Exercise induced asthma: Difference between revisions

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{{Infobox_Disease
__NOTOC__
| Name          = {{PAGENAME}}
| Image          =
| Caption        =
| DiseasesDB    = 31728
| ICD10          =
| ICD9          = {{ICD9|493.81}}
| ICDO          =
| OMIM          =
| MedlinePlus    =
| eMedicineSubj  =
| eMedicineTopic =
| MeshID        = D001250
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{{Asthma}}
{{Asthma}}
{{CMG}}
{{CMG}}; {{AOEIC}} {{LG}}


==Overview==
==Overview==
'''Exercise-induced asthma''', or '''E.I.A.''', is a [[Disease|medical condition]] characterized by shortness of breath induced by sustained aerobic exercise. It shares many features with other types of [[asthma]], and responds to some typical asthma medications, but does not appear to be caused by the same inflammatory reaction as the other types.
Exercise-induced asthma, or E.I.A., is a [[Disease|medical condition]] characterized by [[dyspnea|shortness of breath]] induced by sustained aerobic exercise. In patients with [[bronchial hyperresponsiveness]], vigorous physical activity triggers acute narrowing of the airways<ref name="pmid15579363">Storms WW (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15579363 Asthma associated with exercise.] ''Immunol Allergy Clin North Am'' 25 (1):31-43. [http://dx.doi.org/10.1016/j.iac.2004.09.007 DOI:10.1016/j.iac.2004.09.007] PMID: [http://pubmed.gov/15579363 15579363]</ref> and is measured by the number of [[Asthma laboratory tests#Serum and Sputum Examination|sputum eosinophils]].<ref name="pmid429710">Anderton RC, Cuff MT, Frith PA, Cockcroft DW, Morse JL, Jones NL et al. (1979) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=429710 Bronchial responsiveness to inhaled histamine and exercise.] ''J Allergy Clin Immunol'' 63 (5):315-20. PMID: [http://pubmed.gov/429710 429710]</ref><ref name="pmid18071011">Duong M, Subbarao P, Adelroth E, Obminski G, Strinich T, Inman M et al. (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18071011 Sputum eosinophils and the response of exercise-induced bronchoconstriction to corticosteroid in asthma.] ''Chest'' 133 (2):404-11. [http://dx.doi.org/10.1378/chest.07-2048 DOI:10.1378/chest.07-2048] PMID: [http://pubmed.gov/18071011 18071011]</ref><ref name="pmid11192956">Kivity S, Argaman A, Onn A, Shwartz Y, Man A, Greif J et al. (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11192956 Eosinophil influx into the airways in patients with exercise-induced asthma.] ''Respir Med'' 94 (12):1200-5. [http://dx.doi.org/10.1053/rmed.2000.0951 DOI:10.1053/rmed.2000.0951] PMID: [http://pubmed.gov/11192956 11192956]</ref><ref name="pmid9817162">Yoshikawa T, Shoji S, Fujii T, Kanazawa H, Kudoh S, Hirata K et al. (1998) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9817162 Severity of exercise-induced bronchoconstriction is related to airway eosinophilic inflammation in patients with asthma.] ''Eur Respir J'' 12 (4):879-84. PMID: [http://pubmed.gov/9817162 9817162]</ref> 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 <ref name="pmid39252">McFadden ER, Ingram RH (1979) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=39252 Exercise-induced asthma: Observations on the initiating stimulus.] ''N Engl J Med'' 301 (14):763-9. [http://dx.doi.org/10.1056/NEJM197910043011406 DOI:10.1056/NEJM197910043011406] PMID: [http://pubmed.gov/39252 39252]</ref><ref name="pmid4054253">Anderson SD, Schoeffel RE, Black JL, Daviskas E (1985) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=4054253 Airway cooling as the stimulus to exercise-induced asthma--a re-evaluation.] ''Eur J Respir Dis'' 67 (1):20-30. PMID: [http://pubmed.gov/4054253 4054253]</ref>
*[[Bronchial hyperresponsiveness]]
*Increased duration and intensity of exercise
*Concomitant viral infection
*[[Asthma triggers|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.<ref name="pmid438014">Deal EC, McFadden ER, Ingram RH, Strauss RH, Jaeger JJ (1979) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=438014 Role of respiratory heat exchange in production of exercise-induced asthma.] ''J Appl Physiol'' 46 (3):467-75. PMID: [http://pubmed.gov/438014 438014]</ref><ref name="pmid10680952">Kallings LV, Emtner M, Bäcklund L (1999) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10680952 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: [http://pubmed.gov/10680952 10680952]</ref><ref name="pmid10194152">Freed AN, Davis MS (1999) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10194152 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: [http://pubmed.gov/10194152 10194152]</ref> 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%.<ref name="pmid11399690">Sonna LA, Angel KC, Sharp MA, Knapik JJ, Patton JF, Lilly CM (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11399690 The prevalence of exercise-induced bronchospasm among US Army recruits and its effects on physical performance.] ''Chest'' 119 (6):1676-84. PMID: [http://pubmed.gov/11399690 11399690]</ref><ref name="pmid10193388">Ng'ang'a LW, Odhiambo JA, Mungai MW, Gicheha CM, Nderitu P, Maingi B et al. (1998) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10193388 Prevalence of exercise induced bronchospasm in Kenyan school children: an urban-rural comparison.] ''Thorax'' 53 (11):919-26. PMID: [http://pubmed.gov/10193388 10193388]</ref><ref name="pmid9872197">Kukafka DS, Lang DM, Porter S, Rogers J, Ciccolella D, Polansky M et al. (1998) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9872197 Exercise-induced bronchospasm in high school athletes via a free running test: incidence and epidemiology.] ''Chest'' 114 (6):1613-22. PMID: [http://pubmed.gov/9872197 9872197]</ref> The majority of asthmatics with symptomatic disease have some degree of exercise induced asthma.<ref name="pmid8152449">McFadden ER, Gilbert IA (1994) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=8152449 Exercise-induced asthma.] ''N Engl J Med'' 330 (19):1362-7. [http://dx.doi.org/10.1056/NEJM199405123301907 DOI:10.1056/NEJM199405123301907] PMID: [http://pubmed.gov/8152449 8152449]</ref>
==Diagnosis==
===History and Symptoms===
*Initial [[bronchodilation]] occurs 6-8 minutes after exercise<ref name="pmid2190506">Inman MD, Watson RM, Killian KJ, O'Byrne PM (1990) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=2190506 Methacholine airway responsiveness decreases during exercise in asthmatic subjects.] ''Am Rev Respir Dis'' 141 (6):1414-7. PMID: [http://pubmed.gov/2190506 2190506]</ref> 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|prostaglandin E2]].<ref name="pmid637407">Edmunds AT, Tooley M, Godfrey S (1978) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=637407 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: [http://pubmed.gov/637407 637407]</ref><ref name="pmid8214949">Manning PJ, Watson RM, O'Byrne PM (1993) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=8214949 Exercise-induced refractoriness in asthmatic subjects involves leukotriene and prostaglandin interdependent mechanisms.] ''Am Rev Respir Dis'' 148 (4 Pt 1):950-4. PMID: [http://pubmed.gov/8214949 8214949]</ref>
*Most often than not, approximately 6-10 hours after an initial attack, a rebound attack with milder symptoms often develops without precipitating exertion.<ref name="pmid3968338">Iikura Y, Inui H, Nagakura T, Lee TH (1985) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=3968338 Factors predisposing to exercise-induced late asthmatic responses.] ''J Allergy Clin Immunol'' 75 (2):285-9. PMID: [http://pubmed.gov/3968338 3968338]</ref><ref name="pmid3614292">Rubinstein I, Levison H, Slutsky AS, Hak H, Wells J, Zamel N et al. (1987) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=3614292 Immediate and delayed bronchoconstriction after exercise in patients with asthma.] ''N Engl J Med'' 317 (8):482-5. [http://dx.doi.org/10.1056/NEJM198708203170805 DOI:10.1056/NEJM198708203170805] PMID: [http://pubmed.gov/3614292 3614292]</ref><ref name="pmid9564982">Chhabra SK, Ojha UC (1998) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9564982 Late asthmatic response in exercise-induced asthma.] ''Ann Allergy Asthma Immunol'' 80 (4):323-7. [http://dx.doi.org/10.1016/S1081-1206(10)62977-8 DOI:10.1016/S1081-1206(10)62977-8] PMID: [http://pubmed.gov/9564982 9564982]</ref>
*Severe attacks are often the result of someone with both, allergic and exercise-induced asthma exercising in a [[Asthma triggers|high-allergen environment]] (e.g. walking uphill alongside slowly moving traffic at dusk) and can be fatal.
*Common symptoms include:
:*[[dyspnea|Shortness of breath]]
:*[[Cough]]
:*[[Wheeze]]
:*Altered metal status may be the presentation in severe attacks


==Etiology==
===Physical Examination===
While the potential triggering events for E.I.A. are well delineated, the underlying pathogenesis is poorly understood. It usually occurs after at least several minutes of vigorous, "aerobic" activity, which demands that normal nasal breathing be supplemented by mouth-breathing. The resultant inhalation of air that has not been warmed and humidified by the nasal passages seems to generate increased blood flow to the linings of the bronchial tree, resulting in [[edema]]. Constriction of these vessels then follows, worsening the degree of obstruction to airflow. This sequence generates symptoms similar to those seen in other forms of asthma, but occurs without the inflammatory changes that underlie them.
====Vital Signs====
*[[Tachypnea]]
*[[Tachycardia]]
====HEENT====
[[Cyanosis]] secondary to severe [[hypoxia]]
====Lungs====
High-pitch prolong expiratory [[wheeze]] that may be audible even without a stethoscope.


==Signs and symptoms==
===Other Diagnostic Studies===
During an attack, the E.I.A. victim will likely be [[dyspnea|short of breath]] and/or [[coughing]], with an [[tachypnea|elevated respiratory rate]] and [[wheezing]], which may be audible even without a [[stethoscope]]. Examination will usually reveal the wheezing and a prolonged expiratory phase. In the occasional severe attack, altered level of consciousness and cyanosis due to depressed oxygenation of the blood may occur. 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.  
====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.<ref name="pmid17433829">Weiler JM, Bonini S, Coifman R, Craig T, Delgado L, Capão-Filipe M et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17433829 American Academy of Allergy, Asthma & Immunology Work Group report: exercise-induced asthma.] ''J Allergy Clin Immunol'' 119 (6):1349-58. [http://dx.doi.org/10.1016/j.jaci.2007.02.041 DOI:10.1016/j.jaci.2007.02.041] PMID: [http://pubmed.gov/17433829 17433829]</ref>
*In athletes, documentation of [[bronchospasm|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 [[steroids|inhaled corticosteroids]] and is usually associated with a reduction in respiratory symptoms on exercise.<ref name="pmid16630932">Anderson SD, Sue-Chu M, Perry CP, Gratziou C, Kippelen P, McKenzie DC et al. (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16630932 Bronchial challenges in athletes applying to inhale a beta2-agonist at the 2004 Summer Olympics.] ''J Allergy Clin Immunol'' 117 (4):767-73. [http://dx.doi.org/10.1016/j.jaci.2005.12.1355 DOI:10.1016/j.jaci.2005.12.1355] PMID: [http://pubmed.gov/16630932 16630932]</ref><ref name="pmid14674930">Bonini S, Brusasco V, Carlsen KH, Delgado L, Del Giacco SR, Giacco SD et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14674930 Diagnosis of asthma and permitted use of inhaled beta2-agonists in athletes.] ''Allergy'' 59 (1):33-6. PMID: [http://pubmed.gov/14674930 14674930]</ref><ref name="pmid17433829">Weiler JM, Bonini S, Coifman R, Craig T, Delgado L, Capão-Filipe M et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17433829 American Academy of Allergy, Asthma & Immunology Work Group report: exercise-induced asthma.] ''J Allergy Clin Immunol'' 119 (6):1349-58. [http://dx.doi.org/10.1016/j.jaci.2007.02.041 DOI:10.1016/j.jaci.2007.02.041] PMID: [http://pubmed.gov/17433829 17433829]</ref>


In most cases, a relative "refractory period" follows resolution of an attack. During this approximately one hour period, resumption of exercise will likely produce either none or mild symptoms. Curiously as well, some 6-10 hours after the initial attack, a rebound attack with milder symptoms often develops without precipitating exertion.
==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 [[Asthma pulmonary function test#Peak Expiratory Flow Rate|peak expiratory flow rate]] performed before and after the exercise. [[Asthma bronchial challenge test#Methacholine Challenge Test|Methacholine challenge test]] is another alternative to objectively assess response to therapy.<ref name="pmid10821721">Hofstra WB, Neijens HJ, Duiverman EJ, Kouwenberg JM, Mulder PG, Kuethe MC et al. (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10821721 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: [http://pubmed.gov/10821721 10821721]</ref><ref name="pmid8575573">Freezer NJ, Croasdell H, Doull IJ, Holgate ST (1995) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=8575573 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: [http://pubmed.gov/8575573 8575573]</ref>
 
*Fish oil supplementation may represent a potentially beneficial non-pharmacologic intervention for patients with exercise-induced asthma.<ref name="pmid16424411">Mickleborough TD, Lindley MR, Ionescu AA, Fly AD (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16424411 Protective effect of fish oil supplementation on exercise-induced bronchoconstriction in asthma.] ''Chest'' 129 (1):39-49. [http://dx.doi.org/10.1378/chest.129.1.39 DOI:10.1378/chest.129.1.39] PMID: [http://pubmed.gov/16424411 16424411]</ref>
 
*The most common medication approach is to use a [[Beta-adrenergic agonist|beta agonist]] about twenty minutes before exercise.<ref name="pmid41866">Anderson S, Seale JP, Ferris L, Schoeffel R, Lindsay DA (1979) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=41866 An evaluation of pharmacotherapy for exercise-induced asthma.] ''J Allergy Clin Immunol'' 64 (6 pt 2):612-24. PMID: [http://pubmed.gov/41866 41866]</ref>
 
:*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.<ref name="pmid12030726">Richter K, Janicki S, Jörres RA, Magnussen H (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12030726 Acute protection against exercise-induced bronchoconstriction by formoterol, salmeterol and terbutaline.] ''Eur Respir J'' 19 (5):865-71. PMID: [http://pubmed.gov/12030726 12030726]</ref>
 
:*[[Tachyphylaxis]] developed to the protective effect of long and short-acting [[Beta-adrenergic agonist|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.<ref name="pmid11956046">Hancox RJ, Subbarao P, Kamada D, Watson RM, Hargreave FE, Inman MD (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11956046 Beta2-agonist tolerance and exercise-induced bronchospasm.] ''Am J Respir Crit Care Med'' 165 (8):1068-70. PMID: [http://pubmed.gov/11956046 11956046]</ref><ref name="pmid8542164">Inman MD, O'Byrne PM (1996) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=8542164 The effect of regular inhaled albuterol on exercise-induced bronchoconstriction.] ''Am J Respir Crit Care Med'' 153 (1):65-9. PMID: [http://pubmed.gov/8542164 8542164]</ref><ref name="pmid9664089">Nelson JA, Strauss L, Skowronski M, Ciufo R, Novak R, McFadden ER (1998) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9664089 Effect of long-term salmeterol treatment on exercise-induced asthma.] ''N Engl J Med'' 339 (3):141-6. [http://dx.doi.org/10.1056/NEJM199807163390301 DOI:10.1056/NEJM199807163390301] PMID: [http://pubmed.gov/9664089 9664089]</ref><ref name="pmid11831450">García R, Guerra P, Feo F, Galindo PA, Gómez E, Borja J et al. (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11831450 Tachyphylaxis following regular use of formoterol in exercise-induced bronchospasm.] ''J Investig Allergol Clin Immunol'' 11 (3):176-82. PMID: [http://pubmed.gov/11831450 11831450]</ref><ref name="pmid9113940">Simons FE, Gerstner TV, Cheang MS (1997) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9113940 Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment.] ''Pediatrics'' 99 (5):655-9. PMID: [http://pubmed.gov/9113940 9113940]</ref>


==Treatment==
*[[Nedocromil]] and [[cromolyn]] administered by a pressurized aerosol has shown to provide equal protection against exercise-induced asthma in children.<ref name="pmid7930301">de Benedictis FM, Tuteri G, Bertotto A, Bruni L, Vaccaro R (1994) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=7930301 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: [http://pubmed.gov/7930301 7930301]</ref> A small randomized study, has shown the additive effects of combining [[cromolyn]] and [[Beta-adrenergic agonist|beta-2 agonist]] and may be indicated in high-performance athletes.<ref name="pmid6412606">Latimer KM, O'Byrne PM, Morris MM, Roberts R, Hargreave FE (1983) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=6412606 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: [http://pubmed.gov/6412606 6412606]</ref> [[Nedocromil|Nedocromil sodium]] used before exercise has shown to reduce the severity and duration of exercise-induced bronchoconstriction.<ref name="pmid10933081">Spooner C, Rowe BH, Saunders LD (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10933081 Nedocromil sodium in the treatment of exercise-induced asthma: a meta-analysis.] ''Eur Respir J'' 16 (1):30-7. PMID: [http://pubmed.gov/10933081 10933081]</ref><ref name="pmid11869595">Spooner CH, Saunders LD, Rowe BH (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11869595 Nedocromil sodium for preventing exercise-induced bronchoconstriction.] ''Cochrane Database Syst Rev''  (1):CD001183. [http://dx.doi.org/10.1002/14651858.CD001183 DOI:10.1002/14651858.CD001183] PMID: [http://pubmed.gov/11869595 11869595]</ref>
As with any asthma, the best treatment is avoidance, when possible, of conditions predisposing to attacks. 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.
 
*[[Steroids|Inhaled corticosteroids]] used for weeks and months before exercise significantly attenuated exercise-induced bronchoconstriction; however, it does not provide any short-term benefit.<ref name="pmid10893016">Jónasson G, Carlsen KH, Hultquist C (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10893016 Low-dose budesonide improves exercise-induced bronchospasm in schoolchildren.] ''Pediatr Allergy Immunol'' 11 (2):120-5. PMID: [http://pubmed.gov/10893016 10893016]</ref><ref name="pmid9864004">Jónasson G, Carlsen KH, Blomqvist P (1998) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9864004 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: [http://pubmed.gov/9864004 9864004]</ref><ref name="pmid17980416">Stelmach I, Grzelewski T, Majak P, Jerzynska J, Stelmach W, Kuna P (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17980416 Effect of different antiasthmatic treatments on exercise-induced bronchoconstriction in children with asthma.] ''J Allergy Clin Immunol'' 121 (2):383-9. [http://dx.doi.org/10.1016/j.jaci.2007.09.007 DOI:10.1016/j.jaci.2007.09.007] PMID: [http://pubmed.gov/17980416 17980416]</ref><ref name="pmid17636704">Koh MS, Tee A, Lasserson TJ, Irving LB (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17636704 Inhaled corticosteroids compared to placebo for prevention of exercise induced bronchoconstriction.] ''Cochrane Database Syst Rev''  (3):CD002739. [http://dx.doi.org/10.1002/14651858.CD002739.pub3 DOI:10.1002/14651858.CD002739.pub3] PMID: [http://pubmed.gov/17636704 17636704]</ref>


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.
*[[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.<ref name="pmid9516894">Reiss TF, Hill JB, Harman E, Zhang J, Tanaka WK, Bronsky E et al. (1997) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9516894 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: [http://pubmed.gov/9516894 9516894]</ref><ref name="pmid9664090">Leff JA, Busse WW, Pearlman D, Bronsky EA, Kemp J, Hendeles L et al. (1998) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9664090 Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction.] ''N Engl J Med'' 339 (3):147-52. [http://dx.doi.org/10.1056/NEJM199807163390302 DOI:10.1056/NEJM199807163390302] PMID: [http://pubmed.gov/9664090 9664090]</ref> However, [[Leukotriene|leukotriene inhibitors]] are not effective in all patients with exercise induced asthma.<ref name="pmid12220476">Mastalerz L, Gawlewicz-Mroczka A, Nizankowska E, Cmiel A, Szczeklik A (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12220476 Protection against exercise-induced bronchoconstriction by montelukast in aspirin-sensitive and aspirin-tolerant patients with asthma.] ''Clin Exp Allergy'' 32 (9):1360-5. PMID: [http://pubmed.gov/12220476 12220476]</ref>


The most common medication approach is to use a [[beta agonist]] about twenty minutes before exercise. Some physicians prescribe inhaled anti-inflammatory mists such as [[corticosteroids]] or [[leukotriene antagonist]]s, and [[mast cell stabilizer]]s have also proven effective. 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.<ref name="pmid17573489">{{cite journal |author=Philip G, Pearlman DS, Villarán C, ''et al'' |title=Single-dose montelukast or salmeterol as protection against exercise-induced bronchoconstriction |journal=Chest |volume=132 |issue=3 |pages=875–83 |year=2007 |pmid=17573489 |doi=10.1378/chest.07-0550}}</ref>
*Other pharmacological agents that have been hypothesized to provide therapeutic benefits in patients with exercise induced asthma include [[frusemide]],<ref name="pmid2899239">Bianco S, Vaghi A, Robuschi M, Pasargiklian M (1988) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=2899239 Prevention of exercise-induced bronchoconstriction by inhaled frusemide.] ''Lancet'' 2 (8605):252-5. PMID: [http://pubmed.gov/2899239 2899239]</ref> [[prostaglandin|prostaglandin-E2]],<ref name="pmid8173753">Melillo E, Woolley KL, Manning PJ, Watson RM, O'Byrne PM (1994) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=8173753 Effect of inhaled PGE2 on exercise-induced bronchoconstriction in asthmatic subjects.] ''Am J Respir Crit Care Med'' 149 (5):1138-41. PMID: [http://pubmed.gov/8173753 8173753]</ref> [[indomethacin]],<ref name="pmid9001307">Shimizu T, Mochizuki H, Shigeta M, Morikawa A (1997) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9001307 Effect of inhaled indomethacin on exercise-induced bronchoconstriction in children with asthma.] ''Am J Respir Crit Care Med'' 155 (1):170-3. PMID: [http://pubmed.gov/9001307 9001307]</ref> and [[heparin]].<ref name="pmid10430731">Ahmed T, Gonzalez BJ, Danta I (1999) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10430731 Prevention of exercise-induced bronchoconstriction by inhaled low-molecular-weight heparin.] ''Am J Respir Crit Care Med'' 160 (2):576-81. PMID: [http://pubmed.gov/10430731 10430731]</ref>


==Prognosis==
*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.
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.
*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.


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.<ref name="pmid17573489">Philip G, Pearlman DS, Villarán C, Legrand C, Loeys T, Langdon RB et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17573489 Single-dose montelukast or salmeterol as protection against exercise-induced bronchoconstriction.] ''Chest'' 132 (3):875-83. [http://dx.doi.org/10.1378/chest.07-0550 DOI:10.1378/chest.07-0550] PMID: [http://pubmed.gov/17573489 17573489]</ref>


*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]].<ref name="pmid17980416">Stelmach I, Grzelewski T, Majak P, Jerzynska J, Stelmach W, Kuna P (2008) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17980416 Effect of different antiasthmatic treatments on exercise-induced bronchoconstriction in children with asthma.] ''J Allergy Clin Immunol'' 121 (2):383-9. [http://dx.doi.org/10.1016/j.jaci.2007.09.007 DOI:10.1016/j.jaci.2007.09.007] PMID: [http://pubmed.gov/17980416 17980416]</ref>
==References==
==References==
{{reflist|2}}
{{reflist|2}}
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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

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:

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.
  • 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]
  • 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]
  • 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

  • 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

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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
  7. ↑ 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
  8. ↑ 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
  9. ↑ 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
  10. ↑ 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
  11. ↑ 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
  12. ↑ 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
  13. ↑ 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
  14. ↑ McFadden ER, Gilbert IA (1994) Exercise-induced asthma. N Engl J Med 330 (19):1362-7. DOI:10.1056/NEJM199405123301907 PMID: 8152449
  15. ↑ 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
  16. ↑ 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
  17. ↑ 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
  18. ↑ 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
  19. ↑ 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
  20. ↑ 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. ↑ 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
  22. ↑ 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
  23. ↑ 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
  24. ↑ 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
  25. ↑ 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
  26. ↑ 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
  27. ↑ 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
  28. ↑ 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
  29. ↑ 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
  30. ↑ 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
  31. ↑ 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
  32. ↑ 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
  33. ↑ 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
  34. ↑ 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
  35. ↑ 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
  36. ↑ 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
  37. ↑ 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
  38. ↑ 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
  39. ↑ 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. ↑ 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
  41. ↑ 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
  42. ↑ 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
  43. ↑ 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
  44. ↑ 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
  45. ↑ Bianco S, Vaghi A, Robuschi M, Pasargiklian M (1988) Prevention of exercise-induced bronchoconstriction by inhaled frusemide. Lancet 2 (8605):252-5. PMID: 2899239
  46. ↑ 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
  47. ↑ 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
  48. ↑ 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
  49. ↑ 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

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