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Physiological variables also affect the results. Exhaled NO levels have been shown to be<br />

higher in males than females, are reduced with cunent Smoking, recent ingestion <strong>of</strong> water'<br />

alcohol or caffeine and increased with accidental gut contamination or after nitrogen-<br />

compound rich meals. Levels <strong>of</strong> NO also increase with age throughout childhood' but not<br />

adulthood, possibly in relation to pneumatisation <strong>of</strong> the sinuses. Relationships with height,<br />

weight, surface area, menstrual cycle in non-asthmatic women' or a circadian rhythm has not<br />

been demonstrated. However, there remains only one range <strong>of</strong> 'normal' values given for oral<br />

or nasal NO.<br />

By far the most work in exhaled and nasal NO has been undertaken in atopic and/or asthmatic<br />

subjects with comparison to healthy controls. NO appears to correlate well with the<br />

inflammatory cells, lung function and bronchial hyper-responsiveness in steroid naive<br />

asthmatics and less well in those on IHCS or oral steroids. It does not correlate well with<br />

.severity, <strong>of</strong> asthma as the NO result here is attenuated by treatment, and it is the requirement<br />

for the higher levels <strong>of</strong> treatment with possible breakthrough symptoms that determine the<br />

severity category in asthma guidelines(Anonymous 1997 GINA 20O2; GINA 2005; SIGN<br />

2005). <strong>The</strong>re is the potential for No measurements to contribute to diagnosis, management<br />

when measured longitudinally in individuals (on any medication), and to wafii <strong>of</strong> loss <strong>of</strong><br />

Control. NO measurement can also be used as an outcome measure for ant-inflammatory<br />

agents used in asthma treatment. However there are some cautions to be made. Firstly, it does<br />

not appear useful to guide acute asthma treatment. Secondly, measurement <strong>of</strong> sputum<br />

eosinophils appear as, or more, accurate than NO itself, and the changes in the eosinophil<br />

counts may be a more accurate predictor <strong>of</strong> loss <strong>of</strong> control and a better target to tailor<br />

treatment. It is increasingly apparent that, like most parameters we measure' it is likely to be<br />

the pattern from a number <strong>of</strong> investigations along with an individual's history that best<br />

describes their clinical disease rather than a single marker' <strong>The</strong> effect <strong>of</strong> atopy alone on<br />

exhaled NO levels needs to be kept in mind with overlapping results between asthmatic and<br />

atopic subjects. Unfortunately, smoking renders the test inaccurate and unhelpful' In addition'<br />

the presence <strong>of</strong> high NO levels may be a marker for respiratory diseases that are steroid<br />

sensitive no matter what the underlying disease is labelled.<br />

In exercise, NO drops during single breath measurements, but the NO output is increased<br />

when taking into account the increased rate <strong>of</strong> breathing. An inability to increase the NO<br />

output during exercise was associated with more severe cardiac disease and, in elite athletes'<br />

worse performance suggesting that the increased NO output may depend on the ability to<br />

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