ABSTRACT
In 1987 it was first determined that nitric oxide (NO) was the previously uncharacterized endothelium-derived relaxing factor (1,2). In the next 13 years it was established that nitric oxide can be produced enzymatically in mammalian tissues and that the NO so formed is a multifunctional biological mediator with many roles in a wide range of physiological systems. Specifically, it is now known that NO is an integral part of nonspecific host defense systems, participates in neurodevelopment and neurotransmission, and regulates various autonomical functions including vascular and bronchial tone and gastrointestinal peristalsis. NO may also both propagate and attenuate systemic inflammatory processes. Using chemiluminescence, Gustafson and colleagues first demonstrated in 1991 that NO could be detected in the exhaled gas of animals and humans (3). Since that time many investigative groups have confirmed this observation and documented that the level of NO in the exhaled gas (FENO) is influenced by various disease states, experimental manipulations, and measurement techniques. Indeed, the lit-
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erature relating to exhaled NO in human disease appears to be increasing exponentially. However, there is still considerable uncertainty as to the precise sources of the NO which is recovered in the expirate. In the sections which follow, we review the enzymatic formation of NO, summarize the available data to indicate which of these enzymes contributes NO to the expirate, and then discuss the cellular and anatomic compartments from which the NO so formed contributes to the fraction of expired nitric oxide (FENO).
