Physiology of exhaled nitric oxide

Nitric oxide in exhaled air denotes the ongoing enzymatic production of this "simple" but essential mediator molecule in the respiratory system where it exerts important physiological functions. To appreciate the value of exhaled nitric oxide measurements one must comprehend that nitric oxide in exhaled air does not represent a waste product from systemic sources passively excreted by the blood. Nitric oxide production in the respiratory system is a necessity at birth and continuous throughout life. In fact, post mortem during circulatory arrest in experimental animals airway levels of exhaled nitric oxide increases provided that ventilation of the lungs are maintained. Experimental studies of exhaled nitric oxide show that the enzymatic production of nitric oxide in the lung is a constant process that endure many investigational provocations. However, there are a few intriguing physiological and pathophysiological conditions, pharmacological treatments and other experimental manoeuvres (e.g. stretch, carbon dioxide, inflammation, catecholamines) that per se alter (increase or decrease) the levels of exhaled nitric oxide. These biological observations and clinical findings becomes even more intriguing considering the fact that for some of these alterations in respiratory NO production we do not know if they are beneficial or detrimental. The standard method for measurements of exhaled nitric oxide is based on the highly specific and sensitive chemiluminescence technique and was first described in 1991. However, the method is not without pitfalls and precaution must be taken when interpreting exhaled nitric oxide data. Particular attention should be paid to physiological factors that are known to confound exhaled nitric oxide measurements and consequently predispose for erroneous conclusions. Thus, in this chapter we summarize the fundamental findings of exhaled nitric oxide measurements and give the reader a basic survey of the physiological regulation of exhaled nitric oxide.