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INNOVATIVE METHODOLOGY

A simple technique to characterize proximal and peripheral nitric oxide exchange using constant flow exhalations and an axial diffusion model

¹Department of Biomedical Engineering, ²Department of Chemical Engineering and Materials Science, ³Department of Medicine, Division of Pulmonary and Critical Care, University of California, Irvine, Irvine, California; and ⁴Drexel University, Philadelphia, Pennsylvania

Submitted 11 May 2006 ; accepted in final form 26 July 2006

The most common technique employed to describe pulmonary gas exchange of nitric oxide (NO) combines multiple constant flow exhalations with a two-compartment model (2CM) that neglects 1) the trumpet shape (increasing surface area per unit volume) of the airway tree and 2) gas phase axial diffusion of NO. However, recent evidence suggests that these features of the lungs are important determinants of NO exchange. The goal of this study is to present an algorithm that characterizes NO exchange using multiple constant flow exhalations and a model that considers the trumpet shape of the airway tree and axial diffusion (model TMAD). Solution of the diffusion equation for the TMAD for exhalation flows >100 ml/s can be reduced to the same linear relationship between the NO elimination rate and the flow; however, the interpretation of the slope and the intercept depend on the model. We tested the TMAD in healthy subjects (n = 8) using commonly used and easily performed exhalation flows (100, 150, 200, and 250 ml/s). Compared with the 2CM, estimates (mean ± SD) from the TMAD for the maximum airway flux are statistically higher (J'aw_NO = 770 ± 470 compared with 440 ± 270 pl/s), whereas estimates for the steady-state alveolar concentration are statistically lower (CA_NO = 0.66 ± 0.98 compared with 1.2 ± 0.80 parts/billion). Furthermore, CA_NO from the TMAD is not different from zero. We conclude that proximal (airways) NO production is larger than previously predicted with the 2CM and that peripheral (respiratory bronchioles and alveoli) NO is near zero in healthy subjects.

model; airway; alveolar

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