The safety and effects of the beta-blocker, nadolol, in mild asthma: An open-label pilot study

被引:99
作者
Hanania, Nicola A. [1 ]
Singh, Supria [1 ]
El-Wali, Rami [1 ]
Flashner, Michael [2 ]
Franklin, Amie E. [2 ]
Garner, William J. [2 ]
Dickey, Burton F. [3 ]
Parra, Sergio [5 ]
Ruoss, Stephen [4 ]
Shardonofsky, Felix [6 ]
O'Connor, Brian J. [7 ]
Page, Clive [8 ]
Bond, Richard A. [5 ]
机构
[1] Baylor Coll Med, Pulm & Crit Care Med Sect, Houston, TX 77030 USA
[2] Inverseon Inc, San Francisco, CA USA
[3] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA
[4] Stanford Univ, Sch Med, Div Pulm & Crit Care Med, Stanford, CA 94305 USA
[5] Univ Houston, Dept Pharmacol & Pharmaceut Sci, Houston, TX USA
[6] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA
[7] Kings Coll London, Sch Med, Div Asthma Allergy & Lung Biol, London, England
[8] Kings Coll London, Div Pharmaceut Sci, Sackler Inst Pulm Pharmacol, London, England
基金
美国国家卫生研究院;
关键词
Asthma; Beta-blockers; Beta(2)-adrenoceptor agonist; Airway hyperresponsiveness;
D O I
10.1016/j.pupt.2007.07.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Beta-blockers are currently contraindicated in asthma because their acute administration may be associated with worsening bronchospasm. However. their effects and safety with their chronic administration are not well evaluated. The rationale for this pilot study was based on the paradigm shift that was observed with the use of beta-blockers in congestive heart failure, which once contraindicated because of their acute detrimental effects, have now been shown to reduce mortality with their chronic use. We hypothesized that certain beta-blockers may also be safe and useful in chronic asthma therapy. In this prospective, open-label, pilot study, we evaluated the safety and effects of escalating doses of the beta-blocker, nadolol, administered over 9 weeks to 10 Subjects with mild asthma. Dose escalation was performed on a weekly basis based on pre-determined safety, lung function.. asthma control and hemodynamic parameters. The primary objective was to evaluate safety and secondary objectives were to evaluate effects oil airway hyperresponsiveness, and indices of respiratory function. The escalating administration of nadolol was well tolerated. In 8 Out of the 10 subjects, 9 weeks of nadolol treatment produced a significant, dose-dependent increase in PC(20) that reached 2.1 doubling doses at 40 mg (P<0.0042). However, there was also a dose-independent 5% reduction in mean FEV1 over the study period (P<0.01). We conclude that in most patients with mild asthma, the dose-escalating administration of the beta-blocker, nadolol, is well tolerated and may have beneficial effects on airway hyperresponsiveness. Our findings warrant further testing in future larger trials. (C) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:134 / 141
页数:8
相关论文
共 45 条
[1]   Beta-blocker goes on trial as asthma therapy [J].
Abbott, A .
NATURE, 2004, 432 (7013) :7-7
[2]  
Abramson Michael J, 2003, Am J Respir Med, V2, P287
[3]  
[Anonymous], P AM THORAC SOC
[4]   β-agonists:: What is the evidence that their use increases the risk of asthma morbidity and mortality? [J].
Beasley, R ;
Pearce, N ;
Crane, J ;
Burgess, C .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1999, 104 (02) :S18-S30
[5]   Can intellectualism stifle scientific discovery? [J].
Bond, RA .
NATURE REVIEWS DRUG DISCOVERY, 2002, 1 (10) :825-829
[6]   Is paradoxical pharmacology a strategy worth pursuing? [J].
Bond, RA .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2001, 22 (06) :273-276
[7]   Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure [J].
Bristow, MR ;
Gilbert, EM ;
Abraham, WT ;
Adams, KF ;
Fowler, MB ;
Hershberger, RE ;
Kubo, SH ;
Narahara, KA ;
Ingersoll, H ;
Krueger, S ;
Young, S ;
Shusterman, N .
CIRCULATION, 1996, 94 (11) :2807-2816
[8]   Effects of acute and chronic administration of β-adrenoceptor ligands on airway function in a murine model of asthma [J].
Callaerts-Vegh, Z ;
Evans, KLJ ;
Dudekula, N ;
Cuba, D ;
Knoll, BJ ;
Callaerts, PFK ;
Giles, H ;
Shardonofsky, FR ;
Bond, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (14) :4948-4953
[9]   REGULAR INHALED SALBUTAMOL AND AIRWAY RESPONSIVENESS TO ALLERGEN [J].
COCKCROFT, DW ;
MCPARLAND, CP ;
BRITTO, SA ;
SWYSTUN, VA ;
RUTHERFORD, BC .
LANCET, 1993, 342 (8875) :833-837
[10]  
Crapo RO, 2000, AM J RESP CRIT CARE, V161, P309