Use of hyperpolarized helium-3 MRI to assess response to ivacaftor treatment in patients with cystic fibrosis

被引:67
作者
Altes, Talissa A. [1 ]
Johnson, Mac [2 ]
Fidler, Meredith [2 ]
Botfield, Martyn [2 ]
Tustison, Nicholas J. [3 ]
Leiva-Salinas, Carlos [4 ]
de lange, Eduard E. [4 ]
Froh, Deborah [5 ]
Mugler, John P., III [6 ]
机构
[1] Univ Missouri, Dept Radiol, One Hosp Dr, Columbia, MO 65212 USA
[2] Vertex Pharmaceut Inc, 50 Northern Ave, Boston, MA 02210 USA
[3] Univ Virginia, 480 Ray C Hunt Dr,Snyder Bldg,Off 124, Charlottesville, VA 22903 USA
[4] Univ Virginia, Univ Hosp, First Floor 1215 Lee St, Charlottesville, VA 22908 USA
[5] Univ Virginia, 100 Hosp Dr 5408, Charlottesville, VA 22903 USA
[6] Univ Virginia, Snyder Translat Res Bldg,Room 154, Charlottesville, VA 22903 USA
关键词
cystic fibrosis transmembrane conductance regulator modulator; forced expiratory volume; pulmonary; OUTCOME MEASURES; G551D MUTATION; LUNG-FUNCTION; SMALL AIRWAYS; CHILDREN; EFFICACY; SPIROMETRY; SAFETY; DISEASE;
D O I
10.1016/j.jcf.2016.12.004
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Background: This pilot study evaluated the effect of short-and long-term ivacaftor treatment on hyperpolarized He-3-magnetic resonance imaging (MRI) defined ventilation defects in patients with cystic fibrosis aged >= 12 years with a G551D-CFTR mutation. Methods: Part A (single-blind) comprised 4 weeks of ivacafior treatment; Part B (open-label) comprised 48 weeks of treatment. The primary outcome was change from baseline in total ventilation defect (TVD; total defect volume:total lung volume ratio). Results: Mean change in TVD ranged from -8.2% (p = 0.0547) to 12.8% (p = 0.0078) in Part A (n = 8) and -6.3% (p = 0.1953) to 9.0% (p = 0.0547) in Part B (n = 8) as assessed by human reader and computer algorithm, respectively. Conclusions: TVD responded to ivacaftor therapy. He-3-MRI provides an individual quantification of disease burden that may be able to detect aspects of the disease missed by population-based spirometry metrics. Assessments by human reader.and computer algorithm exhibit similar trends, but the latter appears more sensitive. (C) 2016 The Authors. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.
引用
收藏
页码:267 / 274
页数:8
相关论文
共 28 条
[1]   Hyperpolarized 3He MR lung ventilation imaging in asthmatics:: Preliminary findings [J].
Altes, TA ;
Powers, PL ;
Knight-Scott, J ;
Rakes, G ;
Platts-Mills, TAE ;
de Lange, EE ;
Alford, BA ;
Mugler, JP ;
Brookeman, JR .
JOURNAL OF MAGNETIC RESONANCE IMAGING, 2001, 13 (03) :378-384
[2]  
Altes TA, 2012, P INT SOC MAG RESON, V20, P1355
[3]  
[Anonymous], 2015, KAL PACK INS
[4]   Hyperpolarized 3He MR for Sensitive Imaging of Ventilation Function and Treatment Efficiency in Young Cystic Fibrosis Patients with Normal Lung Function [J].
Bannier, Elise ;
Cieslar, Katarzyna ;
Mosbah, Karim ;
Aubert, Francoise ;
Duboeuf, Francois ;
Salhi, Zahir ;
Gaillard, Sophie ;
Berthezene, Yves ;
Cremillieux, Yannick ;
Reix, Philippe .
RADIOLOGY, 2010, 255 (01) :225-232
[5]   RELATIONS BETWEEN STRUCTURAL-CHANGES IN SMALL AIRWAYS AND PULMONARY-FUNCTION TESTS [J].
COSIO, M ;
GHEZZO, H ;
HOGG, JC ;
CORBIN, R ;
LOVELAND, M ;
DOSMAN, J ;
MACKLEM, PT .
NEW ENGLAND JOURNAL OF MEDICINE, 1978, 298 (23) :1277-1281
[6]   Efficacy and Safety of Ivacaftor in Patients Aged 6 to 11 Years with Cystic Fibrosis with a G551D Mutation [J].
Davies, Jane C. ;
Wainwright, Claire E. ;
Canny, Gerard J. ;
Chilvers, Mark A. ;
Howenstine, Michelle S. ;
Munck, Anne ;
Mainz, Jochen G. ;
Rodriguez, Sally ;
Li, Haihong ;
Yen, Karl ;
Ordonez, Claudia L. ;
Ahrens, Richard .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2013, 187 (11) :1219-1225
[7]   Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation [J].
De Boeck, Kris ;
Munck, Anne ;
Walker, Seth ;
Faro, Albert ;
Hiatt, Peter ;
Gilmartin, Geoffrey ;
Higgins, Mark .
JOURNAL OF CYSTIC FIBROSIS, 2014, 13 (06) :674-680
[8]   Cystic fibrosis:: Combined hyperpolarized 3He-enhanced and conventional proton MR imaging in the lung -: Preliminary observations [J].
Donnelly, LF ;
MacFall, JR ;
McAdams, HP ;
Majure, JM ;
Smith, J ;
Frush, DP ;
Bogonad, P ;
Charles, HC ;
Ravin, CE .
RADIOLOGY, 1999, 212 (03) :885-889
[9]  
European Medicines Agency, 2012, Report of the workshop on endpoints for cystic fibrosis clinical trials (EMA/769571/2012)
[10]   Clinically Useful Spirometry in Preschool-Aged Children: Evaluation of the 2007 American Thoracic Society Guidelines [J].
Gaffin, Jonathan M. ;
Shotola, Nancy Lichtenberg ;
Martin, Thomas R. ;
Phipatanakul, Wanda .
JOURNAL OF ASTHMA, 2010, 47 (07) :762-767