Airway cell involvement in intermittent hypoxia-induced airway inflammation.

PURPOSE: Respiratory inflammation has been described in patients with obstructive sleep apnea syndrome, but it is unknown whether the increased neutrophil and interleukin (IL)-8 levels observed in induced sputum reflect systemic or local airway inflammation. We assessed the potential role of resident cells in intermittent hypoxia-induced airway inflammation. METHODS: Airway epithelial cells (AEC) and bronchial smooth muscle cells (BSMC) were exposed to intermittent hypoxia (IH) in vitro. Cell supernatants were assessed for matrix metalloproteinase, growth factor, and cytokine expression. The role of IH on neutrophil and BSMC migration capacities was evaluated, and the effect of supernatants from IH-exposed or control AEC was tested. RESULTS: Compared to normoxic conditions, 24 h of exposure to IH induced a significant increase of MMP-9 and MMP-2 expression and pro-MMP-9 activation (p < 0.05), and IL-8 (p < 0.05), platelet-derived growth factor (PDGF)-AA (p < 0.05), and vascular endothelial growth factor (VEGF) (p < 0.05) expression by AEC and VEGF expression (p = 0.04) by BSMC. Neutrophil chemotaxis and BSMC migration were enhanced by IH and supernatants of IH-exposed AEC (112.00 ± 4.80 versus 0.69 ± 0.43 %, p = 0.0053 and 247 ± 76 versus 21 ± 23, p = 0.009 respectively). This enhanced BSMC migration was totally abolished in the presence of an antibody blocking PDGF-AA. CONCLUSIONS: These data suggest a specific inflammatory response of airway cells to IH, independently of systemic events.

Force distribution on multiple bonds controls the kinetics of adhesion in stretched cells.

We show herein how mechanical forces at macro or micro scales may affect the biological response at the nanoscale. The reason resides in the intimate link between chemistry and mechanics at the molecular level. These interactions occur under dynamic conditions such as the shear stress induced by flowing blood or the intracellular tension. Thus, resisting removal by mechanical forces, e.g., shear stresses, is a general property of cells provided by cellular adhesion. Using classical models issued from theoretical physics, we review the force regulation phenomena of the single bond. However, to understand the force regulation of cellular adhesion sites, we need to consider the collective behavior of receptor-ligand bonds. We discuss the applicability of single bond theories to describe collective bond behavior. Depending on bond configuration, e.g., presently "parallel" and "zipper", the number of bonds and dissociation forces variably affect the kinetics of multiple bonds. We reveal a marked efficiency of the collective organization to stabilize multiple bonds by sharply increasing bond lifetime compared to single bond. These theoretical predictions are then compared to experimental results of the literature concerning the kinetic parameters of bonds measured by atomic force microscopy and by shear flow. These comparisons reveal that the force-control of bonds strongly depends on whether the force distribution on multiple bonds is homogeneous, e.g., in AFM experiments, or heterogeneous, e.g., in shear flow experiments. This reinforces the need of calculating the stress/strain fields exerted on living tissues or cells at various scales and certainly down to the molecular scale.

Comparison of patient-ventilator interfaces based on their computerized effective dead space.

PURPOSE: Non-invasive ventilation is largely used to treat acute and chronic respiratory failure. This ventilation encounters a non-negligible rate of failure related to the used interface/mask, but the reasons for this failure remain unclear. In order to shed light on this issue and to better understand the effects of the geometrical design of interfaces, we aimed to quantify flow, pressure and gas composition in terms of CO(2) and O(2) at the passage through different types of interface (oronasal mask, integral mask and helmet). In particular, we postulated that due to specific gas flow passing throughout the interface, the effective dead space added by the interface is not always related to the whole gas volume included in the interface. METHODS: Numerical simulations, using computational fluid dynamics, were used to describe pressure, flow and gas composition during ventilation with the different interfaces. RESULTS: Between the different interfaces the effective dead spaces differed only modestly (110-370 ml), whereas their internal volumes were markedly different (110-10,000 ml). Effective dead space was limited to half the tidal volume for the most voluminous interface, whereas it was close to the interface gas volume for the less voluminous interfaces. Pressure variations induced by the flow ventilation throughout the interface were negligible. CONCLUSIONS: Effective dead space is not related to the internal gas volume included in the interface, suggesting that this internal volume should not be considered as a limiting factor for their efficacy during non-invasive ventilation. Patient's comfort and synchrony have also to be taken into account.

Effect of manufacturer-inserted mask leaks on ventilator performance.

Most pressure-support devices use a single circuit with an exhalation port integrated in the mask. The aim of the current study was to compare the effects of masks having different manufacturer-inserted leaks on ventilator performance. We simulated chronic obstructive pulmonary disease and restrictive disease. Four ventilators (VENTImotion (Weinmann, Hamburg, Germany), VPAP III STA (ResMed, Saint Priest, France), Synchrony 2 (Respironics, Nantes, France) and Vivo 40 (Breas, Saint Priest)) were tested with the recommended masks and with the masks having the largest and smallest leaks. Tests were performed with pressure support levels of 10, 15 and 20 cmH(2)O. The in vivo evaluation compared two ventilators using recommended masks opposed in terms of exhaled port resistance. The ventilators were tested with their recommended mask, and after mask exchange. The mask with the largest leak induced auto-triggering and/or increased inspiratory-trigger sensitivity was the VENTImotion under both simulated conditions and VPAP III STA under the simulated obstructive-disease condition. The mask with the smallest leak-increased inspiratory-trigger delay was Synchrony 2 in the simulated obstructive-disease condition and increased rebreathing. The in vivo study confirmed the bench results. When switching to a mask that has a different leak, evaluation is needed to adjust trigger sensitivity and pressurisation level and to check the absence of rebreathing.

Prestress and adhesion site dynamics control cell sensitivity to extracellular stiffness.

This study aims at improving the understanding of mechanisms responsible for cell sensitivity to extracellular environment. We explain how substrate mechanical properties can modulate the force regulation of cell sensitive elements primarily adhesion sites. We present a theoretical and experimental comparison between two radically different approaches of the force regulation of adhesion sites that depends on their either stationary or dynamic behavior. The most classical stationary model fails to predict cell sensitivity to substrate stiffness whereas the dynamic model predicts extracellular stiffness dependence. This is due to a time dependent reaction force in response to actomyosin traction force exerted on cell sensitive elements. We purposely used two cellular models, i.e., alveolar epithelial cells and alveolar macrophages exhibiting respectively stationary and dynamic adhesion sites, and compared their sensitivity to theoretical predictions. Mechanical and structural results show that alveolar epithelial cells exhibit significant prestress supported by evident stress fibers and lacks sensitivity to substrate stiffness. On the other hand, alveolar macrophages exhibit low prestress and exhibit sensitivity to substrate stiffness. Altogether, theory and experiments consistently show that adhesion site dynamics and cytoskeleton prestress control cell sensitivity to extracellular environment with an optimal sensitivity expected in the intermediate range.

Mechanical and structural assessment of cortical and deep cytoskeleton reveals substrate-dependent alveolar macrophage remodeling.

The sensitivity of alveolar macrophages to substrate properties has been described in a recent paper (Féréol et al., Cell Motil. Cytoskel. 63 (2006), 321-340). It is presently re-analyzed in terms of F-actin structure (assessed from 3D-reconstructions in fixed cells) and mechanical properties (assessed by Magnetic Twisting Cytometry experiments in living cells) of cortical and deep cytoskeleton structures for rigid plastic (Young Modulus: 3 MPa) or glass (70 MPa) substrates and a soft (approximately 0.1 kPa) confluent monolayer of alveolar epithelial cells. The cortical cytoskeleton component (lowest F-actin density) is represented by the rapid and softer viscoelastic compartment while the deep cytoskeleton component (intermediate F-actin density) is represented by the slow and stiffer compartment. Stiffness of both cortical and deep cytoskeleton is significantly decreased when soft confluent monolayer of alveolar epithelial cells replace the rigid plastic substrate while F-actin reconstructions reveal a consistent actin cytoskeleton remodeling observable on both cytoskeleton components.

Performance of ventilators for noninvasive positive-pressure ventilation in children.

The aim of the present study was to evaluate the performance characteristics of all the ventilators proposed for home noninvasive positive-pressure ventilation in children in France. The ventilators (one volume-targeted, 12 pressure-targeted and four dual) were evaluated on a bench which simulated six different paediatric ventilatory patterns. For each ventilator, the quality of the inspiratory and expiratory trigger and the ability to reach and maintain the preset pressures and volumes were evaluated with the six patient profiles. The performance of the ventilators showed great variability, and depended upon the type of trigger (flow or pressure), type of circuit and patient profile. Differences were observed between the preset and measured airway pressure and between the tidal volume measured by the ventilator and on the bench. Leaks were associated with an inability to detect the patient's inspiratory effort or autotriggering. No single ventilator was able to adequately ventilate the six paediatric profiles. Only a few ventilators were able to ventilate the profiles simulating the youngest patients. A systematic paediatric bench evaluation is recommended for every ventilator proposed for home ventilation, in order to detect any dysfunction and guide the choice of the appropriate ventilator for a specific patient.

Mechanisms governing the visco-elastic responses of living cells assessed by foam and tensegrity models.

The visco-elastic properties of living cells, measured to date by various authors, vary considerably, depending on the experimental methods and/or on the theoretical models used. In the present study, two mechanisms thought to be involved in cellular visco-elastic responses were analysed, based on the idea that the cytoskeleton plays a fundamental role in cellular mechanical responses. For this purpose, the predictions of an open unit-cell model and a 30-element visco-elastic tensegrity model were tested, taking into consideration similar properties of the constitutive F-actin. The quantitative predictions of the time constant and viscosity modulus obtained by both models were compared with previously published experimental data obtained from living cells. The small viscosity modulus values (10(0)-10(3) Pa x s) predicted by the tensegrity model may reflect the combined contributions of the spatially rearranged constitutive filaments and the internal tension to the overall cytoskeleton response to external loading. In contrast, the high viscosity modulus values (10(3)-10(5) Pa x s) predicted by the unit-cell model may rather reflect the mechanical response of the cytoskeleton to the bending of the constitutive filaments and/or to the deformation of internal components. The present results suggest the existence of a close link between the overall visco-elastic response of micromanipulated cells and the underlying architecture.

Segmental analysis of nasal cavity compliance by acoustic rhinometry.

To explore the determinants of possible collapse of the nasal valve region, a common cause of nasal obstruction, we evaluated the mechanical properties of the nasal wall. In this study, we determined the nasal cross-sectional area-to-negative pressure ratio (nasal wall compliance) in the anterior part of the nose in six healthy subjects by measuring nasal area by acoustic rhinometry at pressures ranging from atmospheric pressure to a negative pressure of -10 cmH(2)O. Measurements were performed at baseline and after nasal mucosal decongestion (oxymetazoline). At baseline, nasal wall compliance increased progressively from the nasal valve (0.031 +/- 0.016 cm2/cmH(2)O, mean +/- SD) to the anterior and medial part of the inferior turbinate (0.045 +/- 0.024 cm2/cmH(2)O) and to the middle meatus region (0.056 +/- 0.029 cm2/cmH(2)O). After decongestant, compliances decreased and became similar in the three regions. On the basis of these results, we hypothesize that compliance of the nasal wall is partly related to mucosal blood volume and quantity of vascular tissue, which differ in the three regions, increasing from the nasal valve to the middle meatus.

Snoring detection during auto-nasal continuous positive airway pressure.

A bench study using an artificial lung model was performed to evaluate the snoring detection sensitivity of six (commercially available) auto-nasal continuous positive airway pressure (NCPAP) devices. Snoring was simulated by a loudspeaker connected to the lung model and abruptly activated during 1 s of each inspiratory period to induce pressure oscillation. The oscillation frequencies chosen were 30, 60, 90, and 120 Hz. For each frequency, the amplitude of the pressure oscillation produced by the loudspeaker was adjusted to find the threshold at which the auto-nCPAP devices detected snoring. Differences in pressure-amplitude thresholds of up to three-fold were found across auto-nCPAP devices. A randomized clinical study to compare the effects of the least sensitive (Virtuoso LX; Respironics, Nantes, France) and one of the most sensitive, (Goodknight 418A; Malinckrodt, Nancy, France) devices, in two groups of six patients with obstructive sleep apnoea syndrome was then conducted. Goodknight 418A was more sensitive than Virtuoso LX for detecting snoring (mean +/- SD 92 +/- 11% versus 50 +/- 39% respectively, p = 0.03). To conclude, striking differences exist between auto-nasal continuous positive airway pressure devices in sensitivity for detecting snoring.

In vivo physiologic comparison of two ventilators used for domiciliary ventilation in children with cystic fibrosis.

OBJECTIVE: Home noninvasive mechanical ventilation (NIMV) is used with increasing frequency for the treatment of patients with respiratory failure caused by cystic fibrosis, yet the optimal mode of ventilation in such children is unknown. We compared the physiologic short-term effects of two ventilators with different modes (one pressure support and the other assist control/volume-targeted [AC/VT]) commonly used for domiciliary ventilation. DESIGN: Prospective, randomized, crossover comparison of two ventilators with different modes. SETTING: Tertiary pediatric university hospital. PATIENTS: Eight children with cystic fibrosis (age, 11-17 yrs) and chronic respiratory failure (pH 7.4 +/- 0.0; PaO2, 57.5 +/- 7.5 torr; PaCO2, 46.1 +/- 2.5 torr), naive to NIMV. INTERVENTIONS: Two 20-min runs of pressure support and AC/VT ventilation were performed in random order, each run being preceded and followed by 20 mins of spontaneous breathing. MEASUREMENTS: Flow and airway pressure and esophageal and gastric pressures were measured to calculate esophageal (PTPes) and diaphragmatic pressure-time product (PTPdi) and the work of breathing. RESULTS: The two NIMV sessions significantly improved blood gas variables and increased tidal volume with no change in respiratory rate. Indexes of respiratory effort decreased significantly during the two modes of NIMV compared with spontaneous breathing, with PTPdi/min decreasing from 497.8 +/- 115.4 cm H2O x sec x min(-1) during spontaneous breathing to 127.8 +/- 98.3 cm H2O x sec x min(-1) and 184.3 +/- 79.8 cm H2O x sec x min(-1), during AC/VT and pressure support, respectively (p <.0001), and the work of breathing decreasing from 1.83 +/- 0.12 J.L-1 during spontaneous breathing to 0.48 +/- 0.32 J.L-1 and 0.75 +/- 0.30 J.L-1, during AC/VT and pressure support, respectively (p <.0001). In addition, the effect of AC/VT ventilation was significantly superior to pressure support judged by PTPes and the work of breathing, but this result was explained by three patients who adapted extremely well to the AC/VT ventilation, with the disappearance of ventilator triggering, in effect adopting a controlled mode. There was a correlation between the improvement in PTPdi/min or the work of breathing and patient's subjective impression of comfort during the AC/VT ventilation. CONCLUSIONS: In awake, stable children with cystic fibrosis, both AC/VT and pressure support unloaded the respiratory muscles. The disappearance of ventilator triggering occurred in a subgroup of patients during AC/VT ventilation, and this explained the good tolerance and the superiority of this mode in the present study.

Helium-oxygen in the postextubation period decreases inspiratory effort.

After tracheal extubation, upper and total airway resistances may frequently be increased resulting in an increase in inspiratory effort to breathe. We tested whether breathing a helium-oxygen mixture (HeO(2)) would reduce inspiratory effort in the period after extubation. Eighteen consecutive patients with no chronic obstructive pulmonary disease who had received mechanical ventilation (> 48 h) were successively studied immediately after extubation (N(2)O(2)), 15 min after breathing HeO(2), and after return to N(2)O(2). Effort to breathe, assessed by the transdiaphragmatic pressure swings (DeltaPdi) and the pressure-time index of the diaphragm (PTI), comfort, and gas exchange, were the main end points. The mean reduction of the transdiaphragmatic pressure under HeO(2) was 19 +/- 5%. All but three patients presented a decrease in transdiaphragmatic pressure under HeO(2), ranging from - 4 to - 55%, and a significant reduction in DeltaPdi was observed between HeO(2) and N(2)O(2) (10.2 +/- 0.7 versus 8.6 +/- 1.1 versus 10.0 +/- 0.8 cm H(2)O for the three consecutive periods; p < 0.05). PTI also differed significantly between HeO(2) and N(2)O(2) (197 +/- 19 versus 166 +/- 22 versus 201 +/- 23 cm H(2)O/s/min for the three periods; p < 0.05). Breathing HeO(2) significantly improved comfort, whereas gas exchange was not modified. We conclude that the use of HeO(2) in the immediate postextubation period decreases inspiratory effort and improves comfort.

Dual assessment of airway area profile and respiratory input impedance from a single transient wave.

This report concerns the inference of geometric and mechanical airway characteristics based on information derived from a single transient planar wave recorded at the airway opening. We describe a new method to simultaneously measure upper airway area and respiratory input impedance by performing dual analysis of a single pressure wave. The algorithms required to reconstruct airway dimensions and mechanical characteristics were developed, implemented, and tested with reference to known physical models. Our method appears suitable to estimate, even under severe intensive care unit conditions, the respiratory system frequency response (above 10 Hz) in intubated patients and the patency of the endotracheal tube used to connect the patients to the ventilator.

Optimization of aerosol deposition by pressure support in children with cystic fibrosis: an experimental and clinical study.

Nebulized aerosols are commonly used to deliver drugs into the lungs of patients with cystic fibrosis (CF). The aim of this study was to assess the effectiveness of pressure-support (PS) ventilation in increasing aerosol deposition within the lungs of children with CF. An in vitro study demonstrated the feasibility of coupling a breath-actuated nebulizer to a PS device. An in vivo study was done with 18 children (ages 6 to 21 yr) with clinically stable CF, each of whom underwent both a standard and a PS-driven ventilation scan (control session and PS session, respectively). In addition, a perfusion scan was used to determine lung outlines and to construct a geometric model for quantifying aerosol deposition by radioactivity counting in MBq. Homogeneity of nebulization was evaluated from the four first-order moments of aerosol distribution in the peripheral and central lung regions. The time-activity nebulization curve was linear in all patients, with higher slopes during the PS than during the control session (0.43 +/- 0.07 [mean +/- SD] MBq/min and 0.32 +/- 0.23 MBq/min, respectively; p < 0.018). Quantitatively, aerosol deposition was about 30% greater after the PS session (4.4 +/- 2.7 MBq) than after the control session (3.4 +/- 2.1 MBq; p < 0.05). Similarly, deposition efficacy (as a percentage of nebulizer output) was significantly better during the PS session than during the control session (15.3 +/- 8.3% versus 11.5 +/- 5.7%, p < 0.05). No differences in the regional deposition pattern or in homogeneity of uptake were observed. In conclusion, our data show that driving the delivery of a nebulized aerosol by noninvasive PS ventilation enhances total lung aerosol deposition without increasing particle impaction in the proximal airways.

Detection of positional airway obstruction in neonates by acoustic reflection.

In neonates intubated with an uncuffed endotracheal tube (ETT), positional changes of the head may induce obstruction (side position-related ETT obstruction [SPRO]) due to abutment of the beveled distal ETT orifice against the tracheal wall. We studied whether the acoustic reflection (ACR) method, a 4-s measurement that maps cross-sectional area as a function of the distance along the ETT and the airways, could detect SPRO. Eleven preterm newborns intubated with 2.5-mm ETTs and clinically suspected of having SPRO were studied with the head oriented to the left and to the right. In all patients there was a marked decrease in the ACR-measured area beyond the distal tip of the ETT in the presence of obstruction (decrease = 38 +/- 22% [mean +/- SD] of the ETT inside area), while the ACR-measured area increased markedly in the absence of obstruction (increase = 49 +/- 17%). For six of the 11 infants, we also recorded the maximal flow produced by a set mechanical inflation pressure. This maximal flow decreased in the presence of obstruction (decrease = 47 +/- 18%), and was constantly associated with a decrease in ACR-measured area beyond the ETT. In conclusion, ACR measurement is an efficient method for diagnosing positional ETT obstruction in intubated newborns.

Noninvasive ventilation with helium-oxygen in acute exacerbations of chronic obstructive pulmonary disease.

The use of helium-oxygen (HeO(2)) was tested in combination with noninvasive ventilation (NIV) in 10 patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). Effort to breathe as assessed by the respiratory muscle pressure-time index (PTI), work of breathing (WOB), and gas exchange were the main endpoints. Results of NIV-HeO(2) were compared with those obtained with standard NIV (AirO(2)), at two levels of pressure-support ventilation (PSV), 9 +/- 2 cm H(2)O and 18 +/- 3 cm H(2)O. Significant reductions in PTI were observed between HeO(2) and AirO(2) at both the low PSV level (n = 9; 160 +/- 58 versus 198 +/- 78 cm H(2)O/s/ min; p < 0.05) and the high PSV level (n = 10; 100 +/- 45 versus 150 +/- 82 cm H(2)O/s/min; p < 0.01). WOB also differed significantly between HeO(2) and AirO(2) (7.8 +/- 4.1 versus 10.9 +/- 6.1 J/min at the low PSV level, p < 0.05; and 5.7 +/- 3.3 versus 9.2 +/- 5. J/min, p < 0.01 at the high PSV level). HeO(2) reduced Pa(CO(2)) at both the low PSV level (61 +/- 13 versus 64 +/- 15 mm Hg; p < 0.05) and the high PSV level (56 +/- 13 versus 58 +/- 14 mm Hg; p < 0.05), without significantly changing breathing pattern or oxygenation. We conclude that use of HeO(2) during NIV markedly enhances the ability of NIV to reduce patient effort and to improve gas exchange.

Positive pressure generation by pneumatic and electronic O2 regulators: a bench experimental evaluation.

BACKGROUND: The introduction of advanced anti-G protection into agile fast fighter aircraft may result in the regular use of positive pressure breathing (PPB) for G protection by aircrew. Since PPB results in an external additional work of breathing (WoB), we compared the mechanical performance of the pneumatic and electronic O2 regulators designed for "Mirage 2000" and "Rafale" aircraft. HYPOTHESIS: Since mask pressure is regulated by the electronic device in relation to flow, mask pressure will remain constant throughout the respiratory cycle, so that PPB-related additional WoB will be less with the electronic regulator. METHODS: In a bench dynamic study performed with a sinusoidal pump, we measured variations in mask pressure (deltaP) and calculated WoB at 0, 3 and 6 kPa of PPB (0, 30 and 60 cm H2O, respectively), for 0.5, 1 and 2 L of volume and for 10, 15 and 20 cycles per minute of respiratory rate. RESULTS: We found that, compared with the pneumatic device, inspiratory and expiratory WoB with the electronic device were respectively lower by approximately 25% (p < 0.05) and by approximately 10% (NS) at 3 and 6 kPa of PPB, for all respiratory conditions. Nevertheless, we also observed remaining variations in mask pressure with the electronic regulator, due to complex impedance of the inspiratory circuit, since the device uses the pressure measured into the regulator. CONCLUSIONS: We concluded that the electronic control of mask pressure is relatively efficient but that the device would be improved by placing the site of the pressure measurement into the mask.

Estimation of inspiratory pressure drop in neonatal and pediatric endotracheal tubes.

Endotracheal tubes (ETTs) constitute a resistive extra load for intubated patients. The ETT pressure drop (DeltaP(ETT)) is usually described by empirical equations that are specific to one ETT only. Our laboratory previously showed that, in adult ETTs, DeltaP(ETT) is given by the Blasius formula (F. Lofaso, B. Louis, L. Brochard, A. Harf, and D. Isabey. Am. Rev. Respir. Dis. 146: 974-979, 1992). Here, we also propose a general formulation for neonatal and pediatric ETTs on the basis of adimensional analysis of the pressure-flow relationship. Pressure and flow were directly measured in seven ETTs (internal diameter: 2.5-7.0 mm). The measured pressure drop was compared with the predicted drop given by general laws for a curved tube. In neonatal ETTs (2.5-3.5 mm) the flow regime is laminar. The DeltaP(ETT) can be estimated by the Ito formula, which replaces Poiseuille's law for curved tubes. For pediatric ETTs (4.0-7.0 mm), DeltaP(ETT) depends on the following flow regime: for laminar flow, it must be calculated by the Ito formula, and for turbulent flow, by the Blasius formula. Both formulas allow for ETT geometry and gas properties.

Physiological effects of alveolar, tracheal, and "standard" pressure supports.

Pressure support (PS) is characterized by a pressure plateau, which is usually generated at the ventilator level (PS(vent)). We have built a PS device in which the pressure plateau can be obtained at the upper airway level (PS(aw)) or at the alveolar level (PS(A)). The effect of these different PS modes was evaluated in seven healthy men during air breathing and 5% CO(2) breathing. Minute ventilation during air breathing was higher with PS(A) than with PS(aw) and lower with PS(vent) (16 +/- 3, 14 +/- 3, and 11 +/- 2 l/min, respectively). By contrast, there were no significant differences in minute ventilation during 5% CO(2) breathing (25 +/- 5, 27 +/- 7, and 23 +/- 5 l/min, respectively). The esophageal pressure-time product per minute was lower with PS(A) than with PS(aw) and PS(vent) during air breathing (29 +/- 26, 44 +/- 44, and 48 +/- 30 cmH(2)O. s, respectively) and 5% CO(2) breathing (97 +/- 40, 145 +/- 62, and 220 +/- 41 cmH(2)O. s, respectively). In conclusion, during PS, moving the inspiratory pressure plateau from the ventilator to the alveolar level reduces pressure output, particularly at high ventilation levels.