The influence of flowrate and gas density on positive airway pressure for high flow nasal cannula applied to infant airway replicas.

High flow nasal cannula (HFNC) therapy has been previously shown to produce positive upper airway pressures in adult and child patients. This work aimed to evaluate and quantify the effects of HFNC flowrate and gas type on airway pressures measured in vitro in infant airway replicas. Ten realistic infant airway replicas, extending from nares to trachea, were connected in turn to a lung simulator and were supplied gas flows through HFNC.

Dose variability of supplemental oxygen therapy with open patient interfaces based on in vitro measurements using a physiologically realistic upper airway model.

Background: Supplemental oxygen therapy is widely used in hospitals and in the home for chronic care. However, there are several fundamental problems with the application of this therapy such that patients are often exposed to arterial oxygen concentrations outside of the intended target range. This paper reports volume-averaged tracheal oxygen concentration measurements (FtO2) from in vitro experiments conducted using a physiologically realistic upper airway model.

In Vitro-In Silico Comparison of Pulsed Oxygen Delivery From Portable Oxygen Concentrators Versus Continuous Flow Oxygen Delivery.

Background: Portable oxygen concentrators (POCs) deliver oxygen in intermittent pulses. The challenge of establishing equivalence between continuous flow oxygen and nominal pulse flow settings on different POCs is well known. In vitro bench measurements and in silico mathematical modeling were used to compare the performance of 4 POCs versus continuous flow oxygen by predicting the F at the trachea and entering the acini.

Correlation of high flow nasal cannula outlet area with gas clearance and pressure in adult upper airway replicas.

Background: Primary benefits of high flow nasal cannula therapy include washout of carbon dioxide rich exhaled gas and increased airway pressures during tidal breathing. This work reports on the influence of high flow nasal cannula outlet area on upper airways gas clearance and tracheal pressures using measurements in five realistic adult nose-throat airway replicas.

Methods: Two commercial high flow nasal cannulas and one generic nasal cannula of varying size were compared.

Comparison of pulsed versus continuous oxygen delivery using realistic adult nasal airway replicas.

Background: Portable oxygen concentrators (POCs) typically include pulse flow (PF) modes to conserve oxygen. The primary aims of this study were to develop a predictive in vitro model for inhaled oxygen delivery using a set of realistic airway replicas, and to compare PF for a commercial POC with steady flow (SF) from a compressed oxygen cylinder.

Methods: Experiments were carried out using a stationary compressed oxygen cylinder, a POC, and 15 adult nasal airway replicas based on airway geometries derived from medical images.

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).

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

A quantitative description of the morphology of lung structure is essential prior to any form of predictive modeling of ventilation or aerosol deposition implemented within the lung. The human lung is a very complex organ, with airway structures that span two orders of magnitude and having a multitude of interfaces between air, tissue and blood. As such, current medical imaging protocols cannot provide medical practitioners and researchers with in-vivo knowledge of deeper lung structures.

Gas transport during and preclinical testing of inert gas therapies.

New gas therapies using inert gases such as xenon and argon are being studied, which require and preclinical experiments. Examples of the kinetics of gas transport during such experiments are analyzed in this paper. Using analytical and numerical models, we analyze an experiment for gas transport to a 96 cell well plate and an delivery to a small animal chamber, where the key processes considered are the wash-in of test gas into an apparatus dead volume, the diffusion of test gas through the liquid media in a well of a cell test plate, and the pharmacokinetics in a rat.

An in silico analysis of oxygen uptake of a mild COPD patient during rest and exercise using a portable oxygen concentrator.

Oxygen treatment based on intermittent-flow devices with pulse delivery modes available from portable oxygen concentrators (POCs) depends on the characteristics of the delivered pulse such as volume, pulse width (the time of the pulse to be delivered), and pulse delay (the time for the pulse to be initiated from the start of inhalation) as well as a patient's breathing characteristics, disease state, and respiratory morphology. This article presents a physiological-based analysis of the performance, in terms of blood oxygenation, of a commercial POC at different settings using an in silico model of a COPD patient at rest and during exercise. The analysis encompasses experimental measurements of pulse volume, width, and time delay of the POC at three different settings and two breathing rates related to rest and exercise.

Modelling levels of nitrous oxide exposure for healthcare professionals during EMONO usage.

Background: Computational fluid dynamics (CFD) has been used to compute nitrous oxide (N2O) levels within a room during the administration of an equimolar mix of N2O/oxygen (EMONO) in the clinical setting. This study modelled realistic scenarios of EMONO usage in hospital or primary care, in order to estimate the potential N2O exposure of healthcare professionals (HCP) with routine EMONO use and to provide guidance for EMONO users.

Methods: Sixteen scenarios were defined by carrying out a survey of practitioners.

Realistic glottal motion and airflow rate during human breathing.

The glottal geometry is a key factor in the aerosol delivery efficiency for treatment of lung diseases. However, while glottal vibrations were extensively studied during human phonation, the realistic glottal motion during breathing is poorly understood. Therefore, most current studies assume an idealized steady glottis in the context of respiratory dynamics, and thus neglect the flow unsteadiness related to this motion.

Pharmacokinetic analysis of the chronic administration of the inert gases Xe and Ar using a physiological based model.

Background: New gas therapies using inert gases such as xenon and argon are being studied, which would require chronically administered repeating doses. The pharmacokinetics of this type of administration has not been addressed in the literature.

Methods: A physiologically based pharmacokinetics (PBPK) model for humans, pigs, mice, and rats has been developed to investigate the unique aspects of the chronic administration of inert gas therapies.

Controlled, Parametric, Individualized, 2-D and 3-D Imaging Measurements of Aerosol Deposition in the Respiratory Tract of Asthmatic Human Subjects for Model Validation.

Background: Computer modeling is used to predict inhaled aerosol deposition in the lung based on definition of the aerosol characteristics and the breathing pattern and airway anatomy of the subject. Validation of the models is limited by the lack of detailed experimental data. Three-dimensional imaging provides an opportunity to address this unmet need.

Phase-contrast helium-3 MRI of aerosol deposition in human airways.

One of the key challenges in the study of health-related aerosols is predicting and monitoring sites of particle deposition in the respiratory tract. The potential health risks of ambient exposure to environmental or workplace aerosols and the beneficial effects of medical aerosols are strongly influenced by the site of aerosol deposition along the respiratory tract. Nuclear medicine is the only current modality that combines quantification and regional localization of aerosol deposition, and this technique remains limited by its spatial and temporal resolutions and by patient exposure to radiation.

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

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.

Inhalation pressure distributions for medical gas mixtures calculated in an infant airway morphology model.

A numerical pressure loss model previously used for adult human airways has been modified to simulate the inhalation pressure distribution in a healthy 9-month-old infant lung morphology model. Pressure distributions are calculated for air as well as helium and xenon mixtures with oxygen to investigate the effects of gas density and viscosity variations for this age group. The results indicate that there are significant pressure losses in infant extrathoracic airways due to inertial effects leading to much higher pressures to drive nominal flows in the infant airway model than for an adult airway model.

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.

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 (99m)Tc-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).

Frictional resistance sheds light on the multicomponent nature of nasal obstruction: a combined in vivo and computational fluid dynamics study.

Exploring nasal flow contributes to better understanding of pathophysiological functions of nasal cavities. We combined the rhinomanometry measurements of 11 patients and computational fluid dynamics (CFD) simulations in 3 nasal airway models to dissect the complex mechanisms that determine nasal flow obstruction: spatial complexity and pressure-dependent deformability of nasal airways. We quantified spatial complexity by calculating longitudinal variations of hydraulic diameter, perimeter and area of nasal cavities, and their impact on flow characteristics by examining the longitudinal variations of the kinetic energy coefficient and the kinetic to potential energy ratio.

Airway morphology from high resolution computed tomography in healthy subjects and patients with moderate persistent asthma.

Models of the human respiratory tract developed in the past were based on measurements made on human tracheobronchial airways of healthy subjects. With the exception of a few morphometric characteristics such as the bronchial wall thickness (WT), very little has been published concerning the effects of disease on the tree structure and geometrical features. In this study, a commercial software package was used to segment the airway tree of seven healthy and six moderately persistent asthmatic patients from high resolution computed tomography images.

A technique for determination of lung outline and regional lung air volume distribution from computed tomography.

Background: Determination of the lung outline and regional lung air volume is of value in analysis of three-dimensional (3D) distribution of aerosol deposition from radionuclide imaging. This study describes a technique for using computed tomography (CT) scans for this purpose.

Methods: Low-resolution CT scans of the thorax were obtained during tidal breathing in 11 healthy control male subjects on two occasions.

Methods for evaluation of helium/oxygen delivery through non-rebreather facemasks.

Background: Inhalation of low-density helium/oxygen mixtures has been used both to lower the airway resistance and work of breathing of patients with obstructive lung disease and to transport pharmaceutical aerosols to obstructed lung regions. However, recent clinical investigations have highlighted the potential for entrainment of room air to dilute helium/oxygen mixtures delivered through non-rebreather facemasks, thereby increasing the density of the inhaled gas mixture and limiting intended therapeutic effects. This article describes the development of benchtop methods using face models for evaluating delivery of helium/oxygen mixtures through facemasks.

Bench experiments comparing simulated inspiratory effort when breathing helium-oxygen mixtures to that during positive pressure support with air.

Background: Inhalation of helium-oxygen (He/O2) mixtures has been explored as a means to lower the work of breathing of patients with obstructive lung disease. Non-invasive ventilation (NIV) with positive pressure support is also used for this purpose. The bench experiments presented herein were conducted in order to compare simulated patient inspiratory effort breathing He/O2 with that breathing medical air, with or without pressure support, across a range of adult, obstructive disease patterns.

Bench and mathematical modeling of the effects of breathing a helium/oxygen mixture on expiratory time constants in the presence of heterogeneous airway obstructions.

Background: Expiratory time constants are used to quantify emptying of the lung as a whole, and emptying of individual lung compartments. Breathing low-density helium/oxygen mixtures may modify regional time constants so as to redistribute ventilation, potentially reducing gas trapping and hyperinflation for patients with obstructive lung disease. In the present work, bench and mathematical models of the lung were used to study the influence of heterogeneous patterns of obstruction on compartmental and whole-lung time constants.