Original Articles: Mechanisms of AllergyAllergen-induced impairment of bronchoprotective nitric oxide synthesis in asthma☆,☆☆
Section snippets
Subjects
Ten nonsmoking, house dust mite–atopic individuals with clinically stable asthma participated in the study (Table I).
Patient no. Sex Age (y) Atopic status* FVC (% predicted)† FEV1 (% predicted)† PC20FEV1 Histamine (mg/mL)‡ 1 F 20 5 108 90 0.61 2 F 20 4 95 94 0.29 3 M 21 3 100 81 0.74 4 M 24 6 98 87 1.77 5 M 26 4 112 92 1.0 6 F 21 4 109 103 1.33 7 M 20 5 102 97 0.36 8 M 19 4 93 96 4.23 9 F 26 4 96 100 1.94 10 F 24 3 107 104 3.34 *As determined by the number of wheal responses to 10 common allergen extracts (Vivodiagnost, ALK, Benelux).
The stability of asthma between the challenge days
Baseline FEV1 was not different between the diluent/allergen days (mean ± SEM): 3.83 ± 0.17 L (period 1), 3.78 ± 0.15 L (period 2), 3.83 ± 0.18 L (period 3), respectively (MANOVA, P = .42). Baseline FEV1 did not change significantly between the BK challenge days and was not affected by placebo or L-NMMA pretreatment (Table IV).
Empty Cell Period 1 Period 2 Period 3 Day 3 Day 10 Day 3 Day 10 Day 3 Day 10
Discussion
The present study shows that increased AHR to BK, induced by allergen exposure in asthma, is due to impaired production of bronchoprotective NO, a phenomenon that is associated with downregulation of ecNOS and upregulation of iNOS within the airway epithelium. These findings underscore the relevance of bronchoprotection by endogenous NO to limit AHR in asthma and warrant the development of treatment strategies to restore ecNOS activity during asthma exacerbations.
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2018, European Journal of PharmacologyCitation Excerpt :This effect is due to the capability of bradykinin to activate cholinergic nerves (Reynolds et al., 1999), since bradykinin can stimulate airway parasympathetic ganglion neurons independently of sensory nerve activation, therefore providing an alternative mechanism for regulating airway parasympathetic tone (Kajekar and Myers, 2000). On the other hand, epithelium-derived bronchoprotective factors such as nitric oxide are released by bradykinin (Figini et al., 1996; Ricciardolo et al., 2000) negatively modulating enhanced bronchial hyperresponsiveness in mild asthma (Ricciardolo et al., 1996, 2001) (Fig. 1). A further study also showed the impairment of the bronchoprotective nitric oxide on the bradykinin-induced airway hyperresponsiveness in moderate-to-severe asthma suggesting the loss of this protective mechanism in difficult-to-control patients (Ricciardolo et al., 1997).
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2015, Allergologia et ImmunopathologiaCitation Excerpt :A significant relationship between BHR to bradykinin, but not to methacholine, and eosinophilic inflammation was previously highlighted in mild-to-moderate asthmatics treated or not with corticosteroids62 proposing BHR to bradykinin as a clinical marker to assess asthma severity. Ricciardolo et al.54 firstly demonstrated that allergen exposure is able to raise FeNO during late asthmatic response and to worsen BHR to bradykinin63; then they reported the direct association between high FeNO levels and increased number of eosinophils or potentiated BHR to bradykinin in atopic asthmatics after allergen exposure indicating that FeNO can reflect the loss of asthma control.43 The gold standard for asthma treatment is to achieve and maintain asthma control.64,65
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Supported by a Research Fellowship of the European Respiratory Society and by the Netherlands Asthma Foundation (grant 96.10).
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Reprint requests: P. J. Sterk, MD, PhD, Department of Pulmonology, Lung Function Lab, C2-P, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, NL-2300 RC Leiden, The Netherlands. ([email protected] )