半胱氨酰白三烯受體拮抗劑在guidelines中的地位

1、,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,LTRA在Guidelines中的地位,,王永清,常州市第一人民醫(yī)院,MK說明書外應(yīng)用,1 commonly associated with asthma: exercise induced asthma, rhinitis, chronic obstructive pulmonary disease, interstitial lung disease, chroni

2、c urticaria, atopic dermatitis, allergic fungal disease, nasal polyposis, and paranasal sinus diseasenot connected to asthma: migraine, respiratory syncytial virus postbronchiolitis, systemic mastocytosis, cystic

3、fibrosis, pancreatitis, vulvovaginal candidiasis, cancer, atherosclerosis, eosinophils cystitis, otitis media, capsular contracture, and eosinophilic gastrointestinal disorders,--Riccioni G, Curr Med Chem. 2019,,,,,,,,,,

4、,,,,,,,,,,,,,,,,,,,目錄contents,,01,哮喘,,02,哮喘合并AR,,03,病毒誘發(fā)哮喘或喘息,,04,運(yùn)動(dòng)誘發(fā)哮喘,,05,阿司匹林哮喘,,,,,,,,,,,,,,,,,,,,,,,,,,,,01,哮喘,PRACTALL2019 日本兒童哮喘指南2019 中國(guó)兒童哮喘指南2019 ICON2019 GINA2019 BTS,,,,,01,全球成人及兒童輕度哮喘的發(fā)病率約為40%~70%在美國(guó)一

5、項(xiàng)含826未經(jīng)治療的哮喘兒童研究發(fā)現(xiàn)，5歲以下的兒童更易患輕度哮喘 (間歇性41%，持續(xù)性10%)美國(guó)指南允許5歲以上兒童輕度哮喘，可以MK、色酮或茶堿替用ICS，或MK、LABA、茶堿聯(lián)用ICS英國(guó)指南內(nèi)容與美國(guó)者類似,British Thoracic Society and Scottish Intercollegiate Guidelines Network. 2019 British Guideline on the Ma

6、nagement of Asthma. sign.ac.uk/ guidelines/fulltext/63/index.html,兒童輕度間歇和輕度持續(xù)性哮喘,LTRAs對(duì)各型哮喘療效,,,,01,,01,,,,,01,PRACTALL----LTRA為輕度哮喘一線治療,PRACTALL-P18,,,,,,,,01,PRACTALL----大于2歲兒童,PRACTALL-P15,,,,常規(guī)控制劑治療的主要目標(biāo)是減少氣道炎癥,LTRA

7、持續(xù)性哮喘可選的一線治療有證據(jù)顯示口服孟魯司特是兒童輕度哮喘的首選控制劑，它可提供氣道保護(hù)的作用，在過敏性哮喘的學(xué)齡前兒童中通過檢測(cè)一氧化氮證實(shí)LTRA可減少氣道炎癥較小的年齡（<10歲）和高水平的尿白三烯支持使用LTRA治療患者不能或不愿意使用ICS因?yàn)樽饔脵C(jī)制不同，聯(lián)合ICS治療可互補(bǔ)治療2-5歲患兒的病毒誘發(fā)喘息可以減少急性發(fā)作頻率對(duì)于6個(gè)月患兒也顯示有益處,,,,,01,2019 日本兒童哮喘指南,P346,

8、可抑制支氣管收縮和氣道炎癥，在長(zhǎng)程控制中有效大多數(shù)研究顯示，LTRAs應(yīng)用1-2周內(nèi)即改善肺功能、降低發(fā)作頻率輕持型哮喘，LTRAs與ICSs同樣有效作為ICSs的附加治療，LTRAs證實(shí)同樣有效,,,,,01,2019 日本兒童哮喘指南----<2歲兒童,,,,,,,,,01,2019 日本兒童哮喘指南----2-5歲兒童,,,,,,,,,01,2019 日本兒童哮喘指南----6-15歲兒童,,2019 中國(guó)兒童支

9、氣管哮喘診斷與防治指南:LTRA,,,,,01,,,,,01,2019 中國(guó)兒童支氣管哮喘診斷與防治指南----<6歲兒童,,,,,,01,2019 中國(guó)兒童支氣管哮喘診斷與防治指南----≧6歲兒童,,,,,01,LTRA可以改善各年齡段患者的臨床癥狀、肺功能水平以及減少急性發(fā)作次數(shù)初級(jí)治療方案中，可作為低劑量ICS后的第二治療選擇，或?yàn)橐痪€治療的備選藥物升級(jí)治療中，也可作為聯(lián)合用藥PRACTALL中建議，LTRA可

10、能特別適用于合并鼻炎的患者,International Consensus On (ICON) Pediatric Asthma 2019,2019ICON 對(duì)兒童哮喘應(yīng)用LTRA的評(píng)價(jià),,,,,01,2019 ICON,Figure 4 The stepwise approach to asthma treatment in childhood aims at disease control.,GINA 2016, Box 6-5,

11、Infrequentviral wheezing and no or few interval symptoms,Symptom pattern consistent with asthma and asthma symptoms not well-controlled, or ≥3 exacerbations per year Symptom pattern not consistent with asthma but wh

12、eezing episodes occur frequently, e.g. every 6–8 weeks. Give diagnostic trial for 3 months.,Asthma diagnosis, and not well-controlled on low dose ICS,Not well-controlled on double ICS,First check diagnosis, inhaler ski

13、lls, adherence, exposures,CONSIDER THIS STEP FOR CHILDREN WITH:,RELIEVER,Other controller options,PREFERRED CONTROLLER CHOICE,As-needed short-acting beta2-agonist (all children),Leukotriene receptor antagonist (LTRA

14、)Intermittent ICS,Low dose ICS + LTRA,Add LTRA Inc. ICSfrequencyAdd intermitt ICS,Daily low dose ICS,Double ‘low dose’ ICS,Continue controller & refer for specialist assessment,STEP 1,STEP 2,STEP 3,STEP 4,,,,,

15、01,2019 GINA---- ≤5歲兒童,,,,,01,2019 GINA,GINA 2016, page43,,,,,01,2019 BTS英國(guó)哮喘管理指南,,,,,01,2019 BTS英國(guó)哮喘管理指南,2019 BTS-P63,Step 2,,,,,01,2019 BTS英國(guó)哮喘管理指南,2019 BTS-P64,Step 3,,,,,01,2019 BTS英國(guó)哮喘管理指南,2019 BTS-P66,Step 4,,,,,01

16、,2019 BTS英國(guó)哮喘管理指南-Summary of stepwise management in children aged 5-12 years,2019 BTS-P73,,,,,01,2019 BTS英國(guó)哮喘管理指南- Summary of stepwise management in children less than 5 years,2019 BTS-P74,,,,,01,南非兒童哮喘工作組指南,哮喘輕度急性發(fā)作后，早期

17、口服孟魯司特可以有效緩解哮喘癥狀，并降低后續(xù)醫(yī)療需求。,British Thoracic Society and Scottish Intercollegiate Guidelines Network (SIGN). British guideline on the management of asthma. A national clinical guideline. (SIGN publication no. 101). sign.

18、ac.uk/guidelines/fulltext/101/index.html (accessed 10 Sep 2019).,不可以將孟魯司特作為急救藥物。,2019 BTS英國(guó)哮喘管理指南,,,,,01,,2019 BTS英國(guó)哮喘管理指南,,,,,01,哮喘輕度急性發(fā)作，≥2歲者,,,,,01,哮喘：何時(shí)更適合用LTRAs？,Fitzgerald DA, Treat Respir Med, 2019;5:407-411,,,,,,

19、,,,,,,,,,,,,,,,,,,,,,,02,哮喘+AR,PRACTALL2019 AIRA2019 中國(guó)兒童哮喘指南2019 GINA,,,,,02,PRACTALL----伴隨鼻炎的哮喘患者,PRACTALL-P15,,,LTRA may be particularly useful if the patient has concomitant rhinitis.LTRA對(duì)伴隨鼻炎的患者尤其有效,,,,,02,2019-

20、ARIA,45.白三烯受體拮抗劑能否用于AR合并哮喘的患者？推薦,AIRA-P474,,,,,02,2019 中國(guó)兒童支氣管哮喘診斷與防治指南----白三烯調(diào)節(jié)劑,目前應(yīng)用于兒童臨床的主要為白三烯受體拮抗劑（LTRA）孟魯司特，可單獨(dú)應(yīng)用于輕度持續(xù)性哮喘的治療，尤其適用于無法應(yīng)用或不愿使用ICS，或伴變應(yīng)性鼻炎的患兒。,P177,,,,,02,2019 GINA,,2019 GINA-P45,,,,,,,,,,,,,,,,,,,,,,

21、,,,,,,03,病毒誘發(fā)哮喘或喘息,PRACTALL2019 中國(guó)兒童哮喘指南2019 GINA,,,,,03,PRACTALL----LTRA治療病毒喘,PRACTALL-P18,,,每日使用LTRA作為控制劑治療病毒喘（長(zhǎng)期或短期治療）,,,,,03,2019 中國(guó)兒童支氣管哮喘診斷與防治指南,LTRA對(duì)<6歲兒童持續(xù)性喘息、反復(fù)病毒誘發(fā)喘息及間歇性喘息部分有效，并可降低氣道高反應(yīng)性有證據(jù)表明，在呼吸道感染早期服用LT

22、RA，可以減少學(xué)齡前間歇性哮喘患兒的病毒誘發(fā)性喘息發(fā)作，并可能降低后續(xù)醫(yī)療需求,P177,,,,,03,2019 GINA---- ≤5歲兒童,Step 2 (children ≤5 years) – initial controller+ as-needed SABA,IndicationChild with symptom pattern consistent with asthma, and symptoms not well

23、-controlled, or ≥3 exacerbations per yearMay also be used as a diagnostic trial for children with frequent wheezing episodesPreferred option: regular daily low dose ICS + as-needed inhaled SABAGive for ≥3 months to es

24、tablish effectiveness, and review responseOther options depend on symptom pattern(Persistent asthma) – regular leukotriene receptor antagonist (LTRA) leads to modest reduction in symptoms and need for OCS compared with

25、 placebo (Intermittent viral-induced wheeze) – regular LTRA improves some outcomes but does not reduce risk of exacerbations(Frequent viral-induced wheeze with interval symptoms) – consider episodic or as-needed ICS, b

26、ut give a trial of regular ICS first,2019GINA-P107,,,,,,,,,,,,,,,,,,,,,,,,,,,,04,運(yùn)動(dòng)誘發(fā)哮喘,PRACTALL2019 日本兒童哮喘指南2019 ICON2019 GINA2019 BTS,,,,,04,PRACTALL,PRACTALL-P18,,,,近來有研究顯示LTRA可作為ICS的替代治療運(yùn)動(dòng)誘發(fā)哮喘，因LTRA對(duì)運(yùn)動(dòng)誘發(fā)引起的FEV1下降

27、有快速、持續(xù)、長(zhǎng)期的作用常規(guī)使用不會(huì)產(chǎn)生耐藥作用影響保護(hù)效應(yīng),,,,,04,2019 日本兒童哮喘指南----EIA的治療,EIA: exercise-induced asthma,P352,,,,,04,2019 ICON,ICON-P987,,孟魯司特治療運(yùn)動(dòng)誘發(fā)哮喘有獨(dú)特的療效，優(yōu)于其他治療,,,,,04,2019 GINA---- Exercise-induced bronchoconstriction (EIB),2019

28、 GINA-P65,,,,,,,,,,,04,2019 BTS英國(guó)哮喘管理指南,2019 BTS-P76,,,,,,,,,,,,,,,,,,,,,,,,,,,,,05,阿司匹林哮喘,2019 GINA2019 BTS,,,,,05,2019 GINA---- Aspirin-exacerbated respiratory disease,2019 GINA-P68,,,,,,,05,2019 BTS英國(guó)哮喘管理指南,2019 BTS-

29、P77,,,,,癥狀為基礎(chǔ)的定位 -合并AR -1-2級(jí)/0-1級(jí)年齡為基礎(chǔ)的定位 -年幼兒基因藥理學(xué)定位尿LTE4/FeNO定位,也是小結(jié)：LTRA治療兒童哮喘定位,PC20: provocation concentration. 使FEV1下降20%時(shí)累計(jì)吸入激發(fā)物的濃度,哮喘Step2治療：ICS vs MK,Pijnenburg MW, Paediatr Re

30、spir Rev, 2019;16:101-107,,,,,,12-80歲患者,也算小結(jié)：來自真實(shí)世界的哮喘研究,Price D, N Engl J Med, 2019;364:1695-707,,,,,05,,12-80歲患者,哮喘：來自真實(shí)世界的研究,Price D, N Engl J Med, 2019;364:1695-707,醫(yī)療補(bǔ)助項(xiàng)目（n=7804）,健康計(jì)劃（n=11334）,也算小結(jié)：PEAL Network

31、 哮喘患兒LTRA/ICS用藥12個(gè)月亞組分析,Wu AC, et al. Use of Leukotriene Receptor Antagonists Are Associated with a Similar Risk of Asthma Exacerbations as Inhaled Corticosteroids. Allergy Clin Immunol Pract. 2019 ;2(5):607-13.,,,p&

32、lt;0.001,,p<0.001,,PEAL Network (population-based Effectiveness in Asthma and Lung Disease)2019.1.1-2019.12.31資料，4-17歲兒童被納入。結(jié)論：真實(shí)世界中預(yù)防哮喘急發(fā)，LTRA和ICS同樣有效；合并AR初始用LTRA者因哮喘急發(fā)去ED者更少,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,THANK Y