New Insights Into Pathogenesis of Exercise-induced Bronchoconstriction

Teal S. Hallstrand

Disclosures

Curr Opin Allergy Clin Immunol. 2012;12(1):42-48. 

In This Article

Conclusion

Recent studies have advanced our understanding of EIB as a distinct syndrome in asthma that is related to indirect AHR, and is notable for increased production of CysLTs and shedding of epithelial cells into the airway lumen (Fig. 4).[53] Exercise challenge serves as a stimulus to the airway epithelium and adjacent leukocytes resulting in sustained CysLT and PGD2 release in association with smooth muscle contraction and the release of MUC5AC that may be the consequence of sensory nerve activation. Several lines of evidence indicate that mast cells and eosinophils serve as the principal sources of inflammatory eicosanoids in this disorder. Recent work has identified the strong expression of sPLA2-X in the airway epithelium and elevated levels of sPLA2-X protein in BAL fluid of patients with asthma. A genome-wide expression study identified TGM2 with increased expression in asthma and found that TGM2 serves as a regulator of sPLA2-X. The sPLA2-X enzyme acts on target cells such as eosinophils to initiate cellular eicosanoid synthesis. These studies suggest that the airway epithelium serves as an important regulator of the production of inflammatory eicosanoids by leukocytes.

Figure 4.

Disease model of exercise-induced bronchoconstriction (EIB) pathogenesis. Asthmatic patients with EIB have increased concentrations of shed epithelial cells, CysLTs, and CysLT/PGE2 ratio in induced sputum. Exercise challenge initiates the production of CysLTs, PGD2, and 15S-HETE, and a reduction in PGE2. The release of sPLA2-X by the airway epithelium may initiate CysLT production in adjacent leukocytes. Contraction of the airway smooth muscle and mucin release occurs in part through retrograde axonal transmission in sensory nerves that release neurokinin A. 15-LO-1, 15-lipoxygenase-1; 5-LO, 5-lipoxygenase; COX, cyclooxygenase; cPLA2, cytosolic phospholipase A2; CysLT, cysteinyl leukotriene; MUC5AC, mucin 5AC; PGE2, prostaglandin E2; PL, phospholipids; sPLA2-X, secreted phospholipase A2 group X. Adapted from reference [53].

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