Simulation of the effect of airway disease on respiratory airways

Airway disease such as tumours and asthma lead to lung injuries. Therefore, a better understanding of airway mechanics parameters is very important to avoid lung injuries in patients undergoing mechanical ventilation for treatment of respiratory problems in intensive-care medicine as well as pulmonary medicine. The objective of this study was to investigate the role of airway diseases such as asthma and tumours on airway mechanics parameters using coupled fluid–solid computational analysis. The results obtained indicate that both tumours and asthma greatly affect the airway mechanics parameters (airflow velocity increased by about 15% and the strains increased by about 40%). Strain results of this study highlight significant changes in levels of airway parameters, which may translate into higher health risk associated with airway tumours and the asthmatic airways. These results combined with optimization suggest that it is possible to develop mechanical ventilation protocols to avoid lung injuries in patients.     

Simulation of the effect of airway disease on respiratory airways

Airway disease such as tumours and asthma lead to lung injuries. Therefore, a better understanding of airway mechanics parameters is very important to avoid lung injuries in patients undergoing mechanical ventilation for treatment of respiratory problems in intensive-care medicine as well as pulmonary medicine. The objective of this study was to investigate the role of airway diseases such as asthma and tumours on airway mechanics parameters using coupled fluid-solid computational analysis. The results obtained indicate that both tumours and asthma greatly affect the airway mechanics parameters (airflow velocity increased by about 15% and the strains increased by about 40%). Strain results of this study highlight significant changes in levels of airway parameters, which may translate into higher health risk associated with airway tumours and the asthmatic airways. These results combined with optimization suggest that it is possible to develop mechanical ventilation protocols to avoid lung injuries in patients.     

Imaging of the three-dimensional alveolar structure and the alveolar mechanics of a ventilated and perfused isolated rabbit lung with Fourier domain optical coherence tomography

In this feasibility study, Fourier domain optical coherence tomography (FDOCT) is used for visualizing the 3-D structure of fixated lung parenchyma and to capture real-time cross sectional images of the subpleural alveolar mechanics in a ventilated and perfused isolated rabbit lung. The compact and modular setup of the FDOCT system allows us to image the first 500 microm of subpleural lung parenchyma with a 3-D resolution of 16 x 16 x 8 microm (in air). During mechanical ventilation, real-time cross sectional FDOCT images visualize the inflation and deflation of alveoli and alveolar sacks (acini) in successive images of end-inspiratory and end-expiratory phase. The FDOCT imaging shows the relation of local alveolar mechanics to the setting of tidal volume (VT), peak airway pressure, and positive end-expiratory pressure (PEEP). Application of PEEP leads to persistent recruitment of alveoli and acini in the end-expiratory phase, compared to ventilation without PEEP where alveolar collapse and reinflation are observed. The imaging of alveolar mechanics by FDOCT will help to determine the amount of mechanical stress put on the alveolar walls during tidal ventilation, which is a key factor in understanding the development of ventilator induced lung injury (VILI).     

The contribution of the pulmonary microvascular pressure in the maintenance of an open lung during mechanical ventilation

Changes in pulmonary hemodynamics modify the mechanical properties of the lungs. The effects of alterations in pulmonary capillary pressure (Pc) were investigated on the airway and lung tissue mechanics during positive-pressure ventilation and following lung recruitment maneuvers. Isolated, mechanically normoventilated (PEEP 2.5 cmH(2)O) rat lungs were perfused with Pc set to 0 (unperfused), 5, 10 or 15 mmHg, in random sequence. The pulmonary input impedance (ZL) was measured at end-expiration before and after a 10-min long ventilation. After inflation of the lung to 30 cmH(2)O during P-V curve recordings, another set of ZL was measured to evaluate the degree of recruitment. The PEEP was then decreased to 0.5 cmH(2)O and the sequence was repeated. Airway resistance and parenchymal damping and elastance (H) were estimated from ZL by model fitting. From the P-V curves, elastance (E) and hysteresis indices were determined. Mechanical ventilation at both PEEP levels resulted primarily in elevations in the tissue parameters, with the greatest increases at the 0 Pc level (H changes of 27.8+/-4.2 and 61.3+/-3.7% at 2.5 and 0.5 cmH(2)O PEEP, respectively). The maintenance of physiological Pc (10 mmHg) led to a significantly lower elevation in H (11.6+/-1.5% versus 31.4+/-3.6%). The changes in the oscillatory mechanics were also reflected in E and the hysteresis of the P-V curves. These findings indicate that pulmonary hypoperfusion during mechanical ventilation forecasts a parenchymal mechanical deterioration. Physiological pressure in the pulmonary capillaries is therefore an important mechanical factor promoting maintenance of the stability of the alveolar architecture during positive-pressure mechanical ventilation.     

Impact of Positive End-Expiratory Pressure During Heterogeneous Lung Injury: Insights from Computed Tomographic Image Functional Modeling

Image Functional Modeling (IFM) synthesizes three dimensional airway networks with imaging and mechanics data to relate structure to function. The goal of this study was to advance IFM to establish a method of exploring how heterogeneous alveolar flooding and collapse during lung injury would impact regional respiratory mechanics and flow distributions within the lung at distinct positive end-expiratory pressure (PEEP) levels. We estimated regional respiratory system elastance from computed tomography (CT) scans taken in 5 saline-lavaged sheep at PEEP levels from 7.5 to 20 cmH₂O. These data were anatomically mapped into a computational sheep lung model, which was used to predict the corresponding impact of PEEP on dynamic flow distribution. Under pre-injury conditions and during lung injury, respiratory system elastance was determined to be spatially heterogeneous and the values were distributed with a hyperbolic distribution in the range of measured values. Increases in PEEP appear to modulate the heterogeneity of the flow distribution throughout the injured lung. Moderate increases in PEEP decreased the heterogeneity of elastance and predicted flow distribution, although heterogeneity began to increase for PEEP levels above 12.5–15 cmH₂O. By combining regional respiratory system elastance estimated from CT with our computational lung model, we can potentially predict the dynamic distribution of the tidal volume during mechanical ventilation and thus identify specific areas of the lung at risk of being overdistended.     

小潮气量和传统潮气量机械通气治疗小儿重症肺炎的疗效对比分析

目的：对比分析小潮气量和传统潮气量机械通气治疗小儿重症肺炎的疗效。方法：对2013年6月至2015年6月在我院进行接治的100例小儿重症肺炎进行研究,将患儿随机分为对照组和观察组,各50例,对照组的患儿采用传统潮气量,潮气量为10~12 mL/kg;观察组的患儿采用小潮气量,潮气量为6~8 mL/kg,对治疗过程中两组患儿临床参数的变化进行对比分析。结果：观察组患儿的机械通气时间明显多于对照组(t=11.0770,P=0.0000),观察组患儿的病死率明显高于对照组(χ2=5.4825,P=0.0192),治疗过程中,两组患儿的平均气道压(Paw)、吸入氧浓度(fraction of inspiration O2,FiO2)、高呼吸末正压(positive end expiratory pressure,PEEP)、吸气峰压(peak inflating pressure,PIP)等临床各指标的变化无明显差异(P>0.05),观察组与对照组存活患儿的反复呼吸道感染发生率无明显差异(χ2=0.0624,P=0.8028)。结论：对重症肺炎患儿进行机械通气时,传统潮气量的治疗效果优于小潮气量。     

Pulmonary clearance of inhaled [99Tcm]DTPA: effects of ventilation pattern

While a rise in lung volume is known to increase the pulmonary clearance of technetium-99m-labelled dietylene triamine pentaacetate ([99Tcm]DTPA), little interest has been focused on the effects of changes in ventilation frequency, tidal volume and airway pressure. We studied adult, anaesthetized and intubated rabbits during three ventilation patterns (VP) using pressure controlled ventilation (ServoVentilator 900C). VP was either deep slow (f = 20 min-1, tidal volume (VT) = 30 +/- 4 ml kg-1 and positive end-expiratory pressure (PEEP) = 0.2 kPa [VP 20/0.2, n = 8]) or rapid shallow (f = 80 min-1, VT = 11 +/- 2 ml kg-1 and PEEP = 0.2 or 0.4 kPa [VP 80/0.2, n = 6 and VP 80/0.4, n = 6]). The mean airway pressure was similar at VP 20/0.2 and VP 80/0.4. During administration of [99Tcm]DTPA aerosol all animals were ventilated under the same conditions (f = 40 min-1 and PEEP = 0.2 kPa). The pulmonary clearance rate expressed as the half-life time (T1/2) of [99Tcm]DTPA was at VP 80/0.2 = 113 +/- 31 min, at VP 80/0.4 = 70 +/- 24 min (P less than 0.01 compared to VP 80/0.2) and at VP 20/0.2 = 36 +/- 18 min (P less than 0.001 compared to VP 80/0.2 and P less than 0.01 compared to VP 80/0.4). We conclude that the pulmonary clearance of [99Tcm]DTPA increases (1) during rapid shallow ventilation when PEEP is increased from 0.2 to 0.4 kPa; (2) during deep slow ventilation relative to rapid shallow ventilation even when the mean airway pressure is similar.     

Advanced lung ventilation system (ALVS) with linear respiratory mechanics assumption for waveform optimization of dual-controlled ventilation

The present paper describes the functional features of an advanced lung ventilation system (ALVS) properly designed for the optimization of conventional dual-controlled ventilation (DCV), i.e. with pressure-controlled ventilation with ensured tidal or minute volume. Considering the particular clinical conditions of patients treated with controlled ventilation the analysis and synthesis of ALVS control have been performed assuming a linear respiratory mechanics. Moreover, new airways pressure waveforms with more physiological shape can be tested on simulators of respiratory system in order to evaluate their clinical application. This is obtained through the implementation of a compensation procedure making the desired airways pressure waveform independent on patient airways resistance and lung compliance variations along with a complete real-time monitoring of respiratory system parameters leading the ventilator setting. The experimental results obtained with a lung simulator agree with the theoretical ones and show that ALVS performance is useful for the research activity aiming at the improvement of both diagnostic evaluation and therapeutic outcome relative to mechanical ventilation treatments.     

The fall in exhaled nitric oxide with ventilation at low lung volumes in rabbits: an index of small airway injury

The mechanisms involved in the fall of exhaled nitric oxide (NOe) concentration occurring in normal, anesthetized open chest rabbits with prolonged mechanical ventilation (MV) at low lung volume have been investigated. NOe, pH of exhaled vapor condensate, serum prostaglandin E(2), and F(2alpha), tumor necrosis factor (TNF-alpha), PaO(2), PaCO(2), pHa, and lung mechanics were assessed before, during, and after 3-4h of MV at zero end-expiratory pressure (ZEEP), with fixed tidal volume (9 ml kg(-1)) and frequency, as well as before and after 3-4h of MV on PEEP only. Lung histology and wet-to-dry ratio (W/D), and prostaglandin and TNF-alpha in bronchoalveolar lavage fluid (BALF) were also assessed. While MV on PEEP had no effect on the parameters above, MV on ZEEP caused a marked fall (45%) of NOe, with a persistent increase of airway resistance (45%) and lung elastance (12%). Changes in NOe were independent of prostaglandin and TNF-alpha levels, systemic hypoxia, hypercapnia and acidosis, bronchiolar and alveolar interstitial edema, and pH of exhaled vapor condensate. In contrast, there was a significant relationship between the decrease in NOe and bronchiolar epithelial injury score. This indicates that the fall in NOe, which occurs in the absence of an inflammatory response, is due to the epithelial damage caused by the abnormal stresses related to cyclic opening and closing of small airways with MV on ZEEP, and suggests its use as a sign of peripheral airway injury.     

外柱细胞软化对Corti器感音影响的生物力学研究

Corti器的感音过程容易受到内部结构属性变化的影响。外柱细胞血管舒张刺激磷蛋白缺失会减缓肌动蛋白丝的形成,从而产生听力延迟。本研究运用COMSOL建立三维有限元模型研究肌动蛋白缺失导致外柱细胞软化时,Corti器感音过程中基底膜和外毛细胞与Deiters细胞结合点的力学行为变化。结果表明,外柱细胞软化会削弱外毛细胞主动力对基底膜位移增益的放大作用,但削弱作用并不会立即产生,Corti器存在维持正常功能的“缓冲”阶段。在100 dB和120 dB之间可能存在一个声压级临界值,在该临界值两侧外柱细胞软化对基底膜应力变化的影响是截然相反的。另外外柱细胞软化对不同外毛细胞与Deiters细胞结合点力学行为的影响也不同,位移增益优先级会因此产生改变。     

Effect of repeated induced airway collapse during total liquid ventilation

Negative pressure generated during the expiratory phase of total liquid ventilation (TLV) may induce airway collapse. Evaluation of the effect of repeated airway collapse is crucial to optimize this technique. A total of 24 New Zealand White rabbits were randomly divided into four groups. Ventilation was performed for 6 hours with different strategies: conventional gas ventilation, TLV without airway collapse, and TLV with collapse induced in either 75 or 150 sequential breaths. In the treated groups, airway collapse was induced by increasing the perfluorocarbon drainage velocity while maintaining the minute ventilation constant. Airway pressure, gas exchange, and blood pressure were monitored at 30-minute intervals. At the end of the experiment, airway and lung parenchyma specimens were processed for light microscopy. No evidence of fluorothorax was noticed in any of the four groups at autopsy examination. Minimal signs of inflammation were noticed in all airway and lung parenchyma specimens, but no evident structural alteration was visible. Adequate gas exchange and systemic blood pressure were maintained during all the studies. Repeated airway collapse is not associated with structural changes in the respiratory system and does not alter the gas exchange ability of the lungs.     

Respiratory airflow pattern in patients with chronic airway obstruction

Previous experimental evidence has shown that in healthy humans inspiratory airflow waveform can be optimized according to minimum rate of work criteria when the respiratory energetic requirements become a substantial fraction of the general metabolism (i.e., during exercise hyperpnea and maximum voluntary ventilation). In patients with chronic airway obstruction (CAO) the relative energetic expenditure devoted to respiration is also greatly enhanced at rest. To investigate the performance of a system also controlling airflow wave pattern in this condition we evaluated by Fourier analysis the harmonic content of respiratory flow waves recorded at rest and during exercise hyperpnea (25 and 50 W on cycloergometer) in 15 patients. The results were compared with those we previously obtained in normal subjects and with some theoretical models. It was found that, while normal subjects display at rest an inspiratory flow waveform reasonably close to a sinusoidal model and adopt a more rectangular and economical flow shape during exercise hyperpnea, patients with CAO show a rather rectangular inspiratory flow shape also at rest, without any remarkable change at higher levels of ventilation. So, in general terms, the airflow pattern employed by patients at rest entails a reduction in the rate of dynamic inspiratory work of about 12% over that required by a sinusoidal waveform, and no further advantage is observed during exercise hyperpnea. Some features of the expiratory flow wave were also analysed. As no model of the respiratory system mechanics presently developed can explain the findings obtained in CAO patients purely on the basis of their altered mechanical parameters, it has been suggested that more complex control of respiratory airflow is operating in this class of patient.     

Optimal Pressure Waveforms for Pressure-Limited Ventilation

In this paper, we find the pressure waveform that minimizesthe work of distending the alveoli in the lungs while achievingthe desired mean airway pressure and alveolar tidal volume.The model used takes into account the compliance of the airway.The main result is a formula for the pressure waveform at themouth as a function of time and lung parameters.     

Optimal pressure waveforms for pressure-limited ventilation

In this paper, we find the pressure waveform that minimizes the work of distending the alveoli in the lungs while achieving the desired mean airway pressure and alveolar tidal volume. The model used takes into account the compliance of the airway. The main result is a formula for the pressure waveform at the mouth as a function of time and lung parameters.     

Impact of supplemental oxygen in mechanically ventilated adult and infant mice

The aim of the present study was to determine the short-term effects of hyperoxia on respiratory mechanics in mechanically ventilated infant and adult mice. Eight and two week old BALB/c mice were exposed to inspired oxygen fractions [Formula: see text] of 0.21, 0.3, 0.6, and 1.0, respectively, during 120 min of mechanical ventilation. Respiratory system mechanics and inflammatory responses were measured. Using the low-frequency forced oscillation technique no differences were found in airway resistance between different [Formula: see text] groups when corrected for changes in gas viscosity. Coefficients of lung tissue damping and elastance were not different between groups and showed similar changes over time in both age groups. Inflammatory responses did not differ between groups at either age. Hyperoxia had no impact on respiratory mechanics during mechanical ventilation with low tidal volume and positive end-expiratory pressure. Hence, supplemental oxygen can safely be applied during short-term mechanical ventilation strategies in infant and adult mice.     

Quantifying the roles of tidal volume and PEEP in the pathogenesis of ventilator-induced lung injury

Management of patients with acute lung injury (ALI) rests on achieving a balance between the gas exchanging benefits of mechanical ventilation and the exacerbation of tissue damage in the form of ventilator-induced lung injury (VILI). Optimizing this balance requires an injury cost function relating injury progression to the measurable pressures, flows, and volumes delivered during mechanical ventilation. With this in mind, we mechanically ventilated naive, anesthetized, paralyzed mice for 4 h using either a low or high tidal volume (Vt) with either moderate or zero positive end-expiratory pressure (PEEP). The derecruitability of the lung was assessed every 15 min in terms of the degree of increase in lung elastance occurring over 3 min following a recruitment maneuver. Mice could be safely ventilated for 4 h with either a high Vt or zero PEEP, but when both conditions were applied simultaneously the lung became increasingly unstable, demonstrating worsening injury. We were able to mimic these data using a computational model of dynamic recruitment and derecruitment that simulates the effects of progressively increasing surface tension at the air–liquid interface, suggesting that the VILI in our animal model progressed via a vicious cycle of alveolar leak, degradation of surfactant function, and increasing tissue stress. We thus propose that the task of ventilating the injured lung is usefully understood in terms of the Vt–PEEP plane. Within this plane, non-injurious combinations of Vt and PEEP lie within a “safe region”, the boundaries of which shrink as VILI develops.     

Ovalbumin aerosol challenge in actively sensitized guinea pigs: relationship between airway microvascular leakage and airflow obstruction

Airway inflammation is a common feature of asthma, and one of the cardinal features of inflammation is increased microvascular permeability. We investigated the characteristics of inhaled ovalbumin challenge-induced airflow obstruction and airway microvascular leakage in vivo in mechanically ventilated guinea pigs actively sensitized to ovalbumin. A method was used to quantify both airflow obstruction and airway microvascular leakage in order to investigate the relationship between these 2 pathophysiological features in the same animal. Airway microvascular leakage was assessed by Evans blue dye extravasation into airway tissues. Actively sensitized guinea pigs developed both acute airflow obstruction (increased lung resistance and reduced dynamic lung compliance) and Evans blue dye extravasation in response to exposure to aerosolised ovalbumin. Evans blue dye extravasation was preferentially distributed in the distal airways and correlated with airflow obstruction. The results show that inhaled allergen induced both acute airflow obstruction and airway microvascular leakage.     

Impact of mechanical ventilation and fluid load on pulmonary glycosaminoglycans

The combined effect of mechanical ventilation and fluid load on pulmonary glycasaminoglycans (GAGs) was studied in anaesthetized rats ((BW 290±21.8 (SE)g) mechanically ventilated for 4h: (a) at low (～7.5mlkg(-1)) or high (～23mlkg(-1)) tidal volume (V(T)) and zero alveolar pressure; (b) at low or high V(T) at 5cmH(2)O positive end-expiratory pressure (PEEP); (c) with or without 7mlkg(-1)h(-1) intravenous infusion of Phosphate Buffer Solution (PBS). Compared to spontaneous breathing, GAGs extractability decreased by 52.1±1.5% and 42.2±7.3% in not-infused lungs mechanically ventilated at low V(T) or at high V(T) and PEEP, respectively. In contrast, in infused lungs, GAGs extractability increased by 56.1±4.0% in spontaneous ventilation and PEEP and up to 81.1% in all mechanically ventilated lungs, except at low V(T) without PEEP. In the absence of an inflammatory process, these results suggest that PEEP was protective at low but not at high V(T) when alveolar structures experience exceedingly high stresses. When combined to mechanical ventilation, fluid load might exacerbate edema development and lung injury.     

Short-term exposure to high-pressure ventilation leads to pulmonary biotrauma and systemic inflammation in the rat

Though often lifesaving, mechanical ventilation itself bears the risk of lung damage [ventilator-induced lung injury (VILI)]. The underlying molecular mechanisms have not been fully elucidated, but stress-induced mediators seem to play an important role in biotrauma related to VILI. Our purpose was to evaluate an animal model of VILI that allows the observation of pathophysiologic changes along with parameters of biotrauma. For VILI induction, rats (n=16) were ventilated with a peak airway pressure (pmax) of 45 cm H2O and end-expiratory pressure (PEEP) of 0 for 20 min, followed by an observation time of 4 h. In the control group (n=8) the animals were ventilated with a pmax of 20 cm H2O and PEEP of 4. High-pressure ventilation resulted in an increase in paCO2 and a decrease in paO2 and mean arterial pressure. Only 4 animals out of 16 survived 4 h and VILI lungs showed severe macroscopic and microscopic damage, oedema and neutrophil influx. High-pressure ventilation increased the cytokine levels of macrophage inflammatory protein-2 and IL-1beta in bronchoalveolar lavage and plasma. VILI also induced pulmonary heat shock protein-70 expression and the activity of matrix metalloproteinases. The animal model used enabled us to observe the effect of high-pressure ventilation on mortality, lung damage/function and biotrauma. Thus, by combining barotrauma with biotrauma, this animal model may be suitable for studying therapeutical approaches to VILI.     

Guidelines for mechanical lung function measurements in psychophysiology

Studies in psychophysiology and behavioral medicine have uncovered associations among psychological processes, behavior, and lung function. However, methodological issues specific to the measurement of mechanical lung function have rarely been discussed. This report presents an overview of the physiology, techniques, and experimental methods of mechanical lung function measurements relevant to this research context. Techniques to measure lung volumes, airflow, airway resistance, respiratory resistance, and airflow perception are introduced and discussed. Confounding factors such as ventilation, medication, environmental factors, physical activity, and instructional and experimenter effects are outlined, and issues specific to children and clinical groups are discussed. Recommendations are presented to increase the degree of standardization in the research application and publication of mechanical lung function measurements in psychophysiology.