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Treatment of Idiopathic Pulmonary Fibrosis with Losartan: A Pilot Project

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Abstract

Background

Idiopathic pulmonary fibrosis is a progressive interstitial lung disease with no current effective therapies. Treatment has focused on antifibrotic agents to stop proliferation of fibroblasts and collagen deposition in the lung. We present the first clinical trial data on the use of losartan, an antifibrotic agent, to treat idiopathic pulmonary fibrosis. The primary objective was to evaluate the effect of losartan on progression of idiopathic pulmonary fibrosis measured by the change in percentage of predicted forced vital capacity (%FVC) after 12 months. Secondary outcomes included the change in forced expiratory volume at 1 second, diffusing capacity of carbon monoxide, 6-minute walk test distance, and baseline/transition dyspnea index.

Methods

Patients with idiopathic pulmonary fibrosis and a baseline %FVC of ≥50 % were treated with losartan 50 mg by mouth daily for 12 months. Pulmonary function testing, 6-minute walk, and breathlessness indices were measured every 3 months.

Results

Twenty participants with idiopathic pulmonary fibrosis were enrolled and 17 patients were evaluable for response. Twelve patients had a stable or improved %FVC at study month 12. Similar findings were observed in secondary end-point measures, including 58, 71, and 65 % of patients with stable or improved forced expiratory volume at 1 second, diffusing capacity for carbon monoxide, and 6-minute walk test distance, respectively. No treatment-related adverse events that resulted in early study discontinuation were reported.

Conclusion

Losartan stabilized lung function in patients with idiopathic pulmonary fibrosis over 12 months. Losartan is a promising agent for the treatment of idiopathic pulmonary fibrosis and has a low toxicity profile.

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References

  1. ATS/ERS (2000) Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. Am J Respir Crit Care Med 161(2 Pt 1):646–664

    Google Scholar 

  2. Bjoraker JA, Ryu JH, Edwin MK, Myers JL, Tazelaar HD, Schroeder DR, Offord KP (1998) Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 157:199–203

    PubMed  CAS  Google Scholar 

  3. King TE Jr, Tooze JA, Schwarz MI (2001) Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model. Am J Respir Crit Care Med 164:1171–1181

    PubMed  Google Scholar 

  4. Marshall RP, Gohlke P, Chambers RC et al (2004) Angiotensin II and the fibroproliferative response to acute lung injury. Am J Physiol Lung Cell Mol Physiol 286:L156–L164

    Article  PubMed  CAS  Google Scholar 

  5. Papp M, Li X, Zhuang J et al (2002) Angiotensin receptor subtype AT(1) mediates alveolar epithelial cell apoptosis in response to ANG II. Am J Physiol Lung Cell Mol Physiol 282:L714–L718

    Google Scholar 

  6. Yao HW, Zhu JP, Zhao MH, Lu Y (2006) Losartan attenuates bleomycin-induced pulmonary fibrosis in rats. Respiration 73(2):236–242

    PubMed  CAS  Google Scholar 

  7. Molteni A, Moulder JE, Cohen EF et al (2000) Control of radiation-induced pneumopathy and lung fibrosis by angiotensin-converting enzyme inhibitors and an angiotensin II type 1 receptor blocker. Int J Radiat Biol 76(4):523–532

    Article  PubMed  CAS  Google Scholar 

  8. Li X, Rayford H, Uhal BD (2003) Essential roles for angiotensin receptor AT1a in bleomycin-induced apoptosis and lung fibrosis in mice. Am J Pathol 163:2523–2530

    Article  PubMed  CAS  Google Scholar 

  9. Wei H, Li D, Lu H et al (2000) Effects of angiotensin II receptor blockade on hepatic fibrosis in rats. Zhonghua Gan Zang Bing Za Zhi 8(5):302–304

    PubMed  CAS  Google Scholar 

  10. Wei HS, Li DG, Lu HM et al (2000) Effects of AT1 receptor antagonist, losartan, on rat hepatic fibrosis induced by CCl(4). World J Gastroenterol 6(4):540–545

    PubMed  CAS  Google Scholar 

  11. Wei YH, Jun L, Qiang CJ (2004) Effect of losartan, an angiotensin II antagonist, on hepatic fibrosis induced by CCl4 in rats. Dig Dis Sci 49(10):1589–1594

    Article  PubMed  CAS  Google Scholar 

  12. Molina-Molina M, Serrano-Mollar A, Bulbena O et al (2006) Losartan attenuates bleomycin-induced lung fibrosis by increasing prostaglandin-E2 synthesis. Thorax 61:604–610

    Article  PubMed  CAS  Google Scholar 

  13. Park DH, Baik SK, Choi YH et al (2007) Inhibitory effect of angiotensin blockade on hepatic fibrosis in common bile duct-ligated rats. Korean J Hepatol 13(1):61–69

    PubMed  Google Scholar 

  14. Croquet V, Moal F, Veal N et al (2002) Hemodynamic and antifibrotic effects of losartan in rats with liver fibrosis and/or portal hypertension. J Hepatol 37(6):773–780

    Article  PubMed  CAS  Google Scholar 

  15. Kellner D, Chen J, Richardson I et al (2006) Angiotensin receptor blockade decreases fibrosis and fibroblast expression in a rat model of unilateral ureteral obstruction. J Urol 172(2):806–812

    Article  Google Scholar 

  16. Moulder JE, Fish BL, Cohen EP (1998) Angiotensin II receptor antagonist in the treatment and prevention of radiation nephropathy. Int J Radiat Biol 73(4):415–421

    Article  PubMed  CAS  Google Scholar 

  17. Liang X, Xie X, Yang T, Sun M, Zhao S (2002) Apoptosis, myocardial fibrosis and angiotensin II in the left ventricle of hypertensive rats treated with fosinopril or losartan. Chin Med J (Engl) 115(9):1287–1291

    Google Scholar 

  18. Lim DS, Lutucuta S, Bachireddy P, Youker K, Evans A, Entman M, Roberts R, Marian AJ (2001) Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy. Circulation 103:789–791

    Article  PubMed  CAS  Google Scholar 

  19. Sookoian S, Fernández MA, Castaño G (2005) Effects of six months losartan administration on liver fibrosis in chronic hepatitis C patients: a pilot study. World J Gastroenterol 11(48):7560–7563

    PubMed  CAS  Google Scholar 

  20. Shibasaki Y, Nishiue T, Masaki H, Tamura K, Matsumoto N, Mori Y et al (2005) Impact of the angiotensin II receptor antagonist, losartan, on myocardial fibrosis in patients with end-stage renal disease: assessment by ultrasonic integrated backscatter and biochemical markers. Hypertens Res 28:787–795

    Article  PubMed  CAS  Google Scholar 

  21. Díez J, Querejeta R, López B, González A, Larman M, Martínez Ubago JL (2002) Losartan-dependent regression of myocardial fibrosis is associated with reduction of left ventricular chamber stiffness in hypertensive patients. Circulation 106(25):12–17

    Google Scholar 

  22. Yokohama S, Yoneda M, Haneda M, Okamoto S, Okada M, Aso K, Hasegawa T, Tokusashi Y, Miyokawa N, Nakamura K (2004) Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology 40(5):1222–1225

    Article  PubMed  CAS  Google Scholar 

  23. Enright PL, Beck KC, Sherrill DL (2004) Repeatability of spirometry in 18,000 adult patients. Am J Respir Crit Care Med 169:235–238

    Article  PubMed  Google Scholar 

  24. Swigris JJ, Wamboldt FS, Behr J, du Bois RM, King TE, Raghu G, Brown K (2010) The 6 minute walk in idiopathic pulmonary fibrosis: longitudinal changes and minimum important difference. Thorax 65:173–177

    Article  PubMed  Google Scholar 

  25. Brenner BM, Cooper ME, de Zeeuw D et al (2001) Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345(12):861–869

    Article  PubMed  CAS  Google Scholar 

  26. López G, Querejeta R, Larman M, Díez J (2005) Myocardial COX-2 overexpression and fibrosis in hypertensive heart disease. Am J Hypertens 18(5 Pt 2):A223–A233

    Google Scholar 

  27. Raghu G, Brown KK, Bradford WZ et al (2004) A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis. N Engl J Med 250(2):125–133

    Article  Google Scholar 

  28. Raghu G, Brown KK, Costabel U et al (2008) Treatment of idiopathic pulmonary fibrosis with etanercept: an exploratory, placebo-controlled trial. Am J Respir Crit Care Med 178(9):948–955

    Article  PubMed  CAS  Google Scholar 

  29. Daniels CE, Lasky JA, Limper AH, Mieras K, Gabor E, Schroeder DR (2010) Imatinib treatment for idiopathic pulmonary fibrosis: randomized placebo-controlled trial results. Am J Respir Crit Care Med 181(6):604–610

    Article  PubMed  CAS  Google Scholar 

  30. King TE Jr, Behr J, Brown KK et al (2008) BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 177(1):75–81

    Article  PubMed  CAS  Google Scholar 

  31. King TE Jr, Brown KK, Raghu G, duBois RM, Lynch DA, Martinez F, Valeyre D, Leconte I, Morganti A, Roux S, Behr J (2011) BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 184:92–99

    Article  PubMed  Google Scholar 

  32. Raghu G, Johnson WC, Lockhart D, Mageto Y (1999) 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

    PubMed  CAS  Google Scholar 

  33. Noble PW, Albera C, Bradford WZ et al (2011) Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet 377(9779):1760–1769

    Article  PubMed  CAS  Google Scholar 

  34. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK (2011) An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183(6):788–824

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the SunCoast CCOP Research Base (award No. U10CA081920 from the National Cancer Institute). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

Conflict of interest

The authors have no conflicts of interest or financial ties to disclose.

Ethical standards

The experiment complies with the current laws of the United States of America.

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Authors and Affiliations

  1. Division of Pulmonology, Department of Pediatrics, University of South Florida College of Medicine, Tampa, FL, USA

    Marisa Couluris

  2. Division of Pulmonary and Critical Care, Department of Medicine, University of Cincinnati, Cincinnati, OH, USA

    Brent W. Kinder & Ralph J. Panos

  3. Division of Epidemiology, Department of Pediatrics, University of South Florida College of Medicine, Tampa, FL, USA

    Ping Xu, Margaret Gross-King & Jeffrey Krischer

  4. Department of Pediatrics, University of South Florida, 3650 Spectrum Blvd., Suite 100, Tampa, FL, 33612, USA

    Marisa Couluris

Authors
  1. Marisa Couluris
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  2. Brent W. Kinder
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  3. Ping Xu
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  4. Margaret Gross-King
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  5. Jeffrey Krischer
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Correspondence to Marisa Couluris.

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Couluris, M., Kinder, B.W., Xu, P. et al. Treatment of Idiopathic Pulmonary Fibrosis with Losartan: A Pilot Project. Lung 190, 523–527 (2012). https://doi.org/10.1007/s00408-012-9410-z

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  • DOI: https://doi.org/10.1007/s00408-012-9410-z

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