Disciplina MCP5777 Estudio Profundo del Tratamiento da Fibrosis Intersticial Pulmonar Idiopática. Duración Total

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1 Disciplina MCP5777 Estudio Profundo del Tratamiento da Fibrosis Intersticial Pulmonar Idiopática Área de Concentración: 5150 Creación: 27/11/2014 Activación: 27/11/2014 Nro. de Créditos: 1 Carga Horaria: Teórica Práctica Estudios Duración Total (por semana) (por semana) (por semana) semanas 15 horas Docentes Responsables: Ronaldo Adib Kairalla Carlos Roberto Ribeiro de Carvalho Bruno Guedes Baldi Objetivos: Discutir y analizar críticamente las opciones terapéuticas disponibles para la fibrosis pulmonar idiopática (FPI), teniendo en cuenta los aspectos fisiopatológicos y las nuevas opciones farmacológicas las que, basadas en estudios recientes, trajeron perspectivas más favorables a los pacientes. Justificativa: El mejor entendimiento de los mecanismos de lesión de la membrana alvéolo-capilar y de la respuesta reparadora en la fibrosis pulmonar idiopática (FPI) que se han adquirido en los últimos años, asociados al surgimiento de nuevas perspectivas de tratamiento con bloqueadores de la fibrosis, como la pirferidona y los inhibidores de la fibrosis tirosinquinasa, mejoran la perspectiva de los pacientes portadores de FPI. Esta disciplina tiene como objetivo la presentación y discusión de estos nuevos conceptos y de los resultados observados con los nuevos tratamientos de la FPI, además de discutir la monitorización óptima de la respuesta terapéutica. Contenido: Aulas Teóricas: 1. Estudio profundo de la fisiopatología da fibrosis pulmonar idiopática (FPI). 2. Correlación entre patología y función pulmonar en la FPI. Seminarios 1. Estudio profundo de la etiología y patogénesis de la fibrosis pulmonar

2 idiopática, incluyendo evaluación de modelos experimentales utilizados en la FPI pulmonar. 2. Evaluación de los factores prognósticos establecidos, incluyendo parámetros clínicos, tomográficos, funcionales e histopatológicos. 3. Estudio crítico del tratamiento farmacológico con corticoesteroides, inmunosupresores y n-acetil-cisteína. 4. Estudio crítico del tratamiento farmacológico con medicamentos que actúan sobre la fibrosis, como la pirferidona y los inhibidores de tirosinquinasa. 5. Tratamiento farmacológico: perspectivas futuras. 6. Evaluación de los parámetros utilizados para la evaluación de la respuesta terapéutica. 7. Análisis crítico del trasplante pulmonar como opción terapéutica Forma de Evaluación: 1. Presentación del seminario 2. Participación en las discusiones de los temas. Observación: Bibliografía: 1. American Thoracic Society. (2000) Idiopathic pulmonary fibrosis: diagnosis and treatment: international consensus statement; American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 161(2 pt 1), Alton, EW, Johnson, M, Turner-Warwick, M. Advanced cryptogenic fibrosing alveolitis: preliminary report on treatment with cyclosporin A. Respir Med 1989; 83: Baughman, RP, Lower, EE. Use of intermittent, intravenous cyclophosphamide for idiopathic pulmonary fibrosis. Chest 1992; 102: Carrington, CB, Gaensler, EA, Coutu, RE, et al. Natural history and treated course of usual and desquamative interstitial pneumonia. N Engl J Med 1978; 298: Cegla, UH. Treatment of idiopathic fibrosing alveolitis. Therapeutic experiences with azathioprine-prednisolone and D-penicillamine-prednisolone combination therapy. Schw Med Woch 1977; 107: Chapela, R, Zuniga, G, Selman, M. D-penicillamine in the therapy of fibrotic lung diseases. Int Jour Clin Pharm Ther Tox 1986; 24: Costabel, U, Matthys, H. Different therapies and factors influencing response to therapy in idiopathic diffuse fibrosing alveolitis. Respiration 1981; 42: Johnson, MA, Kwan, S, Snell, NJC, et al. Randomized controlled trial comparing prednisolone alone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis. Thorax 1989; 44: Keogh, BA, Bernardo, J, Hunninghake, GW, et al. Effect of intermittent high dose parenteral corticosteroids on the alveolitis of idiopathic pulmonary fibrosis. Am Rev Respir Dis 1983; 127: Panos, RJ, Mortenson, R, Niccoli, SA, King, TE Jr. Clinical deterioration in patients with idiopathic pulmonary fibrosis. Causes and assessment. Am J Med 1990; 88: Peters, SG, McDougall, JC, Douglas, WW, et al. Colchicine in the treatment of pulmonary fibrosis. Chest 1993; 103: Raghu, G, Depaso, WJ, Cain, K, et al. Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: A prospective, double-blind randomized, placebo-controlled clinical trial. Am Rev Respir Dis 1991; 144: Schwartz, DA, Helmers, RA, Galvin, JR, et al. Determinants of survival in

3 idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1994; 149: Schwartz, DA, Van Fossen, DS, Davis, CS, et al. Determinants of progression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1994; 149: Turner-Warwick, M, Burrows, B, Johnson, A. Cryptogenic fibrosing alveolitis: Response to corticosteroid treatment and its effect on survival. Thorax 1980; 35: Winterbauer, RH, Hammar, SP, Hallman, KO, et al. Diffuse interstitial pneumonitis: Clinicopathologic correlations in 20 patients treated with prednisone/azathioprine. Am J Med 1978; 65: Behr J, Maier K, Degenkolb B, Krombach F, Vogelmeier C. Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis. Adjunctive therapy to maintenance immunosuppression. Am J Respir Crit Care Med 156: , American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This Joint Statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS Board of Directors, June 2001 and by The ERS Executive Committee, Am. J. Respir. Crit. Care Med. 165: , Selman M, King TE, Pardo A. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med 134:136-51, Ziesche R, Hofbauer E, Wittmann K, Petkov V, Block LH.A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis. N Engl J Med 341:1264-9, Douglas WW, Ryu JH, Schroeder DR.Idiopathic pulmonary fibrosis: Impact of oxygen and colchicine, prednisone, or no therapy on survival. Am J Respir Crit Care Med 161:1172-8, Raghu, G Idiopathic pulmonary fibrosis: treatment options in pursuit of evidencebased approaches. Eur Respir J 2006;28, Ask, K, Martin, GE, Kolb, M, et al Targeting genes for treatment in idiopathic pulmonary fibrosis: challenges and opportunities, promises and pitfalls. Proc Am Thorac Soc 2006;3, Cool, CD, Groshong, SD, Rai, PR, et al Fibroblast foci are not discrete sites of lung injury or repair: the fibroblast reticulum. Am J Respir Crit Care Med 2006;174, Lama, VN, Phan, SH The extrapulmonary origin of fibroblasts: stem/progenitor cells and beyond. Proc Am Thorac Soc 2006;3, Azuma, A, Nukiwa, T, Tsuboi, E, et al Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2005;171, Martinez, FJ, Safrin, S, Weycker, D, et al The clinical course of patients with idiopathic pulmonary fibrosis. Ann Int Med 2005;142, Lynch, DA, Travis, WA, Muller, NL, et al Idiopathic interstitial pneumonias: CT features. Radiology 2005;236, Aziz, AZ, Wells, AU, Bateman, ED, et al Interstitial lung disease: effects of thin-

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5 44. King Jr TE, Behr J, Brown KK, et al. A Randomized Placebo-Controlled Trial of Bosentan in Patients with Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med 2008;177: King Jr TE, Brown KK, Raghu G, et al. A Randomized, Controlled Trial of Bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011;184: Olschewski, H, Ghofrani, HA, Walmrath, D, et al Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis. Am J Respir Crit Care Med 1999;160: Ghofrani, HA, Wiedemann, R, Rose, F, et al Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. Lancet 2002;360: Homma, S, Sakamoto, S, Kawabata, M, et al Cyclosporin treatment in steroidresistant and acutely exacerbated interstitial pneumonia. Intern Med 2005;44: Shulgina L, Cahn AP, Chilvers ER, et al. Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: a randomized controlled trial. Thorax 2013;68: du Bois RM, Nathan SD, Richeldi L, et al. Idiopathic pulmonary fibrosis: lung function is a clinically meaningful endpoint for Phase III Trials. Am J Respir Crit Care Med 2010;186: King Jr TE, Albera C, Bradford WZ, et al. Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomized, placebo-controlled trial. Lancet 2009;374: King Jr TE, Bradford WZ, Castro-Bernardini S, et al. A phase III trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med 2014;370: Noble PW, Albera C, Bradford WZ, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet 2011;377: Noth I, Anstrom KJ, Calvert SB, et al. A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2012;1: Raghu G, Collard HR, Anstrom KJ, et al. Idiopathic pulmonary fibrosis: clinically meaningful primary endpoints in phase 3 clinical trials. Am J Respir Crit Care Med 2012;185: Idiopathic pulmonary fibrosis clinical research network, Martinez FJ, de Andrade JA, Anstrom KJ, et al. Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med 2014;370: Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014;370:

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