PMC

Eicosanoid formation from arachidonic acid via the 5- and 15-lipoxygenase and cyclooxygenase pathways. COX, cyclooxygenase; CysLT, cysteinyl leukotriene; FLAP, 5-lipoxygenase–activating protein; HETE, hydroxyeicosatetraenoic acid; LO, lipoxygenase; PG, prostaglandin; PLA2, phospholipase A₂; TX, thromboxane.

Mast-cell degranulation following exercise challenge in asthmatics with EIB. The levels of histamine (A) and tryptase (B) were measured in induced sputum supernatant at baseline and on a separate day 30 minutes after exercise challenge. Significant increases in both histamine and tryptase were observed following exercise challenge in subjects with EIB. (Data from Hallstrand TS, Moody MW, Wurfel MM, et al. Inflammatory basis of exercise-induced bronchoconstriction. Am J Respir Crit Care Med 2005;172:679–86.)

Basic overview of the epithelial response to water loss from the airway surface liquid. As ventilation increases, water is lost from the airway surface liquid, resulting in transient hyperosmolarity and the passive movement of water from airway epithelial cells (arrows) to restore the osmolarity of the airway surface liquid. The movement of water causes epithelial cells to shrink and initiates cellular signaling events, including an increase in intracellular calcium (Ca²⁺). The addition of osmotically active substances such as mannitol and hypertonic saline similarly cause water movement to restore the surface osmolarity.

Disease model of exercise-induced bronchoconstriction (EIB) pathogenesis. Studies examining differences between asthmatics with EIB to those without EIB have identified an increased concentration of shed epithelial cells, and infiltration of the airways with eosinophils and mast cells. There is an alteration in the balance of lipid mediators notable for an increase in cysteinyl leukotrienes (CysLTs), CysLT/prostaglandin E₂ (PGE₂) ratio, and 8-isoprostanes, and a reduction in lipoxin A4. eNO, exhaled nitric oxide. (Adapted from Hallstrand TS, Henderson WR Jr. Role of leukotrienes in exercise-induced bronchoconstriction. Curr Allergy Asthma Rep 2009;9:18–25.)

Goblet cell mucin release following exercise challenge in asthmatics with EIB. The levels of the gel-forming mucin MUC5AC were measured before and after exercise challenge in induced sputum supernatant in subjects with EIB. The induced sputum samples were dialyzed to remove the dithiothreitol (DTT) before analysis. A significant increase in MUC5AC was observed following exercise challenge. (Data from Hallstrand TS, Debley JS, Farin FM, et al. Role of MUC5AC in the pathogenesis of exercise-induced bronchoconstriction. J Allergy Clin Immunol 2007;119:1092–8.)

Ratio of CysLTs to PGE₂ in induced sputum following exercise challenge. The levels of CysLTs and PGE₂ were measured in induced sputum in a group of asthmatics with EIB (A) and in a nonasthmatic control group (B) at baseline and after exercise challenge. The results demonstrate opposing effects of an increase in the CysLT/PGE₂ ratio after challenge in the asthma group, whereas the ratio decreased after challenge in the control group. (Data from Hallstrand TS, Chi EY, Singer AG, et al. Secreted phospholipase A2 group X over-expression in asthma and bronchial hyperresponsiveness. Am J Respir Crit Care Med 2007;176:1072–8.)