Variability in uptake efficiency for pulsed versus constant concentration delivery of inhaled nitric oxide

BACKGROUND: Nitric oxide (NO) is currently administered using devices that maintain constant inspired NO concentrations. Alternatively, devices that deliver a pulse of NO during the early phase of inspiration may have use in optimizing NO dosing efficiency and in extending application of NO to long-term use by ambulatory, spontaneously breathing patients. The extent to which the amount of NO delivered for a given pulse sequence determines alveolar concentrations and uptake, and the extent to which this relationship varies with breathing pattern, physiological, and pathophysiological parameters, warrants investigation. METHODS: A mathematical model was used to analyze inhaled nitric oxide (NO) transport through the conducting airways, and to predict uptake from the alveolar region of the lung. Pulsed delivery was compared with delivery of a constant concentration of NO in the inhaled gas. RESULTS: Pulsed delivery was predicted to offer significant improvement in uptake efficiency compared with constant concentration delivery. Uptake from the alveolar region depended on pulse timing, tidal volume, respiratory rate, lung and dead space volume, and the diffusing capacity of the lung for NO (D(L)NO). It was predicted that variation in uptake efficiency with breathing pattern can be limited using a pulse time of less than 100 ms, with a delay of less than 50 ms between the onset of inhalation and pulse delivery. Nonlinear variation in uptake efficiency with D(L)NO was predicted, with uptake efficiency falling off sharply as D(L)NO decreased below ~50-60 ml/min/mm Hg. Gas mixing in the conducting airways played an important role in determining uptake, such that consideration of bulk convection alone would lead to errors in assessing efficiency of pulsed delivery systems. CONCLUSIONS: Pulsed NO delivery improves uptake efficiency compared with constant concentration delivery. Optimization of pulse timing is critical in limiting intra- and inter-subject variability in dosing

Controlled, parametric, individualized, 2D and 3D imaging measurements of aerosol deposition in the respiratory tract of healthy human volunteers: in vivo data analysis

Background: To provide a validation dataset for aerosol deposition modeling, a clinical trial was performed in which the inhalation parameters and the inhaled aerosol were controlled or characterized.Methods: Eleven, healthy, never-smokers, male participants completed the study. Each participant performed two inhalations of 99mTc-labeled aerosol from a vibrating mesh nebulizer, which differed by a single controlled parameter (aerosol particle size: “small” or “large”; inhalation: “deep” or “shallow”; carrier gas: air or a helium–oxygen mix). The deposition measurements were made by planar imaging, and single photon emission computed tomography–computed tomography (SPECT-CT).Results: The difference between the mean activity measured by two-dimensional imaging and that delivered from the nebulizer was 2.7%, which was not statistically significant. The total activity deposited was significantly lower in the left lung than in the right lung (p&lt;0.0001) with a mean ratio (left/right) of 0.87±0.1 standard deviation (SD). However, when normalized to lung air volume, the left lung deposition was significantly higher (p=0.0085) with a mean ratio of 1.08±0.12 SD. A comparison of the three-dimensional central-to-peripheral (nC/P3D) ratio showed that it was significantly higher for the left lung (p&lt;0.0001) with a mean ratio (left/right) of 1.36±0.20 SD. The effect of particle size was statistically significant on the nC/P3D ratio (p=0.0014), extrathoracic deposition (p=0.0037), and 24-hr clearance (p&lt;0.0001), contrary to the inhalation parameters, which showed no effect.Conclusions: This article presents the results of an analysis of the in vivo deposition data, obtained in a clinical study designed to provide data for model validation. This study has demonstrated the value of SPECT imaging over planar, the influence of particle size on regional distribution within the lung, and differences in deposition between the left and right lungs.<br/

Determination of regional lung air volume distribution at mid-tidal breathing from computed tomography: A retrospective study of normal variability and reproducibility

© 2014 Fleming et al.; licensee BioMed Central Ltd. Background: Determination of regional lung air volume has several clinical applications. This study investigates the use of mid-tidal breathing CT scans to provide regional lung volume data.Methods: Low resolution CT scans of the thorax were obtained during tidal breathing in 11 healthy control male subjects, each on two separate occasions. A 3D map of air volume was derived, and total lung volume calculated. The regional distribution of air volume from centre to periphery of the lung was analysed using a radial transform and also using one dimensional profiles in three orthogonal directions.Results: The total air volumes for the right and left lungs were 1035 +/- 280 ml and 864 +/- 315 ml, respectively (mean and SD). The corresponding fractional air volume concentrations (FAVC) were 0.680 +/- 0.044 and 0.658 +/- 0.062. All differences between the right and left lung were highly significant (p < 0.0001). The coefficients of variation of repeated measurement of right and left lung air volumes and FAVC were 6.5% and 6.9% and 2.5% and 3.6%, respectively. FAVC correlated significantly with lung space volume (r = 0.78) (p < 0.005). FAVC increased from the centre towards the periphery of the lung. Central to peripheral ratios were significantly higher for the right (0.100 +/- 0.007 SD) than the left (0.089 +/- 0.013 SD) (p < 0.0001).Conclusion: A technique for measuring the distribution of air volume in the lung at mid-tidal breathing is described. Mean values and reproducibility are described for healthy male control subjects. Fractional air volume concentration is shown to increase with lung size.Air Liquid

Laryngeal two-phase flow in realistic breathing conditions

International audienceLiquid aerosols are efficient vectors for drug delivery in upper and lower respiratory tract. Characteristics of inhaled particles, flow properties, and airway morphology represent the main influential factors of the transport mechanisms. Numerous works have been carried out to characterize the airflow behaviour during human breathing [Baier, 1977; Brancatisano, 1983], and to determine the trajectories of inhaled particles through the extrathoracic region. Recent studies [Brouns, 2007] have shown the relevance of the laryngeal geometry and, more precisely, the impact of glottal aperture on fluid dynamics and aerosol deposition mechanics. In this study we focus on two main objectives: i) determine the glottal dynamics during two breathing conditions (eupnea and tachypnea); ii) predict the influence of both carrier gas and aerosols' properties on the unsteady laryngeal flow and the aerosol deposition, using CFD simulations in a simplified 3D glottis model during these two breathing conditions

Glottal motion and its impact on the respiratory flow

National audienceThe aim of this study was (i) to characterise the glottal dynamics during human breathing in vivo using laryngofiberscopy and synchronised airflow recordings and (ii) to quantify the effects of a mobile glottis and unsteady flow conditions on laryngeal jet-flow dynamics using CFD modelling. The in vivo study showed that the glottis can be extremely variable during breathing and hence influence airflow characteristics. A glottal area widening was quantified during inspiration, with a typical ratio of 3:1 as compared to expiration. Airflow rate variations differ from harmonic signal during eupnea as well as tachypnea. The correlation between flow-rate and glottal area will be discussed and compared to previous clinical investigations. Preliminary 2D CFD simulations of the glottal jet were carried out based on the measured flow-rate and glottal changes during eupnea. Impact of unsteady flow conditions on the jet development is demonstrated

Glottal dynamics and laryngeal airflow during human breathing

Voiced sounds production is a result of complex interactions between fluid flow and mechanical behavior of laryngeal tissues. Therefore, during the last decades, numerous experimental, theoretical and computational works have been performed to characterize both aerodynamics of glottal airflow and vocal folds vibrations during human phonation. Yet, the majority of these works have focused on the specificities of glottal self-sustained oscillations once installed, and main physical models of laryngeal source are initialized in a prephonatory position close to glottal adduction. The transient dynamics from respiratory phase to phonatory phase is still poorly understood. This is partly due to the lack of investigations of glottal motion during human breathing. Therefore, the objective of the present study is to characterize the glottis dynamics in the context of respiratory biomechanics and to quantify its impact on fluid/structure interactions within the larynx. This work will rely on an original numerical flow modeling in upper airways, accounting for the glottal geometry observed during a respiratory cycle and corresponding to realistic inspiratory and expiratory flow rates. The proposed methodology combines an in-vivo exploratory approach based on medical imaging with a numerical approach. At first, an idealized volume geometry of the upper airways is reconstructed using anatomical data extracted from CT-SCAN images acquired in glottal static conditions. Then, the physiological correlates of a complete respiratory cycle are observed by means of video recording of laryngofibroscopic examination and synchronized oral airflow measurements. Glottal dynamics can then be deduced from an image processing analysis and used for the elaboration of a parametrical mechanical model of the glottal aperture. Finally, numerical flow simulations are realized in the complete geometry, using measured oral airflows and glottal geometries during inspiration and expiration. Simulated aerodynamics of the glottal jet are studied and compared in stationary and physiological instationary flow conditions, for both motionless and realistic glottal configuration

The effect of disease and respiration on airway shape in patients with moderate persistent asthma

Computational models of gas transport and aerosol deposition frequently utilize idealized models of bronchial tree structure, where airways are considered a network of bifurcating cylinders. However, changes in the shape of the lung during respiration affect the geometry of the airways, especially in disease conditions. In this study, the internal airway geometry was examined, concentrating on comparisons between mean lung volume (MLV) and total lung capacity (TLC). A set of High Resolution CT images were acquired during breath hold on a group of moderate persistent asthmatics at MLV and TLC after challenge with a broncho-constrictor (methacholine) and the airway trees were segmented and measured. The airway hydraulic diameter (Dh) was calculated through the use of average lumen area (Ai) and average internal perimeter (Pi) at both lung volumes and was found to be systematically higher at TLC by 13.5±9% on average, with the lower lobes displaying higher percent change in comparison to the lower lobes. The average internal diameter (Din) was evaluated to be 12.4±6.8% (MLV) and 10.8±6.3% (TLC) lower than the Dh, for all the examined bronchi, a result displaying statistical significance. Finally, the airway distensibility per bronchial segment and per generation was calculated to have an average value of 0.45±0.28, exhibiting high variability both between and within lung regions and generations. Mixed constriction/dilation patterns were recorded between the lung volumes, where a number of airways either failed to dilate or even constricted when observed at TLC. We conclude that the Dh is higher than Din, a fact that may have considerable effects on bronchial resistance or airway loss at proximal regions. Differences in caliber changes between lung regions are indicative of asthma-expression variability in the lung. However, airway distensibility at generation 3 seems to predict distensibility more distally

The Creation and Statistical Evaluation of a Deterministic Model of the Human Bronchial Tree from HRCT Images - Fig 7

<p>a) The average, major and minor child branching angle for our model (blue) and the model of Tawhai et al. <b>[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168026#pone.0168026.ref031" target="_blank">31</a>]</b> (red) and Bordas et al. <b>[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168026#pone.0168026.ref032" target="_blank">32</a>]</b> (green). The error bars are standard deviations. b) The statistical distribution of the branching angle in our model.</p

The frequency distribution of the planar rotation angle in our model.

<p>The frequency distribution of the planar rotation angle in our model.</p