An official JRS statement: The principles of fractional exhaled nitric oxide (FeNO) measurement and interpretation of the results in clinical practice

Abstract

Nitric oxide (NO) is produced in the body and has been shown to have diverse actions in the abundance of research that has been performed on it since the 1970s, leading to Furchgott, Murad, and Ignarro receiving the Nobel Prize in Physiology or Medicine in 1998. NO is produced by nitric oxide synthase (NOS). NOS is broadly distributed, being found in the nerves, blood vessels, airway epithelium, and inflammatory cells. In asthma, inflammatory cytokines induce NOS activity in the airway epithelium and inflammatory cells, producing large amounts of NO. Measurement of fractional exhaled nitric oxide (FeNO) is a simple, safe, and quantitative method of assessing airway inflammation. The FeNO measurement method has been standardized and, in recent years, this noninvasive test has been broadly used to support the diagnosis of asthma, monitor airway inflammation, and detect asthma overlap in chronic obstructive pulmonary disease (COPD) patients. Since the normal upper limit of FeNO for healthy Japanese adults is 37ppb, values of 35ppb or more are likely to be interpreted as a signature of inflammatory condition presenting features with asthma, and this value is used in clinical practice. Research is also underway for clinical application of these measurements in other respiratory diseases such as COPD and interstitial lung disease. Currently, there remains some confusion regarding the significance of these measurements and the interpretation of the results. This statement is designed to provide a simple explanation including the principles of FeNO measurements, the measurement methods, and the interpretation of the measurement results.