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the direct to the indirect method led to an increase in flow rate from 440mUmin to 665<br />

mUmin. This may have been enough to account for the different results.<br />

Clearly, at the time <strong>of</strong> this research, there were major and unexplained differences between<br />

results from different investigators as documented in Table 6.1. <strong>The</strong>se results showed that the<br />

levels <strong>of</strong> NO measured in exhalate were critically dependent on measurement conditions. This<br />

may be related to expired flow rates but other factors may be important. It has been suggested<br />

that orally-exhaled NO concentrations correlate with the inhaled ambient concentrations <strong>of</strong><br />

NO @otsch, Demirakca et al. 1996), although we found in a subsequent experiment a high<br />

ambient NO rendered exhaled NO levels difficult to interpret @yrnes, Dinarevic et al. 1997).<br />

Our current study was only undertaken if the ambient NO levels were low -<br />

while we aimed<br />

for less than l0ppb, on one occasion by the end <strong>of</strong> the session the ambient NO had drifted up<br />

to llppb hence the range given from l-llppb in the results. As mentioned the greater NO<br />

levels and wider variations seen in females may be due to possible effects <strong>of</strong> the menstrual<br />

cycle (Kharitonov, Iogan-Sinclair et al. 1994) and this was not controlled for in the present<br />

study. However, as the measurements were done sequentially on each subject on the same<br />

day, conclusions as to the origin <strong>of</strong> NO from this study should not be affected.<br />

As increasing research on NO in exhaled air was being undertaken in subjects in health and<br />

different respiratory and vascular diseases at the time, it was increasingly important to<br />

understand where and at what level NO was being generated so that abnormal results could be<br />

properly interpreted.<br />

NB: <strong>The</strong> results <strong>of</strong> this researchformed the basis <strong>of</strong> the following publications:<br />

. Byrnes CA, Dinareyic S, Bzsst CA, Bush A, Shinebournes EA. Is nitric oxide produced at<br />

airway or alveolar level? European Respiratory Joumal 1997 10 (5) 1021-1025<br />

. Byrnes CA, Bush A and Shineboume EA "Methods to Measure Expiratory Nitric Oxide in<br />

People" in "A Volume <strong>of</strong> Methods in Enrymology" edited by Lcster Packeter Academic<br />

Press Inc. 1996.<br />

t52

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