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Exhaled nitric oxide analysis and applications

Author
Raed A Dweik, MD, FACP, FCCP, FRCP(C), FCCM, FAHA
Section Editor
Peter J Barnes, DM, DSc, FRCP, FRS
Deputy Editor
Helen Hollingsworth, MD

INTRODUCTION

Nitric oxide (NO) is a gaseous molecule initially considered to have a health-related role only in the context of its formation from the combustion of fossil fuels and its contribution to air pollution. However, this view has been greatly modified since the 1987 discovery that the free radical NO is the previously uncharacterized endothelial-derived relaxing factor. It is now clear that NO plays an important role in most human organ systems.

Within the respiratory system, NO regulates vascular and bronchial tone (promoting dilation of both vessels and airways), facilitates the coordinated beating of ciliated epithelial cells, and acts as an important neurotransmitter for non-adrenergic, non-cholinergic neurons that run in the bronchial wall [1-8]. This molecule can be detected in exhaled gas as the fraction of exhaled NO (FENO), which varies in health and disease.

The biology of NO, techniques available for measuring this gas in exhaled breath, and potential uses of these measurements in clinical practice will be reviewed here. The therapeutic use of inhaled NO is discussed separately. (See "Inhaled nitric oxide in adults with pulmonary hypertension" and "Acute respiratory distress syndrome: Investigational or ineffective pharmacotherapy in adults" and "Primary lung graft dysfunction", section on 'Nitric oxide'.)

FORMATION OF NO

In biological systems, nitric oxide (NO) is formed by the action of one of the isoforms of the enzyme nitric oxide synthase (NOS). Three such isoforms have been identified and are termed type I or neuronal cell NOS (nNOS), type II or inducible NOS (iNOS), and type III or endothelial cell NOS (eNOS) (table 1) [9,10]. Although these enzymes are distinct proteins encoded by genes on disparate chromosomes, all three catalyze the adduction of the guanidino nitrogen of the amino acid arginine to molecular oxygen, yielding NO and water (figure 1) [11].

Regulation of NOS — While the three isoforms of NOS catalyze the same reaction, regulation of the activity of these isozymes occurs through distinct processes. Both nNOS and eNOS are usually constitutively active and produce low amounts of NO, with output varying with changes in the intracellular calcium concentration. In contrast, iNOS binds calcium so avidly that its function is not influenced by calcium fluxes within the physiologic range. While not constitutively active in most settings, iNOS is constitutively expressed in the airway epithelium of normal and asthmatic subjects [12,13]. iNOS also has the capacity to generate large quantities of NO when transcriptionally upregulated by inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin 1 (IL-1)-beta, interferon (IFN)-gamma, IL-4, and IL-13 [9,10,14]. In vitro evidence suggests that this upregulation can be abolished by glucocorticoids in vitro [15] and in vivo [12].

                   

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Literature review current through: Nov 2016. | This topic last updated: Mon Jul 11 00:00:00 GMT+00:00 2016.
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