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experienced staff to undertake the procedure, and laboratory staff to process samples within a
short time frame. It also represents a significant time commitment - even in the most
experienced hands and a sample taken in the shortest time, the minimum time to from start to
getting a result for one sample is estimated to be 100 minutes (Holz, Kips et al. 2000). Both
blood and urine sampling have been found to be less useful, probably because the site of
measurement is distant from the site of interest, the lung. In addition, apart from obtaining
urine samples, the other sampling procedures all require a hospital or clinical setting.
These studies started to come about at the same time as my own research commenced. In view
of all these difficulties a simpler, direct, non-invasive technique for measuring airway
inflammation was sought, that could be achieved easily by children, and could be repeated
regularly with time. Because measurement of lung function is a common procedure in
children and does not involve collecting specimens and there is no anaesthesia or needles, the
result is instant -
a test analogous to this would seem ideal.
In 1987 came the announcement that a gaseous molecule, NO, was responsible for acting as
both a widespread physiological mediator and was also involved in host defense (Hibbs,
Taintor et al. 1987; Ignarro, Buga et al. 1987 Khan and Furchgott 1987). This resulted in an
explosion of research in the early 1990s identifying both NO and the enzymes that produced it
- the nitric oxide synthases (NOS) in all biological systems. NO was shown to play a major
role in host defense and inflammation within the lung as in other systems. Toward the end of
1995,I also went to a one day seminar on NO at the Royal Society of Medicine in I-ondon to
hear Professor Salvador Moncada, one of the major early researchers into NO in the
cardiovascular system, talk. I was struck by the importance of this one tiny molecule, and the
unfolding story with more to come. This seemed like a great opportunity to further explore the
possibility of NO as a potential marker for airway inflammation; however there were a
number of hurdles to overcome. Measuring NO was going to be difficult given its gaseous,
short lived and highly reactive nature. As well there was the difficulty of measuring levels in
exhaled air from human subjects, especially in children.
This research was conducted at the Royal Brompton Hospital in London from the mid 1990s.
On returning to New Zealand, it was acceptable to submit this research over time as a thesis.
Some of the findings within this thesis are now well-known, but were unknown, new and
exciting when first demonstrated. The findings contributed to the knowledge as to what
technical aspects were important in the measurement of NO, to the standardising of protocols
for measurement, and to what were important capabilities to be developed for the newer NO
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