The Olympics have arrived: The challenge of exercise‐induced bronchoconstriction in athletes

Exercise-induced bronchoconstriction (EIB) refers to the transient narrowing of the airways in response to vigorous exercise and can occur alone or in those with active asthma.1 This scenario is very relevant in the context of the Paris 2024 Olympic Games. It is well understood that both EIB and asthma have a high prevalence in elite athletes when compared to the general population.2 Further, airway inflammation in the athlete may present as a TH2 high or TH2 low phenotype, where TH2 high athletes have a higher prevalence of allergy.3 Considering the well-known potential progression of those with allergy to active asthma, it is perhaps not surprising that some athletes can develop asthma following years of participation in competitive sport.2 EIB is also common in the non-athletes with active asthma.1, 4 Those with EIB alone may have less significant falls in FEV1 than those with EIB and asthma. However, moderate to severe falls in FEV1 in athletes, as observed in the asthmatics with EIB, are possible. Resting lung function and respiratory symptoms do not predict severity of EIB and guidelines recommend that EIB is objectively documented using recommended challenge tests.1 Tests to identify EIB are now more accessible and the surrogates of laboratory exercise tests have been shown to have a higher sensitivity at identifying EIB than laboratory exercise tests (e.g., bronchial provocation tests using eucapnic voluntary hypernea or inhaled mannitol).1, 4, 5 The high prevalence of EIB in athletes has been documented often through screening athletes with these challenge tests identifying abnormal falls in FEV1, and this has been observed in athletes with, and without a previous diagnosis of asthma or EIB.6 Thus, while we know much about the nature of asthma and EIB and the efficacy of similar pharmacologic interventions, we know little about the long-term consequences of active asthma and/or EIB alone in the elite athlete. It is unclear if EIB with or without asthma limits best exercise performance. To date study designs investigating the impact of EIB on performance are limited to the use of VO2 peak as the single primary outcome.7 However, this may not be an adequate analysis to address a broader range of questions around the presence of EIB. That is, what does active steroid sensitive airway inflammation, if not optimally treated, determine about sporting performance and respiratory health of the athlete in the future? With our current understanding of the development of clinical asthma, and its potential to develop in adulthood, it is perhaps prudent to deepen our understanding of the relationship of EIB and asthma. Untreated and poorly managed asthma is associated with poorer clinical outcomes and prognosis, with an associated accelerated decline in lung function over time. This can result from active untreated airway inflammation leading to airway structural changes. While there is limited robust evidence that EIB advances to active asthma, those with the high TH2 phenotype may be at higher risk for asthma later in life. Together, when considering the 'occupational exposure' of elite athletes to repeated airway dehydration via hyperpnoea from regular intensive exercise, increased likelihood of lung deposition to air pollutants or airborne allergens, athletes with established airway inflammation may have an additional future risk of airway disease.8 While guidelines state EIB should be objectively identified, little is stated about objective monitoring to determine optimal treatment benefits.1 We know that inhaled corticosteroids (ICS), the mainstay treatment of asthma, when taken daily can attenuate EIB.9 Following months of daily ICS treatment, EIB in children can resemble what is observed in healthy subjects with no EIB, that is, fall in FEV1 <10%.10 Surprisingly, there are no similar studies of this duration in adults or athletes with EIB. However, the first study showing inhibition of airway hyperresponsiveness (AHR) in adults taking daily ICS using inhaled mannitol was published in Respirology over 20 years ago, and this was recently validated in a larger population.11, 12 We understand that the pathophysiology of EIB in athletes and asthmatics are similar including the mechanisms of bronchospasm.4 The presence of airway mast cells with or without eosinophilia, when osmotically activated, lead to the release of potent bronchoconstricting mediators that act on the airway smooth muscle to cause airway narrowing—known as 'indirect' AHR. Daily ICS reduce the numbers of airway inflammatory cells, leading to a reduction in source of bronchoconstricting mediator. It is now known mast cells are reduced in association with the improvement of AHR to mannitol with daily ICS over 6 weeks.13 Thus, inhibition of indirect AHR in the presence of a sufficient treatment duration of daily ICS, can identify 'remission' of EIB. There are now discussions about achieving 'remission' in those with severe asthma.14 This is due to treatments that potently target eosinophils and possibly mast cells using monoclonal anti-bodies, leading to significantly quiesced disease reflected in symptom control and improved lung function. AHR to mannitol is inhibited with monoclonal antibody targets of interlukin-5 and thymic stromal lymphopoietin (TLSP), thus, loss of indirect AHR to mannitol has been proposed to be a marker for documenting 'remission'.15 Hence, considering this, an achievable endpoint in many with EIB alone or with associated mild to moderate asthma, could be the documentation of resolution of indirect AHR/EIB with daily ICS. Therefore, does quiescence of airway inflammation with therapies that leads to inhibition of indirect AHR lead to other clinical benefits? Reduced likelihood of future EIB and sustained best lung function, reduced future risk of developing asthma and better longer-term sporting performance? In Australia, the police and defence forces screen applicants who are at risk of asthma or EIB. If AHR to mannitol is documented, a treatment period of approximately 3 months of daily ICS is commenced.12 It has been observed a high proportion of those assessed can achieve meaningful inhibition of AHR to mannitol, and thus reduce the risk of EIB.(Figure 1) In principle, loss of indirect AHR is a realistic and meaningful marker of quiesced TH2 pathology that is responsible for the loss of the key pathophysiologic feature of both asthma and EIB. Considering all this, there may be much more to achieve. The Olympics have arrived and the above considerations are highly pertinent to this global event. Respiratory physicians and exercise physiologists have a key role to play in preventing and mitigating EIB in athletes. It is also imperative that appropriate treatment that complies with international regulations is always provided. Open access publishing facilitated by The University of Newcastle, as part of the Wiley - The University of Newcastle agreement via the Council of Australian University Librarians. John D. Brannan developed inhaled mannitol as a bronchial provocation test, however now receives no royalties for its sale in the last 3 years. He consults to the manufacturer and distributors of inhaled mannitol (AridolTM/OsmohaleTM) however has received no payment for this in the last 3 years. Martin R. Lindley has no conflict of interest to disclose.