Mannitol as a Challenge Test to Identify Exercise-induced Bronchoconstriction in Elite Athletes

Abstract

Bronchial provocation tests provide objective criteria for asthma and exercise-induced bronchoconstriction (EIB) and were recommended to justify the use of inhaled beta2-agonists by athletes at the Winter Olympics 2002. Eucapnic voluntary hyperpnea (EVH) was one test recommended to identify EIB. Provocation with EVH requires a special dry gas mixture limiting its availability. Provocation tests with osmotic aerosols require less expensive equipment that is easily portable. We assessed the sensitivity of a challenge with mannitol to identify responsiveness to EVH in 50 elite summer sport athletes who were unselected if they had respiratory symptoms. Asthma was previously diagnosed by a doctor in 27 subjects, and 21 subjects were currently under treatment for EIB or asthma. The mean predicted FEV1 was 103.6 +/- 10.8%, FVC was 99 +/- 13.3%, and mean forced expiratory flow during the middle half of the FVC was 104 +/- 22.7%. A total of 25 subjects were positive to EVH challenge (mean percentage of fall in FEV1 was 25.4 +/- 15% SD), and 26 subjects had a positive mannitol challenge (geometric mean [95% confidence interval] provoking dose causing a 10% fall in forced expiratory volume in one second [PD10] was 202 mg [134, 300], with 24 of the subjects positive to both challenges). Mannitol had a sensitivity of 96% and specificity of 92% to identify a positive response to EVH and, as such, could be used as an alternative to EVH to identify EIB.

Evidence of mast cell activation and leukotriene release after mannitol inhalation

“…Similar time courses of the urinary excretion of 9a,11b-prostagladin F 2 were seen after exercise [6] and mannitol (present study). These findings lend further support to the concept that the stimulus and mechanism of airway narrowing to mannitol and exercise are similar [8,9]. The authors also conclude that mannitol causes bronchoconstriction only in the asthmatics, because only the asthmatic subjects display increased bronchial responsiveness to the liberated mediators.…”

“…A positive response to mannitol identifies asthmatics with EIB [8,9] and there are no significant airway responses to mannitol in healthy nonasthmatics [10]. Inhaled mannitol is thought to cause airways to narrow in asthmatics by a similar mechanism to exercise, that is by increasing the osmolarity of the airway surface liquid [8].…”

Exercise‐induced asthma, respiratory and allergic disorders in elite athletes: epidemiology, mechanisms and diagnosis: Part I of the report from the Joint Task Force of the European Respiratory Society (ERS) and the European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA2LEN

“…In one study, only 18 of 44 children with a 15% fall in FEV 1 after exercise responded to histamine (139). A similar low sensitivity using methacholine to identify responses to eucapnic voluntary hyperpnoea was found in elite summer athletes (115). Only 36% of the athletes having a fall of 10% or more after eucapnic voluntary hyperpnoea had response to 7.8 lmol of methacholine.…”

“…Other indirect stimuli have also been used to assess bronchial responsiveness including inhalation of cold, dry air (111), dry air (112), hyperosmolar aerosols like hypertonic saline (113) and inhaled mannitol (112,114,115) and inhalation of adenosine monophosphate (AMP) (116). Generally, it might be stated that indirect tests are more specific for asthma, whereas the direct tests are more sensitive, but not to the same extent as the difference between asthma and other chronic lung disorders (101,116,117).…”

“…However, when performed for 4 min with dry cold air it has been shown to have a low sensitivity in adults to detect asthma and bronchial responsiveness (118). Mannitol and eucapnic hyperventilation have been shown to have a comparable sensitivity (115); in contrast one report shows higher sensitivity of eucapnic hyperventilation in young athletes to detect BHR than methacholine (89). In order to have a high sensitivity, a reduction of 10% in FEV 1 has been considered as the appropriate limit for indirect tests compared with 15%, which have traditionally been used for some of these tests (for mannitol 15%).…”