Treatment of Idiopathic Pulmonary Fibrosis with Losartan: A Pilot Project

被引:60
作者
Couluris, Marisa [1 ]
Kinder, Brent W. [2 ]
Xu, Ping [3 ]
Gross-King, Margaret [3 ]
Krischer, Jeffrey [3 ]
Panos, Ralph J. [2 ]
机构
[1] Univ S Florida, Dept Pediat, Coll Med, Div Pulmonol, Tampa, FL 33612 USA
[2] Univ Cincinnati, Dept Med, Div Pulm & Crit Care, Cincinnati, OH 45221 USA
[3] Univ S Florida, Dept Pediat, Coll Med, Div Epidemiol, Tampa, FL 33612 USA
关键词
Pulmonary fibrosis; Angiotensin receptor blocker; Forced vital capacity; Dyspnea; Six-minute walk test; PLACEBO-CONTROLLED TRIAL; II RECEPTOR ANTAGONIST; ANGIOTENSIN-II; LUNG FIBROSIS; MYOCARDIAL FIBROSIS; LIVER FIBROSIS; PIRFENIDONE; BOSENTAN; MODEL;
D O I
10.1007/s00408-012-9410-z
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
100201 [内科学];
摘要
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. Patients with idiopathic pulmonary fibrosis and a baseline %FVC of a parts per thousand yen50 % 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. 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. 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.
引用
收藏
页码:523 / 527
页数:5
相关论文
共 34 条
[1]
Amer Thoracic Soc, 2000, AM J RESP CRIT CARE, V161, P646
[2]
Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis [J].
Bjoraker, JA ;
Ryu, JH ;
Edwin, MK ;
Myers, JL ;
Tazelaar, HD ;
Schroeder, DR ;
Offord, KP .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1998, 157 (01) :199-203
[3]
Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy [J].
Brenner, BM ;
Cooper, ME ;
de Zeeuw, D ;
Keane, WF ;
Mitch, WE ;
Parving, HH ;
Remuzzi, G ;
Snapinn, SM ;
Zhang, ZX ;
Shahinfar, S .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 345 (12) :861-869
[4]
Hemodynamic and antifibrotic effects of losartan in rats with liver fibrosis and/or portal hypertension [J].
Croquet, V ;
Moal, F ;
Veal, N ;
Wang, JH ;
Oberti, F ;
Roux, J ;
Vuillemin, E ;
Gallois, Y ;
Douay, O ;
Chappard, D ;
Calès, P .
JOURNAL OF HEPATOLOGY, 2002, 37 (06) :773-780
[5]
Imatinib Treatment for Idiopathic Pulmonary Fibrosis Randomized Placebo-controlled Trial Results [J].
Daniels, Craig E. ;
Lasky, Joseph A. ;
Limper, Andrew H. ;
Mieras, Kathleen ;
Gabor, Edith ;
Schroeder, Darrell R. .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2010, 181 (06) :604-610
[6]
Losartan-dependent regression of myocardial fibrosis is associated with reduction of left ventricular chamber stiffness in hypertensive patients [J].
Díez, J ;
Querejeta, R ;
López, B ;
González, A ;
Larman, M ;
Ubago, JLM .
CIRCULATION, 2002, 105 (21) :2512-2517
[7]
Repeatability of spirometry in 18,000 adult patients [J].
Enright, PL ;
Beck, KC ;
Sherrill, DL .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2004, 169 (02) :235-238
[8]
Angiotensin receptor blockade decreases fibrosis and fibroblast expression in a rat model of unilateral ureteral obstruction [J].
Kellner, Daniel ;
Chen, Jie ;
Richardson, Ingride ;
Seshan, Surya V. ;
el Chaar, Maher ;
Vaughan, E. D., Jr. ;
Poppas, Dix ;
Felsen, Diane .
JOURNAL OF UROLOGY, 2006, 176 (02) :806-812
[9]
BUILD-1:: A randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis [J].
King, Talmadge E., Jr. ;
Behr, Juergen ;
Brown, Kevin K. ;
du Bois, Roland M. ;
Lancaster, Lisa ;
de Andrade, Joao A. ;
Staehler, Gerd ;
Leconte, Isabelle ;
Roux, Sebastien ;
Raghu, Ganesh .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2008, 177 (01) :75-81
[10]
BUILD-3: A Randomized, Controlled Trial of Bosentan in Idiopathic Pulmonary Fibrosis [J].
King, Talmadge E., Jr. ;
Brown, Kevin K. ;
Raghu, Ganesh ;
du Bois, Roland M. ;
Lynch, David A. ;
Martinez, Fernando ;
Valeyre, Dominique ;
Leconte, Isabelle ;
Morganti, Adele ;
Roux, Sebastien ;
Behr, Juergen .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2011, 184 (01) :92-99