A REVIEW OF THE IMPACT OF EXERCISE-INDUCED ...
Word Count: 3970. Abstract count: 205.THE IMPACT OF Exercise-induced bronchoconstriction ON ATHLETIC PERFORMANCe – A SYSTEMATIC REVIEWOliver J. Price1, James H. Hull1, 2, Vibeke Backer3, Morten Hostrup3, Les Ansley11Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom (UK). 2Department of Respiratory Medicine, Royal Brompton Hospital, UK. 3Department of Respiratory Medicine, Bispebjerg University Hospital, Copenhagen, Denmark.Corresponding author: Dr. Les AnsleyFaculty of Health and Life Sciences, Northumbria University,Newcastle, NE1 8ST.Tel: + 44 191 243 7773Email: les.ansley@northumbria.ac.ukRunning title: Exercise-induced bronchoconstriction and athletic performance. ABSTRACTBackground: Exercise-induced bronchoconstriction (EIB) describes the phenomenon of transient airway narrowing in association with physical activity. Although it may seem likely that EIB would have a detrimental impact on athletic performance this has yet to be established. Objectives: Therefore, the aim of this review is to provide a systematic appraisal of the current status of knowledge regarding EIB and exercise performance and to highlight potential mechanisms by which performance may be compromised by EIB. Data sources and study selection: PubMed/Medline and EBSCO databases were searched up to May 2014 using the search parameter: [(‘exercise’ OR ‘athlete’) AND (‘asthma’ OR ‘bronchoconstriction’ OR ‘hypersensitivity’) AND ‘performance’]. This search string returned 243 citations. After systematically reviewing all of the abstracts, 101 duplicate papers were removed, with 132 papers excluded for not including an exercise performance outcome measure. Results: The remaining ten studies that met the initial criteria were included in this review; six evaluated the performance of physically active individuals with asthma and/or EIB while four assessed the effects of medication on performance in a comparable population. Conclusion: The evidence concludes that whilst it is reasonable to suspect that EIB does impact athletic performance, there is currently insufficient evidence to provide a definitive answer. Key points:Further work is required to establish the impact of exercise-induced bronchoconstriction on athletic performance.Future studies should address the impact of sport-specific protocols that are conducted in provocative environments.Disease severity and athletic standard need to be accounted for in the interpretation of future results.1. BackgroundAt the London 2012 Summer Olympic Games, first and third place across all athletic track events were separated by 1% of the winner’s time ADDIN EN.CITE <EndNote><Cite><Author>IOC</Author><Year>2012</Year><RecNum>629</RecNum><DisplayText>[1]</DisplayText><record><rec-number>629</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">629</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>IOC</author></authors></contributors><titles><secondary-title>;[1]. Tiny margins decide success in elite sport and any small impingement on the ability of an athlete to perform maximally can affect competition outcome. The capacity of the cardiovascular system is generally considered to be the limiting factor underpinning peak aerobic exercise performance ADDIN EN.CITE <EndNote><Cite><Author>Bassett JR</Author><Year>2000</Year><RecNum>285</RecNum><DisplayText>[2]</DisplayText><record><rec-number>285</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">285</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bassett JR, D.R.</author><author>Howley, E.T.</author></authors></contributors><titles><title>Limiting factors for maximum oxygen uptake and determinants of endurance performance</title><secondary-title>Medicine and Science in Sports and Exercise</secondary-title></titles><periodical><full-title>Medicine and Science in Sports and Exercise</full-title><abbr-1>Med Sci Sports Exerc</abbr-1></periodical><pages>70-84</pages><volume>32</volume><number>1</number><dates><year>2000</year></dates><isbn>0195-9131</isbn><urls></urls></record></Cite></EndNote>[2], whilst in contrast the respiratory system is usually regarded as over-engineered for the demands during intense exercise ADDIN EN.CITE <EndNote><Cite><Author>Dempsey</Author><Year>1986</Year><RecNum>274</RecNum><DisplayText>[3]</DisplayText><record><rec-number>274</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">274</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dempsey, J.A.</author></authors></contributors><titles><title>JB Wolffe memorial lecture. Is the lung built for exercise?</title><secondary-title>Medicine and science in sports and exercise</secondary-title></titles><periodical><full-title>Medicine and Science in Sports and Exercise</full-title><abbr-1>Med Sci Sports Exerc</abbr-1></periodical><pages>143-155</pages><volume>18</volume><number>2</number><dates><year>1986</year></dates><isbn>0195-9131</isbn><urls></urls></record></Cite></EndNote>[3]. Despite this, it is now established that a significant proportion of elite athletes exhibit an ‘abnormal’ airway response to intense exercise exposure. More specifically, up to half of certain cohorts of elite athletes such as swimmers and cross country skiers, appear to develop a post exercise transient narrowing of the airways ADDIN EN.CITE <EndNote><Cite><Author>Price</Author><Year>2013</Year><RecNum>592</RecNum><DisplayText>[4]</DisplayText><record><rec-number>592</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">592</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Price, O J</author><author>Ansley, L</author><author>Menzies-Gow, A</author><author>Cullinan, P</author><author>Hull, J H</author></authors></contributors><titles><title>Airway dysfunction in elite athletes–an occupational lung disease?</title><secondary-title>Allergy</secondary-title></titles><periodical><full-title>Allergy</full-title><abbr-1>Allergy</abbr-1></periodical><pages>1343-1352</pages><volume>68</volume><number>11</number><dates><year>2013</year></dates><isbn>1398-9995</isbn><urls></urls></record></Cite></EndNote>[4]. This phenomenon, termed exercise-induced bronchoconstriction (EIB), can occur either in the presence or absence of other characteristic features of asthma ADDIN EN.CITE <EndNote><Cite><Author>Weiler</Author><Year>2007</Year><RecNum>209</RecNum><DisplayText>[5]</DisplayText><record><rec-number>209</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">209</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Weiler, J.M.</author><author>Bonini, S.</author><author>Coifman, R.</author><author>Craig, T.</author><author>Randolph, MD</author><author>Storms, W.</author><author>City, M.D.I.</author><author>Iowa, R.</author><author>Millville, NJ</author><author>Hershey, P.</author></authors></contributors><titles><title>American Academy of Allergy, Asthma & Immunology Work Group report: exercise-induced asthma</title><secondary-title>The Journal of allergy and clinical immunology</secondary-title></titles><periodical><full-title>The Journal of allergy and clinical immunology</full-title><abbr-1>J Allergy Clin Immunol</abbr-1></periodical><pages>1349-1358</pages><volume>119</volume><number>6</number><section>1349</section><dates><year>2007</year></dates><urls></urls></record></Cite></EndNote>[5]. Indeed, EIB in elite athletes has a distinct pathogenesis and athletes frequently exceed normal resting lung function ADDIN EN.CITE <EndNote><Cite><Author>Haahtela</Author><Year>2008</Year><RecNum>39</RecNum><DisplayText>[6]</DisplayText><record><rec-number>39</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">39</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Haahtela, T.</author><author>Malmberg, P.</author><author>Moreira, A.</author></authors></contributors><titles><title>Mechanisms of asthma in Olympic athletes–practical implications</title><secondary-title>Allergy</secondary-title></titles><periodical><full-title>Allergy</full-title><abbr-1>Allergy</abbr-1></periodical><pages>685-694</pages><volume>63</volume><number>6</number><dates><year>2008</year></dates><isbn>1398-9995</isbn><urls></urls></record></Cite></EndNote>[6]. Moreover it is common to encounter athletes with a significant reduction in lung function post exercise who perceive few respiratory symptoms. It is now recognised that endurance athletes are susceptible to the development of airway dysfunction yet still win a disproportionately high percentage of Olympic medals ADDIN EN.CITE <EndNote><Cite><Author>McKenzie</Author><Year>2011</Year><RecNum>312</RecNum><DisplayText>[7, 8]</DisplayText><record><rec-number>312</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">312</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McKenzie, D.C.</author><author>Fitch, K.D.</author></authors></contributors><titles><title>The asthmatic athlete: inhaled beta-2 agonists, sport performance, and doping</title><secondary-title>Clinical Journal of Sport Medicine</secondary-title></titles><periodical><full-title>Clinical journal of sport medicine</full-title><abbr-1>Clin J Sport Med</abbr-1></periodical><pages>46-50</pages><volume>21</volume><number>1</number><dates><year>2011</year></dates><isbn>1050-642X</isbn><urls></urls></record></Cite><Cite><Author>Fitch</Author><Year>2012</Year><RecNum>377</RecNum><record><rec-number>377</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">377</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Fitch, K.D.</author></authors></contributors><titles><title>An overview of asthma and airway hyper-responsiveness in Olympic athletes</title><secondary-title>British journal of sports medicine</secondary-title></titles><periodical><full-title>British journal of sports medicine</full-title><abbr-1>Br J Sports Med</abbr-1></periodical><pages>413-416</pages><volume>46</volume><number>6</number><dates><year>2012</year></dates><isbn>1473-0480</isbn><urls></urls></record></Cite></EndNote>[7, 8]. However, there is currently a dearth of scientific literature specifically addressing the impact of EIB on exercise performance. Although several studies have aimed to address this, many fail to account for key confounding factors. For instance, studies permitting a warm-up prior to exercise potentially initiates a refractory period resulting in significantly less severe or an absence of airway narrowing ADDIN EN.CITE <EndNote><Cite><Author>Price</Author><Year>2014</Year><RecNum>670</RecNum><DisplayText>[9, 10]</DisplayText><record><rec-number>670</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">670</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Price, Oliver J</author><author>Hull, James H</author></authors></contributors><titles><title>Asthma in elite athletes: Who cares?</title><secondary-title>Clinical Pulmonary Medicine</secondary-title></titles><periodical><full-title>Clinical Pulmonary Medicine</full-title><abbr-1>Clin Pulmonary Med</abbr-1></periodical><pages>68-75</pages><volume>21</volume><number>2</number><dates><year>2014</year></dates><isbn>1068-0640</isbn><urls></urls></record></Cite><Cite><Author>Stickland</Author><Year>2012</Year><RecNum>733</RecNum><record><rec-number>733</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">733</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stickland, Michael K</author><author>Rowe, Brian H</author><author>Spooner, Carol H</author><author>Vandermeer, Ben</author><author>Dryden, Donna M</author></authors></contributors><titles><title>Effect of warm-up exercise on exercise-induced bronchoconstriction</title><secondary-title>Medicine and Science in Sports and Exercise</secondary-title></titles><periodical><full-title>Medicine and Science in Sports and Exercise</full-title><abbr-1>Med Sci Sports Exerc</abbr-1></periodical><pages>383-91</pages><volume>44</volume><number>3</number><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>[9, 10].Therefore, the aim of this review is to provide an overview of the current status of research in this field, characterize potential mechanisms by which EIB may impact exercise performance and provide recommendations for future research. 2. METHODSA systematic evaluation of peer-reviewed literature from the PubMed/Medline and EBSCO databases was performed from January 1980 until May 2014 using the search parameter: [(‘exercise’ OR ‘athlete’) AND (‘asthma’ OR ‘bronchoconstriction’ OR ‘hypersensitivity’) AND ‘performance’] (English and humans (Filter), loattrfull text (Filter), not review (Filter) AND has abstract (Filter). This initial search returned 243 papers. Two authors independently reviewed the titles and abstracts of potential studies and subsequently screened full-text study reports for inclusion. After systematically reviewing the literature, 101 duplicate papers were removed, with 132 papers excluded for not including an exercise performance outcome measure (Figure 1). As research addressing the impact of EIB on exercise performance in elite athletes is relatively limited, individuals regularly participating in sport and/or physical activity were considered further. Included studies required subjects to have a previous physician diagnosis of asthma and/or objective evidence of EIB (i.e. ≥10% fall in FEV1) following bronchoprovocation testing. Consequently, ten papers met the initial criteria; six purported to evaluate exercise performance in physically active individuals with asthma and/or EIB PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UZWl4ZWlyYTwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+
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ADDIN EN.CITE.DATA [17-20]. These will be considered in more detail in the subsequent sections and form the basis of this review (Table 1). Furthermore, an appraisal of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) ADDIN EN.CITE <EndNote><Cite><Author>Guyatt</Author><Year>2011</Year><RecNum>759</RecNum><DisplayText>[21]</DisplayText><record><rec-number>759</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">759</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Guyatt, Gordon H</author><author>Oxman, Andrew D</author><author>Schünemann, Holger J</author><author>Tugwell, Peter</author><author>Knottnerus, Andre</author></authors></contributors><titles><title>GRADE guidelines: A new series of articles in the Journal of Clinical Epidemiology</title><secondary-title>Journal of clinical epidemiology</secondary-title></titles><periodical><full-title>Journal of clinical epidemiology</full-title></periodical><pages>380-382</pages><volume>64</volume><number>4</number><dates><year>2011</year></dates><isbn>0895-4356</isbn><urls></urls></record></Cite></EndNote>[21] approach has been provided (Table 2).3. RESULTS3.1 Does EIB impact on athletic performance?The limitations to performance during sport are dependent on the nature of the exercise being undertaken. It is unlikely that EIB would affect athletic performance during an event lasting <1 min. However, during exercise of longer duration and with specific aerobic demands, an abnormal airway response could impede performance. 3.2 Maximal oxygen consumptionWhen evaluating an individual’s potential to perform successfully in endurance sport, maximal oxygen consumption (VO2max) is often used as a surrogate measure for aerobic or cardiovascular capacity. As VO2max is a good differentiator of aerobic performance in a heterogeneous group of individuals it is often used to characterize general athletic ability, i.e. VO2max for a male individual of average athletic ability is ~45 mL.kg-1.min-1 and it is unusual to encounter elite level endurance athletes with a VO2max <65 mL.kg-1.min-1.It has been argued that, in asthmatic athletes, VO2max may be limited by factors other than cardiovascular capacity; i.e. by processes that slow the delivery of oxygen such as persistent airway narrowing, alveolar wall thickening and loss of elastic recoil. Certainly adult patients with severe asthma have reduced aerobic capacity ADDIN EN.CITE <EndNote><Cite><Author>McNicholl</Author><Year>2011</Year><RecNum>603</RecNum><DisplayText>[22]</DisplayText><record><rec-number>603</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">603</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McNicholl, Diarmuid M</author><author>Megarry, Jacqui</author><author>McGarvey, Lorcan P</author><author>Riley, Marshall S</author><author>Heaney, Liam G</author></authors></contributors><titles><title>The utility of cardiopulmonary exercise testing in difficult asthma</title><secondary-title>Chest</secondary-title></titles><periodical><full-title>Chest</full-title><abbr-1>Chest</abbr-1></periodical><pages>1117-1123</pages><volume>139</volume><number>5</number><dates><year>2011</year></dates><isbn>0012-3692</isbn><urls></urls></record></Cite></EndNote>[22] and asthmatic children appear to have a lower VO2max and running performance than their non-asthmatic peers ADDIN EN.CITE <EndNote><Cite><Author>Kukafka</Author><Year>1998</Year><RecNum>238</RecNum><DisplayText>[23]</DisplayText><record><rec-number>238</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">238</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kukafka, D.S.</author><author>Ciccolella, D.</author><author>D'Alonzo Jr, G.E.</author><author>Porter, S.</author><author>Rogers, J.</author><author>Lang, D.M.</author><author>Polansky, M.</author></authors></contributors><titles><title>Exercise-induced bronchospasm in high school athletes via a free running test</title><secondary-title>Chest</secondary-title></titles><periodical><full-title>Chest</full-title><abbr-1>Chest</abbr-1></periodical><pages>1613-1622</pages><volume>114</volume><number>6</number><dates><year>1998</year></dates><isbn>0012-3692</isbn><urls></urls></record></Cite></EndNote>[23].Despite this, Freeman et al. ADDIN EN.CITE <EndNote><Cite><Author>Freeman</Author><Year>1990</Year><RecNum>297</RecNum><DisplayText>[14]</DisplayText><record><rec-number>297</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">297</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Freeman, W.</author><author>Williams, C.</author><author>Nute, MGL</author></authors></contributors><titles><title>Endurance running performance in athletes with asthma</title><secondary-title>Journal of sports sciences</secondary-title></titles><periodical><full-title>Journal of sports sciences</full-title><abbr-1>J Sports Sci</abbr-1></periodical><pages>103-117</pages><volume>8</volume><number>2</number><dates><year>1990</year></dates><isbn>0264-0414</isbn><urls></urls></record></Cite></EndNote>[14] reported that asthmatic athletes with moderate severity disease (i.e. FEV1<50% ) can still achieve a high VO2max (i.e. >60 mL.kg-1.min-1). Moreover, cross-sectional studies show no significant differences in VO2max between asthmatic and non-asthmatic runners ADDIN EN.CITE <EndNote><Cite><Author>Freeman</Author><Year>1990</Year><RecNum>299</RecNum><DisplayText>[11, 13]</DisplayText><record><rec-number>299</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">299</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Freeman, W.</author><author>Nute, MG</author><author>Brooks, S.</author><author>Williams, C.</author></authors></contributors><titles><title>Responses of asthmatic and non-asthmatic athletes to prolonged treadmill running</title><secondary-title>British journal of sports medicine</secondary-title></titles><periodical><full-title>British journal of sports medicine</full-title><abbr-1>Br J Sports Med</abbr-1></periodical><pages>183-190</pages><volume>24</volume><number>3</number><dates><year>1990</year></dates><isbn>1473-0480</isbn><urls></urls></record></Cite><Cite><Author>Teixeira</Author><Year>2012</Year><RecNum>598</RecNum><record><rec-number>598</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">598</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Teixeira, Renata Nakata</author><author>Teixeira, Luzimar Raimundo</author><author>Costa, Luiz Augusto Riani</author><author>Martins, Milton Arruda</author><author>Mickleborough, Timothy Derick</author><author>Carvalho, Celso Ricardo Fernandes</author></authors></contributors><titles><title>Exercise-induced bronchoconstriction in elite long-distance runners in Brazil</title><secondary-title>J Bras Pneumol </secondary-title></titles><periodical><full-title>J Bras Pneumol</full-title></periodical><pages>292-298</pages><volume>38</volume><number>3</number><dates><year>2012</year></dates><isbn>1806-3713</isbn><urls></urls></record></Cite></EndNote>[11, 13]. Indeed, some studies report higher VO2max in elite-trained asthmatic cyclists, when compared with non-asthmatic cyclists ADDIN EN.CITE <EndNote><Cite><Author>Medelli</Author><Year>2006</Year><RecNum>300</RecNum><DisplayText>[24]</DisplayText><record><rec-number>300</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">300</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Medelli, J.</author><author>Lounana, J.</author><author>Messan, F.</author><author>Menuet, J.J.</author><author>Petitjean, M.</author></authors></contributors><titles><title>Testing of pulmonary function in a professional cycling team</title><secondary-title>Journal of sports medicine and physical fitness</secondary-title></titles><periodical><full-title>Journal of sports medicine and physical fitness</full-title><abbr-1>J Sports Med Phys Fitness</abbr-1></periodical><pages>298-306</pages><volume>46</volume><number>2</number><dates><year>2006</year></dates><isbn>0022-4707</isbn><urls></urls></record></Cite></EndNote>[24]. However, the environment in which exercise is performed is important in the context of EIB. Stensrud et al. ADDIN EN.CITE <EndNote><Cite><Author>Stensrud</Author><Year>2007</Year><RecNum>527</RecNum><DisplayText>[15, 16]</DisplayText><record><rec-number>527</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">527</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stensrud, T</author><author>Berntsen, S</author><author>Carlsen, K-H</author></authors></contributors><titles><title>Exercise capacity and exercise-induced bronchoconstriction (EIB) in a cold environment</title><secondary-title>Respiratory medicine</secondary-title></titles><periodical><full-title>Respiratory Medicine</full-title><abbr-1>Respir Med</abbr-1></periodical><pages>1529-1536</pages><volume>101</volume><number>7</number><dates><year>2007</year></dates><isbn>0954-6111</isbn><urls></urls></record></Cite><Cite><Author>Stensrud</Author><Year>2006</Year><RecNum>302</RecNum><record><rec-number>302</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">302</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stensrud, T.</author><author>Berntsen, S.</author><author>Carlsen, K.H.</author></authors></contributors><titles><title>Humidity influences exercise capacity in subjects with exercise-induced bronchoconstriction (EIB)</title><secondary-title>Respiratory medicine</secondary-title></titles><periodical><full-title>Respiratory Medicine</full-title><abbr-1>Respir Med</abbr-1></periodical><pages>1633-1641</pages><volume>100</volume><number>9</number><dates><year>2006</year></dates><isbn>0954-6111</isbn><urls></urls></record></Cite></EndNote>[15, 16] found that VO2max and peak running speed (Vpeak) was approximately 5% greater in adults with EIB (mean VO2max: 49 mL.kg-1.min-1) exercising in a humid environment (19.9°C and 95% relative humidity) when compared to results obtained when exercising in standard ambient conditions (20.2°C and 40% relative humidity) ADDIN EN.CITE <EndNote><Cite><Author>Stensrud</Author><Year>2006</Year><RecNum>302</RecNum><DisplayText>[16]</DisplayText><record><rec-number>302</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">302</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stensrud, T.</author><author>Berntsen, S.</author><author>Carlsen, K.H.</author></authors></contributors><titles><title>Humidity influences exercise capacity in subjects with exercise-induced bronchoconstriction (EIB)</title><secondary-title>Respiratory medicine</secondary-title></titles><periodical><full-title>Respiratory Medicine</full-title><abbr-1>Respir Med</abbr-1></periodical><pages>1633-1641</pages><volume>100</volume><number>9</number><dates><year>2006</year></dates><isbn>0954-6111</isbn><urls></urls></record></Cite></EndNote>[16]. Moreover, VO2max and running performance was reduced by 6.5% in subjects with EIB exercising in a cold environment (-18°C and 39.2% relative humidity) ADDIN EN.CITE <EndNote><Cite><Author>Stensrud</Author><Year>2007</Year><RecNum>527</RecNum><DisplayText>[15]</DisplayText><record><rec-number>527</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">527</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stensrud, T</author><author>Berntsen, S</author><author>Carlsen, K-H</author></authors></contributors><titles><title>Exercise capacity and exercise-induced bronchoconstriction (EIB) in a cold environment</title><secondary-title>Respiratory medicine</secondary-title></titles><periodical><full-title>Respiratory Medicine</full-title><abbr-1>Respir Med</abbr-1></periodical><pages>1529-1536</pages><volume>101</volume><number>7</number><dates><year>2007</year></dates><isbn>0954-6111</isbn><urls></urls></record></Cite></EndNote>[15]. Whilst these studies provide some evidence to suggest EIB has a deleterious impact on exercise performance, it is important to note that the study population was replicated, thus limiting the strength of evidence. Furthermore, a decrease in the endurance time of healthy physically active subjects has been observed during exercise in similar environmental conditions ADDIN EN.CITE <EndNote><Cite><Author>Patton</Author><Year>1984</Year><RecNum>610</RecNum><DisplayText>[25]</DisplayText><record><rec-number>610</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">610</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Patton, JOHN F</author><author>Vogel, JAMES A</author></authors></contributors><titles><title>Effects of acute cold exposure on submaximal endurance performance</title><secondary-title>Medicine and Science in Sports and Exercise</secondary-title></titles><periodical><full-title>Medicine and Science in Sports and Exercise</full-title><abbr-1>Med Sci Sports Exerc</abbr-1></periodical><pages>494-497</pages><volume>16</volume><number>5</number><dates><year>1984</year></dates><urls></urls></record></Cite></EndNote>[25]. Moreover, the protocol employed was neither a traditional incremental exercise test nor a performance trial; running speed was set “by a combination of 95% of estimated maximum heart rate and the test leader’s evaluation of exhaustion after eight min” ADDIN EN.CITE <EndNote><Cite><Author>Stensrud</Author><Year>2007</Year><RecNum>527</RecNum><DisplayText>[15, 16]</DisplayText><record><rec-number>527</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">527</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stensrud, T</author><author>Berntsen, S</author><author>Carlsen, K-H</author></authors></contributors><titles><title>Exercise capacity and exercise-induced bronchoconstriction (EIB) in a cold environment</title><secondary-title>Respiratory medicine</secondary-title></titles><periodical><full-title>Respiratory Medicine</full-title><abbr-1>Respir Med</abbr-1></periodical><pages>1529-1536</pages><volume>101</volume><number>7</number><dates><year>2007</year></dates><isbn>0954-6111</isbn><urls></urls></record></Cite><Cite><Author>Stensrud</Author><Year>2006</Year><RecNum>302</RecNum><record><rec-number>302</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">302</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stensrud, T.</author><author>Berntsen, S.</author><author>Carlsen, K.H.</author></authors></contributors><titles><title>Humidity influences exercise capacity in subjects with exercise-induced bronchoconstriction (EIB)</title><secondary-title>Respiratory medicine</secondary-title></titles><periodical><full-title>Respiratory Medicine</full-title><abbr-1>Respir Med</abbr-1></periodical><pages>1633-1641</pages><volume>100</volume><number>9</number><dates><year>2006</year></dates><isbn>0954-6111</isbn><urls></urls></record></Cite></EndNote>[15, 16]. Finally, athletes recruited for this study were well below the level expected for elite or competitive athletes (mean VO2max: 48 mL.kg-1.min-1). Indeed, only one study has examined VO2max in a cohort of subjects with EIB who could truly be considered of competitive athletic ability. Teixeira et al. ADDIN EN.CITE <EndNote><Cite><Author>Teixeira</Author><Year>2012</Year><RecNum>598</RecNum><DisplayText>[11]</DisplayText><record><rec-number>598</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">598</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Teixeira, Renata Nakata</author><author>Teixeira, Luzimar Raimundo</author><author>Costa, Luiz Augusto Riani</author><author>Martins, Milton Arruda</author><author>Mickleborough, Timothy Derick</author><author>Carvalho, Celso Ricardo Fernandes</author></authors></contributors><titles><title>Exercise-induced bronchoconstriction in elite long-distance runners in Brazil</title><secondary-title>J Bras Pneumol </secondary-title></titles><periodical><full-title>J Bras Pneumol</full-title></periodical><pages>292-298</pages><volume>38</volume><number>3</number><dates><year>2012</year></dates><isbn>1806-3713</isbn><urls></urls></record></Cite></EndNote>[11] reported no difference in peak oxygen consumption determined by treadmill ramp protocol between untreated EIB positive (mean VO2max: 63 mL.kg-1.min-1) and EIB negative (mean VO2max: 64 mL.kg-1.min-1) marathon runners. This similarity in peak VO2max between subjects with and without EIB is consistent with an earlier retrospective cohort study conducted in (n = 137) army recruits ADDIN EN.CITE <EndNote><Cite><Author>Sonna</Author><Year>2001</Year><RecNum>235</RecNum><DisplayText>[12]</DisplayText><record><rec-number>235</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">235</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sonna, L.A.</author><author>Angel, K.C.</author><author>Sharp, M.A.</author><author>Knapik, J.J.</author><author>Patton, J.F.</author><author>Lilly, C.M.</author></authors></contributors><titles><title>The prevalence of exercise-induced bronchospasm among US army recruits and its effects on physical performance</title><secondary-title>Chest</secondary-title></titles><periodical><full-title>Chest</full-title><abbr-1>Chest</abbr-1></periodical><pages>1676-1684</pages><volume>119</volume><number>6</number><dates><year>2001</year></dates><isbn>0012-3692</isbn><urls></urls></record></Cite></EndNote>[12] where no difference in baseline VO2max was observed between EIB positive and EIB negative groups. Moreover, performance in a two-mile time trial was not different between groups with both displaying similar features of athletic adaptation to the eight-week training programme.In contrast to aerobic exercise, there have been no studies to date that address anaerobic capacity in athletes with EIB. Whilst Kippelen et al ADDIN EN.CITE <EndNote><Cite><Author>Kippelen</Author><Year>2010</Year><RecNum>459</RecNum><DisplayText>[26]</DisplayText><record><rec-number>459</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">459</key></foreign-keys><ref-type name="Conference Proceedings">10</ref-type><contributors><authors><author>Kippelen, P.</author><author>Bolger, C.</author><author>Malatesta, D.</author><author>Borrani, F.</author></authors></contributors><titles><title>Does exercise-induced bronchoconstriction affect oxygen uptake kinetics in athletes?</title><secondary-title>15th Annual Congress of the European College of Sport Science</secondary-title></titles><dates><year>2010</year></dates><pub-location>Antalya, Turkey.</pub-location><urls></urls></record></Cite></EndNote>[26] reported no difference in VO2 kinetics between recreationally active EIB positive and trained negative controls during high-intensity exercise, no evidence is currently available in elite athletes. 3.3 Performance trialsAlthough VO2max is a good predictor of aerobic exercise performance in the general population, the value of VO2max in differentiating performance in a homogenous group of elite athletes is relatively limited ADDIN EN.CITE <EndNote><Cite><Author>Legaz-Arrese</Author><Year>2007</Year><RecNum>611</RecNum><DisplayText>[27]</DisplayText><record><rec-number>611</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">611</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Legaz-Arrese, A</author><author>Munguía-Izquierdo, D</author><author>Nuviala Nuviala, A</author><author>Serveto-Galindo, O</author><author>Moliner Urdiales, D</author><author>Reverter Masia, J</author></authors></contributors><titles><title>Average VO2max as a function of running performances on different distances</title><secondary-title>Sci Sports</secondary-title></titles><periodical><full-title>Sci Sports</full-title></periodical><pages>43-49</pages><volume>22</volume><number>1</number><dates><year>2007</year></dates><isbn>0765-1597</isbn><urls></urls></record></Cite></EndNote>[27]. This is likely due to contributing factors such as exercise, efficiency and motivation. Several limitations arise from using an incremental or maximal exercise test as a performance outcome measure in trained athletes; specifically, the fact that the nature of the test does not reflect the demands of the sporting event. Similar to Dickinson et al. ADDIN EN.CITE <EndNote><Cite><Author>Dickinson</Author><Year>2011</Year><RecNum>614</RecNum><DisplayText>[28]</DisplayText><record><rec-number>614</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">614</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dickinson, J</author><author>Hu, J</author><author>Chester, N</author><author>Drust, B</author><author>Whyte, G</author><author>Loosemore, M</author></authors></contributors><titles><title>The physiological effect of 800 mcg and 1600 mcg inhaled salbutamol during a football specific treadmill run at high ambient temperatures</title><secondary-title>British journal of sports medicine</secondary-title></titles><periodical><full-title>British journal of sports medicine</full-title><abbr-1>Br J Sports Med</abbr-1></periodical><pages>A19-A20</pages><volume>45</volume><number>15</number><dates><year>2011</year><pub-dates><date>December 1, 2011</date></pub-dates></dates><urls><related-urls><url>;[28], we have previously observed a significant improvement in lung function following the administration of inhaled salbutamol (400 ?g) versus placebo in elite soccer players (n = 11) with asymptomatic EIB, however no difference was detected in multiple sprint times between trials ADDIN EN.CITE <EndNote><Cite><Author>Hull</Author><RecNum>612</RecNum><DisplayText>[29]</DisplayText><record><rec-number>612</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">612</key></foreign-keys><ref-type name="Book Section">5</ref-type><contributors><authors><author>Hull, JH</author><author>Conlon, J</author><author>Gateley, B</author><author>Ansley, L</author></authors></contributors><titles><title>Does salbutamol improve athletic performance in elite soccer players with EIB?</title><secondary-title>C22. Asthma therapy</secondary-title><tertiary-title>American Thoracic Society International Conference Abstracts</tertiary-title></titles><pages>A3969-A3969</pages><num-vols>315</num-vols><dates><year>2012</year></dates><publisher>American Thoracic Society</publisher><urls><related-urls><url>;[29]. In agreement, Kalsen et al. ADDIN EN.CITE <EndNote><Cite><Author>Kalsen</Author><Year>2013</Year><RecNum>647</RecNum><DisplayText>[30]</DisplayText><record><rec-number>647</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">647</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kalsen, Anders</author><author>Hostrup, Morten</author><author>Bangsbo, Jens</author><author>Backer, Vibeke</author></authors></contributors><titles><title>Combined inhalation of beta2-agonists improves swim ergometer sprint performance but not high‐intensity swim performance</title><secondary-title>Scandinavian journal of medicine & science in sports </secondary-title></titles><periodical><full-title>Scandinavian journal of medicine & science in sports</full-title><abbr-1>Scand J Med Sci Sports</abbr-1></periodical><volume>doi: 10.1111/sms.12096</volume><dates><year>2013</year></dates><isbn>1600-0838</isbn><urls></urls></record></Cite></EndNote>[30] observed similar findings in elite swimmers. Furthermore, a recent study by Koch et al. ADDIN EN.CITE <EndNote><Cite><Author>Koch</Author><Year>2013</Year><RecNum>600</RecNum><DisplayText>[20]</DisplayText><record><rec-number>600</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">600</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Koch, Sarah</author><author>MacInnis, Martin J</author><author>Sporer, Benjamin C</author><author>Rupert, James L</author><author>Koehle, Michael S</author></authors></contributors><titles><title>Inhaled salbutamol does not affect athletic performance in asthmatic and non-asthmatic cyclists</title><secondary-title>British journal of sports medicine</secondary-title></titles><periodical><full-title>British journal of sports medicine</full-title><abbr-1>Br J Sports Med</abbr-1></periodical><volume>doi:10.1136/bjsports-2013-092706</volume><dates><year>2013</year></dates><isbn>1473-0480</isbn><urls></urls><electronic-resource-num>doi:10.1136/bjsports-2013-092706</electronic-resource-num></record></Cite></EndNote>[20] addressed the effects of administering 400 ?g salbutamol on lung function, respiratory parameters and a 10 km time-trial performance in 49 trained cyclists (VO2max range: 53-85 mL.kg-1.min-1) with (n = 14) and without (n = 25) EIB. They observed that although salbutamol improved resting lung function in both groups, no difference in performance or perception of effort was detected. Whilst it is acknowledged that the evidence to date is extremely limited, there is no published data to suggest that EIB limits sport-specific exercise performance. 4. Mechanisms by which EIB might impact performanceThere are a number of mechanisms by which bronchoconstriction may hypothetically impede athletic performance, however, if there is an impact then this likely arises due to the interplay between several factors (Figure 2). 4.1 Exercise airflow limitation In both healthy and asthmatic individuals, a bronchodilatory response has been shown to occur with the onset of exercise ADDIN EN.CITE <EndNote><Cite><Author>Crimi</Author><Year>2002</Year><RecNum>728</RecNum><DisplayText>[31]</DisplayText><record><rec-number>728</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">728</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Crimi, Emanuele</author><author>Pellegrino, Riccardo</author><author>Smeraldi, Attilio</author><author>Brusasco, Vito</author></authors></contributors><titles><title>Exercise-induced bronchodilation in natural and induced asthma: effects on ventilatory response and performance</title><secondary-title>Journal of Applied Physiology</secondary-title></titles><periodical><full-title>Journal of Applied Physiology</full-title><abbr-1>J Appl Physiol</abbr-1></periodical><pages>2353-2360</pages><volume>92</volume><number>6</number><dates><year>2002</year></dates><isbn>8750-7587</isbn><urls></urls></record></Cite></EndNote>[31]. However, it is unlikely that mild bronchodilation is of great significance in subjects susceptible to substantial bronchoconstriction (i.e. ≥25% fall in FEV1). In the context of EIB, airflow obstruction and symptoms classically develop in the period (e.g. 5-10 minutes) following exercise. Therefore, it has often been argued that EIB does not impact on in-exercise airflow and therefore is not relevant to exercise performance. During exercise in healthy subjects, peak expiratory flow occurs close to the middle of the expiratory phase of respiration and there is a mild reduction in end-expiratory lung volume (EELV). However, in elite athletes who achieve high levels of ventilation there is evidence of encroachment of the tidal flow loop on the superimposed forced expiratory flow-limb. Moreover EELV may approach or surpass resting functional residual capacity (Figure 3). In recreationally active asthmatic individuals, Haverkamp et al. ADDIN EN.CITE <EndNote><Cite><Author>Haverkamp</Author><Year>2005</Year><RecNum>127</RecNum><DisplayText>[32]</DisplayText><record><rec-number>127</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">127</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Haverkamp, HC</author><author>Dempsey, JA</author><author>Miller, JD</author><author>Romer, LM</author><author>Pegelow, DF</author><author>Rodman, JR</author><author>Eldridge, MW</author></authors></contributors><titles><title>Gas exchange during exercise in habitually active asthmatic subjects</title><secondary-title>Journal of Applied Physiology</secondary-title></titles><periodical><full-title>Journal of Applied Physiology</full-title><abbr-1>J Appl Physiol</abbr-1></periodical><pages>1938-1950</pages><volume>99</volume><number>5</number><dates><year>2005</year></dates><isbn>8750-7587</isbn><urls></urls></record></Cite></EndNote>[32] reported an increase in average pulmonary resistance for the entire exercise duration and for the majority of subjects, expiratory flow limitation was evident. Furthermore, others have shown that EELV increases in exercising asthmatics ADDIN EN.CITE <EndNote><Cite><Author>Kosmas</Author><Year>2004</Year><RecNum>418</RecNum><DisplayText>[33]</DisplayText><record><rec-number>418</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">418</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kosmas, EN</author><author>Milic-Emili, J</author><author>Polychronaki, A</author><author>Dimitroulis, I</author><author>Retsou, S</author><author>Gaga, M</author><author>Koutsoukou, A</author><author>Roussos, Ch</author><author>Koulouris, NG</author></authors></contributors><titles><title>Exercise-induced flow limitation, dynamic hyperinflation and exercise capacity in patients with bronchial asthma</title><secondary-title>European respiratory journal</secondary-title></titles><periodical><full-title>European respiratory journal</full-title><abbr-1>Eur Respir J</abbr-1></periodical><pages>378-384</pages><volume>24</volume><number>3</number><dates><year>2004</year></dates><isbn>0903-1936</isbn><urls></urls></record></Cite></EndNote>[33]. Whilst it is accepted that limitations exist in the current methodology and techniques available to evaluate the impact of in-exercise airflow limitation ADDIN EN.CITE <EndNote><Cite><Author>Calverley</Author><Year>2006</Year><RecNum>615</RecNum><DisplayText>[34]</DisplayText><record><rec-number>615</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">615</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Calverley, PMA</author></authors></contributors><titles><title>Exercise and dyspnoea in COPD</title><secondary-title>European respiratory review</secondary-title></titles><periodical><full-title>European respiratory review</full-title><abbr-1>Eur Respir Rev</abbr-1></periodical><pages>72-79</pages><volume>15</volume><number>100</number><dates><year>2006</year></dates><isbn>0905-9180</isbn><urls></urls></record></Cite></EndNote>[34], it seems possible that changes in maximum expiratory flow volume during exercise may influence airflow and the perception of dyspnoea experienced by athletes with EIB, as they adopt ventilatory strategies to overcome this constraint. 4.2 Increased work and oxygen cost of respiratory musclesDuring exercise in healthy subjects, the oxygen consumption of respiratory muscles accounts for 5-10% of whole body oxygen consumption ADDIN EN.CITE <EndNote><Cite><Author>Aaron</Author><Year>1992</Year><RecNum>352</RecNum><DisplayText>[35]</DisplayText><record><rec-number>352</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">352</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Aaron, EA</author><author>Seow, KC</author><author>Johnson, BD</author><author>Dempsey, JA</author></authors></contributors><titles><title>Oxygen cost of exercise hyperpnea: implications for performance</title><secondary-title>Journal of Applied Physiology</secondary-title></titles><periodical><full-title>Journal of Applied Physiology</full-title><abbr-1>J Appl Physiol</abbr-1></periodical><pages>1818-1825</pages><volume>72</volume><number>5</number><dates><year>1992</year></dates><isbn>8750-7587</isbn><urls></urls></record></Cite></EndNote>[35]. However, alterations in EELV, ventilation-perfusion ratio and airway calibre alter the work, and therefore oxygen consumption of the respiratory muscles ADDIN EN.CITE <EndNote><Cite><Author>Vella</Author><Year>2006</Year><RecNum>306</RecNum><DisplayText>[36]</DisplayText><record><rec-number>306</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">306</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vella, C.A.</author><author>Marks, D.</author><author>Robergs, R.A.</author></authors></contributors><titles><title>Oxygen cost of ventilation during incremental exercise to VO2 max</title><secondary-title>Respirology</secondary-title></titles><periodical><full-title>Respirology</full-title><abbr-1>Respirology</abbr-1></periodical><pages>175-181</pages><volume>11</volume><number>2</number><dates><year>2006</year></dates><isbn>1440-1843</isbn><urls></urls></record></Cite></EndNote>[36]. In support of this concept, Aaron et al. ADDIN EN.CITE <EndNote><Cite><Author>Aaron</Author><Year>1992</Year><RecNum>352</RecNum><DisplayText>[35]</DisplayText><record><rec-number>352</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">352</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Aaron, EA</author><author>Seow, KC</author><author>Johnson, BD</author><author>Dempsey, JA</author></authors></contributors><titles><title>Oxygen cost of exercise hyperpnea: implications for performance</title><secondary-title>Journal of Applied Physiology</secondary-title></titles><periodical><full-title>Journal of Applied Physiology</full-title><abbr-1>J Appl Physiol</abbr-1></periodical><pages>1818-1825</pages><volume>72</volume><number>5</number><dates><year>1992</year></dates><isbn>8750-7587</isbn><urls></urls></record></Cite></EndNote>[35] observed that the oxygen cost of breathing increases to 15% of total oxygen consumption in the presence of severe expiratory airflow limitation. This increased effort of breathing and associated oxygen cost has two potential consequences for exercise performance. Firstly, to drive a higher overall oxygen cost for a given external work load and secondly to potentially drive an earlier onset of respiratory muscle fatigue ADDIN EN.CITE <EndNote><Cite><Author>Dempsey</Author><Year>2006</Year><RecNum>271</RecNum><DisplayText>[37]</DisplayText><record><rec-number>271</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">271</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dempsey, J.A.</author><author>Romer, L.</author><author>Rodman, J.</author><author>Miller, J.</author><author>Smith, C.</author></authors></contributors><titles><title>Consequences of exercise-induced respiratory muscle work</title><secondary-title>Respiratory physiology & neurobiology</secondary-title></titles><periodical><full-title>Respiratory physiology & neurobiology</full-title><abbr-1>Respir Physiol Neurobiol</abbr-1></periodical><pages>242-250</pages><volume>151</volume><number>2-3</number><dates><year>2006</year></dates><isbn>1569-9048</isbn><urls></urls></record></Cite></EndNote>[37]. Increased respiratory muscle loading may also have a deleterious impact on exercise performance via the ‘respiratory muscle metaboreflex’ ADDIN EN.CITE <EndNote><Cite><Author>Harms</Author><Year>2000</Year><RecNum>252</RecNum><DisplayText>[38]</DisplayText><record><rec-number>252</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">252</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Harms, C.A.</author><author>Wetter, T.J.</author><author>Croix, C.M.S.</author><author>Pegelow, D.F.</author><author>Dempsey, J.A.</author></authors></contributors><titles><title>Effects of respiratory muscle work on exercise performance</title><secondary-title>Journal of Applied Physiology</secondary-title></titles><periodical><full-title>Journal of Applied Physiology</full-title><abbr-1>J Appl Physiol</abbr-1></periodical><pages>131-138</pages><volume>89</volume><number>1</number><dates><year>2000</year></dates><isbn>8750-7587</isbn><urls></urls></record></Cite></EndNote>[38]. Strenuous exercise (>80% VO2max) in healthy individuals is associated with a reduction of diaphragmatic force following supra-maximal motor nerve stimulation–indicative of diaphragmatic muscle fatigue. This in turn may increase sympathetic vasoconstrictor outflow, reducing skeletal muscle blood flow ADDIN EN.CITE <EndNote><Cite><Author>Harms</Author><Year>2000</Year><RecNum>252</RecNum><DisplayText>[38]</DisplayText><record><rec-number>252</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">252</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Harms, C.A.</author><author>Wetter, T.J.</author><author>Croix, C.M.S.</author><author>Pegelow, D.F.</author><author>Dempsey, J.A.</author></authors></contributors><titles><title>Effects of respiratory muscle work on exercise performance</title><secondary-title>Journal of Applied Physiology</secondary-title></titles><periodical><full-title>Journal of Applied Physiology</full-title><abbr-1>J Appl Physiol</abbr-1></periodical><pages>131-138</pages><volume>89</volume><number>1</number><dates><year>2000</year></dates><isbn>8750-7587</isbn><urls></urls></record></Cite></EndNote>[38]. It has been suggested that the restricted blood flow augments locomotor muscle fatigue and limits exercise capacity ADDIN EN.CITE <EndNote><Cite><Author>Dempsey</Author><Year>2006</Year><RecNum>271</RecNum><DisplayText>[37]</DisplayText><record><rec-number>271</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">271</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dempsey, J.A.</author><author>Romer, L.</author><author>Rodman, J.</author><author>Miller, J.</author><author>Smith, C.</author></authors></contributors><titles><title>Consequences of exercise-induced respiratory muscle work</title><secondary-title>Respiratory physiology & neurobiology</secondary-title></titles><periodical><full-title>Respiratory physiology & neurobiology</full-title><abbr-1>Respir Physiol Neurobiol</abbr-1></periodical><pages>242-250</pages><volume>151</volume><number>2-3</number><dates><year>2006</year></dates><isbn>1569-9048</isbn><urls></urls></record></Cite></EndNote>[37]. Furthermore, the recruitment of accessory respiratory muscles with diaphragmatic muscle fatigue has been shown to distort the chest wall and reduce the mechanical efficiency of breathing ADDIN EN.CITE <EndNote><Cite><Author>Dempsey</Author><Year>2006</Year><RecNum>271</RecNum><DisplayText>[37]</DisplayText><record><rec-number>271</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">271</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dempsey, J.A.</author><author>Romer, L.</author><author>Rodman, J.</author><author>Miller, J.</author><author>Smith, C.</author></authors></contributors><titles><title>Consequences of exercise-induced respiratory muscle work</title><secondary-title>Respiratory physiology & neurobiology</secondary-title></titles><periodical><full-title>Respiratory physiology & neurobiology</full-title><abbr-1>Respir Physiol Neurobiol</abbr-1></periodical><pages>242-250</pages><volume>151</volume><number>2-3</number><dates><year>2006</year></dates><isbn>1569-9048</isbn><urls></urls></record></Cite></EndNote>[37]. Therefore transient bronchoconstriction may increase respiratory muscle work during exercise resulting in respiratory muscle fatigue, compromised breathing efficiency and reduced oxygen availability to the working limb musculature. 4.3 Dyspnoea and perception of effortDyspnoea describes “a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity”, however the precise genesis is complex and remains incompletely understood ADDIN EN.CITE <EndNote><Cite><Author>Parshall</Author><Year>2012</Year><RecNum>617</RecNum><DisplayText>[39]</DisplayText><record><rec-number>617</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">617</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Parshall, Mark B</author><author>Schwartzstein, Richard M</author><author>Adams, Lewis</author><author>Banzett, Robert B</author><author>Manning, Harold L</author><author>Bourbeau, Jean</author><author>Calverley, Peter M</author><author>Gift, Audrey G</author><author>Harver, Andrew</author><author>Lareau, Suzanne C</author></authors></contributors><titles><title>An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea</title><secondary-title>American journal of respiratory and critical care medicine</secondary-title></titles><periodical><full-title>American journal of respiratory and critical care medicine</full-title><abbr-1>Am J Respir Crit Care Med</abbr-1></periodical><pages>pp. 435-452</pages><volume>185</volume><number>4</number><dates><year>2012</year></dates><urls></urls></record></Cite></EndNote>[39]. It is now established that perceived exertion modulates exercise performance in healthy individuals and that the cues for sensation of perceived exertion are distinct from those of sense of effort ADDIN EN.CITE <EndNote><Cite><Author>Noakes</Author><Year>2004</Year><RecNum>633</RecNum><DisplayText>[40]</DisplayText><record><rec-number>633</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">633</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Noakes, Timothy David</author></authors></contributors><titles><title>Linear relationship between the perception of effort and the duration of constant load exercise that remains</title><secondary-title>Journal of Applied Physiology</secondary-title></titles><periodical><full-title>Journal of Applied Physiology</full-title><abbr-1>J Appl Physiol</abbr-1></periodical><pages>1571-1573</pages><volume>96</volume><number>4</number><dates><year>2004</year></dates><isbn>8750-7587</isbn><urls></urls></record></Cite></EndNote>[40]. Ventilation appears to be an important contributor to perceived exertion during exercise particularly at higher intensities ADDIN EN.CITE <EndNote><Cite><Author>CAEAUELLI</Author><Year>1976</Year><RecNum>635</RecNum><DisplayText>[41]</DisplayText><record><rec-number>635</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">635</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Caeauelli, Enzo</author><author>J Nobel, Bruce J</author></authors></contributors><titles><title>The effect of inspired carbon dioxide on subjective estimates of exertion during exercise</title><secondary-title>Ergonomics</secondary-title></titles><periodical><full-title>Ergonomics</full-title><abbr-1>Ergonomics</abbr-1></periodical><pages>581-589</pages><volume>19</volume><number>5</number><dates><year>1976</year></dates><isbn>0014-0139</isbn><urls></urls></record></Cite></EndNote>[41]. It is postulated that dyspnoea begins with a physiological impairment (i.e. airway dysfunction), that leads to stimulation of pulmonary and extra-pulmonary afferent receptors; leading to afferent feedback where an uncomfortable or unpleasant sensation is perceived (i.e. chest tightness) ADDIN EN.CITE <EndNote><Cite><Author>Widdicombe</Author><Year>2009</Year><RecNum>619</RecNum><DisplayText>[42]</DisplayText><record><rec-number>619</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">619</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Widdicombe, John</author></authors></contributors><titles><title>Lung afferent activity: implications for respiratory sensation</title><secondary-title>Respiratory physiology & neurobiology</secondary-title></titles><periodical><full-title>Respiratory physiology & neurobiology</full-title><abbr-1>Respir Physiol Neurobiol</abbr-1></periodical><pages>2-8</pages><volume>167</volume><number>1</number><dates><year>2009</year></dates><isbn>1569-9048</isbn><urls></urls></record></Cite></EndNote>[42]. More specifically, the sensation of dyspnoea may represent a conscious awareness of outgoing respiratory motor command. As the brainstem or motor cortex provides efferent commands to the ventilatory muscles a copy of this command is sent to the sensory cortex. The exchange between the motor and sensory cortex is termed ‘corollary discharge’ and is thought to be the mechanism by which conscious perception of effort arises ADDIN EN.CITE <EndNote><Cite><Author>Nishino</Author><Year>2011</Year><RecNum>620</RecNum><DisplayText>[43]</DisplayText><record><rec-number>620</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">620</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nishino, T</author></authors></contributors><titles><title>Dyspnoea: underlying mechanisms and treatment</title><secondary-title>British journal of anaesthesia</secondary-title></titles><periodical><full-title>British journal of anaesthesia</full-title><abbr-1>Br J Anaesth</abbr-1></periodical><pages>463-474</pages><volume>106</volume><number>4</number><dates><year>2011</year></dates><isbn>0007-0912</isbn><urls></urls></record></Cite></EndNote>[43]. This exchange has been proposed to determine the severity of dyspnoea and perception of effort during exercise. It is now possible to obtain surrogate indices of ventilatory drive and load imbalance ADDIN EN.CITE <EndNote><Cite><Author>Moxham</Author><Year>2009</Year><RecNum>639</RecNum><DisplayText>[44]</DisplayText><record><rec-number>639</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">639</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Moxham, John</author><author>Jolley, Caroline</author></authors></contributors><titles><title>Breathlessness, fatigue and the respiratory muscles</title><secondary-title>Clinical medicine</secondary-title></titles><periodical><full-title>Clinical medicine</full-title><abbr-1>Clin Med</abbr-1></periodical><pages>448-452</pages><volume>9</volume><number>5</number><dates><year>2009</year></dates><isbn>1470-2118</isbn><urls></urls></record></Cite></EndNote>[44] that can be used to characterize dyspnoea. Therefore it seems reasonable to posit that any condition that disproportionally increases the effort of breathing to the ventilatory load during exercise will amplify the perception of exertion causing premature termination of the exercise bout or a moderation of the intensity at which the exercise is performed. To date, only one study has addressed the impact of inhaled short acting beta2-agonists versus placebo on central nervous system parameters ADDIN EN.CITE <EndNote><Cite><Author>Goubault</Author><Year>2001</Year><RecNum>624</RecNum><DisplayText>[45]</DisplayText><record><rec-number>624</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">624</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Goubault, C</author><author>Perault, MC</author><author>Leleu, E</author><author>Bouquet, S</author><author>Legros, P</author><author>Vandel, B</author><author>Denjean, A</author></authors></contributors><titles><title>Effects of inhaled salbutamol in exercising non-asthmatic athletes</title><secondary-title>Thorax</secondary-title></titles><periodical><full-title>Thorax</full-title><abbr-1>Thorax</abbr-1></periodical><pages>675-679</pages><volume>56</volume><number>9</number><dates><year>2001</year></dates><isbn>1468-3296</isbn><urls></urls></record></Cite></EndNote>[45]. Whilst no differences were observed on psychometric visual analogue scales and psychomotor performance tests between treatments, the cohort consisted of non-asthmatic trained triathletes (n = 23) (mean VO2max: 58 mL.kg-1.min-1) rather than asthmatic subjects. 4.4 Ventilation/perfusion mismatch It is well recognised that a significant proportion (up to a third in some series) of healthy trained endurance athletes exhibit exercise-induced arterial hypoxemia (EIAH); i.e. a drop in oxygen saturation defined as mild 93–95% (or 3–4% <rest), moderate 88–93%, or severe <88% ADDIN EN.CITE <EndNote><Cite><Author>Dempsey</Author><Year>1999</Year><RecNum>272</RecNum><DisplayText>[46]</DisplayText><record><rec-number>272</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">272</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dempsey, J.A.</author><author>Wagner, P.D.</author></authors></contributors><titles><title>Exercise-induced arterial hypoxemia</title><secondary-title>Journal of Applied Physiology</secondary-title></titles><periodical><full-title>Journal of Applied Physiology</full-title><abbr-1>J Appl Physiol</abbr-1></periodical><pages>1997-2006</pages><volume>87</volume><number>6</number><dates><year>1999</year></dates><isbn>8750-7587</isbn><urls></urls></record></Cite></EndNote>[46]. Haverkamp et al. ADDIN EN.CITE <EndNote><Cite><Author>Haverkamp</Author><Year>2005</Year><RecNum>127</RecNum><DisplayText>[32]</DisplayText><record><rec-number>127</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">127</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Haverkamp, HC</author><author>Dempsey, JA</author><author>Miller, JD</author><author>Romer, LM</author><author>Pegelow, DF</author><author>Rodman, JR</author><author>Eldridge, MW</author></authors></contributors><titles><title>Gas exchange during exercise in habitually active asthmatic subjects</title><secondary-title>Journal of Applied Physiology</secondary-title></titles><periodical><full-title>Journal of Applied Physiology</full-title><abbr-1>J Appl Physiol</abbr-1></periodical><pages>1938-1950</pages><volume>99</volume><number>5</number><dates><year>2005</year></dates><isbn>8750-7587</isbn><urls></urls></record></Cite></EndNote>[32] demonstrated EIAH during high-intensity exercise in physically active asthmatics (mean VO2max: 48 mL.kg-1.min-1 ). The decreased effectiveness of gas exchange in this population may be a result of airway inflammation in both the airways and alveolar areas leading to a poorer alveolar ventilation-perfusion ratio, smooth muscle constriction, mucosal and interstitial oedema with infiltration and closing of the small airways ADDIN EN.CITE <EndNote><Cite><Author>Haverkamp</Author><Year>2005</Year><RecNum>127</RecNum><DisplayText>[32]</DisplayText><record><rec-number>127</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">127</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Haverkamp, HC</author><author>Dempsey, JA</author><author>Miller, JD</author><author>Romer, LM</author><author>Pegelow, DF</author><author>Rodman, JR</author><author>Eldridge, MW</author></authors></contributors><titles><title>Gas exchange during exercise in habitually active asthmatic subjects</title><secondary-title>Journal of Applied Physiology</secondary-title></titles><periodical><full-title>Journal of Applied Physiology</full-title><abbr-1>J Appl Physiol</abbr-1></periodical><pages>1938-1950</pages><volume>99</volume><number>5</number><dates><year>2005</year></dates><isbn>8750-7587</isbn><urls></urls></record></Cite></EndNote>[32]. Munoz et al. have previously demonstrated that in mild asthmatics, EIB provokes a greater ventilation-perfusion imbalance. They proposed that this is primarily due to post exercise increases in minute ventilation and cardiac output, benefiting partial pressure of oxygen in arterial blood. In addition, ventilation-perfusion imbalance likely reflects uneven airway narrowing and blood flow redistribution generating unique ventilation-perfusion patterns including the development of areas with low and high ventilation-perfusion ratios ADDIN EN.CITE <EndNote><Cite><Author>Mu?oz</Author><Year>2008</Year><RecNum>605</RecNum><DisplayText>[47]</DisplayText><record><rec-number>605</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">605</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mu?oz, Phillip A</author><author>Gómez, Federico P</author><author>Manrique, Hernán A</author><author>Roca, Josep</author><author>Barberà, Joan A</author><author>Young, Iven H</author><author>Anderson, Sandra D</author><author>Rodríguez-Roisin, Roberto</author></authors></contributors><titles><title>Pulmonary gas exchange response to exercise-and mannitol-induced bronchoconstriction in mild asthma</title><secondary-title>Journal of Applied Physiology</secondary-title></titles><periodical><full-title>Journal of Applied Physiology</full-title><abbr-1>J Appl Physiol</abbr-1></periodical><pages>1477-1485</pages><volume>105</volume><number>5</number><dates><year>2008</year></dates><isbn>8750-7587</isbn><urls></urls></record></Cite></EndNote>[47]. Consequently, depending on severity, EIB may cause ventilation-perfusion imbalance and may impair the respective uptake and elimination of O2 and CO2 into and from the blood. 5. EIB treatment and impact on performanceA significant amount of research has been conducted over the past two decades investigating how asthma treatment may impact on athletic performance. This is extremely pertinent given the fact approximately one fifth of swimmers and cyclists used beta2-agonists at the Summer Olympic Games in 2004 and 2008 ADDIN EN.CITE <EndNote><Cite><Author>McKenzie</Author><Year>2011</Year><RecNum>312</RecNum><DisplayText>[7]</DisplayText><record><rec-number>312</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">312</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McKenzie, D.C.</author><author>Fitch, K.D.</author></authors></contributors><titles><title>The asthmatic athlete: inhaled beta-2 agonists, sport performance, and doping</title><secondary-title>Clinical Journal of Sport Medicine</secondary-title></titles><periodical><full-title>Clinical journal of sport medicine</full-title><abbr-1>Clin J Sport Med</abbr-1></periodical><pages>46-50</pages><volume>21</volume><number>1</number><dates><year>2011</year></dates><isbn>1050-642X</isbn><urls></urls></record></Cite></EndNote>[7]. It is now well established that pharmacological (e.g. inhaled corticosteroids in combination with a pre-exercise inhaled beta-2-agonists and if required leukotriene receptor antagonist / mast cell stabiliser) and possibly non-pharmacological interventions (e.g. fish oil supplementation) are effective in protecting against airway constriction ADDIN EN.CITE <EndNote><Cite><Author>Parsons</Author><Year>2013</Year><RecNum>443</RecNum><DisplayText>[48]</DisplayText><record><rec-number>443</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">443</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Parsons, Jonathan P</author><author>Hallstrand, Teal S</author><author>Mastronarde, John G</author><author>Kaminsky, David A</author><author>Rundell, Kenneth W</author><author>Hull, James H</author><author>Storms, William W</author><author>Weiler, John M</author><author>Cheek, Fern M</author><author>Wilson, Kevin C</author></authors></contributors><titles><title>An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction</title><secondary-title>American journal of respiratory and critical care medicine</secondary-title></titles><periodical><full-title>American journal of respiratory and critical care medicine</full-title><abbr-1>Am J Respir Crit Care Med</abbr-1></periodical><pages>1016-1027</pages><volume>187</volume><number>9</number><dates><year>2013</year></dates><isbn>1535-4970</isbn><urls></urls></record></Cite></EndNote>[48]. However, the mainstay of treatment for protection against EIB is the administration of an inhaled short acting beta2-agonist (e.g. salbutamol) 15 minutes prior to exercise ADDIN EN.CITE <EndNote><Cite><Author>Bonini</Author><Year>2009</Year><RecNum>604</RecNum><DisplayText>[49]</DisplayText><record><rec-number>604</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">604</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bonini, Matteo</author><author>Di Mambro, Corrado</author><author>Calderon, Moises A</author><author>Compalati, Enrico</author><author>Schünemann, Holger</author><author>Durham, Stephen</author><author>Canonica, Giorgio W</author><author>Rowe, Brian H</author></authors></contributors><titles><title>Beta-2 agonists for exercise induced asthma</title><secondary-title>The Cochrane Library</secondary-title></titles><volume>10.1002/14651858.CD003564.pub3.</volume><dates><year>2009</year></dates><isbn>1465-1858</isbn><urls></urls><electronic-resource-num>10.1002/14651858.CD003564.pub3.</electronic-resource-num></record></Cite></EndNote>[49]. 5.1 Impact of medication in non-asthmatic athletesBedi et al. suggested that inhaled albuterol may provide?a competitive advantage for non-asthmatic athletes resulting in speculation that beta-2 agonists are performance enhancing ADDIN EN.CITE <EndNote><Cite><Author>Bedi</Author><Year>1988</Year><RecNum>730</RecNum><DisplayText>[50]</DisplayText><record><rec-number>730</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">730</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bedi, JF</author><author>Gong Jr, H</author><author>Horvath, SM</author></authors></contributors><titles><title>Enhancement of exercise performance with inhaled albuterol</title><secondary-title>Can J Sport Sci</secondary-title></titles><periodical><full-title>Can J Sport Sci</full-title></periodical><pages>144-148</pages><volume>13</volume><number>2</number><dates><year>1988</year></dates><isbn>0833-1235</isbn><urls></urls></record></Cite></EndNote>[50]. However, research to date provides little evidence that inhaled beta2-agonists in prescribed doses provide performance benefits in non-asthmatic subjects ADDIN EN.CITE <EndNote><Cite><Author>Kindermann</Author><Year>2007</Year><RecNum>315</RecNum><DisplayText>[51]</DisplayText><record><rec-number>315</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">315</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kindermann, W.</author></authors></contributors><titles><title>Do inhaled beta(2)-agonists have an ergogenic potential in non-asthmatic competitive athletes?</title><secondary-title>Sports Med</secondary-title></titles><periodical><full-title>Sports Med</full-title></periodical><pages>95-102</pages><volume>37</volume><number>2</number><dates><year>2007</year></dates><isbn>0112-1642</isbn><urls></urls></record></Cite></EndNote>[51]. A recent systematic review and meta-analysis confirmed that no significant effects were detected for inhaled beta2-agonists on endurance, strength or sprint performance in healthy athletes. However, it was highlighted that systemic beta2-agonists may elicit positive effects on physical performance, although the quality of evidence is not currently sufficient to provide a definitive answer ADDIN EN.CITE <EndNote><Cite><Author>Pluim</Author><Year>2011</Year><RecNum>727</RecNum><DisplayText>[52]</DisplayText><record><rec-number>727</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">727</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pluim, Babette M</author><author>de Hon, Olivier</author><author>Staal, J Bart</author><author>Limpens, Jacqueline</author><author>Kuipers, Harm</author><author>Overbeek, Shelley E</author><author>Zwinderman, Aeilko H</author><author>Scholten, Rob JPM</author></authors></contributors><titles><title>β2-agonists and physical performance</title><secondary-title>Sports Med</secondary-title></titles><periodical><full-title>Sports Med</full-title></periodical><pages>39-57</pages><volume>41</volume><number>1</number><dates><year>2011</year></dates><isbn>0112-1642</isbn><urls></urls></record></Cite></EndNote>[52]. In contrast, clenbuterol is now prohibited by the World Anti-Doping Agency (WADA) given the anabolic effects associated with treatment ADDIN EN.CITE <EndNote><Cite ExcludeYear="1"><Author>WADA</Author><RecNum>731</RecNum><DisplayText>[53]</DisplayText><record><rec-number>731</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">731</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>WADA</author></authors></contributors><titles><secondary-title> 2014 (June 25)</access-date></record></Cite></EndNote>[53].In a sport-specific context, Sporer et al. ADDIN EN.CITE <EndNote><Cite><Author>Sporer</Author><Year>2008</Year><RecNum>322</RecNum><DisplayText>[54]</DisplayText><record><rec-number>322</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">322</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sporer, B.C.</author><author>Sheel, A.W.</author><author>McKenzie, D.C.</author></authors></contributors><titles><title>Dose response of inhaled salbutamol on exercise performance and urine concentrations</title><secondary-title>Medicine and Science in Sports and Exercise</secondary-title></titles><periodical><full-title>Medicine and Science in Sports and Exercise</full-title><abbr-1>Med Sci Sports Exerc</abbr-1></periodical><pages>149-157</pages><volume>40</volume><number>1</number><dates><year>2008</year></dates><isbn>0195-9131</isbn><urls></urls></record></Cite></EndNote>[54] observed no effects of 800 ?g salbutamol on 20-km time-trial performance in healthy elite cyclists (mean VO2max: 67 mL.kg-1.min-1). In contrast, some researchers have observed performance benefit; Van Baak et al ADDIN EN.CITE <EndNote><Cite><Author>Van Baak</Author><Year>2004</Year><RecNum>321</RecNum><DisplayText>[55]</DisplayText><record><rec-number>321</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">321</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Van Baak, MA</author><author>De Hon, OM</author><author>Hartgens, F.</author><author>Kuipers, H.</author></authors></contributors><titles><title>Inhaled salbutamol and endurance cycling performance in non-asthmatic athletes</title><secondary-title>International journal of sports medicine</secondary-title></titles><periodical><full-title>International journal of sports medicine</full-title><abbr-1>Int J Sports Med</abbr-1></periodical><pages>533-538</pages><volume>25</volume><number>7</number><dates><year>2004</year></dates><isbn>0172-4622</isbn><urls></urls></record></Cite></EndNote>[55] reported that 800 ?g salbutamol significantly improved time-trial performance in well-trained amateur non-asthmatic male cyclists and triathletes (n = 16) by 1.9 ± 1.8% (P<0.05). However, lung function increased significantly following administration of salbutamol versus placebo suggesting some of the subjects may have had undiagnosed airway obstruction. More recently, Decorte et al. ADDIN EN.CITE <EndNote><Cite><Author>Decorte</Author><Year>2013</Year><RecNum>646</RecNum><DisplayText>[56]</DisplayText><record><rec-number>646</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">646</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Decorte, Nicolas</author><author>Bachasson, Damien</author><author>Guinot, Michel</author><author>Flore, Patrice</author><author>Levy, Patrick</author><author>Verges, Samuel</author><author>Wuyam, Bernard</author></authors></contributors><titles><title>Impact of salbutamol on neuromuscular function in endurance athletes</title><secondary-title>Medicine and science in sports and exercise</secondary-title></titles><periodical><full-title>Medicine and Science in Sports and Exercise</full-title><abbr-1>Med Sci Sports Exerc</abbr-1></periodical><pages>1925-32</pages><volume>45</volume><number>10</number><dates><year>2013</year></dates><urls></urls><electronic-resource-num>doi: 10.1249/MSS.0b013e3182951d2d
</electronic-resource-num></record></Cite></EndNote>[56] observed an increase in muscular endurance following the inhalation of 800 ?g salbutamol. Similarly, Kalsen et al. ADDIN EN.CITE <EndNote><Cite><Author>Kalsen</Author><Year>2013</Year><RecNum>647</RecNum><DisplayText>[30]</DisplayText><record><rec-number>647</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">647</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kalsen, Anders</author><author>Hostrup, Morten</author><author>Bangsbo, Jens</author><author>Backer, Vibeke</author></authors></contributors><titles><title>Combined inhalation of beta2-agonists improves swim ergometer sprint performance but not high‐intensity swim performance</title><secondary-title>Scandinavian journal of medicine & science in sports </secondary-title></titles><periodical><full-title>Scandinavian journal of medicine & science in sports</full-title><abbr-1>Scand J Med Sci Sports</abbr-1></periodical><volume>doi: 10.1111/sms.12096</volume><dates><year>2013</year></dates><isbn>1600-0838</isbn><urls></urls></record></Cite></EndNote>[30] showed an improvement in arm ergometer sprint performance and muscle strength following the inhalation of high doses of beta2-agonists in elite swimmers with and without airway hyperresponsiveness.5.2 Impact of medication in asthmatic athletesIn asthmatic men (mean VO2max: 43 mL.kg-1.min-1) Freeman et al. ADDIN EN.CITE <EndNote><Cite><Author>Freeman</Author><Year>1989</Year><RecNum>402</RecNum><DisplayText>[19]</DisplayText><record><rec-number>402</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">402</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Freeman, W.</author><author>Packe, GE</author><author>Cayton, RM</author></authors></contributors><titles><title>Effect of nebulised salbutamol on maximal exercise performance in men with mild asthma</title><secondary-title>Thorax</secondary-title></titles><periodical><full-title>Thorax</full-title><abbr-1>Thorax</abbr-1></periodical><pages>942-947</pages><volume>44</volume><number>11</number><dates><year>1989</year></dates><isbn>1468-3296</isbn><urls></urls></record></Cite></EndNote>[19] observed no improvements in performance during progressive exercise following nebulization of 5mg of salbutamol despite a significant increase in resting and post-exercise FEV1 ADDIN EN.CITE <EndNote><Cite><Author>Freeman</Author><Year>1989</Year><RecNum>402</RecNum><DisplayText>[19]</DisplayText><record><rec-number>402</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">402</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Freeman, W.</author><author>Packe, GE</author><author>Cayton, RM</author></authors></contributors><titles><title>Effect of nebulised salbutamol on maximal exercise performance in men with mild asthma</title><secondary-title>Thorax</secondary-title></titles><periodical><full-title>Thorax</full-title><abbr-1>Thorax</abbr-1></periodical><pages>942-947</pages><volume>44</volume><number>11</number><dates><year>1989</year></dates><isbn>1468-3296</isbn><urls></urls></record></Cite></EndNote>[19]. Similarly, Ingemann-Hansen ADDIN EN.CITE <EndNote><Cite><Author>Ingemann-Hansen</Author><Year>1980</Year><RecNum>403</RecNum><DisplayText>[57]</DisplayText><record><rec-number>403</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">403</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ingemann-Hansen, T.</author><author>Bundgaard, A.</author><author>Halkj?r-Kristensen, J.</author><author>Weeke, B.</author></authors></contributors><titles><title>Maximal oxygen consumption rate in patients with bronchial asthma-the effect of β2-adrenoreceptor stimulation</title><secondary-title>Scandinavian journal of clinical and laboratory investigation</secondary-title></titles><periodical><full-title>Scandinavian journal of clinical and laboratory investigation</full-title><abbr-1>Scand J Clin Lab Invest</abbr-1></periodical><pages>99-104</pages><volume>40</volume><number>2</number><dates><year>1980</year></dates><isbn>0036-5513</isbn><urls></urls></record></Cite></EndNote>[57] showed no benefits of salbutamol on VO2max or endurance time to exhaustion within a comparable population. In contrast, the administration of montelukast, a leukotriene antagonist, has been shown to improve physical performance and oxygen pulse while reducing the perception of strain at maximal workloads ADDIN EN.CITE <EndNote><Cite><Author>Steinshamn</Author><Year>2002</Year><RecNum>304</RecNum><DisplayText>[17, 18]</DisplayText><record><rec-number>304</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">304</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Steinshamn, S.</author><author>Sandsund, M.</author><author>Sue-Chu, M.</author><author>Bjermer, L.</author></authors></contributors><titles><title>Effects of montelukast on physical performance and exercise economy in adult asthmatics with exercise-induced bronchoconstriction</title><secondary-title>Scandinavian journal of medicine & science in sports</secondary-title></titles><periodical><full-title>Scandinavian journal of medicine & science in sports</full-title><abbr-1>Scand J Med Sci Sports</abbr-1></periodical><pages>211-217</pages><volume>12</volume><number>4</number><dates><year>2002</year></dates><isbn>1600-0838</isbn><urls></urls></record></Cite><Cite><Author>Steinshamn</Author><Year>2004</Year><RecNum>420</RecNum><record><rec-number>420</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">420</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Steinshamn, Sigurd</author><author>Sandsund, Mariann</author><author>Sue-Chu, Malcolm</author><author>Bjermer, Leif</author></authors></contributors><titles><title>Effects of montelukast and salmeterol on physical performance and exercise economy in adult asthmatics with exercise-induced bronchoconstriction</title><secondary-title>Chest</secondary-title></titles><periodical><full-title>Chest</full-title><abbr-1>Chest</abbr-1></periodical><pages>1154-1160</pages><volume>126</volume><number>4</number><dates><year>2004</year></dates><isbn>0012-3692</isbn><urls></urls></record></Cite></EndNote>[17, 18]. However, the subjects recruited in these studies were only moderately trained individuals (mean VO2max: 44 mL.kg-1.min-1) and even at fatigue did not attain a maximal perception of effort score. Thus it is difficult to extrapolate these findings to elite athletic performance.5.3 Impact of supra-therapeutic medication dosesIn non-asthmatic athletes, Dickinson et al. recently observed no effect on endurance, strength or power performance following 6-weeks 1600 ?g inhaled salbutamol (WADA daily upper limit) ADDIN EN.CITE <EndNote><Cite><Author>Dickinson</Author><Year>2014</Year><RecNum>648</RecNum><DisplayText>[58]</DisplayText><record><rec-number>648</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">648</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dickinson, John</author><author>Molphy, John</author><author>Chester, Neil</author><author>Loosemore, Mike</author><author>Whyte, Greg</author></authors></contributors><titles><title>The ergogenic effect of long-term use of high dose salbutamol</title><secondary-title>Clinical journal of sport medicine</secondary-title></titles><periodical><full-title>Clinical journal of sport medicine</full-title><abbr-1>Clin J Sport Med</abbr-1></periodical><volume>doi: 10.1097/JSM.0000000000000076</volume><dates><year>2014</year></dates><isbn>1050-642X</isbn><urls></urls></record></Cite></EndNote>[58]. Furthermore, no significant improvement in 5km time-trial performance was observed following one dose 1600 ?g salbutamol in a comparable population ADDIN EN.CITE <EndNote><Cite><Author>Dickinson</Author><Year>2014</Year><RecNum>732</RecNum><DisplayText>[59]</DisplayText><record><rec-number>732</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">732</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dickinson, John</author><author>Hu, Jiu</author><author>Chester, Neil</author><author>Loosemore, Mike</author><author>Whyte, Greg</author></authors></contributors><titles><title>Acute impact of inhaled short acting B2-agonists on 5 Km running performance</title><secondary-title>J Sports Sci Med</secondary-title></titles><periodical><full-title>J Sports Sci Med</full-title></periodical><pages>271-9</pages><volume>13</volume><number>2</number><dates><year>2014</year></dates><urls></urls></record></Cite></EndNote>[59]. Irrespective of the aforementioned findings, information is currently relatively limited regarding the effect of asthma medication administered at supra-therapeutic doses. Indeed long-term use of high doses of beta2-agonists have been shown to be highly anabolic in several animal studies and increase muscle strength in human studies ADDIN EN.CITE <EndNote><Cite><Author>Caruso</Author><Year>2005</Year><RecNum>328</RecNum><DisplayText>[60]</DisplayText><record><rec-number>328</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">328</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Caruso, J.F.</author><author>Hamill, J.L.</author><author>De Garmo, N.</author></authors></contributors><titles><title>Oral albuterol dosing during the latter stages of a resistance exercise program</title><secondary-title>J Strength Cond Res</secondary-title></titles><periodical><full-title>J Strength Cond Res</full-title></periodical><pages>102-107</pages><volume>19</volume><number>1</number><dates><year>2005</year></dates><isbn>1064-8011</isbn><urls></urls></record></Cite></EndNote>[60] however this effect has yet to be investigated following chronic use of inhaled beta2-agonists. Potentially, very high doses of inhaled beta2-agonists provide the same performance-enhancing effects observed after oral ingestion ADDIN EN.CITE <EndNote><Cite><Author>Elers</Author><Year>2012</Year><RecNum>326</RecNum><DisplayText>[61]</DisplayText><record><rec-number>326</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">326</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Elers, J.</author><author>Pedersen, L.</author><author>Henninge, J.</author><author>Hemmersbach, P.</author><author>Dalhoff, K.</author><author>Backer, V.</author></authors></contributors><titles><title>The pharmacokinetic profile of inhaled and oral salbutamol in elite athletes with asthma and nonasthmatic subjects</title><secondary-title>Clinical journal of sport medicine</secondary-title></titles><periodical><full-title>Clinical journal of sport medicine</full-title><abbr-1>Clin J Sport Med</abbr-1></periodical><pages>140-145</pages><volume>22</volume><number>2</number><dates><year>2012</year></dates><isbn>1050-642X</isbn><urls></urls><electronic-resource-num>doi: 10.1097/JSM.0b013e31823513e1</electronic-resource-num></record></Cite></EndNote>[61]. 6. DISCUSSION6.1 Does EIB impact athletic performance? This review reveals that it is not currently possible to draw a definitive conclusion as to whether EIB impacts athletic performance. Several methodological limitations contribute to this conclusion. Firstly, the experimental designs of studies conducted to date have failed to adequately address the difficulties of studying athletic performance. VO2max is consistently reported as the primary outcome measure however the fact that VO2max is a poor predictor of athletic performance is often overlooked and sport-specific protocols are more appropriate. For instance, a high proportion of elite cyclists administer beta-2 agonists ADDIN EN.CITE <EndNote><Cite><Author>McKenzie</Author><Year>2011</Year><RecNum>312</RecNum><DisplayText>[7]</DisplayText><record><rec-number>312</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">312</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McKenzie, D.C.</author><author>Fitch, K.D.</author></authors></contributors><titles><title>The asthmatic athlete: inhaled beta-2 agonists, sport performance, and doping</title><secondary-title>Clinical Journal of Sport Medicine</secondary-title></titles><periodical><full-title>Clinical journal of sport medicine</full-title><abbr-1>Clin J Sport Med</abbr-1></periodical><pages>46-50</pages><volume>21</volume><number>1</number><dates><year>2011</year></dates><isbn>1050-642X</isbn><urls></urls></record></Cite></EndNote>[7] as an ergogenic aid, yet any performance impact of this treatment will not be adequately detected by an indoor ramp exercise test.In the very few studies that have employed a sport-specific challenge, EIB does not appear to impact performance ADDIN EN.CITE <EndNote><Cite><Author>Koch</Author><Year>2013</Year><RecNum>600</RecNum><DisplayText>[20]</DisplayText><record><rec-number>600</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">600</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Koch, Sarah</author><author>MacInnis, Martin J</author><author>Sporer, Benjamin C</author><author>Rupert, James L</author><author>Koehle, Michael S</author></authors></contributors><titles><title>Inhaled salbutamol does not affect athletic performance in asthmatic and non-asthmatic cyclists</title><secondary-title>British journal of sports medicine</secondary-title></titles><periodical><full-title>British journal of sports medicine</full-title><abbr-1>Br J Sports Med</abbr-1></periodical><volume>doi:10.1136/bjsports-2013-092706</volume><dates><year>2013</year></dates><isbn>1473-0480</isbn><urls></urls><electronic-resource-num>doi:10.1136/bjsports-2013-092706</electronic-resource-num></record></Cite></EndNote>[20]. However, it certainly appears that noxious environmental conditions (i.e. cold dry air) inhibit maximal aerobic capacity ADDIN EN.CITE <EndNote><Cite><Author>Stensrud</Author><Year>2007</Year><RecNum>527</RecNum><DisplayText>[15, 16]</DisplayText><record><rec-number>527</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">527</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stensrud, T</author><author>Berntsen, S</author><author>Carlsen, K-H</author></authors></contributors><titles><title>Exercise capacity and exercise-induced bronchoconstriction (EIB) in a cold environment</title><secondary-title>Respiratory medicine</secondary-title></titles><periodical><full-title>Respiratory Medicine</full-title><abbr-1>Respir Med</abbr-1></periodical><pages>1529-1536</pages><volume>101</volume><number>7</number><dates><year>2007</year></dates><isbn>0954-6111</isbn><urls></urls></record></Cite><Cite><Author>Stensrud</Author><Year>2006</Year><RecNum>302</RecNum><record><rec-number>302</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">302</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stensrud, T.</author><author>Berntsen, S.</author><author>Carlsen, K.H.</author></authors></contributors><titles><title>Humidity influences exercise capacity in subjects with exercise-induced bronchoconstriction (EIB)</title><secondary-title>Respiratory medicine</secondary-title></titles><periodical><full-title>Respiratory Medicine</full-title><abbr-1>Respir Med</abbr-1></periodical><pages>1633-1641</pages><volume>100</volume><number>9</number><dates><year>2006</year></dates><isbn>0954-6111</isbn><urls></urls></record></Cite></EndNote>[15, 16]. However, this has yet to be determined in a sport-specific challenge. Secondly, the athletic level of subjects varies significantly between studies. This point is highlighted throughout this review whereby athletic ability, as determined by VO2max ranges from 40-80 mL.kg-1.min-1; i.e. from recreationally active to elite level. The sustained ventilatory demand between elite and amateur events differs significantly. When considering exercise hyperpnoea is a key determinant of bronchoconstriction in susceptible individuals, extrapolating data derived from amateur or recreational athletes to the elite level is clearly not appropriate. Thirdly, it is unclear whether the research to date has examined the best outcome measure. In this review we highlight the fact that central regulation (i.e. the central governor ADDIN EN.CITE <EndNote><Cite><Author>Noakes</Author><Year>2004</Year><RecNum>633</RecNum><DisplayText>[40]</DisplayText><record><rec-number>633</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">633</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Noakes, Timothy David</author></authors></contributors><titles><title>Linear relationship between the perception of effort and the duration of constant load exercise that remains</title><secondary-title>Journal of Applied Physiology</secondary-title></titles><periodical><full-title>Journal of Applied Physiology</full-title><abbr-1>J Appl Physiol</abbr-1></periodical><pages>1571-1573</pages><volume>96</volume><number>4</number><dates><year>2004</year></dates><isbn>8750-7587</isbn><urls></urls></record></Cite></EndNote>[40]) is a key component dictating peak athletic performance. It is therefore important to note that studies to date have focused on physiological surrogates of performance rather than central outputs / measures of performance impediment such as rating of perceived exertion during exercise tasks. 6.2 Why do asthmatic athletes appear to outperform non-asthmatic elite athletes?Elite level athletes with airway dysfunction have consistently been shown to outperform their healthy peers. However as this review highlights, there is no evidence that inhaled beta-2-agonists enhance athletic performance. Explanations for this disparity proposed include the fact that physiological changes / demands associated with EIB may represent an ‘extra’ training stimulus that non-asthmatic athletes do not experience ADDIN EN.CITE <EndNote><Cite><Author>McKenzie</Author><Year>2011</Year><RecNum>312</RecNum><DisplayText>[7]</DisplayText><record><rec-number>312</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">312</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>McKenzie, D.C.</author><author>Fitch, K.D.</author></authors></contributors><titles><title>The asthmatic athlete: inhaled beta-2 agonists, sport performance, and doping</title><secondary-title>Clinical Journal of Sport Medicine</secondary-title></titles><periodical><full-title>Clinical journal of sport medicine</full-title><abbr-1>Clin J Sport Med</abbr-1></periodical><pages>46-50</pages><volume>21</volume><number>1</number><dates><year>2011</year></dates><isbn>1050-642X</isbn><urls></urls></record></Cite></EndNote>[7]. Others have suggested that airway dysfunction develops in elite athletes throughout the course of their careers by virtue of greater training volume in conjunction with chronic exposure to noxious environmental conditions ADDIN EN.CITE <EndNote><Cite><Author>Price</Author><Year>2013</Year><RecNum>592</RecNum><DisplayText>[4]</DisplayText><record><rec-number>592</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">592</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Price, O J</author><author>Ansley, L</author><author>Menzies-Gow, A</author><author>Cullinan, P</author><author>Hull, J H</author></authors></contributors><titles><title>Airway dysfunction in elite athletes–an occupational lung disease?</title><secondary-title>Allergy</secondary-title></titles><periodical><full-title>Allergy</full-title><abbr-1>Allergy</abbr-1></periodical><pages>1343-1352</pages><volume>68</volume><number>11</number><dates><year>2013</year></dates><isbn>1398-9995</isbn><urls></urls></record></Cite></EndNote>[4] (i.e. those with EIB may have trained harder and longer to gain a competitive advantage). Finally, the development of EIB may allow mechanical advantages in certain sports such as hyperinflation resulting in improved buoyancy and reduced drag co-efficient in swimmers. 6.3 Recommendations for future researchFurther work is needed to explore the impact of EIB on athletic performance, with due consideration of the methodological issues mentioned. More specifically, it is vital that the design of future studies addresses the impact of sport-specific protocols that are conducted in provocative environments and in a homogenous population of athletes. Outcome measures should incorporate metrics of central respiratory drive and the perception of dyspnoea, which is likely to be relevant and pertinent to performance at the elite level. Moreover, further work is needed to explore the physiological consequences of EIB and asthma medication on in-exercise pulmonary performance in sport-specific environments (i.e. using novel techniques of airflow limitation). Finally, athletes included in future studies, should have a similar severity of disease. The degree of impairment to exercise performance is likely to be less in athletes with mild EIB (10 - 25% fall in FEV1) when compared to athletes with more severe airflow limitation. This is relevant in the context of athletic groups ‘screened’ for EIB, many of whom have a mildly positive result to a bronchoprovocation test (e.g. eucapnic voluntary hyperpnoea) and in whom treatment recommendations may be made on the underlying premise that this will ‘improve’ their performance ADDIN EN.CITE <EndNote><Cite><Author>Hull</Author><Year>2007</Year><RecNum>434</RecNum><DisplayText>[62]</DisplayText><record><rec-number>434</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">434</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hull, J.</author><author>Ansley, Les</author><author>Garrod, Rachel</author><author>Dickinson, John W</author></authors></contributors><titles><title>Exercise-induced bronchoconstriction in athletes-should we screen?</title><secondary-title>Medicine and science in sports and exercise</secondary-title></titles><periodical><full-title>Medicine and Science in Sports and Exercise</full-title><abbr-1>Med Sci Sports Exerc</abbr-1></periodical><pages>2117 - 2124</pages><volume>39</volume><number>12</number><dates><year>2007</year></dates><isbn>0195-9131</isbn><urls></urls></record></Cite></EndNote>[62]. 7. CONCLUSIONIn conclusion, the development of EIB may have a deleterious impact on respiratory function during peak exercise however the underlying mechanisms and nature of this impediment remain to be determined. Whilst it is intuitive that EIB, when untreated, has a detrimental impact on elite athletic performance, this has not been established in the literature. Therefore, future work needs to establish the impact of bronchoconstriction on athletic performance and the development of treatment strategies to overcome this potential limitation. Table headingsTable 1. Studies evaluating the consequences of exercise-induced bronchoconstriction on exercise performance parameters.Table 2. Studies appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria ADDIN EN.CITE <EndNote><Cite><Author>Guyatt</Author><Year>2011</Year><RecNum>759</RecNum><DisplayText>[21]</DisplayText><record><rec-number>759</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">759</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Guyatt, Gordon H</author><author>Oxman, Andrew D</author><author>Schünemann, Holger J</author><author>Tugwell, Peter</author><author>Knottnerus, Andre</author></authors></contributors><titles><title>GRADE guidelines: A new series of articles in the Journal of Clinical Epidemiology</title><secondary-title>Journal of clinical epidemiology</secondary-title></titles><periodical><full-title>Journal of clinical epidemiology</full-title></periodical><pages>380-382</pages><volume>64</volume><number>4</number><dates><year>2011</year></dates><isbn>0895-4356</isbn><urls></urls></record></Cite></EndNote>[21].Table SEQ Table \* ARABIC 1.First Author / YearPopulationDiagnosisMethodologySummary of findingsPerformanceFreeman et al. 1990 ADDIN EN.CITE <EndNote><Cite><Author>Freeman</Author><Year>1990</Year><RecNum>299</RecNum><DisplayText>[13]</DisplayText><record><rec-number>299</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">299</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Freeman, W.</author><author>Nute, MG</author><author>Brooks, S.</author><author>Williams, C.</author></authors></contributors><titles><title>Responses of asthmatic and non-asthmatic athletes to prolonged treadmill running</title><secondary-title>British journal of sports medicine</secondary-title></titles><periodical><full-title>British journal of sports medicine</full-title><abbr-1>Br J Sports Med</abbr-1></periodical><pages>183-190</pages><volume>24</volume><number>3</number><dates><year>1990</year></dates><isbn>1473-0480</isbn><urls></urls></record></Cite></EndNote>[13]Asthmatic endurance trained runners (n = 4); mean ± SD VO2max: 56 ± 5 mL.kg-1.min-1Non-asthmatic endurance trained runners (n = 4); mean ± SD VO2max: 66 ± 11 mL.kg-1.min-1Physician diagnosed asthmaMaximal treadmill exercise challengeIncremental exercise challenge2-hr constant run at 70% VO2maxNo differences observed in VO2max or running speed between asthmatic and non-asthmatic runners (P>0.05)Freeman et al.1990 ADDIN EN.CITE <EndNote><Cite><Author>Freeman</Author><Year>1990</Year><RecNum>297</RecNum><DisplayText>[14]</DisplayText><record><rec-number>297</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">297</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Freeman, W.</author><author>Williams, C.</author><author>Nute, MGL</author></authors></contributors><titles><title>Endurance running performance in athletes with asthma</title><secondary-title>Journal of sports sciences</secondary-title></titles><periodical><full-title>Journal of sports sciences</full-title><abbr-1>J Sports Sci</abbr-1></periodical><pages>103-117</pages><volume>8</volume><number>2</number><dates><year>1990</year></dates><isbn>0264-0414</isbn><urls></urls></record></Cite></EndNote>[14]Asthmatic endurance trained runners (n = 16); mean ± SD VO2max: 63 ± 6 mL.kg-1.min-1Physician diagnosed asthmaMaximal treadmill exercise challengeSub-maximal treadmill exercise challengeMild to moderate asthmatics can achieve high VO2max values comparable to healthy individualsSevere asthma may inhibit VO2maxSonna et al. 2001 ADDIN EN.CITE <EndNote><Cite><Author>Sonna</Author><Year>2001</Year><RecNum>235</RecNum><DisplayText>[12]</DisplayText><record><rec-number>235</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">235</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sonna, L.A.</author><author>Angel, K.C.</author><author>Sharp, M.A.</author><author>Knapik, J.J.</author><author>Patton, J.F.</author><author>Lilly, C.M.</author></authors></contributors><titles><title>The prevalence of exercise-induced bronchospasm among US army recruits and its effects on physical performance</title><secondary-title>Chest</secondary-title></titles><periodical><full-title>Chest</full-title><abbr-1>Chest</abbr-1></periodical><pages>1676-1684</pages><volume>119</volume><number>6</number><dates><year>2001</year></dates><isbn>0012-3692</isbn><urls></urls></record></Cite></EndNote>[12]US Army recruits (n = 137); mean ± SD VO2max: 46 ± 1 mL.kg-1.min-1Maximal treadmill exercise challenge EIB definition: ≥15% fall in FEV1 post challenge 8-week basic Army training course7% of the US Army recuits were diagnosed with EIBEIB did not hinder physical performance gains during basic trainingStensrud et al. 2006 ADDIN EN.CITE <EndNote><Cite><Author>Stensrud</Author><Year>2006</Year><RecNum>302</RecNum><DisplayText>[16]</DisplayText><record><rec-number>302</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">302</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stensrud, T.</author><author>Berntsen, S.</author><author>Carlsen, K.H.</author></authors></contributors><titles><title>Humidity influences exercise capacity in subjects with exercise-induced bronchoconstriction (EIB)</title><secondary-title>Respiratory medicine</secondary-title></titles><periodical><full-title>Respiratory Medicine</full-title><abbr-1>Respir Med</abbr-1></periodical><pages>1633-1641</pages><volume>100</volume><number>9</number><dates><year>2006</year></dates><isbn>0954-6111</isbn><urls></urls></record></Cite></EndNote>[16]Patients with objective evidence of EIB (n = 20); mean VO2max: 47 mL.kg-1.min-1 Maximal treadmill exercise challengeEIB definition: ≥10% fall in FEV1 post challengeMaximal treadmill exercise challengeWarm environment (19.9°C and 95% relative humidity)Exercising in a humid environment improved VO2max and Vpeak in subjects with EIB (P<0.05)Stensrud et al. 2007 ADDIN EN.CITE <EndNote><Cite><Author>Stensrud</Author><Year>2007</Year><RecNum>527</RecNum><DisplayText>[15]</DisplayText><record><rec-number>527</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">527</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stensrud, T</author><author>Berntsen, S</author><author>Carlsen, K-H</author></authors></contributors><titles><title>Exercise capacity and exercise-induced bronchoconstriction (EIB) in a cold environment</title><secondary-title>Respiratory medicine</secondary-title></titles><periodical><full-title>Respiratory Medicine</full-title><abbr-1>Respir Med</abbr-1></periodical><pages>1529-1536</pages><volume>101</volume><number>7</number><dates><year>2007</year></dates><isbn>0954-6111</isbn><urls></urls></record></Cite></EndNote>[15]Patients with objective evidence of EIB (n = 20); mean VO2max: 48 mL.kg-1.min-1Maximal treadmill exercise challengeEIB criteria: >10% fall in FEV1 post challengeMaximal treadmill exercise challengeEnvironment: Ambient conditions (20.2°C and 40% relative humidity); Cold environment (-18°C and 39.2% relative humidity).Exercising in a cold environment decreased VO2max and running speed in subjects with EIB (P<0.05)Teixeira et al. 2012 ADDIN EN.CITE <EndNote><Cite><Author>Teixeira</Author><Year>2012</Year><RecNum>598</RecNum><DisplayText>[11]</DisplayText><record><rec-number>598</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">598</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Teixeira, Renata Nakata</author><author>Teixeira, Luzimar Raimundo</author><author>Costa, Luiz Augusto Riani</author><author>Martins, Milton Arruda</author><author>Mickleborough, Timothy Derick</author><author>Carvalho, Celso Ricardo Fernandes</author></authors></contributors><titles><title>Exercise-induced bronchoconstriction in elite long-distance runners in Brazil</title><secondary-title>J Bras Pneumol </secondary-title></titles><periodical><full-title>J Bras Pneumol</full-title></periodical><pages>292-298</pages><volume>38</volume><number>3</number><dates><year>2012</year></dates><isbn>1806-3713</isbn><urls></urls></record></Cite></EndNote>[11]Elite long-distance runners (n = 20); mean ± SD VO2max: 64 ± 6 mL.kg-1.min-1Eucapnic voluntary hyperpnea challengeEIB definition: ≥10% fall in FEV1 post challengeMaximal treadmill exercise challenge25% athletes diagnosed with EIBNo difference was observed in VO2max between athletes with and without EIBMedication Freeman et al. 1989 ADDIN EN.CITE <EndNote><Cite><Author>Freeman</Author><Year>1989</Year><RecNum>402</RecNum><DisplayText>[19]</DisplayText><record><rec-number>402</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">402</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Freeman, W.</author><author>Packe, GE</author><author>Cayton, RM</author></authors></contributors><titles><title>Effect of nebulised salbutamol on maximal exercise performance in men with mild asthma</title><secondary-title>Thorax</secondary-title></titles><periodical><full-title>Thorax</full-title><abbr-1>Thorax</abbr-1></periodical><pages>942-947</pages><volume>44</volume><number>11</number><dates><year>1989</year></dates><isbn>1468-3296</isbn><urls></urls></record></Cite></EndNote>[19]Asthmatic patients (n = 8); mean ± SD VO2max: 43 ± 9 mL.kg-1.min-1Non-asthmatic controls (n = 8); mean ± SD VO2max: 41 ± 6 mL.kg-1.min-1Physician diagnosed asthma5mg nebulised salbutamol or saline placebo administered before a maximal exercise challenge performed on a bicycle ergometer.No difference in maximal workload or VO2max during exercise after salbutamol compared with placebo in asthmatic subjects (P>0.05)Steinshamn et al. 2002 ADDIN EN.CITE <EndNote><Cite><Author>Steinshamn</Author><Year>2002</Year><RecNum>304</RecNum><DisplayText>[17]</DisplayText><record><rec-number>304</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">304</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Steinshamn, S.</author><author>Sandsund, M.</author><author>Sue-Chu, M.</author><author>Bjermer, L.</author></authors></contributors><titles><title>Effects of montelukast on physical performance and exercise economy in adult asthmatics with exercise-induced bronchoconstriction</title><secondary-title>Scandinavian journal of medicine & science in sports</secondary-title></titles><periodical><full-title>Scandinavian journal of medicine & science in sports</full-title><abbr-1>Scand J Med Sci Sports</abbr-1></periodical><pages>211-217</pages><volume>12</volume><number>4</number><dates><year>2002</year></dates><isbn>1600-0838</isbn><urls></urls></record></Cite></EndNote>[17]Asthmatic patients with EIB (n = 16); mean ± SD VO2max: 45 ± 8 mL.kg-1.min-1Treadmill exercise challengeEIB definition : ≥12% fall in FEV1 post challengeMaximal incremental exercise challenge was performed in ambient, sub-zero temperatures (-15?C).10 mg/day montelukast or placebo was adminstered over a 5-day period prior to the test.Montelukast reduced maximum post- exercise fall in FEV1 (P<0.01)Montelukast has a beneficial effect on physical performance in most adults with EIBSteinshamn et al. 2004 ADDIN EN.CITE <EndNote><Cite><Author>Steinshamn</Author><Year>2004</Year><RecNum>420</RecNum><DisplayText>[18]</DisplayText><record><rec-number>420</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">420</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Steinshamn, Sigurd</author><author>Sandsund, Mariann</author><author>Sue-Chu, Malcolm</author><author>Bjermer, Leif</author></authors></contributors><titles><title>Effects of montelukast and salmeterol on physical performance and exercise economy in adult asthmatics with exercise-induced bronchoconstriction</title><secondary-title>Chest</secondary-title></titles><periodical><full-title>Chest</full-title><abbr-1>Chest</abbr-1></periodical><pages>1154-1160</pages><volume>126</volume><number>4</number><dates><year>2004</year></dates><isbn>0012-3692</isbn><urls></urls></record></Cite></EndNote>[18]Asthmatic patients with EIB (n = 18); mean ± SD VO2max: 48 ± 11 mL.kg-1.min-1Treadmill exercise challengeEIB definition : ≥12% fall in FEV1 post challengeProtocol replicated previous methods ADDIN EN.CITE <EndNote><Cite><Author>Steinshamn</Author><Year>2002</Year><RecNum>304</RecNum><DisplayText>[17]</DisplayText><record><rec-number>304</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">304</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Steinshamn, S.</author><author>Sandsund, M.</author><author>Sue-Chu, M.</author><author>Bjermer, L.</author></authors></contributors><titles><title>Effects of montelukast on physical performance and exercise economy in adult asthmatics with exercise-induced bronchoconstriction</title><secondary-title>Scandinavian journal of medicine & science in sports</secondary-title></titles><periodical><full-title>Scandinavian journal of medicine & science in sports</full-title><abbr-1>Scand J Med Sci Sports</abbr-1></periodical><pages>211-217</pages><volume>12</volume><number>4</number><dates><year>2002</year></dates><isbn>1600-0838</isbn><urls></urls></record></Cite></EndNote>[17].Montelukast: 10 mg/day or salmeterol: 50 ?g over a 5 day period.Montelukast reduced maximum post- exercise fall in FEV1 to a greater extent than salmeterol (P<0.001)Montelukast may have a beneficial effect on oxygen pulse, suggesting an improved gas exchange during exerciseKoch et al. 2013 ADDIN EN.CITE <EndNote><Cite><Author>Koch</Author><Year>2013</Year><RecNum>600</RecNum><DisplayText>[20]</DisplayText><record><rec-number>600</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">600</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Koch, Sarah</author><author>MacInnis, Martin J</author><author>Sporer, Benjamin C</author><author>Rupert, James L</author><author>Koehle, Michael S</author></authors></contributors><titles><title>Inhaled salbutamol does not affect athletic performance in asthmatic and non-asthmatic cyclists</title><secondary-title>British journal of sports medicine</secondary-title></titles><periodical><full-title>British journal of sports medicine</full-title><abbr-1>Br J Sports Med</abbr-1></periodical><volume>doi:10.1136/bjsports-2013-092706</volume><dates><year>2013</year></dates><isbn>1473-0480</isbn><urls></urls><electronic-resource-num>doi:10.1136/bjsports-2013-092706</electronic-resource-num></record></Cite></EndNote>[20]Cyclists with EIB (n = 14); mean ± SD VO2max: 65 ± 5 mL.kg-1.min-1Cyclists without EIB (n = 35); mean ± SD VO2max: 66 ± 7 mL.kg-1.min-1Eucapnic voluntary hyperpnea challengeEIB definition: ≥10% fall in FEV1 post challenge10 km time-trials 60 min after the administration of either 400 ?g salbutamol or 400?g placebo.A significant increase in lung function was observed after the inhalation of salbutamol in comparison to placebo (P<0.001)Salbutamol did not effect perception of dyspnoea, leg exertion or mean power output (P>0.05)The increase in lung function following the inhalation of salbutamol did not translate into an increase in 10 km time-trial performanceEIB, Exercise-induced bronchoconstriction; VO2max, maximal oxygen consumption; Vpeak, peak running speed; FEV1, forced expiratory volume in one second. Table 2. First Author / YearDesignLimitationsInconsistencyIndirectnessImprecisionOther considerationsOverallqualityPerformanceFreeman et al. 1990 ADDIN EN.CITE <EndNote><Cite ExcludeYear="1"><Author>13</Author><RecNum>565</RecNum><DisplayText>[63]</DisplayText><record><rec-number>565</rec-number><foreign-keys><key app="EN" db-id="vxs50efpawavvnesrpvpeazer22ezw5sz0wa">565</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>The International Olympic Committee: Documents/Reports/EN/en_report_1302.pdf </author></authors></contributors><titles><title>World Anti-Doping Agency</title><secondary-title>The International Olympic Committee: Documents/Reports/EN/en_report_1302.pdf </secondary-title></titles><dates><year>2008</year></dates><urls></urls></record></Cite></EndNote>[63]ObservationalVO2max is a poor predictor of athletic performance Severity of airway obstruction not definedNo important inconsistenciesAsthmatic subjects recruited rather than individuals with objective evidence of EIBStandard of asthmatic subjects below standard expected for elite or competitive athletes (mean ± SD VO2max: 56 ± 5 mL.kg-1.min-1 )Low subject numbersNo further considerationsVery lowFreeman et al. 1990 [14] ObservationalNo control group employedVO2max is a poor predictor of athletic performanceSeverity of airway obstruction not definedNo important inconsistenciesAsthmatic subjects recruited rather than individuals with objective evidence of EIBStandard of asthmatic ranged from recreational to elite level athleteLow subject numbersNo further considerationsVery lowSonna et al. 2001 [12]ObservationalVO2max is a poor predictor of athletic performanceSeverity of EIB not definedNo important inconsistenciesPhysically active army recruits rather than athletes Standard of asthmatic subjects below standard expected for elite or competitive athletes (mean ± SD VO2max 46 ± 1 mL.kg-1.min-1)No serious imprecisionNo further considerationsVery lowStensrud et al. 2006 [16]Randomised control trialUnable to blind study due to environmental conditionsNo control group employedVO2max is a poor predictor of athletic performanceSeverity of EIB not definedNo important inconsistenciesStandard of asthmatic subjects below standard expected for elite or competitive athletes (mean ± SD VO2max: 47 mL.kg-1.min-1)No serious imprecisionNo further considerationsLowStensrud et al. 2007 [15]. Randomised control trialUnable to blind study due to environmental conditionsNo control group employedVO2max is a poor predictor of athletic performanceStudy population replicated from previous findings (Stensrud, Berntsen & Carlsen, 2006)Severity of EIB not definedNo important inconsistenciesStandard of asthmatic subjects below standard expected for elite or competitive athletes (mean ± SD VO2max: 47 mL.kg-1.min-1)No serious imprecisionNo further considerationsLowTeixeira et al. 2012 [11]ObservationalVO2max is a poor predictor of athletic performanceSeverity of EIB not definedNo important inconsistenciesDirectLow subject numbersNo further considerationsVery lowMedication Freeman et al. 1989 [19]Randomised control trialVO2max is a poor predictor of athletic performanceSeverity of airway obstruction not definedNo important inconsistenciesAsthmatic subjects recruited rather than individuals with objective evidence of EIBStandard of asthmatic subjects below standard expected for elite or competitive athletes (mean ± SD 43 ± 9 mL.kg-1.min-1)No serious imprecisionNo further considerationsLowSteinshamn et al. 2002 [17]Randomised control trialNo control group employedVO2max is a poor predictor of athletic performanceSeverity of EIB not definedNo important inconsistencies Standard of asthmatic subjects below standard expected for elite or competitive athletes (mean ± SD VO2max: 45 ± 8 mL.kg-1.min-1)No serious imprecisionNo further considerationsVery lowSteinshamn et al. 2004 [18]Randomised control trialNo control group employedVO2max is a poor predictor of athletic performanceSeverity of EIB not definedNo important inconsistencies Standard of asthmatic subjects below standard expected for elite or competitive athletes (mean ± SD VO2max: 48 ± 11 mL.kg-1.min-1)No serious imprecisionNo further considerationsVery lowKoch et al. 2013 [20]Randomised control trialSeverity of EIB not definedNo important inconsistenciesDirectNo serious imprecisionNo further considerationsModerateEIB, Exercise-induced bronchoconstriction; VO2max, maximal oxygen consumption.Figure headingsFigure 1. 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