Continuous estimation of respiratory system compliance and airway resistance during pressure-controlled ventilation without end-inspiration occlusion.

BACKGROUND: Assessing mechanical properties of the respiratory system (Cst) during mechanical ventilation necessitates an end-inspiration flow of zero, which requires an end-inspiratory occlusion maneuver. This lung model study aimed to observe the effect of airflow obstruction on the accuracy of respiratory mechanical properties during pressure-controlled ventilation (PCV) by analyzing dynamic signals. METHODS: A Hamilton C3 ventilator was attached to a lung simulator that mimics lung mechanics in healthy, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD) models. PCV and volume-controlled ventilation (VCV) were applied with tidal volume (VT) values of 5.0, 7.0, and 10.0 ml/kg. Performance characteristics and respiratory mechanics were assessed and were calibrated by virtual extrapolation using expiratory time constant (RCexp). RESULTS: During PCV ventilation, drive pressure (DP) was significantly increased in the ARDS model. Peak inspiratory flow (PIF) and peak expiratory flow (PEF) gradually declined with increasing severity of airflow obstruction, while DP, end-inspiration flow (EIF), and inspiratory cycling ratio (EIF/PIF%) increased. Similar estimated values of Crs and airway resistance (Raw) during PCV and VCV ventilation were obtained in healthy adult and mild obstructive models, and the calculated errors did not exceed 5%. An underestimation of Crs and an overestimation of Raw were observed in the severe obstruction model. CONCLUSION: Using the modified dynamic signal analysis approach, respiratory system properties (Crs and Raw) could be accurately estimated in patients with non-severe airflow obstruction in the PCV mode.

Effect of Individualized PEEP Guided by Driving Pressure on Diaphragm Function in Patients Undergoing Laparoscopic Radical Resection of Colorectal Cancer: A Randomized Controlled Trial.

BACKGROUND The concept of driving pressure (ΔP) has been established to optimize mechanical ventilation-induced lung injury. However, little is known about the specific effects of setting individualized positive end-expiratory pressure (PEEP) with driving pressure guidance on patient diaphragm function. MATERIAL AND METHODS Ninety patients were randomized into 3 groups, with PEEP set to 0 in group C; 5 cmH2O in group F; and individualized PEEP in group I, based on esophageal manometry. Diaphragm ultrasound was performed in the supine position at 6 consecutive time points from T0-T5: diaphragm excursion, end-expiratory diaphragm thickness (Tdi-ee), and diaphragm thickening fraction (DTF) were measured. Primary indicators included diaphragm excursion, Tdi-ee, and DTF at T0-T5, and the correlation between postoperative DTF and ΔP. Secondary indicators included respiratory mechanics, hemodynamic changes at intraoperative d0-d4 time points, and postoperative clinical pulmonary infection scores. RESULTS (1) Diaphragm function parameters reached the lowest point at T1 in all groups (P<0.001). (2) Compared with group C, diaphragm excursion decreased, Tdi-ee increased, and DTF was lower in groups I and F at T1-T5, with significant differences (P<0.05), but the differences between groups I and F were not significant (P>0.05). (3) DTF was significantly and positively correlated with mean intraoperative ΔP in each group at T3, and the correlation was stronger at higher levels of ΔP. CONCLUSIONS Individualized PEEP, achieved by esophageal manometry, minimizes diaphragmatic injury caused by mechanical ventilation based on lung protection, but its protection of the diaphragm during laparoscopic surgery is not superior to that of conventional ventilation strategies.

Respiratory drive heterogeneity associated with systemic inflammation and vascular permeability in acute respiratory distress syndrome.

BACKGROUND: In acute respiratory distress syndrome (ARDS), respiratory drive often differs among patients with similar clinical characteristics. Readily observable factors like acid-base state, oxygenation, mechanics, and sedation depth do not fully explain drive heterogeneity. This study evaluated the relationship of systemic inflammation and vascular permeability markers with respiratory drive and clinical outcomes in ARDS. METHODS: ARDS patients enrolled in the multicenter EPVent-2 trial with requisite data and plasma biomarkers were included. Neuromuscular blockade recipients were excluded. Respiratory drive was measured as PES0.1, the change in esophageal pressure during the first 0.1 s of inspiratory effort. Plasma angiopoietin-2, interleukin-6, and interleukin-8 were measured concomitantly, and 60-day clinical outcomes evaluated. RESULTS: 54.8% of 124 included patients had detectable respiratory drive (PES0.1 range of 0-5.1 cm H2O). Angiopoietin-2 and interleukin-8, but not interleukin-6, were associated with respiratory drive independently of acid-base, oxygenation, respiratory mechanics, and sedation depth. Sedation depth was not significantly associated with PES0.1 in an unadjusted model, or after adjusting for mechanics and chemoreceptor input. However, upon adding angiopoietin-2, interleukin-6, or interleukin-8 to models, lighter sedation was significantly associated with higher PES0.1. Risk of death was less with moderate drive (PES0.1 of 0.5-2.9 cm H2O) compared to either lower drive (hazard ratio 1.58, 95% CI 0.82-3.05) or higher drive (2.63, 95% CI 1.21-5.70) (p = 0.049). CONCLUSIONS: Among patients with ARDS, systemic inflammatory and vascular permeability markers were independently associated with higher respiratory drive. The heterogeneous response of respiratory drive to varying sedation depth may be explained in part by differences in inflammation and vascular permeability.

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.

Comparison of volume-controlled ventilation, pressure-controlled ventilation and pressure-controlled ventilation-volume guaranteed in infants and young children in the prone position: A prospective randomized study.

STUDY OBJECTIVE: To explore if the pressure-controlled ventilation (PCV) and pressure-controlled ventilation-volume guaranteed (PCV-VG) modes are superior to volume-controlled ventilation (VCV) in optimizing intraoperative respiratory mechanics in infants and young children in the prone position. DESIGN: A single-center prospective randomized study. SETTING: Children's Hospital, Zhejiang University School of Medicine. PATIENTS: Pediatric patients aged 1 month to 3 years undergoing elective spinal cord detethering surgery. INTERVENTIONS: Patients were randomly allocated to the VCV group, PCV group and PCV-VG group. The target tidal volume (VT) was 8 mL/kg and the respiratory rate (RR) was adjusted to maintain a constant end tidal CO2. MEASUREMENTS: The primary outcome was intraoperative peak airway pressure (Ppeak). Secondary outcomes included other respiratory and ventilation variables, gas exchange values, serum lung injury biomarkers concentration, hemodynamic parameters and postoperative respiratory complications. MAIN RESULTS: A total of 120 patients were included in the final analysis (40 in each group). The VCV group showed higher Ppeak at T2 (10 min after prone positioning) and T3 (30 min after prone positioning) than the PCV and PCV-VG groups (T2: P = 0.015 and P = 0.002, respectively; T3: P = 0.007 and P = 0.009, respectively). The prone-related decrease in dynamic compliance was prevented by PCV and PCV-VG ventilation modalities at T2 and T3 than by VCV (T2: P = 0.008 and P = 0.015, respectively; T3: P = 0.015 and P = 0.014, respectively). Additionally, there were no significant differences in other secondary outcomes among the three groups. CONCLUSION: In infants and young children undergoing spinal cord detethering surgery in the prone position, PCV-VG may be a better ventilation mode due to its ability to mitigate the increase in Ppeak and decrease in Cdyn while maintaining consistent VT.

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.

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.

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.

[Respiratory drive in acute respiratory distress syndrome: evaluation and control].

Acute respiratory distress syndrome (ARDS) is a common critical disease, which often leads to poor prognosis in critically ill patients. The excessive respiratory drive in ARDS is related to lung injury. Control of excessive respiratory drive is helpful to reduce lung injury and mortality of ARDS. The mechanisms of abnormal increase in respiratory drive in ARDS include hypoxemia, hypercapnia, stretch reflex caused by alveolar collapse and inflammatory stimulation. Respiratory drive should be evaluated by clinical manifestations, physiological parameters and respiratory mechanics indexes. It is particularly important to make individual therapy strategies according to the evaluation of respiratory drive. Analgesia and sedation combined with muscle relaxation, high positive end-expiratory pressure (PEEP) and prone position can be used to control excess respiratory drive. This article reviews the evaluation and management of excess respiratory drive in ARDS patients.

How to recognize patients at risk of self-inflicted lung injury.

INTRODUCTION: Patient self-inflicted lung injury (P-SILI) has been proposed as a form of lung injury caused by strong inspiratory efforts consequent to a high respiratory drive in patients with hypoxemic acute respiratory failure (hARF). Increased respiratory drive and effort may lead to variable combinations of deleterious phenomena, such as excessive transpulmonary pressure, pendelluft, intra-tidal recruitment, local lung volutrauma, and pulmonary edema. Gas exchange and respiratory mechanics derangements further increase respiratory drive and effort, thus inducing a vicious circle. Forms of partial ventilatory support may further add to the detrimental effects of P-SILI. Since P-SILI may worsen patient outcome, strategies aimed at identifying and preventing P-SILI would be of great importance. AREAS COVERED: We systematically searched Pubmed since inception until 15 April 2022 to review the patho-physiological mechanisms of P-SILI and the strategies to identify those patients at risk of P-SILI. EXPERT OPINION: Although the concept of P-SILI has been increasingly supported by experimental and clinical data, no study has insofar demonstrated the efficacy of any strategy to identify it in the clinical setting. Further research is thus needed to ascertain the detrimental effects of spontaneous breathing and identify patients with hARF at high risk of developing P-SILI.

Chest wall loading during supine and prone position in patients with COVID-19 ARDS: effects on respiratory mechanics and gas exchange.

BACKGROUND: Recent reports of patients with severe, late-stage COVID-19 ARDS with reduced respiratory system compliance described paradoxical decreases in plateau pressure and increases in respiratory system compliance in response to anterior chest wall loading. We aimed to assess the effect of chest wall loading during supine and prone position in ill patients with COVID-19-related ARDS and to investigate the effect of a low or normal baseline respiratory system compliance on the findings. METHODS: This is a single-center, prospective, cohort study in the intensive care unit of a COVID-19 referral center. Consecutive mechanically ventilated, critically ill patients with COVID-19-related ARDS were enrolled and classified as higher (≥ 40 ml/cmH2O) or lower respiratory system compliance (< 40 ml/cmH2O). The study included four steps, each lasting 6 h: Step 1, supine position, Step 2, 10-kg continuous chest wall compression (supine + weight), Step 3, prone position, Step 4, 10-kg continuous chest wall compression (prone + weight). The mechanical properties of the respiratory system, gas exchange and alveolar dead space were measured at the end of each step. RESULTS: Totally, 40 patients were enrolled. In the whole cohort, neither oxygenation nor respiratory system compliance changed between supine and supine + weight; both increased during prone positioning and were unaffected by chest wall loading in the prone position. Alveolar dead space was unchanged during all the steps. In 16 patients with reduced compliance, PaO2/FiO2 significantly increased from supine to supine + weight and further with prone and prone + weight (107 ± 15.4 vs. 120 ± 18.5 vs. 146 ± 27.0 vs. 159 ± 30.4, respectively; p < 0.001); alveolar dead space decreased from both supine and prone position after chest wall loading, and respiratory system compliance significantly increased from supine to supine + weight and from prone to prone + weight (23.9 ± 3.5 vs. 30.9 ± 5.7 and 31.1 ± 5.7 vs. 37.8 ± 8.7 ml/cmH2O, p < 0.001). The improvement was higher the lower the baseline compliance. CONCLUSIONS: Unlike prone positioning, chest wall loading had no effects on respiratory system compliance, gas exchange or alveolar dead space in an unselected cohort of critically ill patients with C-ARDS. Only patients with a low respiratory system compliance experienced an improvement, with a higher response the lower the baseline compliance.

Dynamic positive end-expiratory pressure strategies using time and pressure recruitment at birth reduce early expression of lung injury in preterm lambs.

Positive end-expiratory pressure (PEEP) is critical to the preterm lung at birth, but the optimal PEEP level remains uncertain. The objective of this study was to determine the effect of maximum PEEP levels at birth on the physiological and injury response in preterm lambs. Steroid-exposed preterm lambs (124-127 days gestation; n = 65) were randomly assigned from birth to either 1) positive pressure ventilation (PPV) at 8 cmH2O PEEP or 3-min dynamic stepwise PEEP strategy (DynPEEP), with either 2) 20 cmH2O maximum PEEP (10 PEEP second steps) or 3) 14 cmH2O maximum PEEP (20-s steps), all followed by standardized PPV for 90 min. Lung mechanics, gas exchange, regional ventilation and aeration (electrical impedance tomography), and histological and molecular measures of lung injury were compared between groups. Dynamic compliance was greatest using a maximum 20 cmH2O (DynPEEP). There were no differences in gas exchange, end-expiratory volume, and ventilator requirements. Regional ventilation became more uniform with time following all PEEP strategies. For all groups, gene expression of markers of early lung injury was greater in the gravity nondependent lung, and inversely related to the magnitude of PEEP, being lowest in the 20 cmH2O DynPEEP group overall. PEEP levels had no impact on lung injury in the dependent lung. Transient high maximum PEEP levels using dynamic PEEP strategies may confer more lung protection at birth.

Exertional dyspnoea in patients with mild-to-severe chronic obstructive pulmonary disease: neuromechanical mechanisms.

In patients with chronic obstructive pulmonary disease (COPD), exertional dyspnoea generally arises when there is imbalance between ventilatory demand and capacity, but the neurophysiological mechanisms are unclear. We therefore determined if disparity between elevated inspiratory neural drive (IND) and tidal volume (VT ) responses (neuromechanical dissociation) impacted dyspnoea intensity and quality during exercise, across the COPD severity spectrum. In this two-centre, cross-sectional observational study, 89 participants with COPD divided into tertiles of FEV1 %predicted (Tertile 1 = FEV1 = 87 ± 9%, Tertile 2 = 60 ± 9%, Tertile 3 = 32 ± 8%) and 18 non-smoking controls, completed a symptom-limited cardiopulmonary exercise test (CPET) with measurement of IND by diaphragm electromyography (EMGdi (%max)). The association between increasing dyspnoea intensity and EMGdi (%max) during CPET was strong (r = 0.730, P < 0.001) and not different between the four groups who showed marked heterogeneity in pulmonary gas exchange and mechanical abnormalities. Significant inspiratory constraints (tidal volume/inspiratory capacity (VT /IC) ≥ 70%) and onset of neuromechanical dissociation (EMGdi (%max):VT /IC > 0.75) occurred at progressively lower minute ventilation ( V ̇ E ${\dot{V}}_{{\rm{E}}}$ ) from Control to Tertile 3. Lower resting IC meant earlier onset of neuromechanical dissociation, heightened dyspnoea intensity and greater propensity (93% in Tertile 3) to select qualitative descriptors of 'unsatisfied inspiration'. We concluded that, regardless of marked variation in mechanical and pulmonary gas exchange abnormalities in our study sample, exertional dyspnoea intensity was linked to the magnitude of EMGdi (%max). Moreover, onset of critical inspiratory constraints and attendant neuromechanical dissociation amplified dyspnoea intensity at higher exercise intensities. Simple measurements of IC and breathing pattern during CPET provide useful insights into mechanisms of dyspnoea and exercise intolerance in individuals with COPD. KEY POINTS: Dyspnoea during exercise is a common and troublesome symptom reported by patients with chronic obstructive pulmonary disease (COPD) and is linked to an elevated inspiratory neural drive (IND). The precise mechanisms of elevated IND and dyspnoea across the continuum of airflow obstruction severity in COPD remains unclear. The present study sought to determine the mechanisms of elevated IND (by diaphragm EMG, EMGdi (%max)) and dyspnoea during cardiopulmonary exercise testing (CPET) across the continuum of COPD severity. There was a strong association between increasing dyspnoea intensity and EMGdi (%max) during CPET across the COPD continuum despite significant heterogeneity in underlying pulmonary gas exchange and respiratory mechanical impairments. Critical inspiratory constraints occurred at progressively lower ventilation during exercise with worsening severity of COPD. This was associated with the progressively lower resting inspiratory capacity with worsening disease severity. Earlier critical inspiratory constraint was associated with earlier neuromechanical dissociation and greater likelihood of reporting the sensation of 'unsatisfied inspiration'.

Biphasic positive airway pressure spontaneous breathing attenuates lung injury in an animal model of severe acute respiratory distress syndrome.

OBJECTIVE: To compare the effects of unassisted spontaneous breathing (SB) and complete muscle paralysis (PC) on early severe acute respiratory distress syndrome (ARDS) in an animal model, and to explore the possibility of biphasic positive airway pressure (BIPAP) as lung protective ventilation support for patients in the early stage of severe ARDS. METHODS: Twelve healthy beagle dogs between the ages of 10 and 15 months were randomly divided into two groups: the SB group (BIPAPSB) and the PC group (BIPAPPC). Arterial blood samples were drawn before modelling. Arterial blood gas analysis and mechanical tests were conducted. The animal model of severe ARDS was established using a deep intravenous injection of oleic acid, and BIPAP ventilation was performed for 8 hours. Lung tissue and blood were taken to detect lung function, inflammatory reactions and degree of pathological damage. RESULTS: At the beginning of the experiment, there was no significant difference in the arterial blood gas analysis between the two groups (p > 0.05). After successful modelling, the oxygenation index and the end-expiratory lung volume in the SB group were significantly higher than those in the PC group 8 hours after MV. Pathologically, the wet-dry ratio and pathological score of the PC group were higher than those of the SB group; the lung injury in the gravity-dependent area in the SB group was less than that in the PC group (p< 0.05). CONCLUSIONS: In the early stage of severe ARDS induced by oleic acid, compared with PC, retention of the BIPAP mode of SB can reduce the risk of lung injury and improve respiratory function.

Simulation to minimise patient self-inflicted lung injury: are we almost there?

Computational modelling has been used to enlighten pathophysiological issues in patients with acute respiratory distress syndrome (ARDS) using a sophisticated, integrated cardiopulmonary model. COVID-19 ARDS is a pathophysiologically distinct entity characterised by dissociation between impairment in gas exchange and respiratory system mechanics, especially in the early stages of ARDS. Weaver and colleagues used computational modelling to elucidate factors contributing to generation of patient self-inflicted lung injury, and evaluated the effects of various spontaneous respiratory efforts with different oxygenation and ventilatory support modes. Their findings indicate that mechanical forces generated in the lung parenchyma are only counterbalanced when the respiratory support mode reduces the intensity of respiratory efforts.

Plasma levels of myokines and inflammatory markers are related with functional and respiratory performance in older adults with COPD and sarcopenia.

This study investigated whether blood-based biomarkers were related to functional test performance and respiratory muscle strength in older adults with COPD and sarcopenia. The participants included in this cross-sectional study were from both sexes and sixty years or older. Based on clinical assessment, participants were categorized in COPD (n = 43) and non-COPD (NCOPD) (n = 43) groups. They were also assessed for body composition and muscular mass by dual-energy X-ray absorptiometry, using the relative skeletal muscle index for the diagnosis of sarcopenia. A series of functional tests, including short physical performance battery (SPPB), 6-minute walking test (6MWT), maximal inspiratory and expiratory pressures (MIP and MEP), were carried out. Plasma levels of myokines (Irisin and BDNF), and soluble TNF receptors (sTNFR1 and sTNFR2) were determined by ELISA. In the multivariate analysis, 6MWD was associated with age, COPD-related sarcopenia and BDNF (R2 = 0.29; f2 = 0.41). SPPB score was associated with COPD-related sarcopenia and sTNFR1 (R2 = 0.25; f2 = 0.33). MIP value was associated with sex, COPD-related sarcopenia, sTNFR2 and Irisin (R2 = 0.24; f2 = 0.31). Finally, MEP value was associated with sex COPD-related sarcopenia (R2 = 0.18; f2 = 0.22). Plasma levels of myokines and inflammatory markers are related with functional and respiratory performance in older adults with COPD and sarcopenia.

Sex differences in pulmonary function parameters among Indigenous Australians with and without chronic airway disease.

BACKGROUND: Studies assessing normative values and sex differences in pulmonary function test parameters (PFTPs) among Indigenous populations are sparse. METHODS: PFTPs were compared between male and female Indigenous Australian adults with and without chest radiologically proven chronic airway diseases (CADs). RESULTS: 485 adults (56% were female) with no significant difference in age, body mass index or smoking status between sexes were included. Females displayed a higher prevalence of radiology without CADs compared to males (66 vs. 52%, respectively). Among patients without CADs, after adjustment for age, stature and smoking, males displayed significantly higher absolute values of Forced Vital Capacity (FVC) (mean difference, 0.41L (0.21,0.62), p<0.001) and Forced Expiratory Volume in one second (FEV1) (mean difference 0.27L (0.07,0.47), p<0.001), with no significant difference in FEV1/FVC ratio (mean difference -0.02 (-0.06, 0.02), p = 0.174). Male and female patients with radiologically proven CADs demonstrated lower FEV1/FVC values. However, compared to females, males showed significantly greater reductions in pre- [-0.53 (-0.74, -0.32) vs. -0.29 (-0.42, -0.16), p = 0.045] and post- [-0.51 (-0.72, -0.3) vs. -0.27 (-0.39, -0.14), p = 0.049] bronchodilator FEV1. CONCLUSIONS: There are significant sex differences in the PFTPs among Indigenous Australians. Recognising these differences may be of value in the accurate diagnosis, management, monitoring and prognostication of CADs in this population.

Flow-controlled expiration improves respiratory mechanics, ventilation, and gas exchange in anesthetized horses.

OBJECTIVE: Mechanical ventilation is usually achieved by active lung inflation during inspiration and passive lung emptying during expiration. By contrast, flow-controlled expiration (FLEX) ventilation actively reduces the rate of lung emptying by causing linear gas flow throughout the expiratory phase. Our aim was to evaluate the effects of FLEX on lung compliance and gas exchange in anesthetized horses in dorsal recumbency. ANIMALS: 8 healthy horses. PROCEDURES: All animals were anesthetized twice and either ventilated beginning with FLEX or conventional volume-controlled ventilation in a randomized, crossover design. Total anesthesia time was 3 hours, with the ventilatory mode being changed after 1.5 hours. During anesthesia, cardiac output (thermodilution), mean arterial blood pressures, central venous pressure, and pulmonary arterial pressure were recorded. Further, peak, plateau, and mean airway pressures and dynamic lung compliance (Cdyn) were measured. Arterial blood gases were analyzed every 15 minutes. Data were analyzed using ANOVA (P < 0.05). RESULTS: FLEX ventilation resulted in significantly higher arterial oxygen partial pressures (521 vs 227 mm Hg) and Cdyn (564 vs 431 mL/cm H2O) values compared to volume-controlled ventilation. The peak and plateau airway pressure were lower, but mean airway pressure was significantly higher (4.8 vs 9.2 cm H2O) in FLEX ventilated horses. No difference for cardiovascular parameters were detected. CLINICAL RELEVANCE: The results of this study showed a significant improvement of the Pao2 and Cdyn without compromising the cardiovascular system when horses were ventilated by use of FLEX compared to conventional ventilation.

Effect of pressure-controlled ventilation-volume guaranteed mode combined with individualized positive end-expiratory pressure on respiratory mechanics, oxygenation and lung injury in patients undergoing laparoscopic surgery in Trendelenburg position.

The study aimed to investigate the efficacy of PCV-VG combined with individual PEEP during laparoscopic surgery in the Trendelenburg position. 120 patients were randomly divided into four groups: VF group (VCV plus 5cmH2O PEEP), PF group (PCV-VG plus 5cmH2O PEEP), VI group (VCV plus individual PEEP), and PI group (PCV-VG plus individual PEEP). Pmean, Ppeak, Cdyn, PaO2/FiO2, VD/VT, A-aDO2 and Qs/Qt were recorded at T1 (15 min after the induction of anesthesia), T2 (60 min after pneumoperitoneum), and T3 (5 min at the end of anesthesia). The CC16 and IL-6 were measured at T1 and T3. Our results showed that the Pmean was increased in VI and PI group, and the Ppeak was lower in PI group at T2. At T2 and T3, the Cdyn of PI group was higher than that in other groups, and PaO2/FiO2 was increased in PI group compared with VF and VI group. At T2 and T3, A-aDO2 of PI and PF group was reduced than that in other groups. The Qs/Qt was decreased in PI group compared with VF and VI group at T2 and T3. At T2, VD/VT in PI group was decreased than other groups. At T3, the concentration of CC16 in PI group was lower compared with other groups, and IL-6 level of PI group was decreased than that in VF and VI group. In conclusion, the patients who underwent laparoscopic surgery, PCV-VG combined with individual PEEP produced favorable lung mechanics and oxygenation, and thus reducing inflammatory response and lung injury.Clinical Trial registry: chictr.org. identifier: ChiCTR-2100044928.