A vagal reflex evoked by airway closure.

Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and, on a moment-by-moment basis, enact vital reflexes to maintain respiratory function1,2. Decreased lung capacity is common and life-threatening across many respiratory diseases, and lung collapse can be acutely evoked by chest wall trauma, pneumothorax or airway compression. Here we characterize a neuronal reflex of the vagus nerve evoked by airway closure that leads to gasping. In vivo vagal ganglion imaging revealed dedicated sensory neurons that detect airway compression but not airway stretch. Vagal neurons expressing PVALB mediate airway closure responses and innervate clusters of lung epithelial cells called neuroepithelial bodies (NEBs). Stimulating NEBs or vagal PVALB neurons evoked gasping in the absence of airway threats, whereas ablating NEBs or vagal PVALB neurons eliminated gasping in response to airway closure. Single-cell RNA sequencing revealed that NEBs uniformly express the mechanoreceptor PIEZO2, and targeted knockout of Piezo2 in NEBs eliminated responses to airway closure. NEBs were dispensable for the Hering-Breuer inspiratory reflex, which indicated that discrete terminal structures detect airway closure and inflation. Similar to the involvement of Merkel cells in touch sensation3,4, NEBs are PIEZO2-expressing epithelial cells and, moreover, are crucial for an aspect of lung mechanosensation. These findings expand our understanding of neuronal diversity in the airways and reveal a dedicated vagal pathway that detects airway closure to help preserve respiratory function.

Driving pressure of respiratory system and lung stress in mechanically ventilated patients with active breathing.

BACKGROUND: During control mechanical ventilation (CMV), the driving pressure of the respiratory system (ΔPrs) serves as a surrogate of transpulmonary driving pressure (ΔPlung). Expiratory muscle activity that decreases end-expiratory lung volume may impair the validity of ΔPrs to reflect ΔPlung. This prospective observational study in patients with acute respiratory distress syndrome (ARDS) ventilated with proportional assist ventilation (PAV+), aimed to investigate: (1) the prevalence of elevated ΔPlung, (2) the ΔPrs-ΔPlung relationship, and (3) whether dynamic transpulmonary pressure (Plungsw) and effort indices (transdiaphragmatic and respiratory muscle pressure swings) remain within safe limits. METHODS: Thirty-one patients instrumented with esophageal and gastric catheters (n = 22) were switched from CMV to PAV+ and respiratory variables were recorded, over a maximum of 24 h. To decrease the contribution of random breaths with irregular characteristics, a 7-breath moving average technique was applied. In each patient, measurements were also analyzed per deciles of increasing lung elastance (Elung). Patients were divided into Group A, if end-inspiratory transpulmonary pressure (PLEI) increased as Elung increased, and Group B, which showed a decrease or no change in PLEI with Elung increase. RESULTS: In 44,836 occluded breaths, ΔPlung ≥ 12 cmH2O was infrequently observed [0.0% (0.0-16.9%) of measurements]. End-expiratory lung volume decrease, due to active expiration, was associated with underestimation of ΔPlung by ΔPrs, as suggested by a negative linear relationship between transpulmonary pressure at end-expiration (PLEE) and ΔPlung/ΔPrs. Group A included 17 and Group B 14 patients. As Elung increased, ΔPlung increased mainly due to PLEI increase in Group A, and PLEE decrease in Group B. Although ΔPrs had an area receiver operating characteristic curve (AUC) of 0.87 (95% confidence intervals 0.82-0.92, P < 0.001) for ΔPlung ≥ 12 cmH2O, this was due exclusively to Group A [0.91 (0.86-0.95), P < 0.001]. In Group B, ΔPrs showed no predictive capacity for detecting ΔPlung ≥ 12 cmH2O [0.65 (0.52-0.78), P > 0.05]. Most of the time Plungsw and effort indices remained within safe range. CONCLUSION: In patients with ARDS ventilated with PAV+, injurious tidal lung stress and effort were infrequent. In the presence of expiratory muscle activity, ΔPrs underestimated ΔPlung. This phenomenon limits the usefulness of ΔPrs as a surrogate of tidal lung stress, regardless of the mode of support.

Pulmonary response prediction through personalized basis functions in a virtual patient model.

BACKGROUND AND OBJECTIVE: Recruitment maneuvers with subsequent positive-end-expiratory-pressure (PEEP) have proven effective in recruiting lung volume and preventing alveoli collapse. However, determining a safe, effective, and patient-specific PEEP is not standardized, and this more optimal PEEP level evolves with patient condition, requiring personalised monitoring and care approaches to maintain optimal ventilation settings. METHODS: This research examines 3 physiologically relevant basis function sets (exponential, parabolic, cumulative) to enable better prediction of elastance evolution for a virtual patient or digital twin model of MV lung mechanics, including novel elements to model and predict distension elastance. Prediction accuracy and robustness are validated against recruitment maneuver data from 18 volume-controlled ventilation (VCV) patients at 7 different baseline PEEP levels (0 to 12 cmH2O) and 14 pressure-controlled ventilation (PCV) patients at 4 different baseline PEEP levels (6 to 12 cmH2O), yielding 623 and 294 prediction cases, respectively. Predictions were made up to 12 cmH2O of added PEEP ahead, covering 6 × 2 cmH2O PEEP steps. RESULTS: The 3 basis function sets yield median absolute peak inspiratory pressure (PIP) prediction error of 1.63 cmH2O for VCV patients, and median peak inspiratory volume (PIV) prediction error of 0.028 L for PCV patients. The exponential basis function set yields a better trade-off of overall performance across VCV and PCV prediction than parabolic and cumulative basis function sets from other studies. Comparing predicted and clinically measured distension prediction in VCV demonstrated consistent, robust high accuracy with R2 = 0.90-0.95. CONCLUSIONS: The results demonstrate recruitment mechanics are best captured by an exponential basis function across different mechanical ventilation modes, matching physiological expectations, and accurately capture, for the first time, distension mechanics to within 5-10 % accuracy. Enabling the risk of lung injury to be predicted before changing ventilator settings. The overall outcomes significantly extend and more fully validate this digital twin or virtual mechanical ventilation patient model.

A Comparative Study of Ex-Vivo Murine Pulmonary Mechanics Under Positive- and Negative-Pressure Ventilation.

Increased ventilator use during the COVID-19 pandemic resurrected persistent questions regarding mechanical ventilation including the difference between physiological and artificial breathing induced by ventilators (i.e., positive- versus negative-pressure ventilation, PPV vs NPV). To address this controversy, we compare murine specimens subjected to PPV and NPV in ex vivo quasi-static loading and quantify pulmonary mechanics via measures of quasi-static and dynamic compliances, transpulmonary pressure, and energetics when varying inflation frequency and volume. Each investigated mechanical parameter yields instance(s) of significant variability between ventilation modes. Most notably, inflation compliance, percent relaxation, and peak pressure are found to be consistently dependent on the ventilation mode. Maximum inflation volume and frequency note varied dependencies contingent on the ventilation mode. Contradictory to limited previous clinical investigations of oxygenation and end-inspiratory measures, the mechanics-focused comprehensive findings presented here indicate lung properties are dependent on loading mode, and importantly, these dependencies differ between smaller versus larger mammalian species despite identical custom-designed PPV/NPV ventilator usage. Results indicate that past contradictory findings regarding ventilation mode comparisons in the field may be linked to the chosen animal model. Understanding the differing fundamental mechanics between PPV and NPV may provide insights for improving ventilation strategies and design to prevent associated lung injuries.

An Initial Investigation of Diaphragm Neurostimulation in Patients with Acute Respiratory Distress Syndrome.

BACKGROUND: Lung protective ventilation aims at limiting lung stress and strain. By reducing the amount of pressure transmitted by the ventilator into the lungs, diaphragm neurostimulation offers a promising approach to minimize ventilator-induced lung injury. This study investigates the physiologic effects of diaphragm neurostimulation in acute respiratory distress syndrome (ARDS) patients. The hypothesis was that diaphragm neurostimulation would improve oxygenation, would limit the distending pressures of the lungs, and would improve cardiac output. METHODS: Patients with moderate ARDS were included after 48 h of invasive mechanical ventilation and had a left subclavian catheter placed to deliver bilateral transvenous phrenic nerve stimulation. Two 60-min volume-controlled mechanical ventilation (control) sessions were interspersed by two 60-min diaphragm neurostimulation sessions delivered continually, in synchrony with the ventilator. Gas exchange, lung mechanics, chest electrical impedance tomography, and cardiac index were continuously monitored and compared across four sessions. The primary endpoint was the Pao2/fraction of inspired oxygen (Fio2) ratio at the end of each session, and the secondary endpoints were lung mechanics and hemodynamics. RESULTS: Thirteen patients were enrolled but the catheter could not be inserted in one, leaving 12 patients for analysis. All sessions were conducted without interruption and well tolerated. The Pao2/Fio2 ratio did not change during the four sessions. Median (interquartile range) plateau pressure was 23 (20 to 31) cm H2O and 21 (17 to 25) cm H2O, driving pressure was 14 (12 to 18) cm H2O and 11 (10 to 13) cm H2O, and end-inspiratory transpulmonary pressure was 9 (5 to 11) cm H2O and 7 (4 to 11) cm H2O during mechanical ventilation alone and during mechanical ventilation + neurostimulation session, respectively. The dorsal/ventral ventilation surface ratio was 0.70 (0.54 to 0.91) when on mechanical ventilation and 1.20 (0.76 to 1.33) during the mechanical ventilation + neurostimulation session. The cardiac index was 2.7 (2.3 to 3.5) l · min-1 · m-2 on mechanical ventilation and 3.0 (2.4 to 3.9) l · min-1 · m-2 on mechanical ventilation + neurostimulation. CONCLUSIONS: This proof-of-concept study showed the feasibility of short-term diaphragm neurostimulation in conjunction with mechanical ventilation in ARDS patients. Diaphragm neurostimulation was associated with positive effects on lung mechanics and on hemodynamics.

Hemodynamic effects of positive end-expiratory pressure.

PURPOSE OF REVIEW: Positive end-expiratory pressure (PEEP) is required in the Berlin definition of acute respiratory distress syndrome and is a cornerstone of its treatment. Application of PEEP increases airway pressure and modifies pleural and transpulmonary pressures according to respiratory mechanics, resulting in blood volume alteration into the pulmonary circulation. This can in turn affect right ventricular preload, afterload and function. At the opposite, PEEP may improve left ventricular function, providing no deleterious effect occurs on the right ventricle. RECENT FINDINGS: This review examines the impact of PEEP on cardiac function with regards to heart-lung interactions, and describes its consequences on organs perfusion and function, including the kidney, gut, liver and the brain. PEEP in itself is not beneficious nor detrimental on end-organ hemodynamics, but its hemodynamic effects vary according to both respiratory mechanics and association with other hemodynamic variables such as central venous or mean arterial pressure. There are parallels in the means of preventing deleterious impact of PEEP on the lungs, heart, kidney, liver and central nervous system. SUMMARY: The quest for optimal PEEP settings has been a prominent goal in ARDS research for the last decades. Intensive care physician must maintain a high degree of vigilance towards hemodynamic effects of PEEP on cardiac function and end-organs circulation.

Esophageal balloon catheter system identification to improve respiratory effort time features and amplitude determination.

Objective. Understanding a patient's respiratory effort and mechanics is essential for the provision of individualized care during mechanical ventilation. However, measurement of transpulmonary pressure (the difference between airway and pleural pressures) is not easily performed in practice. While airway pressures are available on most mechanical ventilators, pleural pressures are measured indirectly by an esophageal balloon catheter. In many cases, esophageal pressure readings take other phenomena into account and are not a reliable measure of pleural pressure.Approach.A system identification approach was applied to provide accurate pleural measures from esophageal pressure readings. First, we used a closed pressurized chamber to stimulate an esophageal balloon and model its dynamics. Second, we created a simplified version of an artificial lung and tried the model with different ventilation configurations. For validation, data from 11 patients (five male and six female) were used to estimate respiratory effort profile and patient mechanics.Main results.After correcting the dynamic response of the balloon catheter, the estimates of resistance and compliance and the corresponding respiratory effort waveform were improved when compared with the adjusted quantities in the test bench. The performance of the estimated model was evaluated using the respiratory pause/occlusion maneuver, demonstrating improved agreement between the airway and esophageal pressure waveforms when using the normalized mean squared error metric. Using the corrected muscle pressure waveform, we detected start and peak times 130 ± 50 ms earlier and a peak amplitude 2.04 ± 1.46 cmH2O higher than the corresponding estimates from esophageal catheter readings.Significance.Compensating the acquired measurements with system identification techniques makes the readings more accurate, possibly better portraying the patient's situation for individualization of ventilation therapy.

The depth of neuromuscular blockade is not related to chest wall elastance and respiratory mechanics in moderate to severe acute respiratory distress syndrome patients. A prospective cohort study.

BACKGROUND: Data concerning the depth of neuromuscular blockade (NMB) required for effective relaxation of the respiratory muscles in ARDS are scarce. We hypothesised that complete versus partial NMB can modify respiratory mechanics. METHOD: Prospective study to compare the respiratory mechanics of ARDS patients according to the NMB depth. Each patient was analysed at two times: deep NMB (facial train of four count (TOFC) = 0) and intermediate NMB (TOFC >0). The primary endpoint was the comparison of chest wall elastance (ELCW) according to the NMB level. RESULTS: 33 ARDS patients were analysed. There was no statistical difference between the ELCW at TOFC = 0 compared to TOFC >0: 7 cmH2O/l [5.7-9.5] versus 7 cmH2O/l [5.3-10.8] (p = 0.36). The depth of NMB did not modify the expiratory nor inspiratory oesophageal pressure (Pesexp = 8 cmH2O [5-9.5] at TOFC = 0 versus 7 cmH2O [5-10] at TOFC >0; (p = 0.16) and Pesinsp = 10 cmH2O [8.2-13] at TOFC = 0 versus 10 cmH2O [8-13] at TOFC >0; (p = 0.12)). CONCLUSION: In ARDS, the relaxation of the respiratory muscles seems to be independent of the NMB level.

Electropneumatic system for the simulation of the pulmonary viscoelastic effect in a mechanical ventilation scenario.

The viscoelastic properties of the lung have important implications during respiratory mechanics in terms of lung movement or work of breathing, for example. However, this property has not been well characterized due to several reasons, such as the complex nature of the lung, difficulty accessing its tissues, and the lack of physical simulators that represent viscoelastic effects. This research proposes an electropneumatic system and a method to simulate the viscoelastic effect from temporary forces generated by the opposition of magnetic poles. The study was tested in a mechanical ventilation scenario with inspiratory pause, using a Hamilton-S1 mechanical ventilator (Hamilton Medical) and a simulator of the human respiratory system (SAMI-SII). The implemented system was able to simulate the stress relaxation response of a Standard Linear Solid model in the Maxwell form and showed the capacity to control elastic and viscous parameters independently. To the best of our knowledge, this is the first system incorporated into a physical lung simulator that represents the viscoelastic effect in a mechanical ventilation scenario.

Real-time changes in rib cage expansion and use of abdominal mechanical stimulation in newborns: a quasi-experimental study.

OBJECTIVE: To assess the rib cage expansion and respiratory rate in newborns using an abdominal stabilization band. METHODS: The study included 32 newborns of both genders, with gestational age between 35 and 41 weeks. The abdominal stabilization band was used for 15 minutes between the xiphoid process and the anterosuperior iliac crest, with an abdominal contention 0.5cm smaller than the abdominal circumference. The rib cage expansion was evaluated by a breathing transducer (Pneumotrace II™) three minutes before using the band, during the use (15 minutes), and ten minutes after removing the band. The Shapiro-Wilk test verified data normality, and the Wilcoxon test compared the variables considering rib cage expansion and respiratory rate. Significance was set to p<0.05. RESULTS: There was an increase in respiratory rate when comparing before and ten minutes after removing (p=0.008) the abdominal stabilization band, as well as when comparing during its use and ten minutes after its removal (p=0.001). There was also an increase in rib cage expansion when comparing before and during the use of the abdominal stabilization band (p=0.005). CONCLUSIONS: The use of the abdominal stabilization band promoted an increase in the rib cage expansion and respiratory rate in the assessed newborns and may be a viable option to improve the respiratory kinematics of this population.

Non-Invasive Assessment of Abdominal/Diaphragmatic and Thoracic/Intercostal Spontaneous Breathing Contributions.

(1) Background: Technically, a simple, inexpensive, and non-invasive method of ascertaining volume changes in thoracic and abdominal cavities are required to expedite the development and validation of pulmonary mechanics models. Clinically, this measure enables the real-time monitoring of muscular recruitment patterns and breathing effort. Thus, it has the potential, for example, to help differentiate between respiratory disease and dysfunctional breathing, which otherwise can present with similar symptoms such as breath rate. Current automatic methods of measuring chest expansion are invasive, intrusive, and/or difficult to conduct in conjunction with pulmonary function testing (spontaneous breathing pressure and flow measurements). (2) Methods: A tape measure and rotary encoder band system developed by the authors was used to directly measure changes in thoracic and abdominal circumferences without the calibration required for analogous strain-gauge-based or image processing solutions. (3) Results: Using scaling factors from the literature allowed for the conversion of thoracic and abdominal motion to lung volume, combining motion measurements correlated to flow-based measured tidal volume (normalised by subject weight) with R2 = 0.79 in data from 29 healthy adult subjects during panting, normal, and deep breathing at 0 cmH2O (ZEEP), 4 cmH2O, and 8 cmH2O PEEP (positive end-expiratory pressure). However, the correlation for individual subjects is substantially higher, indicating size and other physiological differences should be accounted for in scaling. The pattern of abdominal and chest expansion was captured, allowing for the analysis of muscular recruitment patterns over different breathing modes and the differentiation of active and passive modes. (4) Conclusions: The method and measuring device(s) enable the validation of patient-specific lung mechanics models and accurately elucidate diaphragmatic-driven volume changes due to intercostal/chest-wall muscular recruitment and elastic recoil.

Respiratory oscillometry and functional analyses in patients with idiopathic scoliosis.

Scoliosis is a condition that affects the spine and causes chest rotation and trunk distortion. Individuals with severe deformities may experience dyspnea on exertion and develop respiratory failure. Respiratory oscillometry is a simple and non-invasive method that provides detailed information on lung mechanics. This work aims to investigate the potential of oscillometry in the evaluation of respiratory mechanics in patients with scoliosis and its association with physical performance. We analyzed 32 volunteers in the control group and 32 in the scoliosis group. The volunteers underwent traditional pulmonary function tests, oscillometry, and the 6-minute walk test (6MWT). Oscillometric analysis showed increased values of resistance at 4 Hz (R4, P<0.01), 12 Hz (R12, P<0.0001), and 20 Hz (R20, P<0.01). Similar analysis showed reductions in dynamic compliance (Cdyn, P<0.001) and ventilation homogeneity, as evaluated by resonance frequency (fr, P<0.001) and reactance area (Ax, P<0.001). Respiratory work, described by the impedance modulus, also showed increased values (Z4, P<0.01). Functional capacity was reduced in the group with scoliosis (P<0.001). A significant direct correlation was found between Cobb angle and R12, AX, and Z4 (P=0.0237, P=0.0338, and P=0.0147, respectively), and an inverse correlation was found between Cdyn and Cobb angle (P=0.0190). These results provided new information on respiratory mechanics in scoliosis and are consistent with the involved pathophysiology, suggesting that oscillometry may improve lung function tests for patients with scoliosis.

Physiological effects of lung-protective ventilation in patients with lung fibrosis and usual interstitial pneumonia pattern versus primary ARDS: a matched-control study.

BACKGROUND: Although patients with interstitial pneumonia pattern (ILD-UIP) and acute exacerbation (AE) leading to severe acute respiratory failure may require invasive mechanical ventilation (MV), physiological data on lung mechanics during MV are lacking. We aimed at describing the physiological effect of lung-protective ventilation in patients with AE-ILD-UIP compared with primary ARDS. METHODS: Partitioned lung and chest wall mechanics were assessed in a series of AE-ILD-UIP patients matched 1:1 with primary ARDS as controls (based on BMI and PaO2/FiO2 ratio). Three PEEP levels (zero = ZEEP, 4-8 cmH2O = PEEPLOW, and titrated to achieve positive end-expiratory transpulmonary pressure PL,EE = PEEPTITRATED) were used for measurements. RESULTS: Ten AE-ILD-UIP patients and 10 matched ARDS were included. In AE-ILD-UIP median PL,EE at ZEEP was - 4.3 [- 7.6- - 2.3] cmH2O and lung elastance (EL) 44 [40-51] cmH2O/L. At PEEPLOW, PL,EE remained negative and EL did not change (p = 0.995) versus ZEEP. At PEEPTITRATED, PL,EE increased to 0.8 [0.3-1.5] cmH2O and EL to 49 [43-59] (p = 0.004 and p < 0.001 compared to ZEEP and PEEPLOW, respectively). ΔPL decreased at PEEPLOW (p = 0.018) and increased at PEEPTITRATED (p = 0.003). In matched ARDS control PEEP titration to obtain a positive PL,EE did not result in significant changes in EL and ΔPL. CONCLUSIONS: In mechanically ventilated AE-ILD-UIP patients, differently than in patients with primary ARDS, PEEP titrated to obtain a positive PL,EE significantly worsened lung mechanics.

Effects of individualised positive end-expiratory pressure titration on respiratory and haemodynamic parameters during the Trendelenburg position with pneumoperitoneum: A randomised crossover physiologic trial.

BACKGROUND: The Trendelenburg position with pneumoperitoneum during surgery promotes dorsobasal atelectasis formation, which impairs respiratory mechanics and increases lung stress and strain. Positive end-expiratory pressure (PEEP) can reduce pulmonary inhomogeneities and preserve end-expiratory lung volume (EELV), resulting in decreased inspiratory strain and improved gas-exchange. The optimal intraoperative PEEP strategy is unclear. OBJECTIVES: To compare the effects of individualised PEEP titration strategies on set PEEP levels and resulting transpulmonary pressures, respiratory mechanics, gas-exchange and haemodynamics during Trendelenburg position with pneumoperitoneum. DESIGN: Prospective, randomised, crossover single-centre physiologic trial. SETTING: University hospital. PATIENTS: Thirty-six patients receiving robot-assisted laparoscopic radical prostatectomy. INTERVENTIONS: Randomised sequence of three different PEEP strategies: standard PEEP level of 5 cmH 2 O (PEEP 5 ), PEEP titration targeting a minimal driving pressure (PEEP ΔP ) and oesophageal pressure-guided PEEP titration (PEEP Poeso ) targeting an end-expiratory transpulmonary pressure ( PTP ) of 0 cmH 2 O. MAIN OUTCOME MEASURES: The primary endpoint was the PEEP level when set according to PEEP ΔP and PEEP Poeso compared with PEEP of 5 cmH 2 O. Secondary endpoints were respiratory mechanics, lung volumes, gas-exchange and haemodynamic parameters. RESULTS: PEEP levels differed between PEEP ΔP , PEEP Poeso and PEEP5 (18.0 [16.0 to 18.0] vs. 20.0 [18.0 to 24.0]vs. 5.0 [5.0 to 5.0] cmH 2 O; P  < 0.001 each). End-expiratory PTP and lung volume were lower in PEEP ΔP compared with PEEP Poeso ( P  = 0.014 and P  < 0.001, respectively), but driving pressure, lung stress, as well as respiratory system and dynamic elastic power were minimised using PEEP ΔP ( P  < 0.001 each). PEEP ΔP and PEEP Poeso improved gas-exchange, but PEEP Poeso resulted in lower cardiac output compared with PEEP 5 and PEEP ΔP . CONCLUSION: PEEP ΔP ameliorated the effects of Trendelenburg position with pneumoperitoneum during surgery on end-expiratory PTP and lung volume, decreased driving pressure and dynamic elastic power, as well as improved gas-exchange while preserving cardiac output. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00028559, date of registration 2022/04/27). https://drks.de/search/en/trial/DRKS00028559.

Airway and Transpulmonary Driving Pressure by End-Inspiratory Holds During Pressure Support Ventilation.

BACKGROUND: The precision of quasi-static airway driving pressure (ΔP) assessed in pressure support ventilation (PSV) as a surrogate of tidal lung stress is debatable because persistent muscular activity frequently alters the readability of end-inspiratory holds. In this study, we used strict criteria to discard excessive muscular activity during holds and assessed the accuracy of ΔP in predicting global lung stress in PSV. Additionally, we explored whether the physiological effects of high PEEP differed according to the response of respiratory system compliance (CRS). METHODS: Adults with ARDS undergoing PSV were enrolled. An esophageal catheter was inserted to calculate lung stress through transpulmonary driving pressure (ΔPL). ΔP and ΔPL were assessed in PSV at PEEP 5, 10, and 15 cm H2O by end-inspiratory holds. CRS was calculated as tidal volume (VT)/ΔP. We analyzed the effects of high PEEP on pressure-time product per minute (PTPmin), airway pressure at 100 ms (P0.1), and VT over PTP per breath (VT/PTPbr) in subjects with increased versus decreased CRS at high PEEP. RESULTS: Eighteen subjects and 162 end-inspiratory holds were analyzed; 51/162 (31.5%) of the holds had ΔPL ≥ 12 cm H2O. Significant association between ΔP and ΔPL was found at all PEEP levels (P < .001). ΔP had excellent precision to predict ΔPL, with 15 cm H2O being identified as the best threshold for detecting ΔPL ≥ 12 cm H2O (area under the receiver operating characteristics 0.99 [95% CI 0.98-1.00]). CRS changes from low to high PEEP corresponded well with lung compliance changes (R2 0.91, P < .001) When CRS increased, a significant improvement of PTPmin and VT/PTPbr was found, without changes in P0.1. No benefits were observed when CRS decreased. CONCLUSIONS: In subjects with ARDS undergoing PSV, high ΔP assessed by readable end-inspiratory holds accurately detected potentially dangerous thresholds of ΔPL. Using ΔP to assess changes in CRS induced by PEEP during assisted ventilation may inform whether higher PEEP could be beneficial.

Pressure-volume mechanics of inflating and deflating intact whole organ porcine lungs.

Pressure-volume curves of the lung are classical measurements of lung function and are impacted by changes in lung structure due to disease or shifts in air-delivery volume or cycling rate. Diseased and preterm infant lungs have been found to show heterogeneous behavior which is highly frequency dependent. This breathing rate dependency has motivated the exploration of multi-frequency oscillatory ventilators to deliver volume oscillation with optimal frequencies for various portions of the lung to provide more uniform air distribution. The design of these advanced ventilators requires the examination of lung function and mechanics, and an improved understanding of the pressure-volume response of the lung. Therefore, to comprehensively analyze whole lung organ mechanics, we investigate six combinations of varying applied volumes and frequencies using ex-vivo porcine specimens and our custom-designed electromechanical breathing apparatus. Lung responses were evaluated through measurements of inflation and deflation slopes, static compliance, peak pressure and volume, as well as hysteresis, energy loss, and pressure relaxation. Generally, we observed that the lungs were stiffer when subjected to faster breathing rates and lower inflation volumes. The lungs exhibited greater inflation volume dependencies compared to frequency dependencies. This study's reported response of the lung to variations of inflation volume and breathing rate can help the optimization of conventional mechanical ventilators and inform the design of advanced ventilators. Although frequency dependency is found to be minimal in normal porcine lungs, this preliminary study lays a foundation for comparison with pathological lungs, which are known to demonstrate marked rate dependency.

Thoracoabdominal asynchrony in a virtual preterm infant: computational modeling and analysis.

Thoracoabdominal asynchrony (TAA), the asynchronous volume changes between the rib cage and abdomen during breathing, is associated with respiratory distress, progressive lung volume loss, and chronic lung disease in the newborn infant. Preterm infants are prone to TAA risk factors such as weak intercostal muscles, surfactant deficiency, and a flaccid chest wall. The causes of TAA in this fragile population are not fully understood and, to date, the assessment of TAA has not included a mechanistic modeling framework to explore the role these risk factors play in breathing dynamics and how TAA can be resolved. We present a dynamic compartmental model of pulmonary mechanics that simulates TAA in the preterm infant under various adverse clinical conditions, including high chest wall compliance, applied inspiratory resistive loads, bronchopulmonary dysplasia, anesthesia-induced intercostal muscle deactivation, weakened costal diaphragm, impaired lung compliance, and upper airway obstruction. Sensitivity analyses performed to screen and rank model parameter influence on model TAA and respiratory volume outputs show that risk factors are additive so that maximal TAA occurs in a virtual preterm infant with multiple adverse conditions, and addressing risk factors individually causes incremental changes in TAA. An abruptly obstructed upper airway caused immediate nearly paradoxical breathing and tidal volume reduction despite greater effort. In most simulations, increased TAA occurred together with decreased tidal volume. Simulated indices of TAA are consistent with published experimental studies and clinically observed pathophysiology, motivating further investigation into the use of computational modeling for assessing and managing TAA.NEW & NOTEWORTHY A novel model of thoracoabdominal asynchrony incorporates literature-derived mechanics and simulates the impact of risk factors on a virtual preterm infant. Sensitivity analyses were performed to determine the influence of model parameters on TAA and respiratory volume. Predicted phase angles are consistent with prior experimental and clinical results, and influential parameters are associated with clinical scenarios that significantly alter phase angle, motivating further investigation into the use of computational modeling for assessing and managing thoracoabdominal asynchrony.

The oesophageal balloon for respiratory monitoring in ventilated patients: updated clinical review and practical aspects.

There is a well-recognised importance for personalising mechanical ventilation settings to protect the lungs and the diaphragm for each individual patient. Measurement of oesophageal pressure (P oes) as an estimate of pleural pressure allows assessment of partitioned respiratory mechanics and quantification of lung stress, which helps our understanding of the patient's respiratory physiology and could guide individualisation of ventilator settings. Oesophageal manometry also allows breathing effort quantification, which could contribute to improving settings during assisted ventilation and mechanical ventilation weaning. In parallel with technological improvements, P oes monitoring is now available for daily clinical practice. This review provides a fundamental understanding of the relevant physiological concepts that can be assessed using P oes measurements, both during spontaneous breathing and mechanical ventilation. We also present a practical approach for implementing oesophageal manometry at the bedside. While more clinical data are awaited to confirm the benefits of P oes-guided mechanical ventilation and to determine optimal targets under different conditions, we discuss potential practical approaches, including positive end-expiratory pressure setting in controlled ventilation and assessment of inspiratory effort during assisted modes.

Modulation of inspiratory burst duration and frequency by bombesin in vitro.

Mammalian respiratory rhythm-generating circuits in the brainstem are subject to neuromodulation by multiple peptidergic afferent inputs controlling circuit behavior and outputs. Although functionally important, actions of neuropeptide modulators have not been fully characterized. We analyzed at cellular and circuit levels two inspiratory patterns intrinsically generated by the preBötzinger complex (preBötC) and their modulation by the neuropeptides bombesin and substance P (SP) in neonatal rat medullary slices in vitro. We found that, in recordings of hypoglossal nerve and preBötC neuron inspiratory activity, some inspiratory bursts occurring spontaneously under basal conditions have a biphasic shape with longer duration than normal inspiratory bursts and occur at a lower frequency. This biphasic burst pattern has been proposed to represent inspiratory activity underling periodic sighs. Bath-applied bombesin or SP decreased the period and increased the duration of both normal inspiratory and biphasic bursts and their underlying synaptic drives. The ratio of the biphasic long-duration burst period to the normal inspiratory burst period and the ratio of their burst durations remained the same before and after peptidergic modulation. Bombesin increased the frequency of the inspiratory rhythm in a Ca2+-independent manner and the frequency of long-duration bursts in a Ca2+-dependent manner. This finding suggests that period and burst duration coupling are due to intrinsic mechanisms controlling simultaneously timing and burst termination within the inspiratory rhythm-generating network. We propose a model in which signaling cascades activated by bombesin and SP modulate mechanisms controlling inspiratory burst frequency and duration to coordinate preBötC circuit behavioral outputs.

Inspiratory Effort and Respiratory Mechanics in Patients with Acute Exacerbation of Idiopathic Pulmonary fibrosis: A Preliminary Matched Control Study.

BACKGROUND: Patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) may experience severe acute respiratory failure, even requiring ventilatory assistance. Physiological data on lung mechanics during these events are lacking. METHODS: Patients with AE-IPF admitted to Respiratory Intensive Care Unit to receive non-invasive ventilation (NIV) were retrospectively analyzed. Esophageal pressure swing (ΔPes) and respiratory mechanics before and after 2 hours of NIV were collected as primary outcome. The correlation between positive end-expiratory pressure (PEEP) levels and changes of in dynamic compliance (dynCRS) and PaO2/FiO2 ratio was assessed. Further, an exploratory comparison with a historical cohort of ARDS patients matched 1:1 by age, sequential organ failure assessment score, body mass index and PaO2/FiO2 level was performed. RESULTS: At baseline, AE-IPF patients presented a high respiratory drive activation with ΔPes = 27 (21-34) cmH2O, respiratory rate (RR) = 34 (30-39) bpm and minute ventilation (VE) = 21 (20-26) L/min. Two hours after NIV application, ΔPes, RR and VE values showed a significant reduction (16 [14-24] cmH2O, p<0.0001, 27 [25-30] bpm, p=0.001, and 18 [17-20] L/min, p=0.003, respectively) while no significant change was found in dynamic transpulmonary pressure, expiratory tidal volume (Vte), dynCRS and dynamic mechanical power. PEEP levels negatively correlated with PaO2/FiO2 ratio and dynCRS (r=-0.67, p=0.03 and r=-0.27, p=0.4, respectively). When compared to AE-IPF, ARDS patients presented lower baseline ΔPes, RR, VE and dynamic mechanical power. Differently from AE-IPF, in ARDS both Vte and dynCRS increased significantly following NIV (p=0.01 and p=0.004 respectively) with PEEP levels directly associated with PaO2/FiO2 ratio and dynCRS (r=0.24, p=0.5 and r=0.65, p=0.04, respectively). CONCLUSIONS: In this study, patients with AE-IPF showed a high inspiratory effort, whose intensity was reduced by NIV application without a significant improvement in respiratory mechanics. In an exploratory analysis, AE-IPF patients showed a different mechanical behavior under spontaneous unassisted and assisted breathing compared with ARDS patients of similar severity.