Abstract
The aim of this article is to critically review the efficacy and safety data from randomized controlled trials (RCTs) using inhaled corticosteroids (ICSs), long- or short-acting β2-adrenoceptor agonists (LABAs, SABAs), parasympatholytics and oral leukotriene receptor antagonists in the management of exercise-induced bronchoconstriction (EIB) in children with persistent asthma (EIA).
The studies with sufficient information on patient characteristics and outcomes were chosen using a MEDLINE search. Results from the individual searches were combined and repeated. Studies were also found by reviewing the reference lists of the articles not included in this review. Studies focusing solely on individuals with asthma and other allergic co-morbidities (i.e. a degree of bronchial reversibility) were considered in this review. To make the paper evidence-based, the design and the quality of different studies were assessed employing the Sign criteria (evidence level [EL] and grades of recommendation [GR]). No additional statistical analyses were performed. Most of studies included paediatric patients with underlying EIA.
We need to distinguish children with recurrent asthma symptoms in whom EIB is also present (patients with EIA) from asthmatic subjects whose symptoms appear only as a result of exercise (patients with EIB). Further controller treatment is indicated in patients with EIA and further reliever treatment in patients with EIB. ICSs are the first-choice controller drugs for EIA in children with persistent asthma (Sign grade of recommendation [GR]:A). In children with EIA without complete control with ICSs, SABAs (GR:A), leukotriene receptor antagonists (LTRAs) [GR:A] or LABAs (GR:A) may be added to gain control. Treatment with relievers such as SABAs (GR:A), parasympatholytics (GR:B) or, eventually, LABAs (GR:A), administered 10–15 minutes before exercise is the most preferable method of preventing EIB symptoms in children; however, not as monotherapy in children with EIA.
The disadvantages and controversy relating to inhaled β2-adrenoceptor agonist use lie in the development of tolerance to their effect when they are used on a regular basis, and the possibility of a resulting underuse of ICSs in patients with EIA. Researchers and guidelines recommend that if any patient requires treatment with a β2-adrenoceptor agonist more than twice weekly, a low dose of ICSs should be administered. Inhaled parasympatholytics may be effective as preventive relievers in some children with EIB or EIA, especially among those with increased vagal activity. LTRAs have a well balanced efficacy-safety profile in preventing the occurrence of EIB symptoms in children. Compared with LABAs, LTRAs produce persistent attenuation of EIB and possess an additional effect with rescue SABA therapy in persistent asthmatic patients with EIA. A disadvantage of LTRAs is a non-response phenomenon. There are still insufficient data on the efficacy-safety profiles of ICS/LABA combination drugs in the treatment of EIA in children to recommend this treatment without caution. Safety profiles of inhaled SABAs, anticholinergics and montelukast in approved dosages seem sufficient enough to recommend use of these drugs in the prevention of EIB symptoms in children. Many researchers agree that treatment of EIA in children should always be individualized.
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References
From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2006 [online]. Available from URL: http://www.ginasthma.org [Accessed 2008 Nov 24]
Price DB. Choices of therapy for exercise-induced asthma in children. Allergy 2001; 56: Suppl. 66: 12–7
Bacharier LB, Boner A, Carlsen KH, et al. Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report. Allergy 2008 Jan; 63(1): 5–34
Carlsen KH, Anderson SD, Bjermer L, et al. Exercise-induced asthma, respiratory and allergic disorders in elite athletes: epidemiology, mechanisms and diagnosis: part I of the report from the Joint Task Force of the European Respiratory Society (ERS) and the European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA2LEN. Allergy 2008 Apr; 63(4): 387–403
Milgrom H, Taussig LM. Keeping children with exercise-induced asthma active. Pediatrics 1999; 104: e38
Crapo RO, Casaburi R, Coates AL, et al. Guidelines for methacholine and exercise challenge testing - 1999. Am J Respir Crit Care Med 2000 Jan; 161(1): 309–29
Haby MM, Anderson SD, Peat JK, et al. An exercise challenge protocol for epidemiological studies of asthma in children: comparison with histamine challenge. Eur Respir J 1994 Jan; 7(1): 43–9
Vidal C, Fernández-Ovide E, Piñeiro J, et al. Comparison of montelukast versus budesonide in the treatment of exercise-induced bronchoconstriction. Ann Allergy Asthma Immunol 2001 Jun; 86(6): 655–8
Thio BJ, Nagelkerke AF, Ketel AG, et al. Exercise-induced asthma and cardiovascular fitness in asthmatic children. Thorax 1996 Feb; 51(2): 207–9
Larsson K, Carlsen KH, Bonini S. Anti-asthmatic drugs: treatment of athletes and exercise-induced bronchoconstriction. In: Carlsen KH, Delgado L, DelGiacco S, editors. Diagnosis, prevention and treatment of exercise-related asthma, respiratory and allergic disorders in sports. Sheffield: European Respiratory Journals Ltd, 2005: 73–88
Carlsen KH, Anderson SD, Bjermer L, et al. Treatment of exercise-induced asthma, respiratory and allergic disorders in sports and the relationship to doping: part II of the report from the Joint Task Force of European Respiratory Society (ERS) and European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA (2) LEN. Allergy 2008 May; 63(5): 492–505
Weiler JM, Bonini S, Coifman R, et al. American Academy of Allergy, Asthma & Immunology Work Group report: exercise-induced asthma. J Allergy Clin Immunol 2007 Jun; 119(6): 1349–58
Subbarao P, Duong M, Adelroth E, et al. Effect of ciclesonide dose and duration of therapy on exercise-induced bronchoconstriction in patients with asthma. J Allergy Clin Immunol 2006 May; 117(5): 1008–13
Petersen R, Agertoft L, Pedersen S. Treatment of exercise-induced asthma with beclomethasone dipropionate in children with asthma. Eur Respir J 2004 Dec; 24(6): 932–7
Hofstra WB, Neijens HJ, Duiverman EJ, et al. Dose-responses over time to inhaled fluticasone propionate treatment of exercise- and metacholine-induced bronch-oconstriction in children with asthma. Pediatr Pulmonol 2000 Jun; 29(6): 415–23
Jonasson G, Carlsen KH, Blomqvist P. Clinical efficacy of low-dose inhaled budesonide once or twice daily in children with mild asthma not previously treated with steroids. Eur Respir J 1998 Nov; 12(5): 1099–104
Jonasson G, Carlsen K-H, Hultquist C. Low-dose budesonide improves exercise-induced bronchospasm in schoolchildren. Pediatr Allergy Immunol 2000 May; 11(2): 120–5
Jonasson G, Carlsen K-H, Jonasson C, et al. Low dose inhaled budesonide once or twice daily for 27 months in children with mild asthma. Allergy 2000 Aug; 55(8): 740–8
Henriksen JM, Dahl R. Effects of inhaled budesonide alone and in combination with low-dose terbutaline in children with exercise-induced asthma. Am Rev Respir Dis 1983 Dec; 128(6): 993–7
van Essen-Zandvliet EE, Hughes MD, Waalkens HJ, et al. Effects of 22 months of treatment with inhaled corticosteroids and/or beta-2-agonists on lung function, airway responsiveness, and symptoms in children with asthma. The Dutch Chronic Non-specific Lung Disease Study Group. Am Rev Respir Dis 1992 Sep; 146(3): 547–54
Waalkens HJ, van Essen-Zandvliet EE, Gerritsen J, et al. The effect of an inhaled corticosteroid (budesonide) on exercise-induced asthma in children. Dutch CNSLD Study Group. Eur Respir J 1993 May; 6(5): 652–6
Koh MS, Tee A, Lasserson TJ, et al. Inhaled corticosteroids compared to placebo for prevention of exercise induced bronchoconstriction. Cochrane Database Syst Rev 2007 Jul 18; (3): CD002739
Robuschi M, Riva E, Fuccella LM, et al. Prevention of exercise-induced bronchoconstriction by a new leukotriene antagonist (SK&F 104353): a double-blind study versus disodium cromoglycate and placebo. Am Rev Respir Dis 1992 Jun; 145(6): 1285–8
Kemp JP, Dockhorn RJ, Shapiro GG, et al. Montelukast once daily inhibits exercise-induced bronchoconstriction in 6- to 14-year-old children with asthma. J Pediatr 1998 Sep; 133(3): 424–8
Peroni DG, Piacentini GL, Ress M, et al. Time efficacy of a single dose of montelukast on exercise-induced asthma in children. Pediatr Allergy Immunol 2002 Dec; 13(6): 434–7
Peroni DG, Piacentini GL, Pietrobelli A, et al. The combination of single-dose montelukast and loratadine on exercise-induced bronchospasm in children. Eur Respir J 2002 Jul; 20(1): 104–7
Pajaron-Fernandez M, Garcia-Rubia S, Sanchez-Solis M, et al. Montelukast administered in the morning or evening to prevent exercise-induced bronchoconstriction in children. Pediatr Pulmonol 2006 Mar; 41(3): 222–7
Stelmach I, Grzelewski T, Bobrowska-Korzeniowska M, et al. A randomized, double-blind trial of the effect of anti-asthma treatment on lung function in children with asthma. Pulm Pharmacol Ther 2007; 20(6): 691–700
Kim JH, Lee SY, Kim HB, et al. Prolonged effect of montelukast in asthmatic children with exercise-induced bronchoconstriction. Pediatr Pulmonol 2005 Feb; 39(2): 162–6
de Benedictis FM, del Giudice MM, Forenza N, et al. Lack of tolerance to the protective effect of montelukast in exercise-induced bronchoconstriction in children. Eur Respir J 2006 Aug; 28(2): 291–5
Melo RE, Solé D, Naspitz CK. Exercise-induced bronchoconstriction in children: montelukast attenuates the immediate-phase and late-phase responses. J Allergy Clin Immunol 2003 Feb; 111(2): 301–7
Sano F, Solé D, Naspitz CK. Prevalence and characteristics of exercise-induced asthma in children. Pediatr Allergy Immunol 1998 Nov; 9(4): 181–5
Koh YY, Jeong JH, Jin SM, et al. The occurrence of late asthmatic response to exercise after allergen change. Ann Allergy Asthma Immunol 1998 Oct; 81(4): 366–72
Boner AL, Vallone G, Chiesa M, et al. Reproducibility of late phase pulmonary response to exercise and its relationship to bronchial hyperreactivity in children with chronic asthma. Pediatr Pulmonol 1992; 14: 156–9
Lee SY, Kim HB, Kim JH, et al. Responsiveness to montelukast is associated with bronchial hyperresponsiveness and total immunoglobulin E but not polymorphisms in the leukotriene C4 synthase and cysteinyl leukotriene receptor 1 genes in Korean children with exercise-induced asthma (EIA). Clin Exp Allergy 2007 Oct; 37(10): 1487–93
Kim JH, Lee SY, Kim HB, et al. TBXA2R gene polymorphism and responsiveness to leukotriene receptor antagonist in children with asthma. Clin Exp Allergy 2008 Jan; 38(1): 51–9
Tornhamre S, Ehnhage A, Kölbeck KG, et al. Uncoupled regulation of leukotriene C4 synthase in platelets from aspirin-intolerant asthmatics and healthy volunteers after aspirin treatment. Clin Exp Allergy 2002 Nov; 32(11): 1566–73
Kang MJ, Lee SY, Kim HB, et al. Association of IL-13 polymorphisms with leukotriene receptor antagonist drug responsiveness in Korean children with exercise-induced bronchoconstriction. Pharmacogenet Genomics 2008 Jul; 18(7): 551–8
Zhu Z, Homer RJ, Wang Z, et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Investig 1999 Mar; 103(6): 779–88
Chiba Y, Nakazawa S, Todoroki M, et al. Interleukin-13 augments bronchial smooth muscle contractility with an upregulation of RhoA protein. Am J Respir Cell Mol Biol 2009 Feb; 40(2): 159–67
National Asthma Education and Prevention Program. Expert Panel report: guidelines for the diagnosis and management of asthma update on selected topics - 2002. J Allergy Clin Immunol 2002 Nov; 110 (5 Suppl.): S141–219
Shapiro GS, Yegen U, Xiang J, et al. A randomized, double-blind, single-dose, crossover clinical trial of the onset and duration of protection from exercise-induced bronchoconstriction by formoterol and albuterol. Clin Ther 2002 Dec; 24(12): 2077–87
Avila-Castañón L, Casas-Becerra B, Del Río-Navarro BE, et al. Formoterol vs albuterol administered via Turbuhaler system in the emergency treatment of acute asthma in children. Allergol Immunopathol (Madr) 2004 Jan–Feb; 32(1): 18–20
Bronsky EA, Spector SL, Pearlman DS, et al. Albuterol aerosol versus albuterol Rotacaps in exercise-induced bronchospasm in children. J Asthma 1995; 32(3): 207–14
Raissy HH, Harkins M, Kelly F, et al. Pretreatment with albuterol versus montelukast for exercise-induced bronchospasm in children. Pharmacotherapy 2008 Mar; 28(3): 287–94
Zanconato S, Baraldi E, Santuz P, et al. Effect of inhaled disodium cromoglycate and albuterol on energy cost of running in asthmatic children. Pediatr Pulmonol 1990; 8(4): 240–4
Turner DJ, Landau LI, LeSouëf PN. The effect of age on bronchodilator responsiveness. Pediatr Pulmonol 1993 Feb; 15(2): 98–104
dos Santos JM, Costa H, Ståhl E, et al. Bricanyl Turbuhaler and Ventolin Rotahaler in exercise-induced asthma in children. Allergy 1991 Apr; 46(3): 203–5
Shapiro GG, Kemp JP, DeJong R, et al. Effects of albuterol and procaterol on exercise-induced asthma. Ann Allergy 1990 Oct; 65(4): 273–6
Henriksen JM, Agertoft L, Pedersen S. Protective effect and duration of action of inhaled formoterol and salbutamol on exercise-induced asthma in children. J Allergy Clin Immunol 1992 Jun; 89(6): 1176–82
Pfleger A, Eber E, Weinhandl E, et al. Effects of nedocromil and salbutamol on airway reactivity in children with asthma. Eur Respir J 2002 Sep; 20(3): 624–9
de Benedictis FM, Tuteri G, Pazzelli P, et al. Combination drug therapy for the prevention of exercise-induced bronchoconstriction in children. Ann Allergy Asthma Immunol 1998 Apr; 80(4): 352–6
Israel E, Chinchilli VM, Ford JG, et al. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet 2004 Oct 23-29; 364(9444): 1505–12
Berkowitz R, Schwartz E, Bukstein D, et al. Albuterol protects against exercise-induced asthma longer than metaproterenol sulfate. Pediatrics 1986 Feb; 77(2): 173–8
Inman MD, O’Byrne PM. The effect of regular inhaled albuterol on exercise-induced bronchoconstriction. Am J Respir Crit Care Med 1996 Jan; 153(1): 65–9
Juniper EF, Guyatt GH, Feeny DH, et al. Measuring quality of life in children with asthma. Qual Life Res 1996 Feb; 5(1): 35–46
Boner AL, Spezia E, Piovesan P, et al. Inhaled formoterol in the prevention of exercise-induced bronchoconstriction in asthmatic children. Am J Respir Crit Care Med 1994 Apr; 149 (4 Pt 1): 935–9
Daugbjerg P, Nielsen KG, Skov M, et al. Duration of action of formoterol and salbutamol dry-powder inhalation in prevention of exercise-induced asthma in children. Acta Paediatr 1996 Jun; 85(6): 684–7
Grönneröd TA, von Berg A, Schwabe G, et al. Formoterol via Turbuhaler gave better protection than terbutaline against repeated exercise challenge for up to 12 hours in children and adolescents. Respir Med 2000 Jul; 94(7): 661–7
Ferrari M, Segattini C, Zanon R, et al. Comparison of the protective effect of formoterol and of salmeterol against exercise-induced bronchospasm when given immediately before a cycloergometric test. Respiration 2002; 69(6): 509–12
Bronsky EA, Yegen U, Yeh CM, et al. Formoterol provides long-lasting protection against exercise-induced bronchospasm. Ann Allergy Asthma Immunol 2002 Oct; 89(4): 407–12
Hermansen MN, Nielsen KG, Buchvald F, et al. Acute relief of exercise-induced bronchoconstriction by inhaled formoterol in children with persistent asthma. Chest 2006 May; 129(5): 1203–9
García R, Guerra P, Feo F, et al. Tachyphylaxis following regular use of formoterol in exercise-induced bronchospasm. J Investig Allergol Clin Immunol 2001; 11(3): 176–82
Lipworth B, Tan S, Devlin M, et al. Effects of treatment with formoterol on bronchoprotection against methacholine. Am J Med 1998 May; 104(5): 431–8
FitzGerald JM, Chapman KR, Della Cioppa G, et al. Sustained bronchoprotection, bronchodilatation, and symptom control during regular formoterol use in asthma of moderate or greater severity. The Canadian FO/OD1 Study Group. J Allergy Clin Immunol 1999 Mar; 103 (3 Pt 1): 427–35
Davis BE, Reid JK, Cockcroft DW. Formoterol thrice weekly does not result in the development of tolerance to bronchoprotection. Can Respir J 2003 Jan-Feb; 10(1): 23–6
Nielsen KG, Skov M, Klug B, et al. Flow-dependent effect of formoterol dry-powder inhaled from the Aerolizer. Eur Respir J 1997 Sep; 10(9): 2105–9
Green CP, Price JF. Prevention of exercise induced asthma by inhaled salmeterol xinafoate. Arch Dis Child 1992 Aug; 67(8): 1014–7
Newnham DM, Ingram CG, Earnshaw J, et al. Salmeterol provides prolonged protection against exercise-induced bronchoconstriction in a majority of subjects with mild, stable asthma. Respir Med 1993 Aug; 87(6): 439–44
Sichletidis L, Daskalopoulou E, Kyriazis G, et al. Comparative efficacy of salbutamol and salmeterol in exercise-induced asthma. J Int Med Res 1993 Mar-Apr; 21(2): 81–8
Kemp JP, Dockhorn RJ, Busse WW, et al. Prolonged effect of inhaled salmeterol against exercise-induced bronchospasm. Am J Respir Crit Care Med 1994 Dec; 150 (6 Pt 1): 1612–5
Ramage L, Lipworth BJ, Ingram CG, et al. Reduced protection against exercise induced bronchoconstriction after chronic dosing with salmeterol. Respir Med 1994 May; 88(5): 363–8
Nielsen KG, Auk IL, Bojsen K, et al. Clinical effect of Diskus dry-powder inhaler at low and high inspiratory flow-rates in asthmatic children. Eur Respir J 1998 Feb; 11(2): 350–4
Bronsky EA, Pearlman DS, Pobiner BF, et al. Prevention of exercise-induced bronchospasm in pediatric asthma patients: a comparison of two salmeterol powder delivery devices. Pediatrics 1999 Sep; 104 (3 Pt 1): 501–6
de Benedictis FM, Tuteri G, Pazzelli P, et al. Salmeterol in exercise-induced bronchoconstriction in asthmatic children: comparison of two doses. Eur Respir J 1996 Oct; 9(10): 2099–103
Blake K, Pearlman DS, Scott C, et al. Prevention of exercise-induced bronchospasm in pediatric asthma patients: a comparison of salmeterol powder with albuterol. Ann Allergy Asthma Immunol 1999 Feb; 82(2): 205–11
Carlsen KH, Røksund O, Olsholt K, et al. Overnight protection by inhaled salmeterol on exercise-induced asthma in children. Eur Respir J 1995 Nov; 8(11): 1852–5
Simons FE, Gerstner TV, Cheang MS. Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled gluco-corticoid treatment. Pediatrics 1997 May; 99(5): 655–9
Villaran C, O’Neill SJ, Helbling A, et al. Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction. Montelukast/Salmeterol Exercise Study Group. J Allergy Clin Immunol 1999 Sep; 104 (3 Pt 1): 547–53
Nelson JA, Strauss L, Skowronski M, et al. Effect of long-term salmeterol treatment on exercise-induced asthma. N Engl J Med 1998 Jul 16; 339(3): 141–6
Bhagat R, Kalra S, Swystun VA, et al. Rapid onset of tolerance to the bronchoprotective effect of salmeterol. Chest 1995 Nov; 108(5): 1235–9
Yeung R, Nolan GM, Levison H. Comparison of the effects of inhaled SCH 1000 and fenoterol on exercise-induced bronchospasm in children. Pediatrics 1980 Jul; 66(1): 109–14
Knöpfli BH, Bar-Or O, Araújo CG. Effect of ipratropium bromide on EIB in children depends on vagal activity. Med Sci Sports Exerc 2005 Mar; 37(3): 354–9
Boner AL, Vallone G, De Stefano G. Effect of inhaled ipratropium bromide on methacholine and exercise provocation in asthmatic children. Pediatr Pulmonol 1989; 6(2): 81–5
Greenough A, Yuksel B, Everett L, et al. Inhaled ipratropium bromide and terbutaline in asthmatic children. Respir Med 1993; 87: 111–4
Edelman JM, Turpin JA, Bronsky EA, et al. Oral montelukast compared with inhaled salmeterol to prevent exercise-induced bronchoconstriction: a randomized, double-blind trial. Exercise Study Group. Ann Intern Med 2000 Jan 18; 132(2): 97–104
Storms W, Chervinsky P, Ghannam AF, et al. A comparison of the effects of oral montelukast and inhaled salmeterol on response to rescue bronchodilation after challenge. Respir Med 2004 Nov; 98(11): 1051–62
Philip G, Pearlman DS, Villarán C, et al. Single-dose montelukast or salmeterol as protection against exercise-induced bronchoconstriction. Chest 2007 Sep; 132(3): 875–83
Lecheler J, Pfannebecker B, Nguyen DT, et al. Prevention of exercise-induced asthma by a fixed combination of disodium cromoglycate plus reproterol compared with montelukast in young patients. Arzneimittelforschung 2008; 58(6): 303–9
Juergens UR, Stöber M, Libertus H, et al. Different mechanisms of action of beta2-adrenergic receptor agonists: a comparison of reproterol, fenoterol and salbutamol on monocyte cyclic-AMP and leukotriene B4 production in vitro. Eur J Med Res 2004 Jul 30; 9(7): 365–70
Bousquet J, Boulet LP, Peters MJ, et al. Budesonide/ formoterol for maintenance and relief in uncontrolled asthma vs high-dose salmeterol/fluticasone. Respir Med 2007 Dec; 101(12): 2437–46
Pohunek P, Matulka M, Rybnícek O, et al. Dose-related efficacy and safety of formoterol (Oxis) Turbuhaler compared with salmeterol Diskhaler in children with asthma. Pediatr Allergy Immunol 2004 Feb; 15(1): 32–9
Richter K, Janicki S, Jörres RA, et al. Acute protection against exercise-induced bronchoconstriction by formoterol, salmeterol and terbutaline. Eur Respir J 2002 May; 19(5): 865–71
Brogden RN, Faulds D. Salmeterol xinafoate: a review of its pharmacological properties and therapeutic potential in reversible obstructive airways disease. Drugs 1991 Nov; 42(5): 895–912
Bartow RA, Brogden RN. Formoterol. An update of its pharmacological properties and therapeutic efficacy in the management of asthma. Drugs 1998 Feb; 55(2): 303–22
Lasserson TJ, Cates CJ, Ferrara G, et al. Combination fluticasone and salmeterol versus fixed dose combination budesonide and formoterol for chronic asthma in adults and children. Cochrane Database Syst Rev 2008 Jul 16; (3): CD004106
Weiler JM, Nathan RA, Rupp NT, et al. Effect of fluticasone/salmeterol administered via a single device on exercise-induced bronchospasm in patients with persistent asthma. Ann Allergy Asthma Immunol 2005 Jan; 94(1): 65–72
Papi A, Paggiaro P, Nicolini G, et al. Beclomethasone/ formoterol vs fluticasone/salmeterol inhaled combination in moderate to severe asthma. Allergy 2007 Oct; 62(10): 1182–8
Stelmach I, Grzelewski T, Majak P, et al. Effect of different antiasthmatic treatments on exercise-induced bronchoconstriction in children with asthma. J Allergy Clin Immunol 2008 Feb; 121(2): 383–9
Priftis K. Commentary: faculty of 1000 medicine, 28 Mar 2008 [online]. Available from URL: http://www.f1000medicine.com/article/id/1104485/evaluation [Accessed 2008 Nov 25]
Hallstrand T. Commentary: faculty of 1000 medicine, 18 Apr 2008 [online]. Available from URL: http://www.f1000medicine.com/article/id/1104485/evaluation [Accessed 2008 Nov 25]
Litonjua AA. The significance of beta2-adrenergic receptor polymorphisms in asthma. Curr Opin Pulm Med 2006 Jan; 12(1): 12–7
Nelson HS, Weiss ST, Bleecker ER, et al. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest 2006 Jan; 129(1): 15–26
Castle W, Fuller R, Hall J. Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment. BMJ 1993 Apr 17; 306(6884): 1034–7
FDA Public Health Advisory Serevent Diskus (salmeterol xinafoate inhalation powder), Advair Diskus (fluticasone propionate & salmeterol inhalation powder), Foradil Aerolizer (formoterol fumarate inhalation powder). Created: November 18, 2005, updated May 15, 2006 [online]. Available from URL: http://www.fda.gov/cder/drug/advisory/LABA.htm [Accessed 2008 Nov 24]
Palmer CN, Lipworth BJ, Lee S, et al. Arginine-16 beta2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol. Thorax 2006 Nov; 61(11): 940–4
Tötterman KJ, Huhti L, Sutinen E, et al. Tolerability to high doses of formoterol and terbutaline via Turbuhaler for 3 days in stable asthmatic patients. Eur Respir J 1998 Sep; 12(3): 573–9
Rosenborg J, Larsson R, Rott Z, et al. Relative therapeutic index between inhaled formoterol and salbutamol in asthma patients. Respir Med 2002 Jun; 96(6): 412–7
Foucard T, Lönnerholm G. A study with cumulative doses of formoterol and salbutamol in children with asthma. Eur Respir J 1991 Nov; 4(10): 1174–7
Malolepszy J, Böszörményi Nagy G, Selroos O, et al. Safety of formoterol Turbuhaler at cumulative dose of 90 microg in patients with acute bronchial obstruction. Eur Respir J 2001 Dec; 18(6): 928–34
Morice AH, Peterson S, Beckman O, et al. Efficacy and safety of a new pressurised metered-dose inhaler formulation of budesonide/formoterol in children with asthma: a superiority and therapeutic equivalence study. Pulm Pharmacol Ther 2008; 21(1): 152–9
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Grzelewski, T., Stelmach, I. Exercise-Induced Bronchoconstriction in Asthmatic Children. Drugs 69, 1533–1553 (2009). https://doi.org/10.2165/11316720-000000000-00000
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DOI: https://doi.org/10.2165/11316720-000000000-00000