Table 2 Hypotheses of the patho-physiological mechanisms underlying EIAn
Contemporary hypotheses for EIAnPhysiological basis of hypothesesExercise physiology in context of EIAnFuture 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.