病因不明性肺纖維化診斷與治療新知 - tsim.org.tw

1 2013 24 446-452.. (idiopathic pulmonary fibrosis, IPF) .. IPF . (TGF- 1) . (telomere) (glutathione) .. 2011 IPF IPF .. (corticosteroid) (cyclosporine A) . (INF- 1B) (bosentan) (etanercept) . NAC (N-acetylcysteine) prednisolone azathioprine pirfenidone IPF . IPF . (Idiopathic pulmonary fibrosis). (Usual interstitial pneumonia). (Interstitial pneumonia). (cryptogenic fibrosing alveolitis CFA) IIP 7 . (idiopathic pulmonary IPF . fibrosis IPF) 1,2 . 2000 IPF (Consensus Statement) . (idiopathic interstitial pneumonia . IIP) . IPF . 553 . 447. 3 (fibroblast) .. 2010 IPF .. ( ) (usual.)

2 4. interstitial pneumonia UIP) ( ) . IPF IIP .. (interstitial pneumonia IP) IPF . ( ) .. 5. 5 . 1 . (honeycomb lung) . IPF 10 - IPF 10 . 13 20 .. 55-75 . ( 1) IPF . IPF 7,8 . 5,6 .. IPF IPF .. IPF 5% IPF .. ( TGF 1 . ) 9 IPF . IPF 4,5,6 . ( ) . ( . IPF ) IPF . C MUC5B . ELMOD2 (haplotype) . ( ) . IPF .. 448 .. (high (myofibroblast) resolution computed tomography HRCT) . X . 20% . - . ( 33%) ( TGF 1 (DLco) . - ) .. ( ) ( 2010. IPF )4. (TGF- 1) . IPF . UIP . IPF . " " UIP . I ( ).. ( caveolin 1) (paraseptal) . (Matrix metalloproteinases ( ).. MMPs) (remodelling) IPF ( ). (fibroblast foci).

3 MMP7 MMP1 MMP2 Wnt ( ). UIP . SHH Notch BMP ( hyaline membranes organizing (reactivation of developmental program) pneumonia [granulomas] .. IPF ) . IPF (telomere) . (glutathione) IPF . 2,4,5,8,9,10,11 UIP HRCT ( ).. ( ).. ( ).. ( ).. UIP ( .. ( ) [ ] .. ) . HRCT . UIP HRCT . X UIP . 449. ( ) ( ).. CT IPF . ( ). IPF .. IPF ( ). IPF .. ( ).. ( . IPF . ) . HRCT IPF. UIP . UIP . ILD . ( ) . ( ). ( . HRCT. ) . HRCT UIP IPF .. 2000 IPF . ( ) 2010 IPF UIP UIP . IPF. IPF . UIP . HRCT UIP . IPF . IPF .. IPF . IPF IPF IPF IPF.. IPF Hermansky-Pudlak syndrome . ref 4 .. ( ).. IPF . IPF 1.

4 Corticosteroid monotherapy 2. corticosteroid IPF Hermansky-Pudlak syndrome immune-modulator therapy 3. colchicine CT . 4. cyclosporine A 5. interferon 1b 6. etanercept CT ref 4. 7. bosentan 8. acetylcysteine azathioprine .. prednisone ( .. ) 9. anticoagulation ( .. ) .. ( ). IPF .. acetylcysteine monotherapy pirfenidone . ref 20 . 19. 450 . IPF IPF . ( ). corticosteroid . IPF corticosteroid . ( ). IPF IPF .. ( ).. ( . IPF . ) IPF .. ( .. ) .. IPF .. IPF IPF . ( ) .. (forced vital capacity FVC) . IPF corticosteroid (6 minute walk test 6 MWT) . DLco . (progression-free survival PFS).

5 ( IPF FVC 10%) . Acetylcysteine monotherapy . Pirfenidone Pirfenidone . (CAPACITY trials 1, 2) 2011. CAPACITY . 779 . Corticosteroid monotherapy Pirfenidone 72 . FVC 4% . Colchicine . pirfenidone . Cyclosporine A . FVC . Corticosteroid immune-modulator therapy .. Interferon 1b . Lancet . Bosentan . pirfenidone IPF 12 2011. Etanercept . pirfenidone . acetylcysteine azathioprine . prednisone IPF ( FVC 50% . Anticoagulation DLco 35% 6 MWT 150 m) . (FDA) . 2010 5 .. (ASCEND-3 trial) . pirfenidone 13,14,15 Taniguchi .. CAPACITY trials 1, 2 . SP3 trial PFS . 451. pirfenidone . 30% IPF.

6 16 IPF . (NIH) PANTHER- . IPF 80 ( . N-acetylcysteine (NAC) ) . NAC prednisone azathioprine . 2011 10 ( A . ) NAC 1B bosentan ( ) . prednisone azathioprine etanercept ( ) . 13,17. NAC NIH warfarin NAC . ACE-IPF trial warfarin prednisone azathioprine . 256 IPF 2010 . 13. IPF . BIBF 1120 (BIBF1120 . [ PDGF VEGF . bFGF] ) . BIBF1120 432 IPF IPF . 12 . BIBF1120 (150 mg ) . ( ) (financial disclosure) (conflict BIBF1120 IPF of interest) . ( ) 100 . (P = )18 . TOMORROW study 1. American Thoracic Society/European Respiratory Society. International multidisciplinary consensus classification of CNTO888 (CNTO-888.)

7 The idiopathic interstitial pneumonias. Am J Respir Crit Care CC chemokine ligand 2 (CCL2) Med 2002; 165: 277-304. monocyte chemoattractant protein-1 (MCP-1) 2. Eickelberg O, Selman M. Update in diffuse parenchymal lung disease 2009. Am J Respir Crit Care Med 2010; 181: G- CCR2 883-8. CCL2 CCR2 3. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. ) 120 . American Thoracic Society (ATS), and the European Respi- IPF ratory Society (ERS). Am J Respir Crit Care Med 2000; 161: Phase 2 646-64. 4. Raghu G, Collard HR, Egan J, et al.

8 An official ATS/ERS/. Thalidomide Phase 2 JRS/ALAT statement: idiopathic pulmonary fibrosis: Minocycline hydrochloride evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011; 183: 788-824. Sildenafil Zileuton Tetrathiomolybdate . 5. King TE Jr, Pardo A, Selman M. Idiopathic pulmonary Octreotide fibrosis. Lancet 2011; 378: 1949-61. 19 6. Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2006; 174: 810-6. 7. Fukuda Y, Basset F, Ferrans VJ, Yamanaka N. Significance of early intra-alveolar fibrotic lesions and integrin expression 452.

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