Mucosal injury and eicosanoid kinetics during hyperventilation-induced bronchoconstriction

Abstract

Bronchoalveolar lavage (BAL) of canine peripheral airways was performed at various times after hyperventilation, and BAL fluid (BALF) cell and mediator data were used to evaluate two hypotheses: 1) hyperventilation-induced mucosal injury stimulates mediator production, and 2) mucosal damage is correlated with the magnitude of hyperventilation-induced bronchoconstriction. We found that epithelial cells increased in BALF immediately after a 2- and a 5-min dry air challenge (DAC). Prostaglandins D(2) and F(2alpha) and thromboxane B(2) were unchanged immediately after a 2-min DAC but were significantly increased after a 5-min DAC. Leukotriene C(4), D(4), and E(4) did not increase until 5 min after DAC. Hyperventilation with warm moist air did not alter BALF cells or mediators and caused less airway obstruction that occurred earlier than DAC. BALF epithelial cells were correlated with mediator release, and mediator release and epithelial cells were correlated with hyperventilation-induced bronchoconstriction. These observations are consistent with the hypothesis that hyperventilation-induced mucosal damage initiates peripheral airway constriction via the release of biochemical mediators.

Ratio of Leukotriene E4to Exhaled Nitric Oxide and the Therapeutic Response in Children With Exercise-Induced Bronchoconstriction

“…We showed that the levels of sputum LTE 4 significantly increased in the airways 30 minutes after exercise challenge in the montelukast and FP groups. The pathogenesis of EIB involves the release of CysLTs as demonstrated by the release of CysLTs into the airways9,10,36 and the pharmacological inhibition of EIB using drugs that antagonize CysLTs 12. Hallstrand et al10 demonstrated that treatment with CysLT antagonists reduce the severity of EIB and decrease the release of CysLTs into the airways.…”

“…Understanding the pathogenesis of EIB is key to effective treatment. The pathogenesis of EIB involves the release of LTE 4 9,10,36. Thus, treatments that block the activity of LTE 4 are logically used as effective therapies for controlling EIB 28,46.…”

Epithelial shedding is associated with nasal reactions to cold, dry air

“…32 In animal models of dry air-induced bronchospasm, epithelial detachment has been observed after CDA provocation in dogs [33][34][35] and in guinea pigs. 36 Although the relationship between CDA-induced rhinitis and asthma has not been investigated, it is noteworthy that, in our hands, nasal CDA provocation produces stronger biochemical and nasal symptom responses in subjects with allergic rhinitis and asthma compared with individuals with rhinitis alone.…”

Polymorphisms of the PTGDR and LTC4S influence responsiveness to leukotriene receptor antagonists in Korean children with asthma

“…Altogether, we thought that increment of eosinophil count in atopic asthmatics is result worth considering certainly. Increased levels of cysLTs have been detected in airways, 19 exhaled breath condensates 21 and induced sputum, 22 and bronchial hyperresponsiveness has been induced by administration of cysLTs. 35 PTGDR expression was increased by the region including À441C allele 14 and increased expression of the PTGDR augmented the ability of PGD2 to recruit eosinophils and stimulate them to synthesize LTC4.…”

“…[15][16][17] However, the results of a recent study showed that PGD2 activated eosinophils and enhanced LTC4 synthesis in vivo. 18 Accumulating evidence suggests that the cysteinyl leukotrienes (cysLTs) are the primary mediators of exercise-induced bronchoconstriction (EIB), as demonstrated by the detection of cysLTs in the airways, 19 increased levels of urinary leukotriene E4 20 and increased levels of cysLTs in exhaled breath condensates, 21 and in induced sputum 22 from children with EIB. Therefore, we presume that the function of PGD2 may affect the response of the leukotriene receptor antagonist (LTRA), which inhibits the effect of leukotriene, although the PTGDR is not directly included in the LTRA pathway.…”