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technique will have excluded most contamination, and that in any case the degfee<br />

contamination will have been identical because <strong>of</strong> the very careful standardisation<br />

experimental conditions including expiratory mouth pressure. This study was not designed to<br />

differentiate nasal and bronchial sources <strong>of</strong> NO.<br />

I elected to analyse the peak NO rather than the area under the curve. <strong>The</strong> two appear to be<br />

closely correlated (Kharitonov, Yates et al. tgg4; Byrnes, Bush et al. 1996) and had good<br />

correlation coefficients greater than 0.8 for both techniques in this study. I aimed to determine<br />

the sources <strong>of</strong> the two gases, not the total amounts produced, which we would expect to be<br />

independent <strong>of</strong> the experimental conditions. Thus the different behaviour <strong>of</strong> the peak signals<br />

as the experimental conditions change gives more useful information than the area under the<br />

curve.<br />

It might be argued that if airways <strong>of</strong> volume 200mls contribute a peak NO at 85 ppb, a total <strong>of</strong><br />

10-10 mols, and the alveolar expirate (four litres) a plateau <strong>of</strong> 60, a total <strong>of</strong> 10-8 mols, then<br />

most NO comes from the alveoli. This assumes that subjects exhaled to residual volume,<br />

which is not the case. Furthermore, if this model was correct, peak COz (definitely alveolar)<br />

and peak NO should move in the same direction as experimental conditions vary. <strong>The</strong> reverse<br />

was seen. In eight subjects peak No fell using the t-piece while coz rosei in the other four<br />

peak NO fell and peak CO2 also decreased. It is impossible to account for this on a model <strong>of</strong><br />

major alveolar production <strong>of</strong> NO. <strong>The</strong> model that best accounts for our data is continuous<br />

airway production <strong>of</strong> No, diluted variably in a flow-dependent manner by No free (or low<br />

concentration NO) alveolar gas, analogous with a gaseous phase dye dilution method. This<br />

data cannot exclude that alveolar gas contains small amounts <strong>of</strong> NO.<br />

This study also demonstrated that the conditions <strong>of</strong> measurement critically affect No levels<br />

obtained. Thus both the time to reach the No peak and the peak level <strong>of</strong> No reached were<br />

quite different in the two methods used in this study although the patterns <strong>of</strong> the traces were<br />

similar. I considered whether the difference in results could have been artifactual due to minor<br />

differences in the apparatus used in the two techniques. Teflon tubing which does not absorb<br />

NO connected the mouth piece to the NO analyzer.In the t-piece system there was a two and<br />

a half centimetre extension <strong>of</strong> plastic tubing leading from the mouth piece to the actual t-piece<br />

with the teflon tubing then leading to the NO analyzer <strong>of</strong>f one arm and further tubing <strong>of</strong>f the<br />

second arm passing directly to the pneumotachograph for flow analysis. This is unlikely to<br />

account for the magnitude <strong>of</strong> differences obtained. <strong>The</strong> other alteration was that moving from<br />

151<br />

<strong>of</strong><br />

<strong>of</strong>

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