Treatments in Respiratory Medicine

, Volume 3, Issue 6, pp 365–379 | Cite as

Single-Dose Agents in the Prevention of Exercise-Induced Asthma

A Descriptive Review
  • Sandra D. Anderson
Review Article


Exercise-induced asthma (EIA) refers to the transient narrowing of the airways that occurs after vigorous exercise in 50–60% of patients with asthma. The need to condition the air inspired during exercise causes water to be lost from the airway surface, and this is thought to cause the release of inflammatory mediators (histamine, leukotrienes, and prostaglandins) from mast cells. EIA is associated with airway inflammation and its severity is markedly reduced following treatment with inhaled corticosteroids. Drugs that inhibit the release of mediators and drugs that inhibit their contractile effects are the most successful in inhibiting EIA. Single doses of short-acting β2-adrenoceptor agonists, given as aerosols immediately before exercise, are very effective in the majority of patients with asthma, providing about 80% protection for up to 2 hours. Long-acting β2-adrenoceptor agonists (LABAs) given in single doses can be effective for up to 12 hours when used intermittently, but tolerance to the protective effect occurs if they are taken daily. Drugs such as cromolyn sodium (sodium cromoglicate) and nedocromil given as aerosols are less effective than β2-adrenoceptor agonists (β2-agonists), providing 50–60% protection for only 1–2 hours, but they have some advantages. They do not induce tolerance, the aerosol dosage can be easily titrated for the individual, and the protective effect is immediate. Because they cause no significant adverse effects, multiple doses can be used in a day. Leukotriene receptor antagonists, such as montelukast and zafirlukast, are also used for the prevention of EIA and provide 50–60% protection for up to 24 hours when given as tablets. Tolerance to the protective effect does not develop with regular use. If breakthrough EIA occurs, a β2-agonist can be used effectively for rescue medication. For those patients with more persistent symptoms, the use of a LABA in combination with an inhaled corticosteroid has raised a number of issues with respect to the choice of prophylactic treatment for EIA. The most important issue is the development of tolerance to the protective effect of a LABA such that extra treatment may be needed in the middle of a treatment period. Recommending extra doses of a β2-agonist to control EIA is not advisable on the basis that multiple doses can enhance the severity of EIA, delay spontaneous recovery from bronchoconstriction, and enhance responses to other contractile stimuli. It is time to take into account the advantages and disadvantages of the different drugs available to prevent EIA and to recognize that there are some myths related to their use in EIA.


Asthma Fluticasone Propionate Salmeterol Montelukast Formoterol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The author has no conflict of interest directly relevant to the content of this review. The author has provided no information on sources of funding directly relevant to the content of this review.


  1. 1.
    Anderson SD. Exercise-induced asthma. In: Kay AB, editor. Allergy & allergic diseases. Oxford: Blackwell Scientific Publications, 1997: 692–711Google Scholar
  2. 2.
    Silverman M, Anderson SD. Standardization of exercise tests in asthmatic children. Arch Dis Childh 1972; 47: 882–9PubMedCrossRefGoogle Scholar
  3. 3.
    Carlsen KH, Engh G, Mørk M. Exercise induced bronchoconstriction depends on exercise load. Respir Med 2000; 94(8): 750–5PubMedCrossRefGoogle Scholar
  4. 4.
    Chen WY, Horton DJ. Heat and water loss from the airways and exercise-induced asthma. Respiration 1977; 34: 305–13PubMedCrossRefGoogle Scholar
  5. 5.
    Anderson SD, Schoeffel RE, Follet R, et al. Sensitivity to heat and water loss at rest and during exercise in asthmatic patients. Eur J Respir Dis 1982; 63: 459–71PubMedGoogle Scholar
  6. 6.
    Anderson SD, Lambert S, Brannan JD, et al. Laboratory protocol for exercise asthma to evaluate salbutamol given by two devices. Med Sci Sports Exerc 2001; 33(6): 893–900PubMedCrossRefGoogle Scholar
  7. 7.
    Waalkans HJ, van Essen-Zandvliet EEM, Gerritsen J, et al. The effect of an inhaled corticosteroid (budesonide) on exercise-induced asthma in children. Eur Respir J 1993; 6: 652–6Google Scholar
  8. 8.
    Anderson SD, Henriksen JM. Management of exercise-induced asthma. In: Carlsen K-H, Ibsen T, editors. Exercise-induced asthma and sports in asthma. Copenhagen: Munksgaard Press, 1999: 99–108Google Scholar
  9. 9.
    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; 7: 43–9PubMedCrossRefGoogle Scholar
  10. 10.
    Hallstrand TS, Curtis JR, Koepsell TD, et al. Effectiveness of screening examinations to detect unrecognised exercise-induced bronchoconstriction. J Pediatr 2002; 141(3): 343–9PubMedCrossRefGoogle Scholar
  11. 11.
    Thole RT, Sallis RE, Rubin AL, et al. Exercise-induced bronchospam prevalence in collegiate cross-country runner. Med Sci Sports Exerc 2001; 33(2001): 1641–6PubMedGoogle Scholar
  12. 12.
    Rundell KW, Im J, Mayers LB, et al. Self-reported symptoms and exercise-induced asthma in the elite athlete. Med Sci Sports Exerc 2001; 33(2): 208–13PubMedGoogle Scholar
  13. 13.
    Wilber RL, Rundell L, Szmedra L, et al. Incidence of exercise-induced bronchospasm in Olympic Winter Sport athletes. Med Sci Sports Exerc 2000; 32(4): 732–7PubMedCrossRefGoogle Scholar
  14. 14.
    Helenius IJ, Tikkanen HO, Haahtela T. Exercise-induced bronchospasm at low temperature in elite runners. Thorax 1996; 51: 628–9PubMedCrossRefGoogle Scholar
  15. 15.
    Sinclair DG, Sims MM, Hoad NA, et al. Exercise-induced airway narrowing in army recruits with a history of childhood asthma. Eur Respir J 1995; 8(8): 1314–7PubMedCrossRefGoogle Scholar
  16. 16.
    Nish WA, Schwietz LA. Underdiagnosis of asthma in young adults presenting for USAF basic training. Ann Allergy 1992; 69: 239–42PubMedGoogle Scholar
  17. 17.
    McFadden ER, Lenner KA, Strohl KP. Postexertional airway rewarming and thermally induced asthma. J Clin Invest 1986; 78: 18–25PubMedCrossRefGoogle Scholar
  18. 18.
    Anderson SD, Daviskas E. The mechanism of exercise-induced asthma is …. J Allergy Clin Immunol 2000; 106(3): 453–9PubMedCrossRefGoogle Scholar
  19. 19.
    Deal EC, McFadden ER, Ingram RH, et al. Role of respiratory heat exchange in production of exercise-induced asthma. J Appl Physiol 1979; 46: 467–75PubMedGoogle Scholar
  20. 20.
    Aitken ML, Marini JJ. Effect of heat delivery and extraction on airway conductance in normal and in asthmatic subjects. Am Rev Respir Dis 1985; 131: 357–61PubMedGoogle Scholar
  21. 21.
    Anderson SD, Schoeffel RE, Black JL, et al. Airway cooling as the stimulus to exercise-induced asthma: a re-evaluation. Eur J Respir Dis 1985; 67: 20–30PubMedGoogle Scholar
  22. 22.
    Anderson SD, Daviskas E. The airway microvasculature and exercise-induced asthma. Thorax 1992; 47: 748–52PubMedCrossRefGoogle Scholar
  23. 23.
    Argyros GJ, Phillips YY, Rayburn DB, et al. Water loss without heat flux in exercise-induced bronchospasm. Am Rev Respir Dis 1993; 147: 1419–24PubMedGoogle Scholar
  24. 24.
    Peat JK, Toelle BG, Gray EJ, et al. Prevalence and severity of childhood asthma and allergic sensitisation in seven climatic regions of New South Wales. Med J Aust 1995; 163(3): 22–6PubMedGoogle Scholar
  25. 25.
    Koh YI, Choi IS, Lim H. Atopy may be related to exercise-induced bronchospasm in asthma. Clin Exp Allergy 2002; 32: 532–6PubMedCrossRefGoogle Scholar
  26. 26.
    Jones A, Bowen M. Screening for childhood asthma using an exercise test. Br J Gen Pract 1994; 44: 127–31PubMedGoogle Scholar
  27. 27.
    Ernst P, Ghezzo H, Becklake MR. Risk factors for bronchial hyperresponsiveness in late childhood and early adolescence. Eur Respir J 2002; 20: 635–9PubMedCrossRefGoogle Scholar
  28. 28.
    Burr ML, Eldridge BA, Borysiewicz LK. Peak expiratory flow rates before and after exercise in schoolchildren. Arch Dis Child 1974; 49: 923–6PubMedCrossRefGoogle Scholar
  29. 29.
    Burr ML, Butland BK, King S, et al. Changes in asthma prevalence: two surveys 15 years apart. Arch Dis Child 1989; 64: 1452–6PubMedCrossRefGoogle Scholar
  30. 30.
    Keeley DJ, Neill P, Gallivan S. Comparison of the prevalence of reversible airways obstruction in rural and urban Zimbabwean children. Thorax 1991; 46: 549–53PubMedCrossRefGoogle Scholar
  31. 31.
    Ng’ang’a LW, Odhiambo JA, Mungai MW, et al. Prevalence of exercise induced bronchospasm in Kenyan school children: an urban-rural comparison. Thorax 1998; 53: 919–26PubMedCrossRefGoogle Scholar
  32. 32.
    Bye PTP, Anderson SD, Daviskas E, et al. Plasma cyclic AMP levels in response to exercise and terbutaline sulphate aerosol in normal and asthmatic patients. Eur J Respir Dis 1980; 61: 287–97PubMedGoogle Scholar
  33. 33.
    Anderson SD, McEvoy JDS, Bianco S. Changes in lung volumes and airway resistance after exercise in asthmatic subjects. Am Rev Respir Dis 1972; 106: 30–7PubMedGoogle Scholar
  34. 34.
    Pedersen S, Hansen OR. Budesonide treatment of moderate and severe asthma in children: a dose-response study. J Allergy Clin Immunol 1995; 95 (1 Pt 1): 29–33PubMedCrossRefGoogle Scholar
  35. 35.
    Alving K, Lundberg JON, Nordvall SL. Dose dependent reduction of exhaled nitric oxide in asthmatic children by inhaled steroids [abstract]. Am J Respir Crit Care Med 1995; 151: A129Google Scholar
  36. 36.
    Barnes PJ, Pedersen S, Busse WW. Efficacy and safety of inhaled corticosteroids: new developments. Am J Respir Crit Care Med 1998; 157 (3 Pt 2): S1–S53PubMedGoogle Scholar
  37. 37.
    Yoshikawa T, Shoji S, Fujii T, et al. Severity of exercise-induced bronchoconstriction is related to airway eosinophilic inflammation in patients with asthma. Eur Respir J 1998; 12:879–84PubMedCrossRefGoogle Scholar
  38. 38.
    Kivity S, Argaman A, Onn A, et al. Eosinophil influx into the airways in patients with exercise-induced asthma. Respir Med 2000; 94(12): 1200–5PubMedCrossRefGoogle Scholar
  39. 39.
    Crimi E, Balbo A, Milanese M, et al. Airway inflammation and occurrence of delayed bronchoconstriction in exercise-induced asthma. Am Rev Respir Dis 1992; 146: 507–12PubMedGoogle Scholar
  40. 40.
    Godfrey S. The physiological assessment of the effect of DSCG in the asthmatic child. Respiration 1970; 27 Suppl.: 353–6PubMedCrossRefGoogle Scholar
  41. 41.
    Anderson SD, Seale JP, Ferris L, et al. An evaluation of pharmacotherapy for exercise-induced asthma. J Allergy Clin Immunol 1979; 64: 612–24PubMedCrossRefGoogle Scholar
  42. 42.
    Anderson SD. Exercise-induced asthma. In: Middleton E, Reed C, Ellis E, et al., editors. Allergy: principles & practice. 4th ed. St Louis (MO): CV Mosby Company, 1993: 1343–67Google Scholar
  43. 43.
    Bisgaard H. Long-acting beta2-agonists in management of childhood asthma: a critical review of the literature. Pediatr Pulmonol 2000; 29(3): 221–34PubMedCrossRefGoogle Scholar
  44. 44.
    Massie J. Exercise-induced asthma in children. Paediatr Drugs 2002; 4(4): 267–78PubMedGoogle Scholar
  45. 45.
    Palmer LJ, Silverman ES, Weiss ST, et al. PharmacogenetICs of asthma. Am J Respir Crit Care Med 2002; 165: 861–6PubMedCrossRefGoogle Scholar
  46. 46.
    Israel E, Drazen JM, Liggett SB, et al. Effect of polymorphism of the beta (2)-adrenergic receptor on response to regular use of albuterol in asthma. Int Arch Allergy Immunol 2001; 124(1): 183–6PubMedCrossRefGoogle Scholar
  47. 47.
    Lipworth BJ. Airway subsensitivity with long-acting beta 2-agonists. Is there a cause for concern? Drug-Saf 1997; 16(5): 295–308CrossRefGoogle Scholar
  48. 48.
    Jones RS, Wharton MJ, Buston MH. Place of physical exercise and bronchodilator drugs in the assessment of the asthmatic child. Arch Dis Child 1963; 38: 539–45PubMedCrossRefGoogle Scholar
  49. 49.
    Godfrey S, Konig P. Suppression of exercise-induced asthma by salbutamol, theophylline, atropine, cromolyn, and placebo in a group of asthmatic children. PediatrICs 1975; 56: 930–4PubMedGoogle Scholar
  50. 50.
    Silverman M, Andrea T. Time course of effect of disodium cromoglicate on exercise-induced asthma. Arch Dis Child 1972; 47(253): 419–22PubMedCrossRefGoogle Scholar
  51. 51.
    Silverman M, Konig P, Godfrey S. The use of serial exercise test to assess the efficacy and duration of action of drugs in asthma. Thorax 1973; 28: 574–8PubMedCrossRefGoogle Scholar
  52. 52.
    Silverman M, Connolly NM, Balfour-Lynn L, et al. Long-term trial of disodium cromoglicate and isoprenaline in children with asthma. BMJ 1972; 3(823): 378–81PubMedCrossRefGoogle Scholar
  53. 53.
    Anderson SD, Silverman M, Konig P, et al. Exercise-induced asthma: a review. Br J Dis Chest 1975; 69: 1–39PubMedCrossRefGoogle Scholar
  54. 54.
    Anderson SD, Seale JP, Rozea P, et al. Inhaled and oral salbutamol in exercise-induced asthma. Am Rev Respir Dis 1976; 114: 493–500PubMedGoogle Scholar
  55. 55.
    Seale JP, Anderson SD, Lindsay DA. A comparison of oral theophylline and oral salbutamol in exercise-induced asthma. Aust N Z J Med 1977; 7: 270–4PubMedCrossRefGoogle Scholar
  56. 56.
    Poppius H, Salorinne Y. Comparative trial of salbutamol and an anticholinergic drug, SCH 1000, in prevention of exercise-induced asthma. Scand J Respir Dis 1973; 54(3): 142–7PubMedGoogle Scholar
  57. 57.
    Schoeffel RE, Anderson SD, Lindsay DA. Sodium cromoglicate as a pressurized aerosol (Vicrom) in exercise-induced asthma. Aust N Z J Med 1983; 13:157–61PubMedCrossRefGoogle Scholar
  58. 58.
    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; 128: 993–7PubMedGoogle Scholar
  59. 59.
    Henriksen JM. Effect of inhalation of corticosteroids on exercise induced asthma: randomised double blind crossover study of budesonide in asthmatic children. BMJ 1985; 291: 248–9PubMedCrossRefGoogle Scholar
  60. 60.
    Anderson SD, Brannan JD. Long-acting beta2-agonists and exercise-induced asthma: lesson to guide us in the future. Pediatr Drugs 2004; 6(3): 161–75CrossRefGoogle Scholar
  61. 61.
    Woolley M, Anderson SD, Quigley B. Duration of protective effect of terbutaline sulphate and cromolyn sodium alone and in combination on exercise-induced asthma. Chest 1990; 97: 39–45PubMedCrossRefGoogle Scholar
  62. 62.
    Smith CM, Anderson SD, Seale JP. The duration of action of the combination of fenoterol hydrobromide and ipratropium bromide in protecting against asthma provoked by hyperpnea. Chest 1988; 94: 709–17PubMedCrossRefGoogle Scholar
  63. 63.
    Anderson SD, Rodwell LT, Du Toit J, et al. Duration of protection by inhaled salmeterol in exercise-induced asthma. Chest 1991; 100: 1254–60PubMedCrossRefGoogle Scholar
  64. 64.
    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; 87: 439–44PubMedCrossRefGoogle Scholar
  65. 65.
    Kemp JP, Dockhorn RJ, Busse WW, et al. Prolonged effect of inhaled salmeterol against exercise-induced bronchospasm. Am J Respir Crit Care Med 1994; 150: 1612–5PubMedGoogle Scholar
  66. 66.
    Green CP, Price JF. Prevention of exercise induced asthma by inhaled salmeterol zinofoate. Arch Dis Child 1992; 67: 1014–7PubMedCrossRefGoogle Scholar
  67. 67.
    Ramage L, Lipworth BJ, Ingram CG, et al. Reduced protection against exercise induced bronchoconstriction after chronic dosing with salmeterol. Respir Med 1994; 88: 363–8PubMedCrossRefGoogle Scholar
  68. 68.
    Simons FE, Gerstner TV, Cheang MS. Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment. PediatrICs 1997; 99(5): 655–9PubMedCrossRefGoogle Scholar
  69. 69.
    Nelson JA, Strauss L, Skowronski M, et al. Effect of long-term salmeterol treatment on exercise-induced asthma. N Engl J Med 1998; 339(3): 141–6PubMedCrossRefGoogle Scholar
  70. 70.
    Davis BE, Reid JK, Cockcroft DW. Formoterol thrice weekly does not result in the development of tolerance to bronchoprotection. Can Respir J 2003; 10(1): 23–6PubMedGoogle Scholar
  71. 71.
    Shore SA, Drazen JM. Beta-agonists and asthma: too much of a good thing. J Clin Invest 2003; 112: 495–7PubMedGoogle Scholar
  72. 72.
    Bisgaard H. Effect of long-acting beta2 agonists on exacerbation rates of asthma in children. Pediatr Pulmonol 2003; 36(5): 391–8PubMedCrossRefGoogle Scholar
  73. 73.
    Hancox RJ, Aldridge EE, Cowan JO, et al. Tolerance to beta-agonists during acute bronchoconstriction. Eur Respir J 1999; 14(2): 283–7PubMedCrossRefGoogle Scholar
  74. 74.
    Jones CL, Cowan JO, Flannery EM, et al. Reversing the acute bronchoconstriction in asthma: the effect of bronchodilator tolerance after treatment with formoterol. Eur Respir J 2001; 17(3): 368–73PubMedCrossRefGoogle Scholar
  75. 75.
    van der Woude HJ, Winter TH, Aalbers R. Decreased bronchodilating effect of salbutamol in relieving methacholine induced moderate to severe bronchoconstriction during high dose treatment with long action β2 agonists. Thorax 2001; 56: 529–35PubMedCrossRefGoogle Scholar
  76. 76.
    Wraight JM, Hancox RJ, Herbison GP, et al. Bronchodilator tolerance: the impact of increasing bronchoconstriction. Eur Respir J 2003; 21(5): 810–5PubMedCrossRefGoogle Scholar
  77. 77.
    Kalra S, Swystun VA, Bhagat R, et al. Inhaled corticosteroids do not prevent the development of tolerance to the bronchoprotective effect of salmeterol. Chest 1996; 109: 953–6PubMedCrossRefGoogle Scholar
  78. 78.
    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; 89(6): 1176–82PubMedCrossRefGoogle Scholar
  79. 79.
    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; 149: 935–8PubMedGoogle Scholar
  80. 80.
    Patessio A, Podda A, Carone M, et al. Protective effect and duration of action of formoterol aerosol on exercise-induced asthma. Eur Respir J 1991; 4: 296–300PubMedGoogle Scholar
  81. 81.
    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; 9: 2099–103PubMedCrossRefGoogle Scholar
  82. 82.
    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; 94(7): 661–7PubMedCrossRefGoogle Scholar
  83. 83.
    Carlsen KH, Roksund O, Olsholt K, et al. Overnight protection by inhaled salmeterol on exercise-induced asthma in children. Eur Respir J 1995; 8: 1852–5PubMedCrossRefGoogle Scholar
  84. 84.
    Bronsky EA, Yegen Ü, Yeh CM, et al. Formoterol provides long-lasting protection against exercise-induced bronchospasm. Ann Allergy Asthma Immunol 2002; 89: 407–12PubMedCrossRefGoogle Scholar
  85. 85.
    Nielsen KG, Bisgaard H. Bronchodilation and bronchoprotection in asthmatic preschool children from formoterol administered by mechanically actuated dry-powder inhaler and spacer. Am J Respir Crit Care Med 2001; 164: 256–9PubMedGoogle Scholar
  86. 86.
    Nielsen KG, Skov M, Klug B, et al. Flow dependent effect of formoterol dry-powder inhaled from the Aeroliser®. Eur Respir J 1997; 10: 2105–9PubMedCrossRefGoogle Scholar
  87. 87.
    Tullett WM, Tan KM, Wall RT, et al. Dose-response effect of sodium cromoglicate pressurised aerosol in exercise induced asthma. Thorax 1985; 40: 41–4PubMedCrossRefGoogle Scholar
  88. 88.
    Storm van’s Gravesande K, Mattes J, Grossklauss E, et al. Preventative effect of 2 and 10mg of sodium cromoglicate on exercise-induced bronchoconstriction. Eur J Pediatr 2000; 159(10): 759–63PubMedCrossRefGoogle Scholar
  89. 89.
    Comis A, Valletta EA, Sette L, et al. Comparison of nedocromil sodium and sodium cromoglicate administered by pressurized aerosol, with and without a spacer device in exercise-induced asthma in children. Eur Respir J 1993; 6: 523–6PubMedGoogle Scholar
  90. 90.
    Oseid S, Mellbye E, Hem E. Effect of nedocromil sodium on exercise-induced bronchoconstriction exacerbated by inhalation of cold air. Scand J Med Sci Sports 1995; 5: 88–93PubMedCrossRefGoogle Scholar
  91. 91.
    Morton AR, Ogle SL, Fitch KD. Effects of nedocromil sodium, cromolyn sodium, and a placebo in exercise-induced asthma. Ann Allergy 1992; 68: 143–8PubMedGoogle Scholar
  92. 92.
    Spooner C, Rowe BH, Saunders LD. Nedocromil sodium in the treatment of exercise-induced asthma: a meta-analysis. Eur Respir J 2000; 16(1): 30–7PubMedCrossRefGoogle Scholar
  93. 93.
    König P, Hordvik NL, Kreutz C. The preventative effect and duration of action of nedocromil sodium and cromolyn sodium on exercise-induced asthma (EIA) in adults. J Allergy Clin Immunol 1987; 79: 64–8PubMedCrossRefGoogle Scholar
  94. 94.
    Kelly K, Spooner CH, Rowe BH. Nedocromil sodium vs. sodium cromoglicate for preventing exercise-induced bronchoconstriction in asthmatICs (Cochrane Review). Eur Respir J 2001; 17(1): 39–45PubMedCrossRefGoogle Scholar
  95. 95.
    Church MK, Hiroi J. Inhibition of IgE-dependent histamine release from human dispersed lung mast cells by anti-allergic drugs and salbutamol. Br J Pharmacol 1987; 90: 421–9PubMedCrossRefGoogle Scholar
  96. 96.
    Jackson DM, Pollard CD, Roberts SM. The effect of nedocromil sodium on the isolated rabbit vagus nerve. Eur J Pharmacol 1992; 221: 175–7PubMedCrossRefGoogle Scholar
  97. 97.
    Israel E, Dermarkarian R, Rosenberg M, et al. The effects of a 5-lipoxygenase inhibitor on asthma induced by cold, dry air. N Engl J Med 1990; 323: 1740–4PubMedCrossRefGoogle Scholar
  98. 98.
    Meltzer SS, Hasday JD, Cohn J, et al. Inhibition of exercise-induced bronchospasm by zileuton: a 5-lipoxygenase inhibitor. Am J Respir Crit Care Med 1996; 153(3): 931–5PubMedGoogle Scholar
  99. 99.
    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; 133: 424–8PubMedCrossRefGoogle Scholar
  100. 100.
    Leff JA, Busse WW, Pearlman D, et al. Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction. N Engl J Med 1998; 339(3): 147–52PubMedCrossRefGoogle Scholar
  101. 101.
    Lehnigk B, Rabe KF, Dent G, et al. Effects of a 5-lipoxygenase inhibitor, ABT-761, on exercise-induced bronchoconstriction and urinary LTE4 in asthmatic patients. Eur Respir J 1998; 11: 617–23PubMedGoogle Scholar
  102. 102.
    Coreno A, Skowronski M, Kotaur C, et al. Comparative effects of long-acting β2-agonists, leukotriene antagonists, and a 5-lipoxygenase inhibitor on exercise-induced asthma. J Allergy Clin Immunol 2000; 106: 500–6PubMedCrossRefGoogle Scholar
  103. 103.
    Moraes TJ, Selvadurai H. Management of exercise-induced bronchospasm in children. Treat Respir Med 2004; 3(1): 9–15PubMedCrossRefGoogle Scholar
  104. 104.
    Pearlman DS, Ostrom NK, Bronsky EA, et al. The leukotriene D4-receptor antagonist zafirlukast attenuates exercise-induced bronchoconstriction in children. J Pediatr 1999; 134(3): 273–9PubMedCrossRefGoogle Scholar
  105. 105.
    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; 111: 301–7PubMedCrossRefGoogle Scholar
  106. 106.
    Shimizu T, Mochizuki H, Shigeta M, et al. Effect of inhaled indomethacin on exercise-induced bronchoconstriction in children with asthma. Am J Respir Crit Care Med 1997; 155(1): 170–3PubMedGoogle Scholar
  107. 107.
    Finnerty JP, Harvey A, Holgate ST. The relative contributions of histamine and prostanoids to bronchoconstriction provoked by isocapnic hyperventilation in asthma. Eur Respir J 1992; 5: 323–30PubMedGoogle Scholar
  108. 108.
    Finnerty JP, Twentyman OP, Harris A, et al. Effect of GR32191, a potent thromboxane receptor antagonist, on exercise induced bronchoconstriction in asthma. Thorax 1991; 46: 190–2PubMedCrossRefGoogle Scholar
  109. 109.
    Magnussen H, Boerger S, Templin K, et al. Effects of a thromboxane-receptor antagonist, BAY u3405, on prostaglandin D2- and exercise-induced bronchoconstriction. J Allergy Clin Immunol 1992; 89: 1119–26PubMedCrossRefGoogle Scholar
  110. 110.
    O’Byrne PM, Jones GL. The effect of indomethacin on exercise-induced bronchoconstriction and refractoriness after exercise. Am Rev Respir Dis 1986; 134: 69–72PubMedGoogle Scholar
  111. 111.
    Wilson BA, Bar-Or O, O’Byrne PM. The effects of indomethacin on refractoriness following exercise both with and without bronchoconstriction. Eur Respir J 1994; 12: 2174–8CrossRefGoogle Scholar
  112. 112.
    Manning PJ, Watson RM, O’Byrne PM. Exercise-induced refractoriness in asthmatic subjects involves leukotriene and prostaglandin interdependent mechanisms. Am Rev Respir Dis 1993; 148: 950–4PubMedCrossRefGoogle Scholar
  113. 113.
    Melillo E, Woolley KL, Manning PJ, et al. Effect of inhaled PGE2 on exercise-induced bronchoconstriction in asthmatic subjects. Am J Respir Crit Care Med 1994; 149:1138–41PubMedGoogle Scholar
  114. 114.
    Dessanges J-F, Prefaut C, Taytard A, et al. The effect of zafirlukast on repetitive exercise-induced bronchoconstriction: the possible role of leukotrienes in exercise-induced refractoriness. J Allergy Clin Immunol 1999; 104(6): 1155–66PubMedCrossRefGoogle Scholar
  115. 115.
    Anderson SD, Brannan JD. Exercise induced asthma: is there still a case for histamine? J Allergy Clin Immunol 2002; 109 (5 Pt 1): 771–3PubMedCrossRefGoogle Scholar
  116. 116.
    Baki A, Orhan F. The effect of loratadine in exercise-induced asthma. Arch Dis Child 2002; 86: 38–9PubMedCrossRefGoogle Scholar
  117. 117.
    Dahlén B, Roquet A, Inman MD, et al. Influence of zafirlukast and loratadine on exercise-induced bronchoconstriction. J Allergy Clin Immunol 2002; 109 (5 Pt 1): 789–93PubMedCrossRefGoogle Scholar
  118. 118.
    Finnerty JP, Holgate ST. Evidence for the roles of histamine and prostaglandins as mediators in exercise-induced asthma: the inhibitory effect of terfenadine and flurbiprofen alone and in combination. Eur Respir J 1990; 3: 540–7PubMedGoogle Scholar
  119. 119.
    Backer V, Bach-Mortensen N, Becker U, et al. The effect of astemizole on bronchial hyperresponsiveness and exercise-induced asthma in children. Allergy 1989; 44: 209–13PubMedCrossRefGoogle Scholar
  120. 120.
    Patel KR. Terfenadine in exercise-induced asthma. BMJ 1984; 85: 1496–7CrossRefGoogle Scholar
  121. 121.
    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; 19: 104–7CrossRefGoogle Scholar
  122. 122.
    Broide DH, Eisman S, Ramsdell JW, et al. Airway levels of mast cell-derived mediators in exercise-induced asthma. Am Rev Respir Dis 1990; 141: 563–8PubMedCrossRefGoogle Scholar
  123. 123.
    Pliss LB, Ingenito EP, Ingram RH, et al. Assessment of bronchoalveolar cell and mediator response to isocapnic hyperpnea in asthma. Am Rev Respir Dis 1990; 142: 73–8PubMedGoogle Scholar
  124. 124.
    Reiss TF, Hill JB, Harman E, et al. Increased urinary excretion of LTE4 after exercise and attenuation of exercise-induced bronchospasm by montelukast, a cysteinyl leukotriene receptor antagonist. Thorax 1997; 52(12): 1030–5PubMedCrossRefGoogle Scholar
  125. 125.
    O’Sullivan S, Roquet A, Dahlén B, et al. Evidence for mast cell activation during exercise-induced bronchoconstriction. Eur Respir J 1998; 12: 345–50PubMedCrossRefGoogle Scholar
  126. 126.
    Anderson SD, Bye PTP, Schoeffel RE, et al. Arterial plasma histamine levels at rest, during and after exercise in patients with asthma: effects of terbutaline aerosol. Thorax 1981; 36: 259–67PubMedCrossRefGoogle Scholar
  127. 127.
    Hartley JPR, Charles TJ, Monie RDG, et al. Arterial plasma histamine after exercise in normal individuals and in patients with exercise induced asthma. Clin Sci 1981; 61: 151–7PubMedGoogle Scholar
  128. 128.
    Brannan JD, Anderson SD, Freed R, et al. Nedocromil sodium inhibits responsiveness to inhaled mannitol in asthmatic subjects. Am J Respir Crit Care Med 2000; 161: 2096–9PubMedGoogle Scholar
  129. 129.
    Brannan JD, Anderson SD, Gomes K, et al. Fexofenadine decreases sensitivity to and montelukast improves recovery from inhaled mannitol. Am J Respir Crit Care Med 2001; 163: 1420–5PubMedGoogle Scholar
  130. 130.
    Brannan JD, Gulliksson M, Anderson SD, et al. Eformoterol fumarate & sodium cromoglicate (SCG) inhibit the airway response to inhaled mannitol in asthmatICs by mast cell inhibition. J Allergy Clin Immunol 2004; 113Suppl. 1: S190CrossRefGoogle Scholar
  131. 131.
    Brannan JD, Gulliksson M, Anderson SD, et al. Evidence of mast cell activation and leukotriene release after mannitol inhalation. Eur Respir J 2003; 22(3): 491–6PubMedCrossRefGoogle Scholar
  132. 132.
    MIMS annual. Australian ed. Sydney: MediMedia Australia Pty Ltd, 2003Google Scholar
  133. 133.
    Lee DKC, Currie GP, Hall IP, et al. The arginine-16 β2-adrenoceptor polymorphism predisposes to bronchoprotective subsensitivity in patients treated with formoterol and salmeterol. Br J Clin Pharmacol 2004; 57(1): 68–75PubMedCrossRefGoogle Scholar
  134. 134.
    Wooltorton E. Salmeterol (Serevent) asthma trial halted early [letter]. CMAJ 2003; 168(6): 738PubMedGoogle Scholar
  135. 135.
    Mann M, Chowdhury B, Sullivan E, et al. Serious asthma exacerbations in asthmatICs treated with high-dose formoterol. Chest 2003; 124(1): 70–4PubMedCrossRefGoogle Scholar
  136. 136.
    Freed R, Anderson SD, Wyndham J. The use of bronchial provocation tests for identifying asthma: a review of the problems for occupational assessment and a proposal for a new direction. ADF Health 2002; 3(2): 77–85Google Scholar
  137. 137.
    Anderson SD, Fitch K, Perry CP, et al. Responses to bronchial challenge submitted for approval to use inhaled beta2 agonists prior to an event at the 2002 Winter Olympics. J Allergy Clin Immunol 2003; 111(1): 44–9CrossRefGoogle Scholar
  138. 138.
    Anderson SD, Argyros GJ, Magnussen H, et al. Provocation by eucapnic voluntary hyperpnoea to identify exercise induced bronchoconstriction. Br J Sports Med 2001; 35: 344–7PubMedCrossRefGoogle Scholar
  139. 139.
    Smith CM, Anderson SD. Inhalational challenge using hypertonic saline in asthmatic subjects: a comparison with responses to hyperpnoea, methacholine and water. Eur Respir J 1990; 3: 144–51PubMedGoogle Scholar
  140. 140.
    Helenius IJ, Tikkanen HO, Sarna S, et al. Asthma and increased bronchial responsiveness in elite athletes: atopy and sport event as risk factors. J Allergy Clin Immunol 1998; 101(5): 646–52PubMedCrossRefGoogle Scholar
  141. 141.
    Drobnic F, Casan P, Banquells M, et al. Cough after exercise in the elite athlete. Sports Med Training Rehab 1996; 6: 309–15Google Scholar
  142. 142.
    Rundell KW, Spiering BA, Evans TM, et al. Baseline lung function, exercise-induced bronchoconstriction, and asthma-like symptoms in elite women ice hockey players. Med Sci Sports Exerc 2004; 36(3): 405–10PubMedCrossRefGoogle Scholar
  143. 143.
    Hofstra WB, Neijens HJ, Duiverman EJ, et al. Dose-response over time to inhaled fluticasone propionate: treatment of exercise- and methacholine-induced bronchoconstriction in children with asthma. Pediatr Pulmonol 2000; 29(6): 415–23PubMedCrossRefGoogle Scholar
  144. 144.
    Jonasson G, Carlsen KH, Hultquist C. Low-dose budesonide improves exercise-induced bronchospasm in schoolchildren. Pediatr Allergy Immunol 2000; 11(2): 120–5PubMedCrossRefGoogle Scholar
  145. 145.
    Papalia SM. Aspects of inhaled budesonide use in asthma and exercise [PhD dissertation]. Perth: University of Western Australia, 1997Google Scholar
  146. 146.
    van Asperen PP, Mellis CM, Sly PD. The role of corticosteroids in the management of childhood asthma. Med J Aust 2002; 176: 168–73Google Scholar
  147. 147.
    Leuppi JD, Salome CM, Jenkins CR, et al. Predictive markers of asthma exacerbations during stepwise dose-reduction of inhaled corticosteroids. Am J Respir Crit Care Med 2001; 163: 406–12PubMedGoogle Scholar
  148. 148.
    Thio BJ, Slingerland GLM, Nagelkerke AF, et al. Effects of single-dose fluticasone on exercise-induced asthma in asthmatic children: a pilot study. Pediatr Pulmonol 2001; 32: 115–21PubMedCrossRefGoogle Scholar
  149. 149.
    Patel KR, Wall RT. Dose-duration effect of sodium cromoglicate aerosol in exercise-induced asthma. Eur J Respir Dis 1986; 69: 256–60PubMedGoogle Scholar
  150. 150.
    Wilson AJ, Orr LC, Sims EJ, et al. Effects of monotherapy with intranasal corticosteroid or combined oral histamine and leukotriene receptor antagonists in seasonal allergic rhinitis. Clin Exp Allergy 2001; 31: 61–8PubMedGoogle Scholar
  151. 151.
    Richter K, Janicki S, Jorres RA, et al. Acute protection against exercise-induced bronchoconstriction by formoterol, salmeterol and terbutaline. Eur Respir J 2002; 19: 865–71PubMedCrossRefGoogle Scholar
  152. 152.
    Shapiro GS, Yegen Ü, 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; 24(12): 2077–87PubMedCrossRefGoogle Scholar
  153. 153.
    Inman MD, O’Byrne PM. The effect of regular inhaled albuterol on exercise-induced bronchoconstriction. Am J Respir Crit Care Med 1996; 153: 65–9PubMedGoogle Scholar
  154. 154.
    Hancox RJ, Subbarao P, Kamada D, et al. β2-Agonist tolerance and exercise-induced bronchospasm. Am J Respir Crit Care Med 2002; 165(8): 1068–70PubMedGoogle Scholar
  155. 155.
    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; 104 (3 Pt 1): 501–6PubMedCrossRefGoogle Scholar
  156. 156.
    Scola AM, Chong LK, Suvarna SK, et al. Desensitisation of mast cell β2-adrenoceptor-mediated responses by salmeterol and formoterol. Br J Pharmacol 2004; 141(1): 163–71PubMedCrossRefGoogle Scholar
  157. 157.
    Israel E, Chinchilli VM, Ford JG, et al. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled crossover trial. Lancet 2004; 364: 1505–12PubMedCrossRefGoogle Scholar
  158. 158.
    van Veen A, Weller FR, Wierenga EA, et al. A comparison of salmeterol and formoterol in attenuating airway responses to short-acting beta2-agonists. Pulm Pharmacol 2003; 16(3): 153–61CrossRefGoogle Scholar
  159. 159.
    Pfleger A, Eber E, Weinhandl E, et al. Effects of nedocromil and salbutamol on airway reactivity in children with asthma. Eur Respir J 2002; 20: 624–9PubMedCrossRefGoogle Scholar
  160. 160.
    Laursen LC, Johannesson N, Weeke B. Effects of enprophylline and theophylline on exercise-induced asthma. Allergy 1985; 40: 506–9PubMedCrossRefGoogle Scholar
  161. 161.
    Fuglsang G, Hertz B, Holm E-B. No protection by oral terbutaline against exercise-induced asthma in children: a dose-response study. Eur Respir J 1993; 6: 527–30PubMedGoogle Scholar
  162. 162.
    Francis PW, Krastins IR, Levison H. Oral and inhaled salbutamol in the prevention of exercise-induced bronchospasm. PediatrICs 1980; 66(1): 103–8PubMedGoogle Scholar
  163. 163.
    Schoeffel RE, Anderson SD, Seale JP. The protective effect and duration of action of metaproterenol aerosol on exercise-induced asthma. Ann Allergy 1981; 46: 273–5PubMedGoogle Scholar

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© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Department of Respiratory Medicine, 11 WestRoyal Prince Alfred HospitalCamperdownAustralia

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