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pressure over the likely range encountered (such as the lower three pressure settings that I<br />

tested) has no relevant effects on the measurements in most individuals. Conespondingly<br />

there was no difference in NO, CO2, flow or duration <strong>of</strong> exhalation across these readings.<br />

However as two, possibly three, individuals did show an effect, this again suggested the need<br />

also to standardise mouth pressure for exhaled NO measurements.<br />

<strong>The</strong> background NO concentration is variable and occasionally can be extremely high. In<br />

many <strong>of</strong> the published studies, the ambient NO level at the time <strong>of</strong> testing was not stated and I<br />

felt this may be another reason for error in the results obtained between and within groups.<br />

This could occur particularly if testing was done on different days pre and post an intervention<br />

with a subject group when the background levels may differ over time. In three subjects, I<br />

showed that there were large differences in the mean exhaled NO concentration obtained<br />

depending on the concentration <strong>of</strong> the NO being inhaled. In this experiment, the exhaled NO<br />

measured was higher when inhaling low reservoir NO than when inhaling high ambient<br />

levels. Three studies documented inhalation from NO-free air (Alving, Weitzberg et al. 1993;<br />

Schilling, Holzer et al. 1994; Steerenberg, Nierkens et al. 2000) with one having noted that<br />

the ambient air contained high and variable amounts <strong>of</strong> NO concentration (6-192ppb) leading<br />

them to prepare and recommend an NO free reservoir for inhalation (Schilling, Holzer et al.<br />

L994). Another study mentioned that the ambient NO air was recorded and the absolute zero<br />

was adjusted just before each measurement by flushing the NO analyser with NO free<br />

certified air (Kharitonov, Logan-sinclair et al. L994). A number <strong>of</strong> studies recorded levels <strong>of</strong><br />

ambient air at 0-20ppb (Persson, Wiklund et al. 1993), 5-20ppb (Kharitonov, Yates et al.<br />

Lgg6), 0-38ppb (Kharitonov, Yates et al. 1994; Jilma, Kastner et al. 1996; Kimberly,<br />

Nejadnik et al. 1996) and 0-68ppb (Kharitonov, Robbins et al. 1995) but did not seem to<br />

affect the readings and therefore were not taken into account. One goup had specifically<br />

requested two volunteers to inhale an NO concentration <strong>of</strong> 800ppb, hold their breath for<br />

fifteen seconds and then exhale into the NO analyser. As they documented no change in the<br />

NO concentration before and after inhalation, they concluded that the inspired NO must<br />

disappear from the respiratory tract within that time (Kharitonov, Yates et al. 1994).<br />

While the effect <strong>of</strong> ambient NO was either not specifically tested or was not published at this<br />

time by any <strong>of</strong> these other groups, some researchers did investigate whether inhalation via the<br />

nose or the mouth made a difference to the exhaled NO levels measured. This was an area <strong>of</strong><br />

variability, now known to be the degree <strong>of</strong> contamination <strong>of</strong> exhaled NO by nasal and sinus<br />

production. <strong>The</strong> measured NO levels have been found to be greatest in the paranasal sinuses<br />

(Lundberg, Farkas-Szallasi et al. 1995) with an age-dependent increase in keeping with sinus<br />

174

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