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included the expanding knowledge and measurement <strong>of</strong> airway pollution and the connection<br />

between higher or longer duration <strong>of</strong> daily exposure and increased cardiovascular and<br />

respiratory mortality and morbidity. Through the 1990s increasing effort was made to clarify<br />

the effects <strong>of</strong> the different pollutant components. Particulate matter, especially respirable<br />

particles at less than l0 microns in diameter, and ozone have been consistently associated<br />

with excess disease and mortality. However the nitrogen oxides have also had associations<br />

with increased respiratory disease (bronchitis, COPD, pneumonia and asthma) and for more<br />

episodes <strong>of</strong> wheeze with increased symptoms and lower lung function in adults and children<br />

with asthma.<br />

<strong>The</strong> second area led from the startling discovery <strong>of</strong> the gas NO as a ubiquitous, biological<br />

messenger acting as a physiological mediator, a neurotransmitter and a mechanism <strong>of</strong> host<br />

defence. Since this was realised, research into NO in every biological system flourished.<br />

However there were a number <strong>of</strong> hurdles to overcome in measuring this molecule. Measuring<br />

NO was going to be difficult given its gaseous, short lived and highly reactive nature, and<br />

there were also the difficulties <strong>of</strong> measuring levels in exhaled air from human subjects.<br />

In 1992 NO was named Science Magazine's "Molecule <strong>of</strong> the Year". In 1998 Robert F.<br />

Furchgott, Louis J. Ignano and Ferid Murad were winners <strong>of</strong> the 1998 Nobel prize in<br />

Medicine for their research in identifying firstly EDRF, and then renaming and identifying<br />

NO as the mediator in vascular epithelium.<br />

<strong>The</strong> following chapter will discuss the synthesis and control <strong>of</strong> NO production in detail, the<br />

interactions <strong>of</strong> NO with other chemical and biological compounds, and the synthesis and<br />

control <strong>of</strong> the nitric oxide synthase enzymes that produce it. This knowledge is preparatory to<br />

discussing how to measure No concentrations in the respiratory system.<br />

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