In this proposal we respond to the PHS 2005-2 Omnibus Solicitation's call for the development of diagnostic tools for "non-invasive methodologies for measuring airways inflammation in asthma." We propose to develop, test and evaluate a low cost, portable analyzer for the measurement of nitric oxide (NO) in human breath as an indicator of airway inflammation, especially for the diagnosis and treatment of asthma. A method for NO measurement in exhaled breath recently was approved by the U.S. Food and Drug Administration and its equivalent in the European Union for the purpose of diagnosing, monitoring and treating patients with asthma and other airway diseases. The instrumental approach (NIOX(r) of Aerocrine AB) makes use of the highly sensitive technique of NO + O3 chemiluminescence, but that method is too complicated and expensive for use in the home. In preliminary results, we have demonstrated the use of a much simpler technique that uses the NO + O3 reaction in a different way. Instead of measuring chemiluminescence, the loss of O3 is measured by UV absorption at 254 nm using a low pressure mercury lamp. This approach, which recently has been successfully marketed in for atmospheric measurements, gives adequate precision (q2 ppbv) and accuracy (q2%) for breath analysis. In addition to being small, light weight and having low power requirements, this new approach eliminates the need for gas standards contained in high pressure gas cylinders. The simplified "stopped flow" design proposed here eliminates the possibility of interference from major components in breath such as water vapor and carbon dioxide. Because of their slow reaction, VOCs such as isoprene also are not expected to interfere. In Phase I we will develop and test a prototype instrument that will be used in a clinical intercomparison with the FDA-approved NIOX apparatus for establishment of equivalency during Phase II. RELEVANCE TO PUBLIC HEALTH The objective of this work is to develop a low cost, accurate and reliable instrument for use in the home that can be used for optimizing the use of therapeutic drugs in the management of asthma
