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Measurement of Exhaled Nitric Oxide in the Diagnosis and Management of Asthma and Other Respiratory disorders

Posted Jan 28 2010 11:13pm


Clinical Background

The National Heart, Lung, and Blood Institute, in its clinical guidelines regarding the management of asthma, offers the following definition of asthma: (2)

"Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular: mast cells, eosinophils, T lymphocytes, macrophages, neutrophils and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial hyper responsiveness to a variety of stimuli."

Guidelines for the management of persistent asthma stress the importance of long-term suppression of inflammation using steroids, leukotriene inhibitors, or other anti-inflammatory drugs. Existing techniques for monitoring the status of underlying inflammation have focused on bronchoscopy, with lavage and biopsy, or analysis by induced sputum. Given the cumbersome nature of these techniques, the ongoing assessment of asthma focuses not on the status of the underlying chronic inflammation, but rather on regular assessments of respiratory parameters such as FEV-1 and peak flow. Therefore, there has been interest in noninvasive techniques to assess the underlying pathogenic chronic inflammation as reflected by measurements of inflammatory mediators. Two new strategies have been investigated, the measurement of exhaled nitric oxide and the evaluation of exhaled breath condensate.  Nitric oxide (NO) is an important endogenous messenger that is widespread in the human body, functioning for example, to regulate peripheral blood flow, platelet function, immune reactions, and neurotransmission, and also to mediate inflammation. In biologic tissues, nitric oxide is unstable, limiting measurement. However, in the gas phase nitric oxide is fairly stable, permitting its measurement in exhaled air.  While nitric oxide is a volatile mediator that can be measured in exhaled air, most inflammatory mediators are not volatile and thus cannot be detected in the gas phase. Exhaled breath condensate (EBC) consists of exhaled air passed through a condensing or cooling apparatus, resulting in an accumulation of fluid. Although EBC is primarily derived from water vapor, it also contains aerosol particles or respiratory fluid droplets, which in turn contain various nonvolatile inflammatory mediators, such as cytokines, leukotrienes, oxidants, antioxidants, and various other markers of oxidative stress. The pH of EBC can also be measured. Various studies have focused on different components of EBC as inflammatory markers in respiratory disease. 



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