炎癥反應(yīng)的雙通道PPT學(xué)習(xí)教案

1、會(huì)計(jì)學(xué)1炎癥反應(yīng)的雙通道炎癥反應(yīng)的雙通道Slide 2Adapted from Peters-Golden M, Sampson AP J Allergy Clin Immunol 2003;111(suppl 1):S37-S48.第1頁(yè)/共26頁(yè)Slide 3ICS=inhaled corticosteroids; OCS ICS=received oral corticosteroids with or without ICSAdapted from Louis R et al Am J Respir Crit Care Med 2000;161:9-16. 20,00010,0001,

2、000100101Eosinophil 103/gsputumControlgroup輕到中度哮喘ICSlow-dose(n=10)ICShigh-dose(n=15)OCS(n=10)OCS ICS(n=7)重度哮喘p0.01p0.001p0.001p0.01n=74第2頁(yè)/共26頁(yè)Slide 4白三烯白三烯其它炎性介質(zhì)其它炎性介質(zhì)This slide is an artistic rendition.Adapted from Holgate ST, Peters-Golden M J Allergy Clin Immunol 2003;111(1 suppl):S1-S4; Holgate

3、 ST et al J Allergy Clin Immunol 2003;111(1 suppl):S18-S36; Henderson WR Jr et al Am J Respir Crit Care Med 2002;165:108-116; Peters-Golden M, Sampson AP J Allergy Clin Immunol 2003;111(1 suppl):S37-S42; Varner AE, Lemanske RF Jr. In Asthma and Rhinitis. Oxford, UK: Blackwell Science, 2000:1172-1185

4、.無(wú)炎癥反應(yīng)無(wú)炎癥反應(yīng)炎癥反應(yīng)炎癥反應(yīng)哮喘哮喘第3頁(yè)/共26頁(yè)Slide 5NeutrophilMonocyteMacrophageBasophilPluripotent hemopoieticstem cellT CellsEosinophilB LymphocyteCCR3CD4+CD8+CD19M-CSF, GM-CSF, IL-3LTC4, LTD4, LTE4LN5Mast CellLTC4LTD4LTE4M-CSFGM-CSFIL-5IL-3GM-CSFLTC4LTD4LTE4CD14IL5RRepresents the CysLT1 receptorAdapted from Fi

5、gueroa DJ et al Am J Respir Crit Care Med 2001;163:226-233; Mellor et al Proc Natl Acad Sci USA 2001;98:7964-7969CysLT1RCD34+第4頁(yè)/共26頁(yè)Slide 6嗜酸細(xì)胞肺巨噬細(xì)胞Smooth- musclecell B淋巴細(xì)胞CysLT=cysteinyl leukotriene; PBMC=peripheral blood mononuclear cellsAdapted from Figueroa DJ et al Am J Respir Crit Care Med 20

6、01;163:226-233.單核細(xì)胞第5頁(yè)/共26頁(yè)Slide 7Adapted from Peters-Golden M, Sampson AP J Allergy Clin Immunol 2003;111(suppl 1):S37-S48.其它介質(zhì)受體其它介質(zhì)第6頁(yè)/共26頁(yè)Slide 8 Adapted from Hay DWP et al Trends Pharmacol Sci 1995;16:304-309.炎癥細(xì)胞 (肥大細(xì)胞,嗜酸性細(xì)胞)感覺(jué)神經(jīng)(C纖維)CysLTs水腫血管粘液轉(zhuǎn)運(yùn)減少嗜酸性細(xì)胞內(nèi)流陽(yáng)離子蛋白釋放，上皮細(xì)胞損傷收縮和增生氣道平滑肌粘液分泌增多氣道上皮炎癥反

7、應(yīng)的雙通道半胱氨酰白三烯在哮喘中的核心作用第7頁(yè)/共26頁(yè)Slide 9p = NS between groupsAdapted from OShaughnessy KM et al Am Rev Respir Dis 1993;147:1472-1476. 18.7201612840Urinary LTE4excretion(ng/mmolcreatinine)18.4PlaceboFluticasone propionate1000g雖然氟替卡松明顯改善了過(guò)敏原誘導(dǎo)的支氣管狹窄(p 0.02),但在降低尿LTE4濃度方面無(wú)顯著效果治療期14天,洗脫期21天后交叉，最后一天過(guò)敏原刺激N=10

8、第8頁(yè)/共26頁(yè)Slide 10*p0.05 vs. baseline Adapted from Dworski R et al Am J Respir Crit Care Med 1994;149:953-959. 0.30.20.10Urinary LTE4(ng/mgcreatinine)Post-allergen challengeBaselineControlPrednisone*口服強(qiáng)的松對(duì)尿中白三烯量的影響第9頁(yè)/共26頁(yè)Slide 11*p0.02 vs. normal individuals; *p0.05 vs. normal individuals Adapted fro

9、m Pavord ID et al Am J Respir Crit Care Med 1999;160:1905-1909.putumCysLT levels(ng/ml)Controls控制(n=10)6.4All patients with asthma所有哮喘患者(n=26)9.4*Patients with persistent asthma持續(xù)性哮喘(n=10)11.4*Patients with acute attacks急性發(fā)作(n=12)13*吸入糖皮質(zhì)激素對(duì)痰中白三烯水平的影響第10頁(yè)/共26頁(yè)Slide 12LABA = long-acting

10、beta2 agonistAdapted from Currie GP et al Am J Respir Crit Care Med (in press).0100200Change ineosinophils( 106/L)from run-inICS + LABA + MontelukastICS +LABAICSICS +Montelukastp0.05p0.05而白三烯受體拮抗劑孟魯司特在ICS基礎(chǔ)上可進(jìn)一步減少氣道炎癥炎癥反應(yīng)的雙通道長(zhǎng)效2受體激動(dòng)劑不具有抗炎作用第11頁(yè)/共26頁(yè)Slide 13*p0.05 compared with beclomethasoneAdapted

11、from LaViolette M et al Am J Respir Crit Care Med 1999;160:1862-1868. 0.120.100.080.060.040.020Eosinophilcounts(changefrom baseline 103/l)PlaceboBeclomethasoneMontelukast+ beclomethasoneMontelukast*1*Treatment group同時(shí)針對(duì)炎癥雙通道的治療可更好控制哮喘炎癥炎癥反應(yīng)的雙通道白三烯受體拮抗劑孟魯司特可進(jìn)一步減少氣道炎癥第12頁(yè)/共26頁(yè)Slide 14block steroid-sen

12、sitivemediatorsblocks the effects of CysLTs吸入激素孟魯司特The slide represents an artistic rendition.Adapted from Peters-Golden M, Sampson AP J Allergy Clin Immunol 2003;111(1 suppl):S37-S42; Bisgaard H Allergy 2001;56(suppl 66):7-11. 對(duì)類(lèi)固醇敏感的介質(zhì)對(duì)類(lèi)固醇敏感的介質(zhì)play a key role in asthmatic inflammation光胱氨酰白三烯光胱氨酰白三

13、烯play a key role in asthmatic inflammation類(lèi)固醇不能抑制有癥狀的哮喘病人氣道中的半胱氨酰白三烯的形成雙通道雙通道第13頁(yè)/共26頁(yè)Slide 15LTRAs = leukotriene receptor antagonistsAdapted from Peters-Golden M, Sampson AP J Allergy Clin Immunol 2003;111(suppl 1):S37-S48.炎癥反應(yīng)的雙通道白三烯受體拮抗劑的作用第14頁(yè)/共26頁(yè)Slide 16第15頁(yè)/共26頁(yè)17第16頁(yè)/共26頁(yè)18u避免使用阿司匹林和非類(lèi)固醇類(lèi)抗炎藥

14、（NSAIDs）u脫敏治療u白三烯受體拮抗劑及合成阻斷劑u鼻部疾病的治療第17頁(yè)/共26頁(yè)19celecoxib ,rofecoxib celecoxib ,rofecoxib 阿司匹林哮喘的治療與管理第18頁(yè)/共26頁(yè)Slide 20第19頁(yè)/共26頁(yè)Slide 21MP = 孟魯司特鈉 安慰劑 ; SP = 沙美特羅安慰劑10. Bjermer L, Bisgaard H, Bousquet J, et al. Montelukast or salmeterol combined with an inhaled steroid in adult asthma: design and rat

15、ionale of a randomized, double-blind comparative study (the IMPACT Investigation of Montelukast as a Partner Agent for Complementary Therapy-trial) Respir Med. 2000;94:612621. 11. Bjermer L, Bisgaard H, Bousquet J, et al. Montelukast and fluticasone compared with salmeterol and fluticasone in protec

16、ting against asthma exacerbation in adults: one year, double blind, randomised, comparative trial. BMJ. 2003;327:891895.IMPACT是一個(gè)為期52周、隨機(jī)雙盲、雙模擬、平行組、多中心研究。4周導(dǎo)入期（1期）+ 48周雙盲治療期（2期）共1490例患者。鈉主要研究終點(diǎn)為至少一次哮喘急性發(fā)作的患者百分比。第20頁(yè)/共26頁(yè)Slide 22與基線(xiàn)相比，與基線(xiàn)相比，痰嗜酸性粒細(xì)痰嗜酸性粒細(xì)胞評(píng)分胞評(píng)分(03分分) a 孟魯司特鈉孟魯司特鈉10 mg +氟替卡松氟替卡松 200 ug,

17、 b 沙美特羅沙美特羅 100 ug +氟替卡松氟替卡松 200 mg. 痰液分析在所有參加痰液分析在所有參加 IMPACT 研究的的芬蘭中心的病人中進(jìn)行研究的的芬蘭中心的病人中進(jìn)行.孟魯司特鈉+ 氟替卡松 (n=25)a沙美特羅+氟替卡松 (n=16)b-0.7-0.6-0.5-0.4-0.3-0.2-0.100.10.20.30.4降低降低40%P0.05 vs. 基線(xiàn))P=0.01111. Bjermer L, Bisgaard H, Bousquet J, et al. Montelukast and fluticasone compared with salmeterol and f

18、luticasone in protecting against asthma exacerbation in adults: one year, double blind, randomised, comparative trial. BMJ. 2003;327:891895.第22頁(yè)/共26頁(yè)Slide 24IMPACT 研究順爾寧(孟魯司特鈉)+氟替卡松-不良事件發(fā)生率顯著低于沙美特羅+氟替卡松74%P=0.0161%P=0.026.3%10.0%4.6%7.4%11. Bjermer L, Bisgaard H, Bousquet J, et al. Montelukast and fluticasone compared with salmeterol and fluticasone in protecting against