Endogenous nitric oxide in allergic airway disease

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Presentation transcript:

Endogenous nitric oxide in allergic airway disease Philip E. Silkoff, MBBS, MRCPa, Richard A. Robbins, MDb, Benjamin Gaston, MDc, Jon O.N. Lundberg, MD, PhDd, Robert G. Townley, MDe Journal of Allergy and Clinical Immunology Volume 105, Issue 3, Pages 438-448 (March 2000) DOI: 10.1067/mai.2000.104938 Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 1 A Exhaled NO derived from lower respiratory tract may contain NO derived from the nasal and oropharyngeal cavities. B, Exhaled NO derives from 2 compartments, namely, convection of alveolar NO and diffusion of airway NO, driven by a wall-to-lumen concentration difference. Alveolar region contains NO that is derived from that present in inhaled gas, NO diffusing into the inhaled gas stream from bronchial tree, and NO produced from alveolar cells such as macrophages (M). However, NO is avidly taken up by hemoglobin in pulmonary capillary blood; this explains the observation that alveolar levels are very low. C, Endogenous NO derives from conversion of L -arginine (Larg) to L -citrulline (Lcit) by cNOS and iNOS. In the airways NOS isoforms are found in many different cell types, including epithelium (iNOS and cNOS), nerve cells and processes (nNOS), endothelium (eNOS), airway smooth muscle (ASM), and fibroblasts. Epithelium is main site of iNOS induction in asthma, with production of large amounts of NO. This NO may be exhaled as NO or undergo conversion in airway wall or airway lining fluid (ALF), for example, by reaction with superoxide (O2–) to form diverse metabolites. These include nitrosothiols (R-SNO) such as glutathione-S-NO, which are bronchodilators, peroxynitrite (ONOO–), which cause widespread oxidative damage, nitrite (NO2–), and nitrate (NO3–). Journal of Allergy and Clinical Immunology 2000 105, 438-448DOI: (10.1067/mai.2000.104938) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 2 Nasal NO in different disease states. Journal of Allergy and Clinical Immunology 2000 105, 438-448DOI: (10.1067/mai.2000.104938) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 3 Three single breath profiles of exhaled NO and mouth pressure showing reproducible tracings. The NO profile shows a washout phase followed by a steady plateau. Journal of Allergy and Clinical Immunology 2000 105, 438-448DOI: (10.1067/mai.2000.104938) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 4 One configuration for measurement of FENO with restricted breath technique. Journal of Allergy and Clinical Immunology 2000 105, 438-448DOI: (10.1067/mai.2000.104938) Copyright © 2000 Mosby, Inc. Terms and Conditions