A Model of Heterogeneous Ventilation and Nitric Oxide Production in the Lungs
Background: Asthma is a pulmonary disorder characterized by chronic airway inflammation and airflow obstruction that is widespread, but variable in space and time. Although airflow obstruction is routinely monitored with spirometry, assessing inflammation in a non-invasive manner is more difficult. The concentration of nitric oxide (NO) is elevated in the exhaled breath of asthmatics, and has tremendous potential to be a non-invasive marker of inflammation.
NO exchange in the lungs exhibits two distinguishing features that need to be considered for a proper interpretation of the exhaled NO signal. First, exhaled NO is produced in both the airway and alveolar regions of the lung and second, exhaled NO is highly dependent on the exhalation flow. While asthma has always been considered to be a disease of the proximal airways, new evidence indicates significant inflammation in the alveolar regions of the lung as well. In addition, other studies have demonstrated ventilation defects or heterogeneity in the proximal and distal airways. Therefore, a new model of nitric oxide exchange is needed that accounts for heterogeneity in ventilation and NO production. Technology: The invention describes a new mathematical model of nitric oxide exchange within the lungs which accounts for heterogeneous ventilation and production of nitric oxide spatially. The model is able to more accurately simulate the exhaled nitric oxide (eNO) concentration profiles in subjects with asthma, and may be more accurate at simulating profiles in other lung diseases.
Prior art techniques have all assumed nitric oxide exchange to be homogeneous spatially by using a single path "trumpet" model. New experimental evidence suggests that ventilation and NO production is spatially heterogeneous, and the new model suggests this could significantly impact our interpretation of the eNO signal. Application: Asthma is a chronic inflammatory disease of the airways in the lungs affecting more than 18 million people in the U.S. Controlling inflammation is the central focus for managing the underlying disease of asthma and regular use of anti-inflammatory medications is now the mainstay for treatment of symptoms.
Nitric oxide has been shown to be a marker for inflammation and provides a means for monitoring the patient's response to anti-inflammatory therapy. Clinical research strongly suggests that monitoring exhaled NO on a regular basis could significantly improve disease management.
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