A new and more accurate technique to characterize airway nitric oxide using different breath-hold times

2005 ◽  
Vol 98 (5) ◽  
pp. 1869-1877 ◽  
Author(s):  
Hye-Won Shin ◽  
Peter Condorelli ◽  
Steven C. George

Exhaled nitric oxide (NO) arises from both airway and alveolar regions of the lungs, which provides an opportunity to characterize region-specific inflammation. Current methodologies rely on vital capacity breathing maneuvers and controlled exhalation flow rates, which can be difficult to perform, especially for young children and individuals with compromised lung function. In addition, recent theoretical and experimental studies demonstrate that gas-phase axial diffusion of NO has a significant impact on the exhaled NO signal. We have developed a new technique to characterize airway NO, which requires a series of progressively increasing breath-hold times followed by exhalation of only the airway compartment. Using our new technique, we determined values (means ± SE) in healthy adults (20–38 yr, n = 8) for the airway diffusing capacity [4.5 ± 1.6 pl·s−1·parts per billion (ppb)−1], the airway wall concentration (1,340 ± 213 ppb), and the maximum airway wall flux (4,350 ± 811 pl/s). The new technique is simple to perform, and application of this data to simpler models with cylindrical airways and no axial diffusion yields parameters consistent with previous methods. Inclusion of axial diffusion as well as an anatomically correct trumpet-shaped airway geometry results in significant loss of NO from the airways to the alveolar region, profoundly impacting airway NO characterization. In particular, the airway wall concentration is more than an order of magnitude larger than previous estimates in healthy adults and may approach concentrations (∼5 nM) that can influence physiological processes such as smooth muscle tone in disease states such as asthma.

2006 ◽  
Vol 100 (2) ◽  
pp. 623-630 ◽  
Author(s):  
Hye-Won Shin ◽  
Peter Condorelli ◽  
Steven C. George

Exhaled nitric oxide (NO) is highly dependent on exhalation flow; thus exchange dynamics of NO have been described by multicompartment models and a series of flow-independent parameters that describe airway and alveolar exchange. Because the flow-independent NO airway parameters characterize features of the airway tissue (e.g., wall concentration), they should also be independent of the physical properties of the insufflating gas. We measured the total mass of NO exhaled ( AI,II) from the airways after five different breath-hold times (5–30 s) in healthy adults (21–38 yr, n = 9) using air and heliox as the insufflating gas, and then modeled AI,II as a function of breath-hold time to determine airway NO exchange parameters. Increasing breath-hold time results in an increase in AI,II for both air and heliox, but AI,II is reduced by a mean (SD) of 31% (SD 6) ( P < 0.04) in the presence of heliox, independent of breath-hold time. However, mean (SD) values (air, heliox) for the airway wall diffusing capacity [3.70 (SD 4.18), 3.56 pl·s−1·ppb−1 (SD 3.20)], the airway wall concentration [1,439 (SD 487), 1,503 ppb (SD 644>)], and the maximum airway wall flux [4,156 (SD 2,502), 4,412 pl/s (SD 2,906)] using a single-path trumpet-shaped airway model that considers axial diffusion were independent of the insufflating gas ( P > 0.55). We conclude that a single-path trumpet model that considers axial diffusion captures the essential features of airway wall NO exchange and confirm earlier reports that the airway wall concentration in healthy adults exceeds 1 ppm and thus approaches physiological concentrations capable of modulating smooth muscle tone.


2001 ◽  
Vol 91 (5) ◽  
pp. 2173-2181 ◽  
Author(s):  
Hye-Won Shin ◽  
Christine M. Rose-Gottron ◽  
Federico Perez ◽  
Dan M. Cooper ◽  
Archie F. Wilson ◽  
...  

Currently accepted techniques utilize the plateau concentration of nitric oxide (NO) at a constant exhalation flow rate to characterize NO exchange, which cannot sufficiently distinguish airway and alveolar sources. Using nonlinear least squares regression and a two-compartment model, we recently described a new technique (Tsoukias et al. J Appl Physiol 91: 477–487, 2001), which utilizes a preexpiratory breath hold followed by a decreasing flow rate maneuver, to estimate three flow-independent NO parameters: maximum flux of NO from the airways ( J NO,max, pl/s), diffusing capacity of NO in the airways ( D NO,air, pl · s−1 · ppb−1), and steady-state alveolar concentration (Calv,ss, ppb). In healthy adults ( n = 10), the optimal breath-hold time was 20 s, and the mean (95% intramaneuver, intrasubject, and intrapopulation confidence interval) J NO,max, D NO,air, and Calv,ss are 640 (26, 20, and 15%) pl/s, 4.2 (168, 87, and 37%) pl · s−1 · ppb−1, and 2.5 (81, 59, and 21%) ppb, respectively. J NO,maxcan be estimated with the greatest certainty, and the variability of all the parameters within the population of healthy adults is significant. There is no correlation between the flow-independent NO parameters and forced vital capacity or the ratio of forced expiratory volume in 1 s to forced vital capacity. With the use of these parameters, the two-compartment model can accurately predict experimentally measured plateau NO concentrations at a constant flow rate. We conclude that this new technique is simple to perform and can simultaneously characterize airway and alveolar NO exchange in healthy adults with the use of a single breathing maneuver.


2001 ◽  
Vol 91 (1) ◽  
pp. 477-487 ◽  
Author(s):  
Nikolaos M. Tsoukias ◽  
Hye-Won Shin ◽  
Archie F. Wilson ◽  
Steven C. George

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 (Calv,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 Calv,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.


1990 ◽  
Vol 69 (1) ◽  
pp. 222-231 ◽  
Author(s):  
C. L. Tsai ◽  
G. M. Saidel ◽  
E. R. McFadden ◽  
J. M. Fouke

The thermal profiles in the airways of healthy human volunteers and patients with asthma differ after cessation of hyperpnea. The asthmatic patients rewarm their airways more rapidly. To identify thermal properties and processes that could account for the difference between these populations, we developed a model describing the radial transport of heat and water across the trachea. A distinctive feature of the model is a variable parameter describing blood supply to the mucosal and submucosal layers. Simulations performed with the model are initiated by a breath-hold maneuver and are propagative in time. Blood perfusion rates in the airway wall, the thickness of the layer of airway surface liquid, and the mucosa-submucosa thickness, all thought to be more pronounced in asthmatic patients, were varied by changing model parameters and initial conditions. Increasing the thickness of the liquid layer by more than an order of magnitude had little effect on the temperature or water content in the airway lumen. Doubling the blood flow to the mucosa-submucosa resulted in a slight increase in airway temperature. When this effect was coupled, however, with an increase in the thickness of the mucosa-submucosa layer, the increase in temperature was more pronounced. Because the bronchial circulation is the major source of heat to the airway, these results indicate that differences in airway wall thickness coupled with differences in the magnitude or responsiveness of the bronchial microcirculation could account for the differences in intra-airway temperature between the two populations.


2004 ◽  
Vol 97 (3) ◽  
pp. 874-882 ◽  
Author(s):  
Hye-Won Shin ◽  
Peter Condorelli ◽  
Christine M. Rose-Gottron ◽  
Dan M. Cooper ◽  
Steven C. George

Exhaled nitric oxide (NO) is a potential noninvasive index of lung inflammation and is thought to arise from the alveolar and airway regions of the lungs. A two-compartment model has been used to describe NO exchange; however, the model neglects axial diffusion of NO in the gas phase, and recent theoretical studies suggest that this may introduce significant error. We used heliox (80% helium, 20% oxygen) as the insufflating gas to probe the impact of axial diffusion (molecular diffusivity of NO is increased 2.3-fold relative to air) in healthy adults (21–38 yr old, n = 9). Heliox decreased the plateau concentration of exhaled NO by 45% (exhalation flow rate of 50 ml/s). In addition, the total mass of NO exhaled in phase I and II after a 20-s breath hold was reduced by 36%. A single-path trumpet model that considers axial diffusion predicts a 50% increase in the maximum airway flux of NO and a near-zero alveolar concentration (CaNO) and source. Furthermore, when NO elimination is plotted vs. constant exhalation flow rate (range 50–500 ml/s), the slope has been previously interpreted as a nonzero CaNO (range 1–5 ppb); however, the trumpet model predicts a positive slope of 0.4–2.1 ppb despite a zero CaNO because of a diminishing impact of axial diffusion as flow rate increases. We conclude that axial diffusion leads to a significant backdiffusion of NO from the airways to the alveolar region that significantly impacts the partitioning of airway and alveolar contributions to exhaled NO.


2018 ◽  
Vol 84 (10) ◽  
pp. 23-28
Author(s):  
D. A. Golentsov ◽  
A. G. Gulin ◽  
Vladimir A. Likhter ◽  
K. E. Ulybyshev

Destruction of bodies is accompanied by formation of both large and microscopic fragments. Numerous experiments on the rupture of different samples show that those fragments carry a positive electric charge. his phenomenon is of interest from the viewpoint of its potential application to contactless diagnostics of the early stage of destruction of the elements in various technical devices. However, the lack of understanding the nature of this phenomenon restricts the possibility of its practical applications. Experimental studies were carried out using an apparatus that allowed direct measurements of the total charge of the microparticles formed upon sample rupture and determination of their size and quantity. The results of rupture tests of duralumin and electrical steel showed that the size of microparticles is several tens of microns, the particle charge per particle is on the order of 10–14 C, and their amount can be estimated as the ratio of the cross-sectional area of the sample at the point of discontinuity to the square of the microparticle size. A model of charge formation on the microparticles is developed proceeding from the experimental data and current concept of the electron gas in metals. The model makes it possible to determine the charge of the microparticle using data on the particle size and mechanical and electrical properties of the material. Model estimates of the total charge of particles show order-of-magnitude agreement with the experimental data.


1993 ◽  
Vol 264 (4) ◽  
pp. H1245-H1250 ◽  
Author(s):  
J. E. Brian ◽  
R. H. Kennedy

This study was designed to further elucidate the role of the endothelium in regulation of cerebral vascular smooth muscle tone. Dose-dependent vasoconstrictive effects of serotonin (5-HT) were examined in endothelium-intact and endothelium-denuded ring segments prepared from canine basilar and middle cerebral arteries. Some preparations were pretreated with 10(-5) M N omega-nitro-L-arginine (L-NNA), an agent that inhibits the production of L-arginine-derived nitric oxide, one of the compounds proposed to be endothelium-derived relaxing factor. L-NNA alone elicited marked dose-dependent increases in tension in endothelium-intact preparations; a significantly smaller response was seen in endothelium-denuded preparations. The effects of L-NNA on endothelium-intact preparations were partially reversed by washing and treatment with L-arginine. The maximum tension induced by 5-HT was approximately doubled by removal of the endothelium as well as by L-NNA treatment of endothelium-intact preparations; a slight increase in maximum tension occurred in endothelium-denuded preparations treated with L-NNA. The concentration of 5-HT producing half-maximal contraction (ED50) was not affected by L-NNA. These data suggest that L-arginine-derived nitric oxide modulates canine cerebral arterial tone in both the resting state and during contraction with 5-HT.


1997 ◽  
Vol 12 (11) ◽  
pp. 1967-1974 ◽  
Author(s):  
Kazuaki Kuroda ◽  
Mark A. Barton ◽  
Atsushi Onae ◽  
Yukinobu Miki

We propose the application of a new technique, the X pendulum, to determine the Newtonian gravitational constant G. We evaluate the likely experimental errors for configurations realizable with existing technologies and show that improvement of the accuracy by an order of magnitude or more is possible.


2016 ◽  
Vol 47 (5) ◽  
pp. 1348-1356 ◽  
Author(s):  
Sandrah P. Eckel ◽  
Zilu Zhang ◽  
Rima Habre ◽  
Edward B. Rappaport ◽  
William S. Linn ◽  
...  

Mechanisms for the adverse respiratory effects of traffic-related air pollution (TRAP) have yet to be established. We evaluated the acute effects of TRAP exposure on proximal and distal airway inflammation by relating indoor nitric oxide (NO), a marker of TRAP exposure in the indoor microenvironment, to airway and alveolar sources of exhaled nitric oxide (FeNO).FeNO was collected online at four flow rates in 1635 schoolchildren (aged 12–15 years) in southern California (USA) breathing NO-free air. Indoor NO was sampled hourly and linearly interpolated to the time of the FeNO test. Estimated parameters quantifying airway wall diffusivity (DawNO) and flux (J′awNO) and alveolar concentration (CANO) sources of FeNO were related to exposure using linear regression to adjust for potential confounders.We found that TRAP exposure indoors was associated with elevated alveolar NO. A 10 ppb higher indoor NO concentration at the time of the FeNO test was associated with 0.10 ppb higher average CANO (95% CI 0.04–0.16) (equivalent to a 7.1% increase from the mean), 4.0% higher J′awNO (95% CI −2.8–11.3) and 0.2% lower DawNO (95% CI −4.8–4.6).These findings are consistent with an airway response to TRAP exposure that was most marked in the distal airways.


2021 ◽  
Vol 15 (3) ◽  
pp. 1-31
Author(s):  
Haida Zhang ◽  
Zengfeng Huang ◽  
Xuemin Lin ◽  
Zhe Lin ◽  
Wenjie Zhang ◽  
...  

Driven by many real applications, we study the problem of seeded graph matching. Given two graphs and , and a small set of pre-matched node pairs where and , the problem is to identify a matching between and growing from , such that each pair in the matching corresponds to the same underlying entity. Recent studies on efficient and effective seeded graph matching have drawn a great deal of attention and many popular methods are largely based on exploring the similarity between local structures to identify matching pairs. While these recent techniques work provably well on random graphs, their accuracy is low over many real networks. In this work, we propose to utilize higher-order neighboring information to improve the matching accuracy and efficiency. As a result, a new framework of seeded graph matching is proposed, which employs Personalized PageRank (PPR) to quantify the matching score of each node pair. To further boost the matching accuracy, we propose a novel postponing strategy, which postpones the selection of pairs that have competitors with similar matching scores. We show that the postpone strategy indeed significantly improves the matching accuracy. To improve the scalability of matching large graphs, we also propose efficient approximation techniques based on algorithms for computing PPR heavy hitters. Our comprehensive experimental studies on large-scale real datasets demonstrate that, compared with state-of-the-art approaches, our framework not only increases the precision and recall both by a significant margin but also achieves speed-up up to more than one order of magnitude.


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