NITRIC OXIDE AND ASTHMA

Abstract

The free radical NO· is known to be an important mediator in many biologic systems. In the lung, it functions as a signal transducing agent regulating critical functions (such as airway tone and vascular permeability) and aiding in host defense. The increased level of expired NO·in asthmatic subjects reflects an increase in the lung production of NO, although the exact cell of origin of the expired NO is yet to be determined. In the asthmatic subject, the significantly increased levels of NO recovered in the expirate may reflect the homeostatic role of this molecule; however, direct administration of NO in humans has shown limited therapeutic potential in asthma. Not all functions of NO· are salutary; the higher concentration of NO· in the asthmatic airway may increase the accumulation of toxic intermediates, which potentiate the ongoing inflammation. As we improve our understanding of the role of NO in the asthmatic airway and how it interacts with other airway cytokines we may gain insight as to how new therapies such as NOS inhibitors may reduce airway inflammation. Determination of expired NO concentrations in asthmatic subjects reveals a reduction of expired NO and a concomitant improvement in airway obstruction soon after the initiation of corticosteroid therapy. Measurements of exhaled NO· may parallel lower airway inflammation and provide clinicians with a noninvasive measure of pulmonary inflammation, thereby improving our ability to care for patients with asthma.