View - ResearchSpace@Auckland - The University of Auckland

Drazen et al. 1994), and the reactions can form potentially carcinogenic nitrosamines such a
NzOg and NzO+ (Miwa, Stuehr et al. 1987).
6.3 The need for methodological experiments
In a key development, NO was then detected in exhaled air (Gustafsson, Irone et al. 1991;
Archer 1993;[rone, Gustafsson et al. 1994). In 1991 Gustafsson and I-eone first showed that
NO could be detected in the exhaled air of tracheostomized animals and normal humans
(Gustafsson, Irone et al. 1991). Exhaled No was then measured in single and tidal breathing
in eight adult subjects giving levels between 8.3 to 20.3ppb (Borland, Cox et al' 1993)'
Exhaled NO was measured at a mean peak of 3.25ppb in ten subjects with normal breathing,
increasing to 100.25ppb with a sixty second breath hold prior to exhalation, and decreasing to
4.?5ppb with hyperventilation. During exercise, the mean peak levels in five subjects dropped
from gppb to 5-6ppb with 50 and 100 watt exercise on an ergometer cycle, although the total
NO excretion (NO concentration times number of breaths) increased (Persson, Wiklund et al'
1993). It was shown to be increased in normal subjects during a time of upper respiratory tract
infection to a mean peak of 315ppb during symptoms and reducing to a mean peak of 87ppb
three weeks later during recovery (Kharitonov, Yates et al. 1995). NO was shown in three
studies at this time to be lower in chronic smokers, with Persson et al measuring a mean in
mixed exhaled air of 3.9ppb in 6 smokers compared to their 20 normal subjects at 8.4 ppb
(persson, Zetterstrom et al. 1994). Kharitonov et al reporting a lower mean peak of 42ppb in
4l smokers compared to 88ppb in 73 nonsmokers in single exhalations (Kharitonov, Robbins
et al. 1995). Schilling et al documenting a mean of l6ppb in 12 smoking females versus
2lppb in 2l non-smoking females, and a mean of 15ppb in 24 smoking males versus l9ppb in
24 non-smoking males by using a reservoir method to collect tidal breathing (Schilling'
Holzer et al. 1994). In this paper Schilling et al also demonstrated a reduction of exhaled NO
in ten hypertensive patients to a mean of 13.7ppb (Schilling, Holzer et al. 1994). One study
reported varying levels of exhaled NO throughout the menstrual cycle in seven women from a
peak exhaled No at 150ppb midcycle to a low of 59ppb during menstruation (Kharitonov'
logan-Sinclair et al. L994). As by far the greatest amounts of NO in vitro were shown to be
produced from iNOS stimulation, (Nathan 1992; Barnes and Belvisi 1993), it had been
hypothesised to be a measure of airway inflammation (Barnes t993; Barnes and Kharitonov
1996). This seemed to be confirmed when higher levels were found in animal asthma models
when an exacerbation was induced (Persson and Gustafsson 1993; Endo, Uchido et al. 1995)'
and then in adult asthmatic subjects compared to normal subjects in a number of early studies'
Initially Kharitinov et al found levels of 283ppb compared to controls at 80.2ppb, Persson et
r25