Nitric oxide and asthma: a review

Nitric oxide (NO) is synthesized from the amino acid arginine by enzymes called nitric oxide synthases. NO has an important physiologic role in the regulation of vascular tone, response to vascular injury, and hemostasis. It also acts as a neurotransmitter for the nonadrenergic noncholinergic nerves and has important antimicrobial, immunologic, and proinflammatory activities. The lung is rich in nitric oxide synthases, and NO is normally present in the exhaled air. Use of NO in the treatment of asthma has not withstood the test of time and is not recommended. With the advent of analyzers capable of measuring NO rapidly and reliably, however, the analysis of NO in exhaled air is being increasingly recognized as a potential noninvasive test for the evaluation of the inflammatory component of the pathology of patients with asthma. An increase in the exhaled NO has been shown to accompany eosinophic inflammation and to correlate with other indices of inflammation in asthma. Exhaled NO increases during exacerbation and decreases with recovery in patients with asthma. As exhaled NO is not increased during bronchospasm in the absence of coexisting inflammation, it could serve to differentiate between the inflammatory and bronchospastic components in asthma, thereby guiding therapy with steroids and other anti-inflammatory medications. Levels of NO also can be increased in certain other conditions, for example, allergic rhinitis and adult respiratory distress syndrome, but these can be clinically differentiated from asthma and do not lessen the diagnostic value of exhaled NO. Measurements of exhaled NO are influenced by several physiologic and technical variables, which results in a wide variation in the levels reported from the different laboratories. Standardization of technique, a better understanding of the confounding effects of physiologic and environmental variables, and establishment of the normal range and variability of exhaled NO are needed before its measurement could gain wide acceptance as a clinically useful test. Development of less expensive NO analyzers is also an important consideration.