FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 353:2229-2242 November 24, 2005 Number 21 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Hunninghake, G. W. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Idiopathic pulmonary fibrosis is a chronic progressive disorder with a poor prognosis.

Methods We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose of acetylcysteine (600 mg three times daily) added to standard therapy with prednisone plus azathioprine. The primary end points were changes between baseline and month 12 in vital capacity and in single-breath carbon monoxide diffusing capacity (DL_CO).

Results A total of 182 patients were randomly assigned to treatment (92 to acetylcysteine and 90 to placebo). Of these patients, 155 (80 assigned to acetylcysteine and 75 to placebo) had usual interstitial pneumonia, as confirmed by high-resolution computed tomography and histologic findings reviewed by expert committees, and did not withdraw consent before the start of treatment. Fifty-seven of the 80 patients taking acetylcysteine (71 percent) and 51 of the 75 patients taking placebo (68 percent) completed one year of treatment. Acetylcysteine slowed the deterioration of vital capacity and DL_CO: at 12 months, the absolute differences in the change from baseline between patients taking acetylcysteine and those taking placebo were 0.18 liter (95 percent confidence interval, 0.03 to 0.32), or a relative difference of 9 percent, for vital capacity (P=0.02), and 0.75 mmol per minute per kilopascal (95 percent confidence interval, 0.27 to 1.23), or 24 percent, for DL_CO (P=0.003). Mortality during the study was 9 percent among patients taking acetylcysteine and 11 percent among those taking placebo (P=0.69). There were no significant differences in the type or severity of adverse events between patients taking acetylcysteine and those taking placebo, except for a significantly lower rate of myelotoxic effects in the group taking acetylcysteine (P=0.03).

Conclusions Therapy with acetylcysteine at a dose of 600 mg three times daily, added to prednisone and azathioprine, preserves vital capacity and DL_CO in patients with idiopathic pulmonary fibrosis better than does standard therapy alone.

Source Information

From University Hospital, Katholieke Universiteit Leuven, Leuven, Belgium (M.D., M.T., E.K.V., J.V.); Medizinische Klinik I, Klinikum Grosshadern der Ludwig-Maximilians-Universität, Munich, Germany (J.B.); Medizinische Klinik III, Klinikum der Johannes-Gutenberg-Universität, Mainz, Germany (R.B.); Medical Faculty Essen, Ruhrlandklinik, Essen-Heidhausen, Germany (U.C.); Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands (P.N.R.D.); Academic Medical Center, Amsterdam (H.M.J.); University of Edinburgh Medical School, Edinburgh (W.M.); Centre Hospitalier Régional Universitaire de Lille, Hôpital Calmette, Lille, France (B.W.); Hôpital Cardiologique, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France (F.L.); Royal Brompton Hospital, London (A.G.N.); Evelyn Hospital, Cambridge, United Kingdom (C.D.R.F.); Hôpital Antoine-Béclère, Clamart, France (F.C.); Dipartimento Cardio-Toracico, Università degli Studi di Pisa, Pisa, Italy (S.P.); Université Libre de Bruxelles, Erasmus Hospital, Brussels (P.V.); Heart Lung Center Utrecht, St. Antonius Ziekenhuis, Nieuwegein, the Netherlands (J.M.M.B.); Hospital Universitario Virgen del Rocio, Seville, Spain (E.R.-B.); Zambon Group, Bresso, Milan (G.C., I.L., M.S.); and Innopharma, Varedo, Milan (M.M.).

Address reprint requests to Dr. Demedts at the Division of Pneumology, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium, or at maurits.demedts{at}uz.kuleuven.ac.be.

Full Text of this Article

Related Letters:

Acetylcysteine in Pulmonary Fibrosis
Hull J. H.K., Toma T. P., Bhowmik A., Rajakulasingam R., Demedts M., Buhl R., Costabel U., the IFIGENIA Study Group
Extract | Full Text | PDF  
N Engl J Med 2006; 354:1089-1091, Mar 9, 2006. Correspondence

This article has been cited by other articles:

• Korfei, M., Ruppert, C., Mahavadi, P., Henneke, I., Markart, P., Koch, M., Lang, G., Fink, L., Bohle, R.-M., Seeger, W., Weaver, T. E., Guenther, A. (2008). Epithelial Endoplasmic Reticulum Stress and Apoptosis in Sporadic Idiopathic Pulmonary Fibrosis. Am. J. Respir. Crit. Care Med. 178: 838-846 [Abstract] [Full Text]  
• Kim, R., Meyer, K. C. (2008). Review: Therapies for interstitial lung disease: past, present and future. Therapeutic Advances in Respiratory Disease 2: 319-338 [Abstract]  
• Vuorinen, K., Ohlmeier, S., Lepparanta, O., Salmenkivi, K., Myllarniemi, M., Kinnula, V. L. (2008). Peroxiredoxin II Expression and Its Association With Oxidative Stress and Cell Proliferation in Human Idiopathic Pulmonary Fibrosis. J. Histochem. Cytochem. 56: 951-959 [Abstract] [Full Text]  
• Wells, A. U., Behr, J., Silver, R. (2008). Outcome measures in the lung. Rheumatology (Oxford) 47: v48-v50 [Abstract] [Full Text]  
• Wells, A U, Hirani, N, on behalf of the BTS Interstitial Lung Disease Gui, (2008). Interstitial lung disease guideline. Thorax 63: v1-v58 [Full Text]  
• Behr, J., Ryu, J. H. (2008). Pulmonary hypertension in interstitial lung disease. Eur Respir J 31: 1357-1367 [Abstract] [Full Text]  
• Sabroe, I, Parker, L C, Calverley, P M A, Dower, S K, Whyte, M K B (2008). Pathological networking: a new approach to understanding COPD. Postgrad. Med. J. 84: 259-264 [Abstract] [Full Text]  
• Kisseleva, T., Brenner, D. A. (2008). Fibrogenesis of Parenchymal Organs. Proc Am Thorac Soc 5: 338-342 [Abstract] [Full Text]  
• Rogliani, P., Mura, M., Assunta Porretta, M., Saltini, C. (2008). Review: New perspectives in the treatment of idiopathic pulmonary fibrosis. Therapeutic Advances in Respiratory Disease 2: 75-93 [Abstract]  
• Thomeer, M., Demedts, M., Behr, J., Buhl, R., Costabel, U., Flower, C. D. R., Verschakelen, J., Laurent, F., Nicholson, A. G., Verbeken, E. K., Capron, F., Sardina, M., Corvasce, G., Lankhorst, I., the Idiopathic Pulmonary Fibrosis International Gr, (2008). Multidisciplinary interobserver agreement in the diagnosis of idiopathic pulmonary fibrosis. Eur Respir J 31: 585-591 [Abstract] [Full Text]  
• Kinder, B. W., Brown, K. K., Schwarz, M. I., Ix, J. H., Kervitsky, A., King, T. E. Jr (2008). Baseline BAL Neutrophilia Predicts Early Mortality in Idiopathic Pulmonary Fibrosis. Chest 133: 226-232 [Abstract] [Full Text]  
• Fimognari, F. L., Pastorelli, R., Raghu, G. (2007). Corticosteroids May Worsen Gastroesophageal Reflux in Patients With Idiopathic Pulmonary Fibrosis. Chest 132: 1719-1720 [Full Text]  
• du Bois, R., King, T. E Jr (2007). Challenges in pulmonary fibrosis {middle dot} 5: The NSIP/UIP debate. Thorax 62: 1008-1012 [Abstract] [Full Text]  
• Kabuyama, Y., Oshima, K., Kitamura, T., Homma, M., Yamaki, J., Munakata, M., Homma, Y. (2007). Involvement of selenoprotein P in the regulation of redox balance and myofibroblast viability in idiopathic pulmonary fibrosis.. GENES CELLS 12: 1235-1244 [Abstract] [Full Text]  
• Vayalil, P. K., Iles, K. E., Choi, J., Yi, A.-K., Postlethwait, E. M., Liu, R.-M. (2007). Glutathione suppresses TGF-beta-induced PAI-1 expression by inhibiting p38 and JNK MAPK and the binding of AP-1, SP-1, and Smad to the PAI-1 promoter. Am. J. Physiol. Lung Cell. Mol. Physiol. 293: L1281-L1292 [Abstract] [Full Text]  
• Scotton, C. J., Chambers, R. C. (2007). Molecular Targets in Pulmonary Fibrosis: The Myofibroblast in Focus. Chest 132: 1311-1321 [Abstract] [Full Text]  
• Cotter, M. A., Thomas, J., Cassidy, P., Robinette, K., Jenkins, N., Florell, S. R., Leachman, S., Samlowski, W. E., Grossman, D. (2007). N-Acetylcysteine Protects Melanocytes against Oxidative Stress/Damage and Delays Onset of Ultraviolet-Induced Melanoma in Mice. Clin. Cancer Res. 13: 5952-5958 [Abstract] [Full Text]  
• Martinez-Losa, M., Cortijo, J., Juan, G., Ramon, M., Sanz, M. J., Morcillo, E. J. (2007). Modulatory effects of N-acetyl-L-cysteine on human eosinophil apoptosis. Eur Respir J 30: 436-442 [Abstract] [Full Text]  
• Servettaz, A, Guilpain, P, Goulvestre, C, Chereau, C, Hercend, C, Nicco, C, Guillevin, L, Weill, B, Mouthon, L, Batteux, F (2007). Radical oxygen species production induced by advanced oxidation protein products predicts clinical evolution and response to treatment in systemic sclerosis. Ann Rheum Dis 66: 1202-1209 [Abstract] [Full Text]  
• Noth, I., Martinez, F. J. (2007). Recent Advances in Idiopathic Pulmonary Fibrosis. Chest 132: 637-650 [Abstract] [Full Text]  
• du Bois, R. M. (2007). Blocking endothelin: breaking new ground. ERR 16: 24-29 [Abstract] [Full Text]  
• Sabroe, I., Parker, L. C, Calverley, P. M A, Dower, S. K, Whyte, M. K B (2007). Pathological networking: a new approach to understanding COPD. Thorax 62: 733-738 [Abstract] [Full Text]  
• Olson, A. L., Swigris, J. J., Lezotte, D. C., Norris, J. M., Wilson, C. G., Brown, K. K. (2007). Mortality from Pulmonary Fibrosis Increased in the United States from 1992 to 2003. Am. J. Respir. Crit. Care Med. 176: 277-284 [Abstract] [Full Text]  
• Grimble, G. K. (2007). Adverse Gastrointestinal Effects of Arginine and Related Amino Acids. J. Nutr. 137: 1693S-1701S [Abstract] [Full Text]  
• Richeldi, L., Abraham, E. (2007). Identifying Patients with Idiopathic Pulmonary Fibrosis: Quality or Quantity?. Am. J. Respir. Crit. Care Med. 175: 976-977 [Full Text]  
• Tsakiri, K. D., Cronkhite, J. T., Kuan, P. J., Xing, C., Raghu, G., Weissler, J. C., Rosenblatt, R. L., Shay, J. W., Garcia, C. K. (2007). Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc. Natl. Acad. Sci. USA 104: 7552-7557 [Abstract] [Full Text]  
• Kiser, T. H., Oldland, A. R., Fish, D. N. (2007). Stability of acetylcysteine solution repackaged in oral syringes and associated cost savings. Am J Health Syst Pharm 64: 762-766 [Abstract] [Full Text]  
• Gunther, A., Enke, B., Markart, P., Hammerl, P., Morr, H., Behr, J., Stahler, G., Seeger, W., Grimminger, F., Leconte, I., Roux, S., Ghofrani, H-A. (2007). Safety and tolerability of bosentan in idiopathic pulmonary fibrosis: an open label study. Eur Respir J 29: 713-719 [Abstract] [Full Text]  
• Wells, A. U., Hogaboam, C. M. (2007). Update in Diffuse Parenchymal Lung Disease 2006. Am. J. Respir. Crit. Care Med. 175: 655-660 [Full Text]  
• Rudd, R. M, Prescott, R. J, Chalmers, J C, Johnston, I. D A, for the Fibrosing Alveolitis Subcommittee of the R, (2007). British Thoracic Society Study on cryptogenic fibrosing alveolitis: response to treatment and survival. Thorax 62: 62-66 [Abstract] [Full Text]  
• Tino, G. (2006). Clinical Year in Review IV: Interstitial Lung Disease, Cystic Fibrosis, Pulmonary Infections, and Mycobacterial Disease. Proc Am Thorac Soc 3: 650-653 [Full Text]  
• Dempsey, O.J., Kerr, K.M., Gomersall, L., Remmen, H., Currie, G.P. (2006). Idiopathic pulmonary fibrosis: an update. QJM 99: 643-654 [Abstract] [Full Text]  
• Millar, A B (2006). IL-10: another therapeutic target in idiopathic pulmonary fibrosis?. Thorax 61: 835-836 [Full Text]  
• Lederer, D. J., Arcasoy, S. M., Wilt, J. S., D'Ovidio, F., Sonett, J. R., Kawut, S. M. (2006). Six-Minute-Walk Distance Predicts Waiting List Survival in Idiopathic Pulmonary Fibrosis. Am. J. Respir. Crit. Care Med. 174: 659-664 [Abstract] [Full Text]  
• Raghu, G. (2006). Idiopathic pulmonary fibrosis: treatment options in pursuit of evidence-based approaches.. Eur Respir J 28: 463-465 [Full Text]  
• Bourke, S J (2006). Interstitial lung disease: progress and problems.. Postgrad. Med. J. 82: 494-499 [Abstract] [Full Text]  
• Gaston, B., Singel, D., Doctor, A., Stamler, J. S. (2006). S-Nitrosothiol Signaling in Respiratory Biology. Am. J. Respir. Crit. Care Med. 173: 1186-1193 [Abstract] [Full Text]  
• Martinez, F. J., Keane, M. P. (2006). Update in diffuse parenchymal lung diseases 2005.. Am. J. Respir. Crit. Care Med. 173: 1066-1071 [Full Text]  
• Raghu, G., Johnson, W. C. (2006). From the authors. Eur Respir J 27: 1072-1073 [Full Text]  
• Wells, A. U. (2006). Antioxidant therapy in idiopathic pulmonary fibrosis: hope is kindled.. Eur Respir J 27: 664-666 [Full Text]  
• Toma, T (2006). Can acetylcysteine slow lung function decline in idiopathic pulmonary fibrosis?. Thorax 61: 289-289 [Full Text]  
• Hull, J. H.K., Toma, T. P., Bhowmik, A., Rajakulasingam, R., Demedts, M., Buhl, R., Costabel, U., the IFIGENIA Study Group, (2006). Acetylcysteine in Pulmonary Fibrosis. NEJM 354: 1089-1091 [Full Text]  
• Martinez, F. J. (2006). Idiopathic Interstitial Pneumonias: Usual Interstitial Pneumonia versus Nonspecific Interstitial Pneumonia.. Proc Am Thorac Soc 3: 81-95 [Abstract] [Full Text]  
• Kim, D. S., Collard, H. R., King, T. E. Jr. (2006). Classification and natural history of the idiopathic interstitial pneumonias.. Proc Am Thorac Soc 3: 285-292 [Abstract] [Full Text]  
• Martinez, F. J., Flaherty, K. (2006). Pulmonary function testing in idiopathic interstitial pneumonias.. Proc Am Thorac Soc 3: 315-321 [Abstract] [Full Text]  
• Walter, N., Collard, H. R., King, T. E. Jr. (2006). Current perspectives on the treatment of idiopathic pulmonary fibrosis.. Proc Am Thorac Soc 3: 330-338 [Abstract] [Full Text]  
• (2005). Acetylcysteine for Idiopathic Pulmonary Fibrosis. JWatch General 2005: 3-3 [Full Text]  
• Hunninghake, G. W. (2005). Antioxidant Therapy for Idiopathic Pulmonary Fibrosis.. NEJM 353: 2285-2287 [Full Text]