Strategies for treating idiopathic pulmonary fibrosis

Nature Reviews Drug Discovery

Volumn 9, Issue 2, 2010, Pages 129-140

  Du Bois, R M ^a  

^a DEPARTMENT OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCYSTEINE; ANTICOAGULANT AGENT; ANTIINFLAMMATORY AGENT; AZATHIOPRINE; BIBF 1120; BOSENTAN; COLCHICINE; CORTICOSTEROID; CYCLOPHOSPHAMIDE; ETANERCEPT; GAMMA INTERFERON; GAMMA1B INTERFERON; IMATINIB; PIRFENIDONE; PLACEBO; PREDNISOLONE; PREDNISONE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; SILDENAFIL; SURFACTANT PROTEIN A; SURFACTANT PROTEIN C;

6 MINUTE WALK TEST; ANTICOAGULANT THERAPY; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; COMPUTER ASSISTED TOMOGRAPHY; CORTICOSTEROID THERAPY; DIAGNOSTIC ERROR; DISEASE CLASSIFICATION; DISEASE MODEL; DISEASE PREDISPOSITION; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG MECHANISM; DRUG MEGADOSE; ENDOPLASMIC RETICULUM STRESS; EPITHELIUM CELL; FIBROGENESIS; FIBROSING ALVEOLITIS; FUNCTIONAL ASSESSMENT; GASTROINTESTINAL SYMPTOM; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; INFLAMMATION; INTERSTITIAL LUNG DISEASE; LIVER FUNCTION TEST; LOW DRUG DOSE; LUNG ALVEOLUS EPITHELIUM; LUNG FUNCTION; LUNG VOLUME; MONOTHERAPY; PATHOGENESIS; PHOTOSENSITIVITY; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PULMONARY HYPERTENSION; REVIEW; RHEUMATOID ARTHRITIS; RISK FACTOR; SCAR; SIDE EFFECT; SURVIVAL; TELOMERE; UNSPECIFIED SIDE EFFECT; VITAL CAPACITY;

ANIMALS; CLINICAL TRIALS AS TOPIC; DRUG DELIVERY SYSTEMS; DRUG DESIGN; HUMANS; IDIOPATHIC PULMONARY FIBROSIS; LUNG; RESEARCH DESIGN;

EID: 75949130829     PISSN: 14741776     EISSN: 14741784     Source Type: Journal    
DOI: 10.1038/nrd2958     Document Type: Review

References (76)

1. Crystal, R. G. & West, J. B. (eds) The Lung: Scientific Foundations (Raven, New York, 1991).
2. Westall, G. P., Stirling, R. G., Cullinan, P. C. & du Bois, R. M. Interstitial Lung Disease (eds King, T. J. & Schwarz, M. I.) 332-386 (BC Decker, Hamilton, Canada, 2003).
3. Vourlekis, J. S. et al. The effect of pulmonary fibrosis on survival in patients with hypersensitivity pneumonitis. Am. J. Med. 11 6, 662-668 (2004).
4. du Bois, R. M. Evolving concepts in the early and accurate diagnosis of idiopathic pulmonary fibrosis. Clin. Chest Med. 27, S17-S25 (2006)
5. Schwarz, M. I. & King, T. E. Jr (eds). Approach to the Evaluation and Diagnosis of Interstitial Lung Disease (BC Decker, Hamilton, Canada, 2003).
6. du Bois, R. M. Oxford Textbook of Medicine (eds Warrell, D. A., Cox, T. M. & Firth, J. D.) 1439-1446 (Oxford University Press, Oxford, 2003).
7. Du Bois, R. M. & King, T. E. Jr. Challenges in pulmonary fibrosis x 5: the NSIP/UIP debate. Thorax 62, 1008-1012 (2007).
8. American Thoracic Society. American Thoracic Society/European Respiratory Society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Am. J. Respir. Crit. Care Med. 165, 277-304 (2002).
9. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. Am. J. Respir. Crit. Care Med. 161, 646-664 (2000).
10. Olson, A. L. et al. Mortality from pulmonary fibrosis increased in the United States from 1992 to 2003. Am. J. Respir. Crit. Care Med. 176, 277-284 (2007).
11. Selman, M., King, T. E. & Pardo, A. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann. Intern. Med. 134, 136-151 (2001).
12. Iwai, K., Mori, T., Yamada, N., Yamaguchi, M. & Hosoda, Y. Idiopathic pulmonary fibrosis. Epidemiologic approaches to occupational exposure. Am. J. Respir. Crit. Care Med. 150, 670-675 (1994).
13. Hubbard, R., Lewis, S., Richards, K., Johnston, I. & Britton, J. Occupational exposure to metal or wood dust and aetiology of cryptogenic fibrosing alveolitis. Lancet 347, 284-289 (1996). (Pubitemid 26041039)
14. Steele, M. P. et al. Clinical and pathologic features of familial interstitial pneumonia. Am. J. Respir. Crit. Care Med. 172, 1146-1152 (2005).
15. Kuwano, K. et al. Detection of adenovirus E1A DNA in pulmonary fibrosis using nested polymerase chain reaction [see comments]. Eur. Resp. J. 10, 1445-1449 (1997). (Pubitemid 27311053)
16. Ueda, T. et al. Idiopathic pulmonary fibrosis and high prevalence of serum antibodies to hepatitis C virus. Am. Rev. Respir. Dis. 146, 266-268 (1992).
17. Tobin, R. W. et al. Increased prevalence of gastroesophageal reflux in patients with idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 158, 1804-1808 (1998).
18. Raghu, G., Yang, S. T., Spada, C., Hayes, J. & Pellegrini, C. A. Sole treatment of acid gastroesophageal reflux in idiopathic pulmonary fibrosis: a case series. Chest 129, 794-800 (2006).
19. Chambers, R. C. Procoagulant signalling mechanisms in lung inflammation and fibrosis: novel opportunities for pharmacological intervention? Br. J. Pharmacol. 153, S367-S378 (2008).
20. Selman, M. & Pardo, A. Role of epithelial cells in idiopathic pulmonary fibrosis: from innocent targets to serial killers. Proc. Am. Thorac. Soc. 3, 364-372 (2006).
21. Thomas, A. Q. et al. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred. Am. J. Respir. Crit. Care Med. 165, 1322-1328 (2002).
22. Wang, Y. et al. Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. Am. J. Hum. Genet. 84, 52-59 (2009).
23. Kaser, A. & Blumberg, R. S. Endoplasmic reticulum stress in the intestinal epithelium and inflammatory bowel disease. Semin. Immunol. 21, 156-163 (2009).
24. Xu, C., Bailly-Maitre, B. & Reed, J. C. Endoplasmic reticulum stress: cell life and death decisions. J. Clin. Invest. 11 5, 2656-2664 (2005).
25. Armanios, M. Y. et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N. Engl. J. Med. 356, 1317-1326 (2007).
26. Cronkhite, J. T. et al. Telomere shortening in familial and sporadic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 178, 729-737 (2008).
27. Alder, J. K. et al. Short telomeres are a risk factor for idiopathic pulmonary fibrosis. Proc. Natl Acad. Sci. USA 105, 13051-13056 (2008).
28. du Bois, R. M. Genetic factors in pulmonary fibrotic disorders. Semin. Respir. Crit. Care Med. 27, 581-588 (2006).
29. Laurent, G. J., Chambers, R. C., Hill, M. R. & McAnulty, R. J. Regulation of matrix turnover: fibroblasts, forces, factors and fibrosis. Biochem. Soc. Trans. 35, 647-651 (2007).
30. Davies, H. R. & Richeldi, L. Idiopathic pulmonary fibrosis: current and future treatment options. Am. J. Respir. Med. 1, 211-224 (2002).
31. Richeldi, L., Davies, H. R., Ferrara, G. & Franco, F. Corticosteroids for idiopathic pulmonary fibrosis. Cochrane Database Syst. Rev. CD002880 (2003).
32. Davies, H. R., Richeldi, L. & Walters, E. H. Immuno-modulatory agents for idiopathic pulmonary fibrosis. Cochrane Database Syst. Rev. CD003134 (2003).
33. Raghu, G. et al. Azathioprine combined with prednisolone in the treatment of idiopathic pulmonary fibrosis: a prospective, double-blind, randomized, placebo-controlled clinical trial. Am. Rev. Respir. Dis. 144, 291-296 (1991).
34. Douglas, W. W. et al. Colchicine versus prednisone in the treatment of idiopathic pulmonary fibrosis A randomized prospective study. Am. J. Respir. Crit. Care Med. 158, 220-225 (1998).
35. Ziesche, R., Hofbauer, E., Wittmann, K., Petkov, V. & Block, L. H. A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis [see comments]. N. Engl. J. Med. 341, 1264-1269 (1999).
36. Nathan, S. D. et al. Interferon gamma-1b as therapy for idiopathic pulmonary fibrosis: an intrapatient analysis. Respiration 71, 77-82 (2004).
37. Antoniou, K. M. et al. Long-term clinical effects of interferon gamma-1b and colchicine in idiopathic pulmonary fibrosis. Eur. Respir. J. 28, 496-504 (2006).
38. Raghu, G. et al. A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis. N. Engl. J. Med. 350, 125-133 (2004).
39. King, T. E. Jr et al. Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial. Lancet 374, 222-228 (2009).
40. King, T. E. Jr et al. BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 177, 75-81 (2008).
41. Raghu, G., Johnson, W. C., Lockhart, D. & Mageto, Y. Treatment of idiopathic pulmonary fibrosis with a new antifibrotic agent, pirfenidone: results of a prospective, open-label Phase II study. Am. J. Respir. Crit. Care Med. 159, 1061-1069 (1999).
42. Azuma, A. et al. Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 171, 1040-1047 (2005).
43. Demedts, M. et al. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N. Engl. J. Med. 353, 2229-2242 (2005).
44. Hoyles, R. K. et al. A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma. Arthritis Rheum. 54, 3962-3970 (2006).
45. Tashkin, D. P. et al. Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease. Am. J. Respir. Crit. Care Med. 176, 1026-1034 (2007).
46. Tashkin, D. P. et al. Cyclophosphamide versus placebo in scleroderma lung disease. N. Engl. J. Med. 354, 2655-2666 (2006).
47. Raghu, G. et al. Treatment of idiopathic pulmonary fibrosis with etanercept: an exploratory, placebo-controlled trial. Am. J. Respir. Crit. Care Med. 178, 948-955 (2008).
48. Kubo, H. et al. Anticoagulant therapy for idiopathic pulmonary fibrosis. Chest 128, 1475-1482 (2005).
49. Moeller, A., Ask, K., Warburton, D., Gauldie, J. & Kolb, M. The bleomycin animal model: a useful tool to investigate treatment options for idiopathic pulmonary fibrosis? Int. J. Biochem. Cell Biol. 40, 362-382 (2008).
50. Selman, M. et al. Gene expression profiles distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis. Am. J. Respir. Crit. Care Med. 173, 188-198 (2006).
51. Yang, I. V. et al. Gene expression profiling of familial and sporadic interstitial pneumonia. Am. J. Respir. Crit. Care Med. 175, 45-54 (2007).
52. Konishi, K. et al. Gene expression profiles of acute exacerbations of idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 180, 167-175 (2009).
53. Boon, K. et al. Molecular phenotypes distinguish patients with relatively stable from progressive idiopathic pulmonary fibrosis (IPF). PLoS ONE. 4, e5134 (2009).
54. Pardo, A. et al. Up-regulation and profibrotic role of osteopontin in human idiopathic pulmonary fibrosis. PLoS Med. 2, e251 (2005).
55. Chaudhary, N. I. et al. Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis. Eur. Respir. J. 29, 976-985 (2007).
56. Roth, G. J. et al. Design, synthesis, and evaluation of indolinones as triple angiokinase inhibitors and the discovery of a highly specific 6-methoxy carbonyl-substituted indolinone (BIBF 1120). J. Med. Chem. 52, 4466-4480 (2009).
57. Uhal, B. D. The role of apoptosis in pulmonary fibrosis. Eur. Respir. Rev. 17, 138-144 (2008).
58. Basseri, S., Lhotak, S., Sharma, A. M. & Austin, R. C. The chemical chaperone 4-phenylbutyrate inhibits adipogenesis by modulating the unfolded protein response. J. Lipid Res. 50, 2486-2501 (2009).
59. de Almeida, S. F. et al. Chemical chaperones reduce endoplasmic reticulum stress and prevent mutant HFE aggregate formation. J. Biol. Chem. 282, 27905-27912 (2007).
60. Hecker, L. et al. NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury. Nature Med. 15, 1077-1081 (2009).
61. Lambeth, J. D. Nox enzymes, ROS, and chronic disease: an example of antagonistic pleiotropy. Free Radic. Biol. Med. 43, 332-347 (2007).
62. Lambeth, J. D., Krause, K. H. & Clark, R. A. NOX enzymes as novel targets for drug development. Semin. Immunopathol. 30, 339-363 (2008).
63. Kotani, I. et al. Increased procoagulant and antifibrinolytic activities in the lungs with idiopathic pulmonary fibrosis. Thromb. Res. 77, 493-504 (1995).
64. Belperio, J. A. et al. The role of the Th2 CC chemokine ligand CCL17 in pulmonary fibrosis. J. Immunol. 173, 4692-4698 (2004).
65. Keane, M. P., Arenberg, D. A., Moore, B. B., Addison, C. L. & Strieter, R. M. CXC chemokines and angiogenesis/angiostasis. Proc. Assoc. Am. Physicians 11 0, 288-296 (1998).
66. Moore, B. B., Keane, M. P., Addison, C. L., Arenberg, D. A. & Strieter, R. M. CXC chemokine modulation of angiogenesis: the importance of balance between angiogenic and angiostatic members of the family. J. Investig. Med. 46, 113-120 (1998).
67. Keane, M. P. et al. The CXC chemokines, IL-8 and IP-10, regulate angiogenic activity in idiopathic pulmonary fibrosis. J. Immunol. 159, 1437-1443 (1997).
68. Munger, J. S. et al. The integrin αvβ6 binds and activates latent TGF β1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 96, 319-328 (1999).
69. Horan, G. S. et al. Partial inhibition of integrin αvβ6 prevents pulmonary fibrosis without exacerbating inflammation. Am. J. Respir. Crit. Care Med. 177, 56-65 (2008).
70. 1 in pulmonary fibrosis. Chest 120, S49-S53 (2001).
71. Mercer, P. F. et al. Pulmonary epithelium is a prominent source of proteinase-activated receptor-1-inducible CCL2 in pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 179, 414-425 (2009).
72. Gharaee-Kermani, M., McCullumsmith, R. E., Charo, I. F., Kunkel, S. L. & Phan, S. H. CC-chemokine receptor 2 required for bleomycin-induced pulmonary fibrosis. Cytokine 24, 266-276 (2003).
73. Jiang, D. et al. Regulation of pulmonary fibrosis by chemokine receptor CXCR3. J. Clin. Invest. 11 4, 291-299 (2004).
74. Johnson, M. A. et al. Randomized controlled trial comparing prednisolone alone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis. Thorax 44, 280-288 (1989).
75. Tomioka, H. et al. A pilot study of aerosolized N-acetylcysteine for idiopathic pulmonary fibrosis. Respirology 10, 449-455 (2005).
76. Taniguchi, H. et al. Pirfenidone in idiopathic pulmonary fibrosis: a Phase III clinical trial in Japan. Eur. Resp. J. 8 Dec 2009 (doi: 10.1183/09031936.00005209).