Exhaled nitric oxide: a new lung function test Nitric oxide (NO) is produced by many cells within the respiratory tract and endogenous NO may play an important signalling role in the physiological control ofairway function and in the pathophysiology of airway diseases.'3Endo- genous NO is generated from the amino acid L-arginine by the enzyme NO synthase (NOS), of which three distinct isoforms exist.4Constitutive isoforms are found in endo- thelial cells (ecNOS or type III) and neurons (nNOS, type I) and are activated by a rise in intracellular calcium, usually in response to physiological stimuli.A third isoform (iNOS, type II) is induced in several cell types by exposure to pro- inflammatory cytokines and endotoxin and its induction is blocked by glucocorticoids.All three isoforms have been detected in the human respiratory tract."Gustafsson and colleagues first showed that NO can be detected in the exhaled air of animals and normal human subjects9 and this has subsequently been confirmed in many studies.""'5Furthermore, the concentration of exhaled NO is increased in patients with inflammatory diseases of the airways such as asthma" 1216 and bronchiectasis.'7This suggests that exhaled NO may provide a non-invasive means of monitoring inflammation in the respiratory tract and the measurement of exhaled NO has attracted in- creasing interest.However, interpretation of exhaled NO measurements may be difficult and there is a wide variation in the reported levels of NO in exhaled air, suggesting that technical factors are important.How is NO in exhaled air measured?Most studies have measured NO in exhaled air by chemi- luminescence and detection depends on the photochemical reaction between NO and ozone generated in the analyser.'8 Several NO analysers are now commercially available but may need to be converted for online measurement of NO in exhaled air.Most analysers are sensitive to <1 part per billion (ppb) of NO and this is adequate for studies of exhaled air.The specificity of exhaled NO measurements by chemiluminescence has recently been confirmed using gas chromatography-mass spectrometry."5NO may be de-
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