Recent studies have shown that the mixed expired air from asthmatics contains elevated levels of nitric oxide (NO) compared to that recovered from nonasthmatic individuals. These and other observations have led to the hypothesis that NO produced enzymatically by the airway may serve as an indicator of the inflammatory microenvironment of the airway. To better answer this question, a new type of exhaled breath analyzer is needed. Currently available NO analyzers cannot adequately resolve the temporal profile of NO concentration vs expired volume over the course of a single expiration. Physical Sciences Inc. (PSI) proposes to develop and demonstrate a tunable MWIR laser sensor for the rapid, non-invasive measurement of NO and other selected breath species in human breath. The laser source will be built around a type of room-temperature, tunable MWIR semiconductor lasers. In Phase I we will combine the new source with existing ultrasensitive detection technology to demonstrate high speed, in situ measurements of ppb levels of NO in human breath. We will also show the feasibility of incorporating simultaneous dynamic measurements of breath CO2. The goal is to develop an instrument that can yield such measurements at equal to or greater than 10 Hz sampling rates in sample volumes equal to or less than 25 ml. In Phase II, a prototype instrument will be delivered to a leading asthma research group for clinical studies. The study objective will be to non- invasively determine the extent to which the increased NO levels observed in samples of mixed expired air of patients with asthma are due to increased NO in the deadspace fraction versus alveolar fraction of the lung. If the level of NO in the deadspace fraction can be shown to correlate with asthma status, then the basis for an unambiguous, "non-invasive" method of measuring airway inflammation will be established. PROPOSED COMMERCIAL APPLICATIONS: A "non-invasive" and unambiguous method for measuring airway inflammation would be of great value in asthma clinics all over the country. The proposed sensor is also likely to prove useful for assessments of oxidative stress in human subjects.