... 2... 5... 8... 9 Kartagener ( )...10... 11 C 7...12...18...20 IgE ( )...22 ( H P V )...23...24 Vol.7 No.4 December, 2006 : A 1. 1 6 1 20 2007 2. 1 7 3. 1 13 14 27 2 3 4. 1 21 14 00 16 00 5. 1 19 28 2 4 6. 2 10 11 2007 100 6 5 508 19081661 T e l (02) 2311-4670 1. 62nd Annual Meeting of the American Academy of Allergy Asthma Fa x (02) 2311-4732 http://www.air.org.tw and Immunology. Hawii Convention Centre, Honolulu, USA, 23- Feb-07-28-Feb-07 19391392 2. 63rd Annual Meeting of American Academy of Allergy, Asthma & T e l (02) 2311-4670 Fax (02) 2311-4732 Immunolgy. Honolulu, USA, 23-Feb-07 http://www.asthma.org.tw 3. New Advances in Inflammatory Bowel Disease Hilton La Jolla Torrey ( ---- 1000-1500 ) Pines, San Diego, United States, 14-Apr-07 B Vol.7 No.4 December 2006 1
台灣兒童過敏氣喘及免疫學會學會通訊 以氣喘控制為導向之氣喘階梯式治療 徐世達 主任 台北馬偕紀念醫院 小兒過敏免疫科 氣喘之階梯式治療原則 慢性的氣喘病人需要建立長期的藥物治療計劃 這套氣喘病的藥物治療計畫需要包括二部分 1. 一套階梯式的藥物治療方案 2. 一套依據病人的氣喘嚴重度和病人對藥物治療後氣 喘病情控制程度而制定的分階治療計劃 (圖一) 評估氣喘控制程度 氣喘治療的目的是希望大多數的病人能達到並維 持臨床症狀的控制 藉由評估目前氣喘控制程度選擇 最適合的治療藥物 再藉由定期評估與監視來升階或 降階治療方式 希望能以最低階的治療 最低劑量的 藥物 來達到最大的控制效果與最大的安全性 氣喘良好控制的定義是:沒有白天症狀(每星期二次 或以下) 每日活動的沒有受限(包括運動時) 沒有夜 間的症狀或因氣喘而睡眠中段 沒有需要急救藥物的 使用(每星期二次或以下) 正常或幾乎正常的肺功能 及沒有氣喘的急性發作 當以上任一項不符合時 即屬於部分控制 當有 三項以上的結果不符合 或在一星期內有一次以上氣 喘急性發作即屬於控制不佳 (表一) 階梯式的藥物治療方式 - 兩種階梯式治療 方 式 (圖 二 ) 氣喘的階梯式治療方式必須根據氣喘的嚴重度和 病人對藥物治療後氣喘病情控制程度來決定治療階 級 目標是以最少的藥物達到最大的療效 因此在制 2 Vol.7 No.4 December 2006 圖一 氣 喘 控 制 為 導 向 之 治 療 步 驟
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~ 2. (neuropeptides) G- (G-protein-coupled receptors) (local) (regional) (systemic) (IL-10) Y (neuropeptide Y) (neuroendocrine) (a) - - (hypothalamic-pituitary-adrenal axis, HPA axis) IL-1, TNF (glucocorticoid) (b) - - (hypothalamic-pituitary-gonadal axis, HPG axis) HPA-axis-mediated regulation of immunity 1950 D r. K e nd a l l, D r. Reichstein Dr. Hench T B Regional parasympathetic control of immunity (dendritic cell) -12(IL-12) T Th1 Th2 HPA HPA (efferent, afferent fiber) IL-1 ( CMV, Salmonella, ( i m m u n e Regional SNS control of immunity mediators) 3. ( ) 4. ( ) (NK ) pro-inflammatory cytokine( TNF, IL-1, IL-6 IL-12) Y - Streptococcus) (inflammatory reflex) nicotinic muscarinic cholinergic 6 Vol.7 No.4 December 2006
Local peripheral nervous system control ( ) ( CRH, ( HPA substance P CGRP) ) IL-1 IL-6 TNF CRH Substance P neurokinin-1 neurokinin-2 HPA (IL-1, IL-6, TNF) (mast cells) Vol.7 No.4 December 2006 7
( ) 35-50% 35-50% HEPA 8 Vol.7 No.4 December 2006
50% ( ) T IgE ( T IgE) 35-1.34 prednisolone sodium phosphate prednisolone 1 (prednisolone tablets) prednisolone 2003 Vol.7 No.4 December 2006 9
43 ( 57.27 31.44 L/ 6-12 min 54.29 30.04 L/min 2.99 22 ( 30.76L/min, P=0.752) ) 21 ( PIS ) (P=0.091 0.827) FEV1, FEV1/FVC FEF25-75 (P=0.162, 0.48 0.081) pulmonary index score(pis) PIS Kartagener ( ) S k u l l Water's View Air-fluid 2004 E ( 573IU/ml) X Serum 1 -antitrypsin X Cefuroxime Erythromycin Kartagener ( 12800 cmm) 10 Vol.7 No.4 December 2006
X 1 -antitrypsin X Kartagener 3.7% 8.4% Vol.7 No.4 December 2006 11
budesonide GIN A (Global Initiative for Ashtma) loratadine cromolyn cetirizine leukotriene receptor antagonists theophylline( 5-12mcg/mL jitteriness ) albuterol ; C7 0.03% 5 4 (C1 C2 C3) (C5-C9) (DIC) C7 W-135 12 Vol.7 No.4 December 2006
Rifampin B IgG IgA IgM IgE, CH50 C3 C4 C5 C6 C7 C8, PMN bacteria killing PMN Chemotaxis CD3 CD4 CD8 CD19 CD57 Active T cells Multitest CMI G 33% B T (Multitest-C.M.I.) CH50 <6.3 U/ ml( 32.6~39.8) C3 C4 C5 C6 C8 C7 (<5.8mg/dL)( 55-85 mg/l) CH50 (CH50 <6.3 U/mL C7 <5.8mg/dL) C5~C8 CH50 0; C9 CH50 25.9 U/mL C7 27.8 mg/dl CH50 31.2 U/mL C7 22.7 mg/dl 150 5 10 Y W-135 X 7732 3% (CH50) (classical pathway) Classical Pathway 11 C7 CH50 C7 C7 C7 C7 C7 (autosomal co-dominant) C 7 C7 1975 Boyer homozygous (heterozygous) C7 C7 (membrane-attack complex) C7 C7 C7 B A C Y W-135 C7 80% 3 1. Haessig A, Borel JF, Ammann P, Thoeni M, Buetler 17 R. [Essential Hypocomplementemia.]. Pathol Microbiol (Basel) 27 542-7, 1964 (relapse) 2. Boyer JT, Gall EP, Norman ME, Nilsson UR, 10 (recurrent) Zimmerman TS. Hereditary deficiency of the seventh Vol.7 No.4 December 2006 13
台灣兒童過敏氣喘及免疫學會學會通訊 component of complement. J Clin Invest 56 905- common serogroups. Lancet 2 585-8, 1989 8. Fijen CA, Kuijper EJ, te Bulte MT, Daha MR, Dankert 13, 1975 3. Walport MJ. Complement. First of two parts. N Engl J. Assessment of complement deficiency in patients with meningococcal disease in The Netherlands. Clin Infect J Med 344 1058-66, 2001 4. Wurzner R, Orren A, Lachmann PJ. Inherited deficiencies of the terminal components of human complement. Dis 28 98-105, 1999 9. Folds JD, Schmitz JL. 24. Clinical and laboratory assessment of immunity. J Allergy Clin Immunol 111 Immunodefic Rev 3 123-47, 1992 5. Figueroa JE, Densen P. Infectious diseases associated with complement deficiencies. Clin Microbiol Rev 4 (2 Suppl) S702-11, 2003 10. Availability of meningococcal vaccine in single-dose vials for travelers and high-risk persons. MMWR Morb 359-95, 1991 6. Densen P. Complement deficiencies and meningococcal disease. Clin Exp Immunol 86 Suppl 1 57-62, Mortal Wkly Rep 39 763, 1990 11. Potter PC, Frasch CE, van der Sande WJ, Cooper RC, Patel Y, Orren A. Prophylaxis against Neisseria 1991 7. Fijen CA, Kuijper EJ, Hannema AJ, Sjoholm AG, van meningitidis infections and antibody responses in pa- Putten JP. Complement deficiencies in patients over tients with deficiency of the sixth component of ten years old with meningococcal disease due to un- complement. J Infect Dis 161 932-7, 1990 14 Vol.7 No.4 December 2006
(multiple sclerosis, MS) (demyelination) (subendothelial basal lamina) T 20-40 BBB TNF- converting enzyme 10 55 ( TACE MMP ) TNF- M M P (neurotoxic) CD4+ T (myelin sheath) 15 15 (pro-inflammatory cytokines) (microglia) BBB (secondary leukocyte (ataxia) 1. recruitment) IL-12 IL-23 (Relapsing-remitting RRMS) T NO, oxygen radicals (demyelination) B myelin-basic pro- 2. (Primary progressive tein (anti-mbp antibodies) anti-aquaporin-4 PPMS) 3. water channel ( BBB (Secondary progressive SPMS) astrocyte ) myelin specific B (opsonization) MS (phagocytosis) NK (antibody-de- HHV6 pendent cell-mediated cytotoxicity) Chlamydia pneumoniae (matrix metalloproteinase, MMP) (experimental autoimmune encephalomyelitis, (molecular mimicry) EAE) ( ) T EAE T (integrin) VLA-4 T (blood-brain Gutcher IL-18 EAE barrier, BBB) IL-18 receptor (IL-18 ) (integrin receptor)vcam-1 T IL-18 T 18 Vol.7 No.4 December 2006
(Th17 T IL-17) IL-18 Th17 5. Anti-CD20 (Rituximab) pre-b RRMS FDA MS 6. Anti-BAFF( B lymphocyte stimulator(blys)) -inte r fe ro n BAFF B (Betaferon, Avonex, Rebif) glatiramer acetate natalizumab mitoxantrone anti-baff anti-cd20 1. ( -interferon) -interferon- 1b( Bet aser on (Fingolimod) Betaferon) -interferon-1a( Avonex, Rebif) 43-61% interferon- (apoptosis) MMP T B ( plasma cells) (astrocyte) BAFF MS BAFF 7. sphingosine-1-phosphate receptor modulator 226 MS T BBB anti-cd52, anti-il2 receptor 30% MS 2. Glatiramer acetate(copaxone) 1. Gutcher I, Urich E, Wolter K, Prinz M, Becher B. Interleukin 18-independent engagement of interleukin MBP 18 receptor-alpha is required for autoimmune MHC inflammation. Nat Immunol 7(9) 946-53, Epub 2006 MHC MBP specific T Aug 13. 2. Polman CH, O'Connor PW, Havrdova E, et al. A 3. Anti- 4 integrin(natalizumab) randomized, placebo-controlled trial of natalizumab BBB Polman for relapsing multiple sclerosis. N Engl J Med 354(9) 942 MS( RRMS) 899-910, 2006 3. Kappos L, Antel J, Comi G, et al. Oral fingolimod (disability) FDA (FTY720) for relapsing multiple sclerosis. N Engl J MS Med 355(11) 1124-40, 2006 4. Mitoxantrone(Novantrone) anthracenedione 4. Hauser SL, Oksenberg JR. The neurobiology of cytotoxic agent 2000 FDA mu ltiple sclerosis: genes, inflammation, and RRMS SPMS neurodegeneration. Neuron 52(1) 61-76, Review, 2006 Vol.7 No.4 December 2006 19
5-10% 4. 10 2006 allergenicity 52 1 1. 2. 3. 20 Vol.7 No.4 December 2006
IgE ( ) Omalizumab IgE (>800g of beclomethason per day) Omalizumab 12 I g E 12 (<=75kU/l) Omalizumab Omalizumab IgE 25 (latex) phase III 536 IgE 30 700IU/mL Omalizumab 50 150 300mg Omalizumab Omalizumab 3 4 12 300mg Omalizumab Om a l i z u m a b Milgrom phase II 317 Omalizumab Omalizumab (2.5g/Kg) Om a l i z u m a b I g G a nt i - Kg) Om a l i z u m a b (immune complex disease) 300mg phaseiii 1405 Omalizumab Omalizumab IgE Bousquet (>12y) IgE-mediated 6% Omalizumab 3% 22 Vol.7 No.4 December 2006
IgE phase II Reference TNX901(Tanox Biosystems, Houston, TX) 84 1. Omalizumab in asthma Clinical Reviews in Allergy and Immunology 29 3-16, 2005 2. Omalizumab other indications and unanswered questions Clinical Reviews in Allergy and Immunology 29: 17-30, 2005 Omalizumab 3. The importance of IgE antibody levels in anti-ige Omalizumab treatment Allergy 61 1216-1219, 2006 (HPV) / (virus-like particle) FDA 95 6 8 95 9 22 (HPV) (Department of Health and Human Services) Alex Azar H P V ( HPV HPV DNA HPV HPV / (ASCUS) (CIN)) 50% ( ) Vol.7 No.4 December 2006 23
RNA A B C D E F G 7 A B C 1999 10 A VP7(G ) VP4(P G1 G2 G3 G4 G9 G1 G9 42 1 2 RotaTeq 2( 6 12 )/ 4 / 6 3 Rotarix 2 / 4 2 50 5 RotaTeq Rotarix RotaTeq RotaRix G ( ) B FDA 1998 b RotaShield G1-G4 2 / 4 / 6 RotaTeq Rotarix 11 24 Vol.7 No.4 December 2006