT) Asthma Control

41、 Questionnaire (ACQ), etc. lPulmonary function Spirometry, peak expiratory flow (PEF) Forced oscillation technique (FOT) lSputum eosinophil count lFractional exhaled nitric oxide (FeNO) lAirway hyperresponsiveness test Measures of asthma control lNO is found in high concentrations in the exhaled bre

42、ath of asthma patients. lNO is produced by respiratory epithelial cells, eosinophils, neutrophils, and macrophages. lActivity of inducible NO synthase (iNOS) is increased due to inflammatory cytokines, etc. in asthma patients. lFeNO is a noninvasive and measurable biomarker of eosinophilic airway in

43、flammation. Summary of FeNO CHEST MI, Inc. NIOX MINO FeNO as an indicator of adherence Beck-Ripp J, et al.; Eur Respir J 2002;19:1015-9. 25 Compliance with BUD % of prescribed 100 0 50 -50 5075100 Reduction in eNO % Flow of long-term asthma management Compiled under supervision of the Special Commit

44、tee on Asthma Guidelines, General Incorporated Association of Japanese Society of Allergology; Asthma Prevention and Management Guideline 2015 *If the disease is still poorly controlled despite the treatment at Step 3 or above, it is recommended that the patient be referred to a specialist. Treatmen

45、t of other diseases Additional guidance Smoking cessation, change/discontinuation of the drug which may aggravate asthma, and thorough management of complications Referral to a specialist (Treatment Step 4) Cannot attain favorable control with treatment If control has been achieved and maintained, s

46、tep down treatment after 3 months. Is the diagnosis of asthma correct? Does the patient show good adherence to the medication? Is the inhalation technique correct? Are aggravating factors and comorbidity properly controlled? Improvement with a step-up of treatment Yes Yes Yes Yes Yes No No No No Imp

47、act of inhaler technique guidance on PEF Kubo Y and Tohda Y. Asthma 18; 64-68, 2005 (%) (month)12345678910 1112 13 14 15 16 17 18-10 First inhalation guidance 20 5 15 10 0 -5 Guidance should be provided repeatedly to each patient. Subjects: Outpatients with asthma Method: Investigated the implementa

48、tion of inhalation guidance for retraining and improvement in peak flow rate Results: Improvements in peak flow rate were often observed one or two months after guidance even in patients who had used inhalants properly at the time of retraining. On the other hand, the peak flow rate decreased after

49、an average of approximately nine months in patients who had not been retrained. (The above graph shows a typical case of improvement in peak flow rate after retraining.) Improvement rate in PEF Additional guidance Second inhalation guidance Asthma death in Japan Japanese guidelines for adult asthma

50、Asthma dilemma in Japan (Asthma-COPD overlap syndrome) Asthma prevention and management strategy in Japan Asthma deaths in Japan Japanese guidelines for adult asthma Asthma dilemma in Japan Asthma as a variable disease Survey of Patients (The ACQUIRE study) Asthma Control, QUality of LIfe and Emotio

51、nal Feelings in a REal Life Setting - A Postal Mail Survey of Adult Asthma Patients in Japan Mitsuru Adachi et al., Allergology ICS/LABA: Inhaled corticosteroid/long-acting 2-agonist; SABA: Short-acting 2-agonist Partly 73.6% (919) Poor 17.3% (216) Well 9.1% (113) Percentage of patients who experien

52、ced symptoms in their Asthma Diary over one week n=1,248 0 20 40 60 80 100 (%) 87.5 67.0 64.6 44.1 47.0 62.3 46.5 38.5 20.8 33.3 42.9 19.6 3.1 Subjects: 1,248 patients aged 20 years or older with asthma treated in Japan who: 1) were previously given a diagnosis of bronchial asthma by a physician, 2)

53、 are on continuous outpatient treatment, and 3) have been prescribed at least one long-term asthma control drug* for four weeks or more. Method: Surveyed record in asthma diary for one week by postal mailed questionnaire. Districts where the survey was conducted: Nationwide Survey period: May 2014 C

54、OI: AstraZeneca K.K. * If a patient was unable to conduct daily work, school activities, exercise or do house keeping work because of asthma symptoms Mitsuru Adachi et al., Allergology inhaled corticosteroid: ICS/LABA; inhaled corticosteroid/long-acting beta-2 agonist Level of symptoms Allergen Vira

55、l infection common cold Weather Symptoms Worsening/exacerbation Mites Symptoms Immediate strengthening of anti-inflammatory treatment at the onset of an attack (symptoms) Importance of prompt intensification of anti-inflammatory treatment (image) Modified report from: Akiyama K., Pharma Medica. 30: 97-105, 2012 LowElapsed time Level of Inflammation High Airway inflammation Exacerbation For a few days * Coughing, Wheezing, shortness of breath, etc The level of inflammation where an attack (symptoms)* occurs An anti-inflammatory treatment cannot be strengthene