Exercise induced asthma
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [2]
Overview
Exercise-induced asthma, or E.I.A., is a medical condition characterized by shortness of breath induced by sustained aerobic exercise. In patients with bronchial hyperresponsiveness, vigorous physical activity triggers acute narrowing of the airways[1] and is measured by the number of sputum eosinophils.[2][3][4][5] E.I.A. shares many features with other types of asthma, and responds to some typical asthmatic medications, but does not appear to be caused by the same inflammatory reaction as the other types.
Pathophysiology
Triggering Factors
- Exposure to cold or dry air [6][7]
- Bronchial hyperresponsiveness
- Increased duration and intensity of exercise
- Concomitant viral infection
- Environmental allergen
Pathogenesis
- The underlying pathogenesis for E.I.A. is poorly understood.
- E.I.A usually occurs after at least several minutes of vigorous, aerobic activity, which demands supplementation of normal nasal breathing with mouth breathing. The resultant inhalation of air is neither warmed to bod temperature or humidified by the nasal passages; hence, seems to generate increased blood flow to the linings of the bronchial tree, resulting in edema and subsequent constriction of these bronchial vessels, worsening the degree of obstruction to airflow.[8][9][10] This sequence generates symptoms similar to those seen in other forms of asthma, but occurs without the inflammatory changes that underlie them.
Epidemiology and Demographics
The prevalence of E.I.A in the general population is approximately 7-20%.[11][12][13] The majority of asthmatics with symptomatic disease have some degree of exercise induced asthma.[14]
Diagnosis
History and Symptoms
- Initial bronchodilation occurs 6-8 minutes after exercise[15] with subsequent bronchospasm and completely resolves within an hour. During this approximate one hour period, resumption of exercise will likely produce either none or mild symptoms.
- In most cases, a relative refractory period follows resolution of an attack and is thought to be secondary to the release of inhibitory prostaglandins such as prostaglandin E2.[16][17]
- Most often than not, approximately 6-10 hours after an initial attack, a rebound attack with milder symptoms often develops without precipitating exertion.[18][19][20]
- Severe attacks are often the result of someone with both, allergic and exercise-induced asthma exercising in a high-allergen environment (e.g. walking uphill alongside slowly moving traffic at dusk) and can be fatal.
- Common symptoms include:
- Shortness of breath
- Cough
- Wheeze
- Altered metal status may be the presentation in severe attacks
Physical Examination
Vital Signs
HEENT
Cyanosis secondary to severe hypoxia
Lungs
High-pitch prolong expiratory wheeze that may be audible even without a stethoscope.
Other Diagnostic Studies
Exercise Challenge Test
- Exercise challenge test is a direct method to establish diagnosis. Test is considered positive if a 10% reduction in FEV1 is observed after a 6-8min treadmill exercise.[21]
- In athletes, documentation of airway narrowing in response to exercise, aids in the diagnosis and management of asthma by providing evidence of bronchial hyperresponsiveness that will respond to treatment with inhaled corticosteroids and is usually associated with a reduction in respiratory symptoms on exercise.[22][23][21]
Treatment
Medical Therapy
- The major goal of therapy in exercise-induced asthma is to ensure exercise is not avoided.
- In athletes who wish to continue their sport, and/or do so at times in adverse conditions, preventive measures, including altered training techniques and medications, can be taken.
- Some athletes take advantage of the refractory period by precipitating an attack by "warming up" and then timing their competition such that it occurs during the refractory period. Step-wise training works in a similar fashion. An athlete warms up in stages of increasing intensity, using the refractory period generated by each stage to get up to a full workload.
- Therapy should be routinely monitored with the assessment of peak expiratory flow rate performed before and after the exercise. Methacholine challenge test is another alternative to objectively assess response to therapy.[24][25]
- Fish oil supplementation may represent a potentially beneficial non-pharmacologic intervention for patients with exercise-induced asthma.[26]
- The most common medication approach is to use a beta agonist about twenty minutes before exercise.[27]
- Equipotent doses of the bronchodilators such as salmeterol, formoterol and terbutaline have shown to be effective with respect to their short-term protective potency against exercise-induced bronchoconstriction.[28]
- Tachyphylaxis developed to the protective effect of long and short-acting beta-2 agonist and hence is less effective when used for exercise-induced asthma. However, it remains extremely effective in the prevention of bronchospasm when used immediately before exercise.[29][30][31][32][33]
- Nedocromil and cromolyn administered by a pressurized aerosol has shown to provide equal protection against exercise-induced asthma in children.[34] A small randomized study, has shown the additive effects of combining cromolyn and beta-2 agonist and may be indicated in high-performance athletes.[35] Nedocromil sodium used before exercise has shown to reduce the severity and duration of exercise-induced bronchoconstriction.[36][37]
- Inhaled corticosteroids used for weeks and months before exercise significantly attenuated exercise-induced bronchoconstriction; however, it does not provide any short-term benefit.[38][39][40][41]
- Montelukast has shown to provide significant protection against exercise-induced asthma and further reduce the urinary excretion of leukotriene that is commonly observed after exercise.[42][43] However, leukotriene inhibitors are not effective in all patients with exercise induced asthma.[44]
- Other pharmacological agents that have been hypothesized to provide therapeutic benefits in patients with exercise induced asthma include frusemide,[45] prostaglandin-E2,[46] indomethacin,[47] and heparin.[48]
- As evidenced by the many professional athletes who have overcome E.I.A. using some combination of the above treatments, the prognosis is usually very good.
- Olympic swimmers Tom Dolan, Amy Van Dyken, and Nancy Hogshead, baseball Hall of Famer Catfish Hunter, and American football player Jerome Bettis are among the many who have done so.
- At the same time, it should be noted that according to International Olympic Committee statistics, during most of Olympic Games in last 20 years from 1/3 to 2/3 of athletes claimed to have asthma.
- Some medical experts tie such inordinate rates of reported asthma with athletes' desire to use complex medication to help them achieve better results.
Future or Investigational Therapies
- A randomized crossover study compared oral montelukast with inhaled salmeterol, both given two hours before exercise. Both drugs had similar benefit but montelukast lasted 24 hours.[49]
- In a large randomized study in children, monotherapy with montelukast and combination therapy with montelukast and budesonide yielded higher beneficial results in comparison to budesonide monotherapy and combined therapy with budesonide and formoterol.[40]
References
- ↑ Storms WW (2005) Asthma associated with exercise. Immunol Allergy Clin North Am 25 (1):31-43. DOI:10.1016/j.iac.2004.09.007 PMID: 15579363
- ↑ Anderton RC, Cuff MT, Frith PA, Cockcroft DW, Morse JL, Jones NL et al. (1979) Bronchial responsiveness to inhaled histamine and exercise. J Allergy Clin Immunol 63 (5):315-20. PMID: 429710
- ↑ Duong M, Subbarao P, Adelroth E, Obminski G, Strinich T, Inman M et al. (2008) Sputum eosinophils and the response of exercise-induced bronchoconstriction to corticosteroid in asthma. Chest 133 (2):404-11. DOI:10.1378/chest.07-2048 PMID: 18071011
- ↑ Kivity S, Argaman A, Onn A, Shwartz Y, Man A, Greif J et al. (2000) Eosinophil influx into the airways in patients with exercise-induced asthma. Respir Med 94 (12):1200-5. DOI:10.1053/rmed.2000.0951 PMID: 11192956
- ↑ Yoshikawa T, Shoji S, Fujii T, Kanazawa H, Kudoh S, Hirata K et al. (1998) Severity of exercise-induced bronchoconstriction is related to airway eosinophilic inflammation in patients with asthma. Eur Respir J 12 (4):879-84. PMID: 9817162
- ↑ McFadden ER, Ingram RH (1979) Exercise-induced asthma: Observations on the initiating stimulus. N Engl J Med 301 (14):763-9. DOI:10.1056/NEJM197910043011406 PMID: 39252
- ↑ Anderson SD, Schoeffel RE, Black JL, Daviskas E (1985) Airway cooling as the stimulus to exercise-induced asthma--a re-evaluation. Eur J Respir Dis 67 (1):20-30. PMID: 4054253
- ↑ Deal EC, McFadden ER, Ingram RH, Strauss RH, Jaeger JJ (1979) Role of respiratory heat exchange in production of exercise-induced asthma. J Appl Physiol 46 (3):467-75. PMID: 438014
- ↑ Kallings LV, Emtner M, Bäcklund L (1999) Exercise-induced bronchoconstriction in adults with asthma--comparison between running and cycling and between cycling at different air conditions. Ups J Med Sci 104 (3):191-8. PMID: 10680952
- ↑ Freed AN, Davis MS (1999) Hyperventilation with dry air increases airway surface fluid osmolality in canine peripheral airways. Am J Respir Crit Care Med 159 (4 Pt 1):1101-7. PMID: 10194152
- ↑ Sonna LA, Angel KC, Sharp MA, Knapik JJ, Patton JF, Lilly CM (2001) The prevalence of exercise-induced bronchospasm among US Army recruits and its effects on physical performance. Chest 119 (6):1676-84. PMID: 11399690
- ↑ Ng'ang'a LW, Odhiambo JA, Mungai MW, Gicheha CM, Nderitu P, Maingi B et al. (1998) Prevalence of exercise induced bronchospasm in Kenyan school children: an urban-rural comparison. Thorax 53 (11):919-26. PMID: 10193388
- ↑ Kukafka DS, Lang DM, Porter S, Rogers J, Ciccolella D, Polansky M et al. (1998) Exercise-induced bronchospasm in high school athletes via a free running test: incidence and epidemiology. Chest 114 (6):1613-22. PMID: 9872197
- ↑ McFadden ER, Gilbert IA (1994) Exercise-induced asthma. N Engl J Med 330 (19):1362-7. DOI:10.1056/NEJM199405123301907 PMID: 8152449
- ↑ Inman MD, Watson RM, Killian KJ, O'Byrne PM (1990) Methacholine airway responsiveness decreases during exercise in asthmatic subjects. Am Rev Respir Dis 141 (6):1414-7. PMID: 2190506
- ↑ Edmunds AT, Tooley M, Godfrey S (1978) The refractory period after exercise-induced asthma: its duration and relation to the severity of exercise. Am Rev Respir Dis 117 (2):247-54. PMID: 637407
- ↑ Manning PJ, Watson RM, O'Byrne PM (1993) Exercise-induced refractoriness in asthmatic subjects involves leukotriene and prostaglandin interdependent mechanisms. Am Rev Respir Dis 148 (4 Pt 1):950-4. PMID: 8214949
- ↑ Iikura Y, Inui H, Nagakura T, Lee TH (1985) Factors predisposing to exercise-induced late asthmatic responses. J Allergy Clin Immunol 75 (2):285-9. PMID: 3968338
- ↑ Rubinstein I, Levison H, Slutsky AS, Hak H, Wells J, Zamel N et al. (1987) Immediate and delayed bronchoconstriction after exercise in patients with asthma. N Engl J Med 317 (8):482-5. DOI:10.1056/NEJM198708203170805 PMID: 3614292
- ↑ Chhabra SK, Ojha UC (1998) Late asthmatic response in exercise-induced asthma. Ann Allergy Asthma Immunol 80 (4):323-7. DOI:10.1016/S1081-1206(10)62977-8 PMID: 9564982
- ↑ 21.0 21.1 Weiler JM, Bonini S, Coifman R, Craig T, Delgado L, Capão-Filipe M et al. (2007) American Academy of Allergy, Asthma & Immunology Work Group report: exercise-induced asthma. J Allergy Clin Immunol 119 (6):1349-58. DOI:10.1016/j.jaci.2007.02.041 PMID: 17433829
- ↑ Anderson SD, Sue-Chu M, Perry CP, Gratziou C, Kippelen P, McKenzie DC et al. (2006) Bronchial challenges in athletes applying to inhale a beta2-agonist at the 2004 Summer Olympics. J Allergy Clin Immunol 117 (4):767-73. DOI:10.1016/j.jaci.2005.12.1355 PMID: 16630932
- ↑ Bonini S, Brusasco V, Carlsen KH, Delgado L, Del Giacco SR, Giacco SD et al. (2004) Diagnosis of asthma and permitted use of inhaled beta2-agonists in athletes. Allergy 59 (1):33-6. PMID: 14674930
- ↑ Hofstra WB, Neijens HJ, Duiverman EJ, Kouwenberg JM, Mulder PG, Kuethe MC et al. (2000) Dose-responses over time to inhaled fluticasone propionate treatment of exercise- and methacholine-induced bronchoconstriction in children with asthma. Pediatr Pulmonol 29 (6):415-23. PMID: 10821721
- ↑ Freezer NJ, Croasdell H, Doull IJ, Holgate ST (1995) Effect of regular inhaled beclomethasone on exercise and methacholine airway responses in school children with recurrent wheeze. Eur Respir J 8 (9):1488-93. PMID: 8575573
- ↑ Mickleborough TD, Lindley MR, Ionescu AA, Fly AD (2006) Protective effect of fish oil supplementation on exercise-induced bronchoconstriction in asthma. Chest 129 (1):39-49. DOI:10.1378/chest.129.1.39 PMID: 16424411
- ↑ Anderson S, Seale JP, Ferris L, Schoeffel R, Lindsay DA (1979) An evaluation of pharmacotherapy for exercise-induced asthma. J Allergy Clin Immunol 64 (6 pt 2):612-24. PMID: 41866
- ↑ Richter K, Janicki S, Jörres RA, Magnussen H (2002) Acute protection against exercise-induced bronchoconstriction by formoterol, salmeterol and terbutaline. Eur Respir J 19 (5):865-71. PMID: 12030726
- ↑ Hancox RJ, Subbarao P, Kamada D, Watson RM, Hargreave FE, Inman MD (2002) Beta2-agonist tolerance and exercise-induced bronchospasm. Am J Respir Crit Care Med 165 (8):1068-70. PMID: 11956046
- ↑ Inman MD, O'Byrne PM (1996) The effect of regular inhaled albuterol on exercise-induced bronchoconstriction. Am J Respir Crit Care Med 153 (1):65-9. PMID: 8542164
- ↑ Nelson JA, Strauss L, Skowronski M, Ciufo R, Novak R, McFadden ER (1998) Effect of long-term salmeterol treatment on exercise-induced asthma. N Engl J Med 339 (3):141-6. DOI:10.1056/NEJM199807163390301 PMID: 9664089
- ↑ García R, Guerra P, Feo F, Galindo PA, Gómez E, Borja J et al. (2001) Tachyphylaxis following regular use of formoterol in exercise-induced bronchospasm. J Investig Allergol Clin Immunol 11 (3):176-82. PMID: 11831450
- ↑ Simons FE, Gerstner TV, Cheang MS (1997) Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment. Pediatrics 99 (5):655-9. PMID: 9113940
- ↑ de Benedictis FM, Tuteri G, Bertotto A, Bruni L, Vaccaro R (1994) Comparison of the protective effects of cromolyn sodium and nedocromil sodium in the treatment of exercise-induced asthma in children. J Allergy Clin Immunol 94 (4):684-8. PMID: 7930301
- ↑ Latimer KM, O'Byrne PM, Morris MM, Roberts R, Hargreave FE (1983) Bronchoconstriction stimulated by airway cooling. Better protection with combined inhalation of terbutaline sulphate and cromolyn sodium than with either alone. Am Rev Respir Dis 128 (3):440-3. PMID: 6412606
- ↑ Spooner C, Rowe BH, Saunders LD (2000) Nedocromil sodium in the treatment of exercise-induced asthma: a meta-analysis. Eur Respir J 16 (1):30-7. PMID: 10933081
- ↑ Spooner CH, Saunders LD, Rowe BH (2002) Nedocromil sodium for preventing exercise-induced bronchoconstriction. Cochrane Database Syst Rev (1):CD001183. DOI:10.1002/14651858.CD001183 PMID: 11869595
- ↑ Jónasson G, Carlsen KH, Hultquist C (2000) Low-dose budesonide improves exercise-induced bronchospasm in schoolchildren. Pediatr Allergy Immunol 11 (2):120-5. PMID: 10893016
- ↑ Jónasson G, Carlsen KH, Blomqvist P (1998) Clinical efficacy of low-dose inhaled budesonide once or twice daily in children with mild asthma not previously treated with steroids. Eur Respir J 12 (5):1099-104. PMID: 9864004
- ↑ 40.0 40.1 Stelmach I, Grzelewski T, Majak P, Jerzynska J, Stelmach W, Kuna P (2008) Effect of different antiasthmatic treatments on exercise-induced bronchoconstriction in children with asthma. J Allergy Clin Immunol 121 (2):383-9. DOI:10.1016/j.jaci.2007.09.007 PMID: 17980416
- ↑ Koh MS, Tee A, Lasserson TJ, Irving LB (2007) Inhaled corticosteroids compared to placebo for prevention of exercise induced bronchoconstriction. Cochrane Database Syst Rev (3):CD002739. DOI:10.1002/14651858.CD002739.pub3 PMID: 17636704
- ↑ Reiss TF, Hill JB, Harman E, Zhang J, Tanaka WK, Bronsky E et al. (1997) Increased urinary excretion of LTE4 after exercise and attenuation of exercise-induced bronchospasm by montelukast, a cysteinyl leukotriene receptor antagonist. Thorax 52 (12):1030-5. PMID: 9516894
- ↑ Leff JA, Busse WW, Pearlman D, Bronsky EA, Kemp J, Hendeles L et al. (1998) Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction. N Engl J Med 339 (3):147-52. DOI:10.1056/NEJM199807163390302 PMID: 9664090
- ↑ Mastalerz L, Gawlewicz-Mroczka A, Nizankowska E, Cmiel A, Szczeklik A (2002) Protection against exercise-induced bronchoconstriction by montelukast in aspirin-sensitive and aspirin-tolerant patients with asthma. Clin Exp Allergy 32 (9):1360-5. PMID: 12220476
- ↑ Bianco S, Vaghi A, Robuschi M, Pasargiklian M (1988) Prevention of exercise-induced bronchoconstriction by inhaled frusemide. Lancet 2 (8605):252-5. PMID: 2899239
- ↑ Melillo E, Woolley KL, Manning PJ, Watson RM, O'Byrne PM (1994) Effect of inhaled PGE2 on exercise-induced bronchoconstriction in asthmatic subjects. Am J Respir Crit Care Med 149 (5):1138-41. PMID: 8173753
- ↑ Shimizu T, Mochizuki H, Shigeta M, Morikawa A (1997) Effect of inhaled indomethacin on exercise-induced bronchoconstriction in children with asthma. Am J Respir Crit Care Med 155 (1):170-3. PMID: 9001307
- ↑ Ahmed T, Gonzalez BJ, Danta I (1999) Prevention of exercise-induced bronchoconstriction by inhaled low-molecular-weight heparin. Am J Respir Crit Care Med 160 (2):576-81. PMID: 10430731
- ↑ Philip G, Pearlman DS, Villarán C, Legrand C, Loeys T, Langdon RB et al. (2007) Single-dose montelukast or salmeterol as protection against exercise-induced bronchoconstriction. Chest 132 (3):875-83. DOI:10.1378/chest.07-0550 PMID: 17573489