| Contemporary hypotheses for EIAn | Physiological basis of hypotheses | Exercise physiology in context of EIAn | Future research direction. |
| Changes in plasma osmolality during exercise ↑ basophil histamine release. 340 mOsm associated with ↑ in basophil histamine release in FDEIAn. | Exercise can ↑ plasma osmolarity. Dramatic changes in osmolarity can alter basophil histamine release. | Plasma osmolarity is relatively stable during short-term, low intensity exercise. 5% loss of body mass through dehydration required to achieve osmolality of 305 mOsm. | Effect of minor shifts in osmolarity on basophil degranualtion warrants further investigation. |
| ↑acidity in blood results in increased mast cell degranulation as shown by protective effect of sodium bicarbonate in FDEIAn during exercise. | Exercise induces metabolic/lactic acidosis. pH7 provides optimal conditions for mast cell degranulation. | Supramaximal exercise associated with lactic acidosis Acidosis is unlikely to occur in the context of EIAn. | Changes in muscle pH greater than blood, prophylactic effect of sodium bicarbonate warrants further investigation. |
| ↑ exercise-induced gut permeability (GI) results in appearance of gliadin peptides in WDEIA. | Exercise can ↑ GI and potentially ↑ absorption of allergenic peptides. | Only very prolonged exercise is associated with increases in GI. Exercise for 90 mins at 70% VO2max ↓ GI ↑ GI is unlikely to occur in the context of EIAn. | Caution: aspirin, NSAIDs, alcohol ingested can ↑GI permeability during or prior to exercise |
| Exercise-induced ↑ in tissue transglutaminase (tTG) activity results in post-digestion allergenic peptide aggregation. | tTG activity ↑by severe homeostatic disruption and associated ↑ in inflammatory cytokine, free radicals and cortisol release. Dysregulated tTG results in fibrosis, autoimmune disorders. | Short-term, low intensity exercise results in slight, transient ↑ in inflammatory cytokines, free radicals or cortisol. No evidence of tTG/allergen complexes in circulation in EIAn. | Determination of lowest concentration of cytokines to ↑tTG required. |
| Redistribution of blood flow from viscera to active tissues results in exposure of allergen to phenotypically different mast cells. | Exercise results in altered blood flow from the viscera to the active tissues. Mast cell heterogeneity has been demonstrated in a number of tissues in humans. | Mild to severe exercise alters blood flow distribution with greater percentage of cardiac output going to active tissues and reduction to viscera. | Hypothesis warrants further investigation in EIAn patients vs healthy controls. |
Reproduced and modified from [22] with permission from the publisher.