Exercise-induced bronchoconstriction (EIB) is widely prevalent in asthmatic patients. Eosinophilic airway inflammation is considered to be a major factor in the pathogenesis of asthma. However, the effects of eosinophilic airway inflammation on EIB have been elucidated insufficiently. To examine the relationship between the severity of EIB and eosinophilic inflammation, sputum induction and exercise challenge were performed in 21 asthmatic patients. Significantly higher percentages of eosinophils and levels of eosinophil cationic protein (ECP) were found in induced sputum in EIB-positive asthmatics (median (range), eosinophils: 23.5 (11.0-61.0)%; ECP: 1,475 (74.8-17,701) ng x mL(-1)) than in EIB-negative asthmatics (eosinophils: 6.0 (1.0-41.5)% (p=0.006); ECP: 270.6 (10.8-7,700) ng x mL(-1) (p=0.049)). There was a significant correlation between the severity of EIB and the sputum eosinophil percentage (r=0.59, p=0.009) and the level of ECP (r=0.47, p=0.037). The area under the curve of the forced expiratory volume in one second for 30 min after exercise correlated with the percentage of eosinophils (r=0.60, p=0.008) and the level of ECP (r=0.45, p=0.04). There was no correlation between airway responsiveness to methacholine on the one hand and EIB, sputum eosinophils or ECP on the other. In conclusion, these results provide evidence that the severity of bronchoconstriction evoked by exercise is more closely related to eosinophilic airway inflammation than airway hyperresponsiveness to methacholine in asthmatic patients.

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We conclude the increased production of endogenous NO in patients with asthma and COPD, and that NO derivatives in induced sputum are more valuable than exhaled NO in assessing airway inflammation in patients with COPD.

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Vasoactive intestinal peptide (VIP) and nitric oxide (NO) are considered to be nonadrenergic, noncholinergic (NANC) inhibitory neurostransmitters in the airways. It seems likely that these neurotransmitters may be coreleased and act as functional antagonists against bronchoconstrictor stimuli. In the present study, we examined the synergistic effect of NO and VIP on bronchoprotection against histamine in anesthetized guinea pigs. The NO donor, S-nitroso-N-acetylpenicillamine (SNAP) significantly inhibited histamine-induced bronchoconstriction in a dose-dependent manner. VIP also inhibited histamine-induced bronchoconstriction in a dose-dependent manner, but this bronchoprotective effect was short-lived. Additionally, VIP (10(-9) M) had no significant bronchoprotective effect, but a subthreshold dose of SNAP (10(-7) M) significantly potentiated VIP (10(-9) M)-induced bronchoprotection against histamine. Moreover, SNAP (10(-7) M) significantly enhanced VIP (10(-7) M)-induced bronchoprotection for a longer period of time. On the other hand, VIP (10(-9) M) also significantly potentiated SNAP-induced bronchoprotection against histamine. In conclusion, combination therapy with NO donor and VIP receptor agonist may have important advantages in the treatment of bronchial asthma, and both NO and VIP may contribute in complementary fashion to the NANC-induced relaxant response in guinea pig airways.