A single-breath technique with variable flow rate to characterize nitric oxide exchange dynamics in the lungs

Abstract

Current techniques to estimate nitric oxide (NO) production and elimination in the lungs are inherently nonspecific or are cumbersome to perform (multiple-breathing maneuvers). We present a new technique capable of estimating key flow-independent parameters characteristic of NO exchange in the lungs: 1) the steady-state alveolar concentration (C(alv,ss)), 2) the maximum flux of NO from the airways (J(NO,max)), and 3) the diffusing capacity of NO in the airways (D(NO,air)). Importantly, the parameters were estimated from a single experimental single-exhalation maneuver that consisted of a preexpiratory breath hold, followed by an exhalation in which the flow rate progressively decreased. The mean values for J(NO,max), D(NO,air), and C(alv,ss) do not depend on breath-hold time and range from 280-600 pl/s, 3.7-7.1 pl. s(-1). parts per billion (ppb)(-1), and 0.73-2.2 ppb, respectively, in two healthy human subjects. A priori estimates of the parameter confidence intervals demonstrate that a breath hold no longer than 20 s may be adequate and that J(NO,max) can be estimated with the smallest uncertainty and D(NO,air) with the largest, which is consistent with theoretical predictions. We conclude that our new technique can be used to characterize flow-independent NO exchange parameters from a single experimental single-exhalation breathing maneuver.

Probing the impact of axial diffusion on nitric oxide exchange dynamics with heliox

“…The first maneuver was three repetitions of a single-breath maneuver that included a preexpiratory 20-s breath hold followed by a decreasing flow rate (from ϳ6 to ϳ1% of vital capacity per second) (29) to measure C NOpeak, W50, VI,II, and AI,II, and to estimate several flow-independent NO-exchange parameters. A positive pressure of Ͼ5 cmH 2O was maintained to prevent nasal contamination during the breath hold (1).…”

“…A Starling resistor (Hans Rudolph, Kansas City, MO) with a variable resistance was used to progressively decrease the flow rate during the exhalation. A schematic of the experimental apparatus has been previously presented (29). The second maneuver was a vital capacity maneuver performed in triplicate to collect plateau NO concentration on the basis of the American Thoracic Society guidelines (1) in which the exhalation flow rate was maintained at a target of 50 ml/s.…”

“…Experimental single-exhalation profiles with preexpiratory breath hold were characterized empirically by C NOpeak, W50, total VI,II, defined as the minimum point (zero slope or dCENO/dV ϭ 0) in the exhalation profile (29), and AI,II (Fig. 1).…”

“…A detailed description of the mathematical algorithm to calculate the parameters has been previously described (29).…”

“…The characteristics of NO gas exchange are unique compared with other endogenous gases because exhaled NO is thought to have a significant alveolar and airway source (6,8,15,22). A two-compartment model is commonly used to characterize NO exchange dynamics for healthy and diseased lungs (9,11,13,20,21,23,24,27,29), by partitioning exhaled NO into airway and alveolar contributions using three flow-independent NO exchange parameters: maximum flux of NO from the airways (JЈaw NO ), the diffusing capacity of NO in the airways (Daw NO ), and the steady-state alveolar concentration (CA NO ). However, the two-compartment model considers only convection of NO in the airways as a transport mechanism and has neglected axial diffusion of NO in the gas phase to preserve mathematical simplicity.…”