Modeling pulmonary nitric oxide exchange

Abstract

Nitric oxide (NO) was first detected in the exhaled breath more than a decade ago and has since been investigated as a noninvasive means of assessing lung inflammation. Exhaled NO arises from the airway and alveolar compartments, and new analytical methods have been developed to characterize these sources. A simple two-compartment model can adequately represent many of the observed experimental observations of exhaled concentration, including the marked dependence on exhalation flow rate. The model characterizes NO exchange by using three flow-independent exchange parameters. Two of the parameters describe the airway compartment (airway NO diffusing capacity and either the maximum airway wall NO flux or the airway wall NO concentration), and the third parameter describes the alveolar region (steady-state alveolar NO concentration). A potential advantage of the two-compartment model is the ability to partition exhaled NO into an airway and alveolar source and thus improve the specificity of detecting altered NO exchange dynamics that differentially impact these regions of the lungs. Several analytical techniques have been developed to estimate the flow-independent parameters in both health and disease. Future studies will focus on improving our fundamental understanding of NO exchange dynamics, the analytical techniques used to characterize NO exchange dynamics, as well as the physiological interpretation and the clinical relevance of the flow-independent parameters.

Nitric oxide and cardiopulmonary hemodynamics in Tibetan highlanders

“…The lower the exhalation flow rate, the longer the time that the gases passing over the airway wall will be infused with NO from the airway wall; hence, the exhaled NO will be higher. Similar to previous studies (16,25), the low flow of 17 ml/s is the most sensitive here, inasmuch as it reveals that Tibetans have slightly less exhaled NO than controls at sea level. [Analyses performed with the 50 ml/s flow rate revealed similar, significant correlations (data not shown).]…”

“…Possible explanations for the low NO concentration among the high-altitude Tibetans include downregulation of synthesis, higher consumption, or faster rate of transfer from the airway wall. The transfer rate of 0.07 nl⅐s Ϫ1 ⅐ mmHg Ϫ1 is 7-10 times higher than the range of 0.004 -0.013 nl⅐s Ϫ1 ⅐mmHg Ϫ1 reported for sea-level samples, including our sea-level control (16). According to Fick's law, transfer (diffusion) is directly proportional to the PNO difference between the airway wall and lumen and to the area over which diffusion takes place.…”

“…The fraction of NO in exhaled breath was measured using an online method in parts per billion with an NO analyzer (Sievers NOA 280i, Ionics Instruments, Boulder, CO) that has a sensitivity of Ͻ1 ppb and uses a chemiluminescent technique. Nasal NO contamination was minimized by a standardized procedure in which the subject exhales against an expiratory resistance (10 -20 cmH 2O), which causes velum closure (3,16) and generates a plateau level of NO. The exhaled NO reported is the average of three exhalations at a given flow rate.…”

Exhaled NO: Determinants and Clinical Application in Children With Allergic Airway Disease

“…27 Mathematical models of varying complexity have been developed to describe the production and dynamics of NO in the lower respiratory tract. [66][67][68] During exhalation, air passing through the lower respiratory tract is enriched with NO from the bronchial walls. Since the conventional 50 mL/s flow rate is relatively slow, FeNO at 50 mL/s (FeNO50) predominantly reflects NO from the proximal airway.…”

Airway and alveolar nitric oxide production, lung function, and pulmonary blood flow in sickle cell disease

“…In individuals with SCD, F eNO has been previously measured at a single fixed exhalation flow of 50 ml/s (11,13) but measurements at multiple exhalation flows allow partitioning into flow-independent airway and alveolar components (18,19). Using such a technique, SCD children were found to have an elevated airway nitric NO flux, but the alveolar NO concentration did not differ significantly from that found in healthy controls (14).…”