上气道及部分支气管生物力学模型的数值研究

目的建立上气道、气管及部分支气管的生物力学模型,研究不同呼吸模式对气道内气流特性以及气道阻力的影响。方法根据CT扫描资料,建立包括鼻腔、口腔、咽、喉、气管和部分支气管在内的具有真实解剖结构形态的三维有限元呼吸道模型,针对现实中几种典型情况,数值模拟流经鼻、口的气流不同比例情况下气道内的气流特性。结果当仅有少量气流经由口腔吸入时,呼吸道内气流的分布规律以及各部位气道阻力的大小与完全经由鼻腔呼吸的情况相似。当口腔吸入或呼出大量气体,气流主要经由口腔与外界进行交换时,呼吸道内气流场、压力场和剪应力场分布规律明显不同,主要区别体现在鼻腔、口腔气道内。结论建立上气道与气管、支气管生物力学模型,可以从整体上了解呼吸过程中整个上气道至部分支气管中气流的分布情况,为了解与上气道结构相关疾病的发病机制建立数值研究平台。     

呼吸道内颗粒物沉积的数值模拟

目的通过数值模拟方法研究人呼吸过程中吸入的颗粒物在呼吸道内的沉积规律及其影响因素。方法建立正常人呼吸道三维数值模型,模拟吸气过程中气流在呼吸道内的分布规律。在鼻孔或口等气流入口处释放颗粒,模拟悬浮颗粒物随着吸入气流在呼吸道内的沉积过程。同时改变颗粒物直径、密度、呼吸气流速率等参数,通过对比分析,研究颗粒物在呼吸道内沉积的影响因素。结果颗粒物在呼吸道内主要沉积在鼻阈、固有鼻腔气道中部、鼻咽部以及支气管内壁,并且颗粒物的沉积率随着其直径、密度、呼吸气流速率的增大而增加,几个参数对沉积率的影响程度也不相同。结论颗粒物在呼吸道内主要沉积在气道几何形状复杂或者气道走向剧烈改变的位置,颗粒物的直径、密度、呼吸气流速率均会影响到其在呼吸道内的沉积率。研究结果可为空气污染引发呼吸道疾病风险的临床评估提供数值依据。     

OSAHS患者自然睡眠期呼吸模式对上气道流场的影响

目的分析阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea hypopnea syndrome,OSAHS)患者自然睡眠时平静呼吸和呼吸暂停期不同压力边界条件和呼吸模式对气道内气体的流动和生理状态的影响。方法创建OSAHS患者仰卧位自然睡眠状态,并采集CT数据建立三维上气道有限元模型。临床测量患者睡眠期喉腔压力作为边界条件,考虑鼻吸鼻呼、鼻吸口呼、口吸鼻呼、口吸口呼4种典型呼吸模式进行流体力学仿真。结果睡眠期OSAHS患者的呼吸气流呈非稳定、有涡、双向流动,压力边界以及呼吸模式对气体流动的影响明显。用口呼吸与用鼻呼吸相比,气体的最大流速有所升高,压降主要集中在口腔,吸气时升高约30%,呼气时升高1倍。结论采用OSAHS患者自然睡眠期CT数据建模并以临床喉腔压力作为边界条件进行有限元仿真具有意义,研究结果有助于了解OSAHS患者真实自然睡眠状态下的上气道流场特性。     

Comparison of different techniques to measure air leaks during CPAP treatment in neonates

Continuous positive airway pressure (CPAP) is routinely used for respiratory support in neonates. Air leaks are not uncommon and can hinder treatment. This study compared leak flow data obtained using different leak definitions through modeling and in vitro measurements.MethodsUsing a computer simulation of an ideal CPAP system, the relationship between leak flow and three leak definitions was investigated. The leak flow was based on the measured inspiratory, expiratory and averaged breathing flow as commonly used in neonates. The theoretical results were compared with in vitro measurements using a commercial CPAP device for neonates (Leoni, Heinen &; Löwenstein, Germany). Spontaneous breathing was simulated using a mechanical lung model, and defined air leaks were simulated using open silicone tubes of different lengths.ResultsComputer simulations showed that leak calculations were affected by leak flow and breathing pattern, and that the relationships were mostly non-linear. There were large differences in the results between the three leak definitions. The in vitro measurements correlated strongly with the theoretical modeling results. The derived numerical volume correction reduced the leak-dependent volume error in the mean (S.D.) to ?1.6 (4.6)%.ConclusionIt is difficult to compare different measuring conditions and different CPAP devices due to the variation in results depending on the leak definition and the breathing pattern. Leak flow displays would provide superior air leak monitoring.     

典型男性OSAHS患者上气道气流运动特性的数值模拟

目的 研究典型男性阻塞性睡眠呼吸暂停低通气综合症（OSAHS）患者在平静呼吸时上气道气流运动特性,以及气流对软腭和悬雍垂作用的动力特点。方法 基于患者CT影像数据建立可靠的上气道流场几何模型,以临床睡眠监测数据作为数值模拟边界条件的依据,采用低雷诺数的湍流模型计算获得一个完整呼吸周期内上气道气流运动规律。结果OSAHS患者在呼吸过程中,上气道气流流动形式有显著差异。在吸气阶段,上气道腔内流速可达9.808 m/s,最大负压可达-78.856 Pa,鼻腔顶部出现局部回流,软腭受到的最大气流压力为-10.884 Pa,悬雍垂受到的最大气流压力为-51.946 Pa,气流对软腭和悬雍垂造成的最大剪切应力分别为78和311 mPa。在呼气阶段,上气道腔内最大流速为10.330 m/s,最大负压为-51.921 Pa,口咽部和鼻腔顶部均出现局部回流,且口咽部顺时针回流现象显著,软腭受到的最大气流压力为2.603 Pa,悬雍垂受到的最大气流压力为-18.222 Pa,软腭和悬雍垂受到的最大剪切应力分别为51和508 mPa。结论 口咽部是易塌陷的部位,一个呼吸循环过程的数值模拟可以捕捉到上气道流场显著的回流特征,上气道回流直接影响软腭和悬雍垂所受的力,同时也关系到患者呼吸的流畅程度。     

Forced perturbation of respiratory system

An experiment is described in which a small pressure perturbation of short duration is applied to the airways at the mouth during resting breathing. The pressure perturbation and the resulting flow response are utilized to compute three respiratory coefficients (resistance, compliance, and inertance) in line with the conventional one-degree-of-freedom theory. Traditionally, these respiratory coefficients are used in diagnosis of airway and lung disease. We present a simplified procedure requiring a small apparatus and causing very little disturbance to normal breathing. The key point is that the pressure pulse is so small that the flow response is linearly related to it. The advantage of the apparatus is its simplicity. The meaning of the coefficients can only be examined with a continuum mechanics analysis of the respiratory system.     

Time-frequency analysis of breathing signals: in vitro airway model.

Sound signals of respiratory airflow represent summations of acoustic waves of various frequencies, which basically depend on the characteristics of the flow and on those of the surrounding tissue. This study was designed to examine the capability of time-frequency distribution (TFD) of respiratory signals in order to differentiate between unobstructed and obstructed upper airways. In order to investigate the TFD characteristics of defined upper airway geometry we conducted a controlled basic study in a laboratory system with an in vitro isolated airway model, which was either unobstructed or had concentric obstructions of various degrees at different locations along the tube. Pressure fluctuations were acquired with a microphone proximal to the airway opening. A short-term Fourier transform was used to study the TFDs of these signals. The results of the in vitro study showed that the energy of the higher frequencies increased for relatively small incremental changes in: i) reduction of the lumen cross-section, ii) decrease of distance from measurement site to obstruction, and iii) increase of breathing effort. Further development of this method may lead to noninvasive clinical techniques for early diagnosis of upper airway obstructions.     

阻塞性睡眠呼吸暂停低通气综合征患者上气道流体动力学模型的建立

 背景：对阻塞性睡眠呼吸暂停低通气综合征患者上呼吸道内气体流动情况进行分析有助于进一步了解上呼吸道解剖结构与功能间的相互关系,从而认识阻塞性睡眠呼吸暂停低通气综合征的发病机制。 目的：建立阻塞性睡眠呼吸暂停低通气综合征患者上气道三维形态及流体动力学模型,为研究阻塞性睡眠呼吸暂停低通气综合征患者上气道气流动力学特征,探讨其发病机制奠定基础。 方法：对1名男性中度阻塞性睡眠呼吸暂停低通气综合征患者的上气道行CT扫描,将以DICOM格式存储的扫描数据导入Mimics 10.01软件中进行处理,得到上气道三维模型。通过ANSYS ICEM CFD14.0对三维模型进行网格划分后,用 ANSYS 14.0-Fluid Dynamics对上呼吸道内部流场进行数值模拟,获得上气道气流场相关信息。 结果与结论：建立了完整的上气道三维形态及流体动力学模型,共得到上气道网格数为1 751 940个单元,节点数为303 981个节点,上呼吸道内最大流速为11.087 m/s位于咽腔狭窄区域腭咽下界处。上气道流体动力学模型符合人体的生物力学特点,为以后进一步研究阻塞性睡眠呼吸暂停低通气综合征患者上呼吸道气流动力学特征奠定了基础。     

Bellows-less lung system for the human patient simulator

A new bellows-less lung simulator utilising a fixed-volume pressure controller to simulate spontaneous breathing is presented as an alternative to the traditional bellows-driven mechanical lung system in the human patient simulator (HPS). The HPS is a fully interactive, life-like simulator used to train medical students and anaesthesia residents. The lung simulator simulates carinal pressure, which allows for simulation of actively breathing or ventilated patients. In the current HPS implementation, breathing is physically simulated with a pair of bellows and a computer-controlled piston, but, owing to physical and dynamic constraints, the model suffers from a lot of dead space. Furthermore, the set-up incorporates several mechanical components that require time-consuming calibrations, which drives up manufacturing costs. A bellows-less lung simulator has been designed and built which successfully simulates airflow in and out of the mouth by controlling the carina pressure. The new system is able to simulate tidal volumes between 400 and 500 ml, with flow rates of 4.3–5.7l min⁻¹ at a respiratory rate of 12 breaths per minute. The new design not only matches the ventilation performance of the HPS, but also simulates at 60 breaths per minute, which the HPS cannot maintain.     

Prediction of inspiratory flow shapes during sleep with a mathematic model of upper airway forces

STUDY OBJECTIVES: To predict the airflow dynamics during sleep using a mathematic model that incorporates a number of static and dynamic upper airway forces, and to compare the numerical results to clinical flow data recorded from patients with sleep-disordered breathing on and off various treatment options. DESIGN: Upper airway performance was modeled in virtual subjects characterized by parameter settings that describe common combinations of risk factors predisposing to upper airway collapse during sleep. The treatments effect were induced by relevant changes of the initial parameter values. SETTING: Computer simulations at our website (http://www.utu.fi/ml/sovmat/bio/). PARTICIPANTS: Risk factors considered in the simulation settings were sex, obesity, pharyngeal collapsibility, and decreased phasic activity of pharyngeal muscles. INTERVENTIONS: The effects of weight loss, pharyngeal surgery, nasal continuous positive airway pressure, and respiratory stimulation on the inspiratory flow characteristics were tested with the model. MEASUREMENTS AND RESULTS: Numerical predictions were investigated by means of 3 measurable inspiratory airflow characteristics: initial slope, total volume, and flow shape. The model was able to reproduce the inspiratory flow shape characteristics that have previously been described in the literature. Simulation results also supported the observations that a multitude of factors underlie the pharyngeal collapse and, therefore, certain medical therapies that are effective in some conditions may prove ineffective in others. CONCLUSIONS: A mathematic model integrating the current knowledge of upper airway physiology is able to predict individual treatment responses. The model provides a framework for designing novel and potentially feasible treatment alternatives for sleep-disordered breathing.     

The effect of bronchodilator drugs on breath-holding capability in asthma

A method of assessing the relationship between maximum voluntary breath-holding time (BHT) and the partial pressure of end-tidal carbon dioxide (PETCO2) during hyperoxic carbon dioxide rebreathing is described. The resulting index is referred to as the breath-holding capability (BHC). BHC and the maximum rate of early inspiratory pressure fall at the mouth while breathing oxygen at rest (RHdP/dtmax) were measured in normal and asthmatic subjects before and after treatment with nebulized solutions of salbutamol and ipratropium bromide. BHC was low in asthmatics when their airflow resistance was high and rose when the airflow resistance fell as the result of treatment; RHdp/dtmax was high in the asthmatics before treatment and fell after bronchodilator drugs were administered. The fall in respiratory drive which followed bronchodilatation in the asthmatic subjects cannot be solely explained in terms of the resulting fall in viscous and elastic work of breathing. Vagal afferent signals arising in the airways might play a part in modifying respiratory drive in such circumstances.     

Analysis of the interplay between neurochemical control of respiration and upper airway mechanics producing upper airway obstruction during sleep in humans

Increased loop gain (a function of both controller gain and plant gain), which results in instability in feedback control, is of major importance in producing recurrent central apnoeas during sleep but its role in causing obstructive apnoeas is not clear. The purpose of this study was to investigate the role of loop gain in producing obstructive sleep apnoeas. Owing to the complexity of factors that may operate to produce obstruction during sleep, we used a mathematical model to sort them out. The model used was based on our previous model of neurochemical control of breathing, which included the effects of chemical stimuli and changes in alertness on respiratory pattern generator activity. To this we added a model of the upper airways that contained a narrowed section which behaved as a compressible elastic tube and was tethered during inspiration by the contraction of the upper airway dilator muscles. These muscles in the model, as in life, responded to changes in hypoxia, hypercapnia and alertness in a manner similar to the action of the chest wall muscles, opposing the compressive action caused by the negative intraluminal pressure generated during inspiration which was magnified by the Bernoulli Effect. As the velocity of inspiratory airflow increased, with sufficiently large increase in airflow velocity, obstruction occurred. Changes in breathing after sleep onset were simulated. The simulations showed that increases in controller gain caused the more rapid onset of obstructive apnoeas. Apnoea episodes were terminated by arousal. With a constant controller gain, as stiffness decreased, obstructed breaths appeared and periods of obstruction recurred longer after sleep onset before disappearing. Decreased controller gain produced, for example, by breathing oxygen eliminated the obstructive apnoeas resulting from moderate reductions in constricted segment stiffness. This became less effective as stiffness was reduced more. Contraction of the upper airway muscles with hypercapnia and hypoxia could prevent obstructed apnoeas with moderate but not with severe reductions in stiffness. Increases in controller gain, as might occur with hypoxia, converted obstructive to central apnoeas. Breathing CO2 eliminated apnoeas when the activity of the upper airway muscles was considered to change as a function of CO2 to some exponent. Low arousal thresholds and increased upper airway resistance are two factors that promoted the occurrence and persistence of obstructive sleep apnoeas.     

Differentiating obstructive from central and complex sleep apnea using an automated electrocardiogram-based method

STUDY OBJECTIVES: Complex sleep apnea is defined as sleep disordered breathing secondary to simultaneous upper airway obstruction and respiratory control dysfunction. The objective of this study was to assess the utility of an electrocardiogram (ECG)-based cardiopulmonary coupling technique to distinguish obstructive from central or complex sleep apnea. DESIGN: Analysis of archived polysomnographic datasets. SETTING: A laboratory for computational signal analysis. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The PhysioNet Sleep Apnea Database, consisting of 70 polysomnograms including single-lead ECG signals of approximately 8 hours duration, was used to train an ECG-based measure of autonomic and respiratory interactions (cardiopulmonary coupling) to detect periods of apnea and hypopnea, based on the presence of elevated low-frequency coupling (e-LFC). In the PhysioNet BIDMC Congestive Heart Failure Database (ECGs of 15 subjects), a pattern of "narrow spectral band" e-LFC was especially common. The algorithm was then applied to the Sleep Heart Health Study-I dataset, to select the 15 records with the highest amounts of broad and narrow spectral band e-LFC. The latter spectral characteristic seemed to detect not only periods of central apnea, but also obstructive hypopneas with a periodic breathing pattern. Applying the algorithm to 77 sleep laboratory split-night studies showed that the presence of narrow band e-LFC predicted an increased sensitivity to induction of central apneas by positive airway pressure. CONCLUSIONS: ECG-based spectral analysis allows automated, operator-independent characterization of probable interactions between respiratory dyscontrol and upper airway anatomical obstruction. The clinical utility of spectrographic phenotyping, especially in predicting failure of positive airway pressure therapy, remains to be more thoroughly tested.     

Ventilatory and upper-airway resistance responses to upper-airway cooling and CO2 in anaesthetised rats

The effects of upper airway (UA) cool air and CO₂ on breathing and on laryngeal and supraglottic resistances were studied in anaesthetised rats breathing spontaneously through a tracheostomy. Warm, humidified air containing 0, 5 and 9–10% CO₂ and cool, room-humidity air were delivered at constant flow to either the isolated larynx to exit through a pharyngotomy or to the supraglottic UA to exit through the mouth and/or nose (nose open or sealed). Spontaneous tracheal airflow and UA airflows, temperatures and pressures were recorded. CO₂ had no effect on breathing but caused a slight increase in laryngeal resistance which was abolished by cutting the superior laryngeal nerves (SLN). Cool air caused a decrease in respiratory frequency and/or peak inspiratory flow when applied to the isolated larynx or to the supraglottic airway with the nose closed. These effects were abolished by SLN section. With the nose open, the ventilatory inhibition was not abolished by SLN section. Cool air also caused substantial decreases in laryngeal and supraglottic resistances which were attenuated by SLN section and which persisted following recurrent laryngeal nerve section. In conclusion, whilst UA cooling inhibits breathing and decreases UA resistances, UA CO₂ has minimal effects.     

Impact of CPAP interface and mandibular advancement device on upper airway mechanical properties assessed with phrenic nerve stimulation in sleep apnea patients

Oronasal mask (ONM) can be used when mouth leaks impair nasal-CPAP effectiveness. However, ONM's constraint on the chin and straps' traction may alter upper airway (UA) mechanical properties. In contrast, mandibular advancement device associated with nasal-CPAP (NM+MAD) may reduce UA resistance. The aim of this exploratory study was to compare the effects of ONM, NM, and NM+MAD on UA mechanical properties. The three interface modalities were assessed in 11 OSAS patients at 6, 8, 10cmH(2)O CPAP using a phrenic nerve magnetic stimulation (PNMS) protocol. PNMS-twitches' related flow, pharyngeal pressures (nasopharynx, velopharynx, oropharynx) and UA resistances were determined. Regardless of CPAP level, twitch-induced maximum flow was higher with NM+MAD than with ONM. Velopharyngeal resistance was higher with ONM than with NM+MAD. Oropharyngeal resistance was higher with ONM than with NM. In conclusion, NM+MAD reduced velopharyngeal resistance compared to those measured with ONM and NM alone. We hypothesize that this strategy may help reducing the effective pressure level and thus further limit the risk for mouth leaks.     

Serial lung model for simulation and parameter estimation in body plethysmography

A serial lung model with a compressible segment has been implemented to simulate different types of lung and airway disorders such as asthma, emphysema, fibrosis and upper airway obstruction. The model described can be used during normal breathing, and moreover the compliant segment is structured according to more recent physiological data. A parameter estimation technique was applied and its reliability and uniqueness were tested by means of sine wave input signals. The characteristics of the alveolar pressure/flow patterns simulated with the model agree to a great extent with those found in the literature. In the case of absence of noise the parameter estimation routine produced unique solutions for different simulated pathologic classes. The sensitivity of the different parameters depended on the values belonging to each class of pathology. Some more simplified models are presented and their advantages over the complex model in special types of pathology are demonstrated. Noise added to the simulated flow appeared to have no influence on the estimated parameters, in contradiction to the effects with noise added to the pressure signal. In that case effective resistance was accurately estimated. Where parameters had no influence, as for instance upper airway resistance in emphysema or peripheral airway resistance in upper airway obstruction, the measurement accuracy was less. In all other cases, a satisfactory accuracy could be obtained.     

Role of the mechanical properties of tracheobronchial airways in determining the respiratory resistance time course

A physiologically based simulation model of breathing mechanics was considered in an attempt to interpret and explain the time course of input respiratory resistance during the breathing cycle, observed in recent studies on ventilated patients. The model assumes a flow-dependent Rohrer resistance for the upper extrathoracic airways and volume-dependent resistance and elastance for the intermediate airways. A volume-dependent resistance describes the dissipative pressure loss in the lower airways, and two constant elastances represent lung and chest wall elasticity. Simulated mouth flow and pressure signals obtained in a variety of well-controlled conditions were used to analyze total respiratory resistance and elastance estimated by an on-line algorithm based on a time-varying parameter model. These estimates were compared with those provided by classical estimation algorithms based on time-invariant models with two, three, and four parameters. The results show that the four-parameter model is difficult to identify, while the three-parameter one offers no substantial advantage for estimating input resistance with respect to the more simple two-parameter model. In contrast, the time-varying approach provides good on-line estimates of the simulated end-expiration and end-inspiration resistances. These values provide further information of potential clinical utility, with respect to time-invariant models. For example, the results show that the difference between the end-expiration and end-inspiration resistance increases when obstructions shift from the upper to the lower airways. The similarity of the results obtained with measured and simulated data indicates that, in spite of its simplicity, the simulation model describes important physiological mechanisms underlying changes in respiratory input resistance, specifically the mechanical properties of intermediate airways. © 2001 Biomedical Engineering Society. PAC01: 8719Uv, 8719Rr     

Assessment of upper airway mechanics during sleep

Obstructive sleep apnea, which is the most prevalent sleep breathing disorder, is characterized by recurrent episodes of upper airway collapse and reopening. However, the mechanical properties of the upper airway are not directly measured in routine polysomnography because only qualitative sensors (thermistors for flow and thoraco-abdominal bands for pressure) are used. This review focuses on two techniques that quantify upper airway obstruction during sleep. A Starling model of collapsible conduit allows us to interpret the mechanics of the upper airway by means of two parameters: the critical pressure (P_crit) and the upstream resistance (R_up). A simple technique to measure P_crit and R_up involves the application of different levels of continuous positive airway pressure (CPAP) during sleep. The forced oscillation technique is another non-invasive procedure for quantifying upper airway impedance during the breathing cycle in sleep studies. The latest developments in these two methods allow them to be easily applied on a routine basis in order to more fully characterize upper airway mechanics in patients with sleep breathing disorders.     

Airflow Simulations in Infant,Child, and Adult Pulmonary Conducting Airways

The airway structure continuously evolves from birth to adulthood, influencing airflow dynamics and respiratory mechanics. We currently know very little about how airflow patterns change throughout early life and its impact on airway resistance, namely because of experimental limitations. To uncover differences in respiratory dynamics between age groups, we performed subject-specific airflow simulations in an infant, child, and adult conducting airways. Airflow throughout the respiration cycle was calculated by coupling image-based models of the conducting airways to the global respiratory mechanics, where flow was driven by a pressure differential. Trachea diameter was 19, 9, and 4.5 mm for the adult (36 years, female), child (6 years, male), and infant (0.25 years, female), respectively. Mean Reynolds number within the trachea was nearly the same for each subject (1100) and Womersley number was above unity for all three subjects and largest for the adult, highlighting the significance of transient effects. In general, air speeds and airway resistances within the conducting airways were inversely correlated with age; the 3D pressure drop was highest in the infant model. These simulations provide new insight into age-dependent flow dynamics throughout the respiration cycle within subject-specific airways.     

正压通气下呼吸道气阻与顺应性在线测算方法改进

:目的 采用气道正压对患者进行通气治疗,实现对通气患者呼吸道气阻(resistance, R)和顺应性(compliance, C)在线测算。 方法 当呼气末气流为 0 时,在呼气支持压(expiratory positive airway pressure, EPAP)之上叠加 1 个负 脉冲气压,使肺内气压在该脉冲期间高于体外气压,从而向外泄放气流,并对该泄放气流进行处理来测算 R 和 C。 然 后以正常成人、典型急性呼吸窘迫综合征( acute respiratory distress syndrome, ARDS) 患者和慢性阻塞性肺疾病 (chronic obstructive pulmonary disease, COPD)患者为实验对象,建立仿真实验平台,进行仿真实验来测算 R 和 C。 结 果 所测算的正常成人 R 和 C 误差分别为 3. 398% 和-3. 288% ,COPD 患者 R 和 C 误差分别为 1. 265% 和-1. 348% , ARDS 患者 R 和 C 误差分别为 3. 400% 和-3. 286% 。 结论 气道正压通气下,采用呼气末叠加 1 个负脉冲气压在 EPAP 上来测算 R 和 C 的方法具有良好的可行性,研究结果为智能调控通气、精准通气等技术打下坚实基础。