Effect of heterogeneous ventilation and nitric oxide production on exhaled nitric oxide profiles

• Published in: Journal of applied physiology (1985) 2008-06, Vol.104 (6), p.1743-1752
• Main Authors: Suresh, Vinod, Shelley, David A, Shin, Hye-Won, George, Steven C
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Agonists - therapeutic use; Adult; Airway management; Asthma; Asthma, Exercise-Induced - drug therapy; Asthma, Exercise-Induced - metabolism; Asthma, Exercise-Induced - physiopathology; Biological and medical sciences; Breath Tests; Bronchoconstriction; Computer Simulation; Effects; Exercise; Exhalation; Fundamental and applied biological sciences. Psychology; Humans; Lungs; Mathematical models; Models, Anatomic; Models, Biological; Nitric oxide; Nitric Oxide - metabolism; Pulmonary Ventilation; Up-Regulation
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.01355.2007

1 Department of Biomedical Engineering and 2 Department of Chemical Engineering and Materials Science, University of California, Irvine, Irvine, California Submitted 20 December 2007 ; accepted in final form 10 March 2008 Elevated exhaled nitric oxide (NO) in the breath of asthmatic subjects is thought to be a noninvasive marker of lung inflammation. Asthma is also characterized by heterogeneous bronchoconstriction and inflammation, which impact the spatial distribution of ventilation in the lungs. Since exhaled NO arises from both airway and alveolar regions, and its level in exhaled breath depends strongly on flow, spatial heterogeneity in flow patterns and NO production may significantly affect the exhaled NO signal. To investigate the effect of these factors on exhaled NO profiles, we developed a multicompartment mathematical model of NO exchange using a trumpet-shaped central airway segment that bifurcates into two similarly shaped peripheral airway segments, each of which empties into an alveolar compartment. Heterogeneity in flow alone has only a minimal impact on the exhaled NO profile. In contrast, placing 70% of the total airway NO production in the central compartment or the distal poorly ventilated compartment can significantly increase (35%) or decrease (–10%) the plateau concentration, respectively. Reduced ventilation of the peripheral and acinar regions of the lungs with concomitant elevated NO production delays the rise of NO during exhalation, resulting in a positive phase III slope and reduced plateau concentration (–11%). These features compare favorably with experimentally observed profiles in exercise-induced asthma and cannot be simulated with single-path models. We conclude that variability in ventilation and NO production in asthmatic subjects impacts the shape of the exhaled NO profile and thus impacts the physiological interpretation. asthma; inflammation; model; multicompartment Address for reprint requests and other correspondence: S. C. George, Dept. of Biomedical Engineering, 3120 Natural Sciences II, Univ. of California, Irvine, Irvine, CA 92697-2715 (e-mail: scgeorge{at}uci.edu )