American Thoracic Society Documents An Official American Thoracic Society Clinical Practice Guideline: Exercise-induced Bronchoconstriction Jonathan P. Parsons, Teal S. Hallstrand, John G. Mastronarde, David A. Kaminsky, Kenneth W. Rundell, James H. Hull, William W. Storms, John M. Weiler, Fern M. Cheek, Kevin C. Wilson, and Sandra D. Anderson; on behalf of the American Thoracic Society Subcommittee on Exercise-induced Bronchoconstriction THIS OFFICIAL CLINICAL PRACTICE GUIDELINE OF THE AMERICAN THORACIC SOCIETYWASAPPROVEDBYTHEATS BOARD OF DIRECTORS, DECEMBER 2012 CONTENTS proportion of patients with asthma experience exercise-induced respiratory symptoms. EIB has also been shown to occur in sub- Executive Summary jects without a known diagnosis of asthma. Introduction Methods Diagnosis Pathogenesis Role of the Environment d The diagnosis of EIB is established by changes in lung Diagnosis function provoked by exercise, not on the basis of Measuring and Quantifying EIB symptoms. Exercise Challenge Testing to Identify EIB d Serial lung function measurements after a specific exercise Surrogates for Exercise to Identify EIB or hyperpnea challenge are used to determine if EIB is Treatment present and to quantify the severity of the disorder. It is Questions and Recommendations preferable to assess FEV1, because this measurement has General Comments Regarding Therapy better repeatability and is more discriminating than peak Screening for EIB expiratory flow rate. Exercise, Asthma, and Doping d The airway response is expressed as the percent fall in Background: Exercise-induced bronchoconstriction (EIB) describes FEV1 from the baseline value. The difference between acute airway narrowing that occurs as a result of exercise. EIB occurs the pre-exercise FEV1 value and the lowest FEV1 value in a substantial proportion of patients with asthma, but may also recorded within 30 minutes after exercise is expressed as occur in individuals without known asthma. a percentage of the pre-exercise value. The criterion for Methods: Toprovideclinicianswithpracticalguidance,amultidisciplinary the percent fall in FEV1 used to diagnose EIB is >10%. panel of stakeholders was convened to review the pathogenesis of EIB d The severity of EIB can be graded as mild, moderate, or and to develop evidence-based guidelines for the diagnosis and treat- severe if the percent fall in FEV from the pre-exercise ment of EIB. The evidence was appraised and recommendations were 1 level is >10% but ,25%, >25% but ,50%, and >50%, formulated using the Grading of Recommendations, Assessment, Devel- respectively. opment, and Evaluation approach. Results: Recommendations for the treatment of EIB were developed. d A number of surrogates for exercise testing have been The quality of evidence supporting the recommendations was variable, developed that may be easier to implement than exercise ranging from low to high. A strong recommendation was made for challenge. These surrogates include eucapnic voluntary b using a short-acting 2-agonist before exercise in all patients with hyperpnea or hyperventilation, hyperosmolar aerosols, in- EIB. For patients who continue to have symptoms of EIB despite cluding 4.5% saline, and dry powder mannitol. the administration of a short-acting b2-agonist before exercise, strong recommendations were made for a daily inhaled corticoste- Treatment roid, a daily leukotriene receptor antagonist, or a mast cell stabi- lizing agent before exercise. d For patients with EIB, we recommend administration of b Conclusions: The recommendations in this Guideline reflect the an inhaled short-acting 2-agonist (SABA) before exercise currently available evidence. New clinical research data will necessi- (strong recommendation, high-quality evidence). The SABA tate a revision and update in the future. is typically administered 15 minutes before exercise. d A controller agent is generally added whenever SABA EXECUTIVE SUMMARY therapy is used daily or more frequently. Exercise-induced bronchoconstriction (EIB) describes acute air- d For patients with EIB who continue to have symptoms way narrowing that occurs as a result of exercise. A substantial despite using an inhaled SABA before exercise, or who require an inhaled SABA daily or more frequently: d We recommend against daily use of an inhaled long- b This article has an online supplement, which is accessible from this issue’s table of acting 2-agonist as single therapy (strong recommen- contents at www.atsjournals.org dation, moderate-quality evidence). This is based upon Am J Respir Crit Care Med Vol 187, Iss. 9, pp 1016–1027, May 1, 2013 a strong concern for serious side effects. Copyright ª 2013 by the American Thoracic Society d DOI: 10.1164/rccm.201303-0437ST We recommend daily administration of an inhaled corti- Internet address: www.atsjournals.org costeroid (ICS) (strong recommendation, moderate-quality American Thoracic Society Documents 1017 evidence). It may take 2–4 weeks after the initiation of bronchoconstriction” instead of “exercise-induced asthma,” as it therapy to see maximal improvement. does not imply that the patient has underlying chronic asthma or that exercise actually “caused” asthma. For the purposes of this d We recommend against administration of ICS only before document, we will use the terminology “exercise-induced broncho- exercise (strong recommendation, moderate-quality evidence). constriction” without regard to whether it occurs in patients with d We recommend daily administration of a leukotriene or without asthma. receptor antagonist (strong recommendation, moderate- There are substantial data showing that EIB occurs very com- quality evidence). monly in athletes at all levels. Many studies have been performed d We recommend administration of a mast cell stabilizing in Olympic or elite-level athletes that have documented preva- agent before exercise (strong recommendation, high- lence of EIB varying between 30 and 70%, depending on the quality evidence). population studied and methods implemented (1). Studies have also been done on college, high school, and recreational athletes d We suggest administration of an inhaled anticholiner- that have shown a significant prevalence of EIB (2–4). gic agent before exercise (weak recommendation, low- The symptoms of EIB are variable and nonspecific, and pres- quality evidence). ence or absence of specific respiratory symptoms has very poor d In our clinical practices, we generally add a daily in- predictive value for objectively confirmed EIB (4, 5). Clinical haled ICS or a daily leukotriene receptor antagonist presentation may include chest tightness, cough, wheezing, and first, with the choice between these agents made on a dyspnea. These symptoms may only be provoked by exercise or case-by-case basis depending upon patient preferences may only occur in specific environments, such as ice rinks or and baseline lung function. Mast cell stabilizing agents indoor swimming pools. The symptoms are often mild to moder- and inhaled anticholinergic agents play a secondary role. ate in severity and may cause impairment of athletic performance, but are not severe enough to cause significant respiratory distress. d For patients with EIB and allergies who continue to have However, severe episodes of EIB can occur, and respiratory fail- symptoms despite using an inhaled SABA before exercise, ure and even death have occurred in rare cases (6). or who require an inhaled SABA daily or more frequently, Given the significant prevalence of EIB, it is critical that weak rec- we suggest administration of an antihistamine ( evidence-based documents exist to guide health care providers with ommendation moderate-quality evidence , ). In contrast, we regard to the pathogenesis, diagnosis, management, and treatment against recommend administration of antihistamines in of EIB, as well as other critical issues related to EIB, such as en- strong rec- patients with EIB who do not have allergies ( vironmental influences and considerations in Olympic/elite-level ommendation moderate-quality evidence , ). athletes. To provide such guidance, a multidisciplinary panel d For all patients with EIB, we recommend interval or com- was convened to develop evidence-based guidelines. bination warm-up exercise before planned exercise (strong recommendation, moderate-quality evidence). METHODS d For patients with EIB who exercise in cold weather, we These guidelines were developed in accordance with the American Tho- suggest routine use of a device (i.e., mask) that warms and racic Society’s (ATS’s) standards for clinical practice guidelines (Table humidifies the air during exercise (weak recommendation, 1). The methods are described in detail in the online supplement. low-quality evidence). d For patients with EIB who have an interest in dietary PATHOGENESIS modification to control their symptoms: A modest period of high-intensity exercise or, alternatively, in- d We suggest implementation of a low-salt diet (weak creased minute ventilation during isocapnic hyperpnea triggers recommendation, moderate-quality evidence). a prototypical response consisting of bronchoconstriction, which occurs predominantly after the cessation of a short period of d We suggest dietary supplementation with fish oils (weak recommendation, low-quality evidence). d We suggest against dietary supplementation with lyco- TABLE 1. METHODS CHECKLIST pene (weak recommendation, low-quality evidence). Yes No d We suggest dietary supplementation with ascorbic acid Panel assembly (weak recommendation, moderate-quality evidence).