End-expiratory Lung Volume Research Articles

Heterogeneity of Ventilation/Perfusion Mismatch at Different Levels of PEEP and in Mechanical Phenotypes of COVID-19 ARDS.

COVID-19-related ARDS is characterized by severe hypoxemia with initially preserved lung compliance and impaired ventilation/perfusion (V̇/Q̇) matching. PEEP can increase end-expiratory lung volume, but its effect on V̇/Q̇ mismatch in COVID-19-related ARDS is not clear. We enrolled intubated and mechanically ventilated subjects with COVID-19 ARDS and used the automatic lung parameter estimator (ALPE) to measure V̇/Q̇. Respiratory mechanics measurements, shunt, and V̇/Q̇ mismatch (low V̇/Q̇ and high V̇/Q̇) were collected at 3 PEEP levels (clinical PEEP = intermediate PEEP, low PEEP [clinical - 50%], and high PEEP [clinical + 50%]). A mixed-effect model was used to evaluate the impact of PEEP on V̇/Q̇. We also investigated if PEEP might have a different effect on V̇/Q̇ mismatch in 2 different respiratory mechanics phenotypes, that is, high elastance/low compliance (phenotype H) and low elastance/high compliance (phenotype L). Seventeen subjects with COVID-related ARDS age 66 [60-71] y with a PaO2 /FIO2 of 141 ± 74 mm Hg were studied at low PEEP = 5.6 ± 2.2 cm H2O, intermediate PEEP = 10.6 ± 3.8 cm H2O, and high PEEP = 15 ± 5 cm H2O. Shunt, low V̇/Q̇, high V̇/Q̇, and alveolar dead space were not significantly influenced, on average, by PEEP. Respiratory system compliance decreased significantly when increasing PEEP without significant variation of PaO2 /FIO2 (P = .26). In the 2 phenotypes, PEEP had opposite effects on shunt, with a decrease in the phenotype L and an increase in phenotype H (P = .048). In subjects with COVID-related ARDS placed on invasive mechanical ventilation for > 48 h, PEEP had a heterogeneous effect on V̇/Q̇ mismatch and, on average, higher levels were not able to reduce shunt. The subject's compliance could influence the effect of PEEP on V̇/Q̇ mismatch since an increased shunt was observed in subjects with lower compliance, whereas the opposite occurred in those with higher compliance.

A new approach for the detection of obesity-related airway obstruction in lung-healthy individuals

BackgroundSubjects with obesity show an increased prevalence of airway obstruction but it is not clear in each case whether this reflects genuine lung disease. Via intentional increase in end-expiratory lung volume we studied the detection of obesity-induced airway obstruction in lung-healthy obese subjects. MethodsThe primary study population comprised 66 lung-healthy obese subjects and 23 normal weight subjects. Measurements were performed in a body plethysmograph allowing for recording and quantification of breathing loops in terms of specific airway resistance at both normal and intentionally elevated end-expiratory lung volume. The change in volume was documented by a shutter maneuver. ResultsThe voluntary increase of lung volume led to a significant reduction of expiratory airway resistance in 11 of the 66 obese subjects. This reduction could be quantified by a change of total expiratory resistance (sRtEX) of >1 kPa*s but was also clearly visible in the breathing loops. sRtEX showed the largest change among all resistance parameters. The loops of normal weight subjects remained virtually unaffected by the change in lung volume. Moreover, those of 5 obese patients with COPD who were measured for comparison partially showed a reduction of resistance but airway obstruction remained. ConclusionThe proposed breathing maneuver was simple to perform and allowed for a quantitative and qualitative detection of obesity-induced airway obstruction. This might help in reducing the likelihood of misdiagnosis and overtreatment of obese patients.

Negative-pressure-assisted ventilation lowers driving pressure and mechanical power in an ARDS model.

Increased lung heterogeneity from regional alveolar collapse drives ventilator-induced lung injury in patients with acute respiratory distress syndrome (ARDS). New methods of preventing this injury require study. Our study objective was to determine whether the combination of temporary transvenous diaphragm neurostimulation (TTDN) with standard-of-care volume-control mode ventilation changes lung mechanics, reducing ventilator-induced lung injury risk in a preclinical ARDS model. Moderate ARDS was induced using oleic acid administered into the pulmonary artery in pigs, which were ventilated for 12 h postinjury using volume-control mode at 8 mL/kg, positive end-expiratory pressure (PEEP) 5 cmH2O, with respiratory rate and [Formula: see text] set to achieve normal arterial blood gases. Two groups received TTDN, either every second breath [mechanical ventilation (MV) + TTDN50%, n = 6] or every breath (MV + TTDN100%, n = 6). A third group received volume-control ventilation only (MV, n = 6). At study-end, [Formula: see text]/[Formula: see text] was highest and alveolar-arterial oxygen (A-a) gradient was lowest for MV + TTDN100% (P < 0.05). MV + TTDN100% had the smallest end-expiratory lung volume loss and lowest extravascular lung water at study-end (P < 0.05). Static lung compliance was highest and transpulmonary driving pressure was lowest at baseline, postinjury, and study-end in MV + TTDN100% (P < 0.05). The total exposure to transpulmonary driving pressure, mechanical power, and mechanical work was the lowest in MV + TTDN100% (P < 0.05). Lung injury score and total inflammatory cytokine concentration in lung tissue were the lowest in MV + TTDN100% (P < 0.05). Volume-control ventilation plus transvenous diaphragm neurostimulation on every breath improved [Formula: see text]/[Formula: see text], A-a gradient, and alveolar homogeneity, as well as reduced driving pressure, mechanical power, and mechanical work, and resulted in lower lung injury scores and tissue cytokine concentrations in a preclinical ARDS model.NEW & NOTEWORTHY Combining temporary transvenous diaphragm neurostimulation with volume-control ventilation on every breath, called negative-pressure-assisted ventilation, improved gas exchange and alveolar homogeneity in a preclinical model of moderate ARDS. Transpulmonary driving pressure, mechanical power, and mechanical work reductions were observed and resulted in lower lung injury scores and tissue cytokine concentrations in the every-breath-neurostimulation group compared with volume-control ventilation only. Negative-pressure-assisted ventilation is an exciting new potential tool to reduce ventilator-induced lung injury in patients with ARDS.

Flow-controlled ventilation maintains gas exchange and lung aeration in a pediatric model of healthy and injured lungs: A randomized cross-over experimental study.

Flow-controlled ventilation (FCV) is characterized by a constant flow to generate active inspiration and expiration. While the benefit of FCV on gas exchange has been demonstrated in preclinical and clinical studies with adults, the value of this modality for a pediatric population remains unknown. Thus, we aimed at observing the effects of FCV as compared to pressure-regulated volume control (PRVC) ventilation on lung mechanics, gas exchange and lung aeration before and after surfactant depletion in a pediatric model. Ten anesthetized piglets (10.4 ± 0.2 kg) were randomly assigned to start 1-h ventilation with FCV or PRVC before switching the ventilation modes for another hour. This sequence was repeated after inducing lung injury by bronchoalveolar lavage and injurious ventilation. The primary outcome was respiratory tissue elastance. Secondary outcomes included oxygenation index (PaO2/FiO2), PaCO2, intrapulmonary shunt (Qs/Qt), airway resistance, respiratory tissue damping, end-expiratory lung volume, lung clearance index and lung aeration by chest electrical impedance tomography. Measurements were performed at the end of each protocol stage. Ventilation modality had no effect on any respiratory mechanical parameter. Adequate gas exchange was provided by FCV, similar to PRVC, with sufficient CO2 elimination both in healthy and surfactant-depleted lungs (39.46 ± 7.2 mmHg and 46.2 ± 11.4 mmHg for FCV; 36.0 ± 4.1 and 39.5 ± 4.9 mmHg, for PRVC, respectively). Somewhat lower PaO2/FiO2 and higher Qs/Qt were observed in healthy and surfactant depleted lungs during FCV compared to PRVC (p < 0.05, for all). Compared to PRVC, lung aeration was significantly elevated, particularly in the ventral dependent zones during FCV (p < 0.05), but this difference was not evidenced in injured lungs. Somewhat lower oxygenation and higher shunt ratio was observed during FCV, nevertheless lung aeration improved and adequate gas exchange was ensured. Therefore, in the absence of major differences in respiratory mechanics and lung volumes, FCV may be considered as an alternative in ventilation therapy of pediatric patients with healthy and injured lungs.

Effect of flow rate on the end-expiratory lung volume in infants with bronchiolitis using high-flow nasal cannula evaluated through electrical impedance tomography.

To evaluate the effects of four flow rates on the functional residual capacity (FRC) and pulmonary ventilation distribution while using a high-flow nasal cannula (HFNC). Our hypothesis is that flow rates below 1.5 L·kg-1 ·min-1 lead to FRC loss and respiratory distress. A single-center, prospective clinical study. Infants diagnosed with acute viral bronchiolitis were given HFNC. Through a prospective clinical study, the effects of four different flow rates, 2.0, 1.5, 1.0, and 0.5 L·kg-1 ·min-1 , on FRC and the pulmonary ventilation pattern were evaluated using electrical impedance tomography. The impedance variation (delta Z), end-expiratory lung volume (EELZ), respiratory rate, heart rate, respiratory distress score, and saturation/fraction of inspired oxygen ratio (SpO2 /FI O2 ), were also evaluated at each flow rate. Among the 11 infants included, There was a decrease in respiratory distress score at a flow rate of 1.5 L·kg-1 ·min-1 (*p = 0.021), and at a flow rate of 2.0 L·kg-1 ·min-1 (**p = 0.003) compared to 0.5 L·kg-1 ·min-1 . There was also a small but significant increase in SpO2 /FiO2 at flow rates of 1.5 (*p = 0.023), and 2.0 L·kg-1 ·min-1 (**p = 0.008) compared to 0.5 L·kg-1 ·min-1 . There were no other significant changes in the clinical parameters. In the global EELZ measurements, there was a significant increase under a flow rate of 2.0 L·kg-1 ·min-1 as compared to 0.5 L·kg-1 ·min-1 (p = 0.03). In delta Z values, there were no significant variations between the different flow rates. The ∆EELZ increases at the highest flow rates were accompanied by decreased distress scores and improved oxygenation.

Evidence of ventilatory constraints during exercise in hypermobile Ehlers-Danlos syndrome.

Hypermobile Ehlers-Danlos syndrome (hEDS) is a connective tissue disorder with many different symptoms such as pain, fatigue, dysautonomia, or respiratory symptoms. Among the respiratory manifestations described, the most frequent are exertional dyspnea and breathing difficulties. Mechanical ventilatory constraints during exercise could participate in these respiratory manifestations. The objective of this study was to explore the response of pulmonary flow-volume loops to exercise in patients with hEDS and to look for dynamic hyperinflation and expiratory flow limitation during exercise. For this purpose, breathing pattern and tidal exercise flow-volume loops were recorded at two workloads (30% and 80% of the peak power output) of a constant load exercise test. Twelve patients were included (11 women, mean age 41 ± 14years). The results showed a decrease (p = 0.028) in the inspiratory capacity (from 3.12 ± 0.49L to 2.97 ± 0.52L), an increase (p = 0.025) in the end-expiratory lung volume (from 0.73 ± 0.68L to 0.88 ± 0.66L, i.e., from EELV comprising 17 ± 12% to 21 ± 12% of forced vital capacity) between the two workloads in favor of dynamic hyperinflation, and half of the patients had expiratory flow limitations. This exploratory study provides evidence for mechanical ventilatory constraints during exercise in patients with hEDS, which may induce discomfort during exercise and could contribute to the respiratory symptomatology. This study is part of a larger clinical trial (ID: NCT04680793, December 2020).

Capnodynamic monitoring of lung volume and blood flow in response to increased positive end-expiratory pressure in moderate to severe COVID-19 pneumonia: an observational study

BackgroundThe optimal level of positive end-expiratory pressure (PEEP) during mechanical ventilation for COVID-19 pneumonia remains debated and should ideally be guided by responses in both lung volume and perfusion. Capnodynamic monitoring allows both end-expiratory lung volume ({text{EELV}}_{{{text{CO}}_{2} }}) and effective pulmonary blood flow (EPBF) to be determined at the bedside with ongoing ventilation.MethodsPatients with COVID-19-related moderate to severe respiratory failure underwent capnodynamic monitoring of {text{EELV}}_{{{text{CO}}_{2} }} and EPBF during a step increase in PEEP by 50% above the baseline (PEEPlow to PEEPhigh). The primary outcome was a > 20 mm Hg increase in arterial oxygen tension to inspired fraction of oxygen (P/F) ratio to define responders versus non-responders. Secondary outcomes included changes in physiological dead space and correlations with independently determined recruited lung volume and the recruitment-to-inflation ratio at an instantaneous, single breath decrease in PEEP. Mixed factor ANOVA for group mean differences and correlations by Pearson’s correlation coefficient are reported including their 95% confidence intervals.ResultsOf 27 patients studied, 15 responders increased the P/F ratio by 55 [24–86] mm Hg compared to 12 non-responders (p < 0.01) as PEEPlow (11 ± 2.7 cm H2O) was increased to PEEPhigh (18 ± 3.0 cm H2O). The {text{EELV}}_{{{text{CO}}_{2} }} was 461 [82–839] ml less in responders at PEEPlow (p = 0.02) but not statistically different between groups at PEEPhigh. Responders increased both {text{EELV}}_{{{text{CO}}_{2} }} and EPBF at PEEPhigh (r = 0.56 [0.18–0.83], p = 0.03). In contrast, non-responders demonstrated a negative correlation (r = − 0.65 [− 0.12 to − 0.89], p = 0.02) with increased lung volume associated with decreased pulmonary perfusion. Decreased (− 0.06 [− 0.02 to − 0.09] %, p < 0.01) dead space was observed in responders. The change in {text{EELV}}_{{{text{CO}}_{2} }} correlated with both the recruited lung volume (r = 0.85 [0.69–0.93], p < 0.01) and the recruitment-to-inflation ratio (r = 0.87 [0.74–0.94], p < 0.01).ConclusionsIn mechanically ventilated patients with moderate to severe COVID-19 respiratory failure, improved oxygenation in response to increased PEEP was associated with increased end-expiratory lung volume and pulmonary perfusion. The change in end-expiratory lung volume was positively correlated with the lung volume recruited and the recruitment-to-inflation ratio. This study demonstrates the feasibility of capnodynamic monitoring to assess physiological responses to PEEP at the bedside to facilitate an individualised setting of PEEP.Trial registration: NCT05082168 (18th October 2021).

Sex differences in the ventilatory responses to exercise in mild to moderate obesity

New Findings What is the central question of the study? What are the sex differences in ventilatory responses during exercise in adults with obesity? What is the main finding and its importance? Tidal volume and expiratory flows are lower in females when compared with males at higher levels of ventilation despite small increases in end‐expiratory lung volumes. Since dyspnoea on exertion is a frequent complaint, particularly in females with obesity, careful attention should be paid to unpleasant respiratory symptoms and mechanical ventilatory constraints while prescribing exercise. Obesity is associated with altered ventilatory responses, which may be exacerbated in females due to the functional consequences of sex‐related morphological differences in the respiratory system. This study examined sex differences in ventilatory responses during exercise in adults with obesity. Healthy adults with obesity (n = 73; 48 females) underwent pulmonary function testing, underwater weighing, magnetic resonance imaging (MRI), a graded exercise test to exhaustion, and two constant work rate exercise tests; one at a fixed work rate (60 W for females and 105 W for males) and one at a relative intensity (50% of peak oxygen uptake, V˙O2peak). Metabolic, respiratory and perceptual responses were assessed during exercise. Compared with males, females used a smaller proportion of their ventilatory capacity at peak exercise (69.13 ± 14.49 vs. 77.41 ± 17.06% maximum voluntary ventilation, P = 0.0374). Females also utilized a smaller proportion of their forced vital capacity (FVC) at peak exercise (tidal volume: 48.51 ± 9.29 vs. 54.12 ± 10.43%FVC, P = 0.0218). End‐expiratory lung volumes were 2–4% higher in females compared with males during exercise (P < 0.05), while end‐inspiratory lung volumes were similar. Since the males were initiating inspiration from a lower lung volume, they experienced greater expiratory flow limitation during exercise. Ratings of perceived breathlessness during exercise were similar between females and males at comparable levels of ventilation. In summary, sex differences in the manifestations of obesity‐related mechanical ventilatory constraints were observed. Since dyspnoea on exertion is a common complaint in patients with obesity, particularly in females, exercise prescriptions should be tailored with the goal of minimizing unpleasant respiratory sensations.

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

ObjectiveTo 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.MethodsTwelve 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.ResultsAt 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).ConclusionsIn 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.

Influence of respiratory loading on left-ventricular function in cervical spinal cord injury.

Cervical spinal cord injury (C-SCI) negatively impacts cardiac and respiratory function. As the heart and lungs are linked via the pulmonary circuit these systems are interdependent. Here, we utilized inspiratory and expiratory loading to assess whether augmenting the respiratory pump improves left-ventricular (LV) filling and output in individuals with motor-complete C-SCI. We hypothesized LV end-diastolic volume (LVEDV) would increase and decrease with inspiratory and expiratory loading, respectively. Participants (C-SCI: 7M/1F, 35±7years; able-bodied: 7M/1F, 32±6years) were assessed under five conditions during 45° head-up tilt; unloaded, inspiratory loading with -10 and -20cmH2 O oesophageal pressure (Poes ) on inspiration, and expiratory loading with +10 and +20cmH2 O Poes on expiration. An oesophageal balloon catheter monitored Poes , and LV structure and function were assessed by echocardiography. In C-SCI only, (1) +20cmH2 O reduced LVEDV vs. unloaded (81±15 vs. 88±11ml, P=0.006); (2) heart rate was higher during +20cmH2 O compared to unloaded (P=0.001) and +10cmH2 O (P=0.002); (3) cardiac output was higher during +20cmH2 O than unloaded (P=0.002); and (4) end-expiratory lung volume was higher during +20cmH2 O vs. unloaded (63±10 vs. 55±13% total lung capacity, P=0.003) but was unaffected by inspiratory loading. In both groups, -10 and -20cmH2 O had no significant effect on LVEDV. These findings suggest greater expiratory positive pressure acutely impairs LV filling in C-SCI, potentially via impaired venous return, mediastinal constraint and/or direct ventricular interaction subsequent to dynamic hyperinflation. Inspiratory loading did not significantly improve LV function in C-SCI and neither inspiratory nor expiratory loading affected cardiac function or lung volumes in able-bodied participants. KEY POINTS: Cervical spinal cord injury (C-SCI) alters both the cardiac and the respiratory system, but little is known about how these systems interact following injury. Here, we manipulated inspiratory or expiratory intrathoracic pressure (ITP) to mechanistically test the role of the respiratory pump in circulatory function in highly trained individuals with C-SCI and an able-bodied reference group. In individuals with C-SCI, greater ITP during expiratory loading caused dynamic hyperinflation that was associated with impaired left-ventricular filling. More negative ITP during inspiratory loading did not significantly alter left-ventricular volumes in either group. Interventions that prevent dynamic hyperinflation and/or enhance the ability to generate expiratory pressures may help preserve left-ventricular filling in individuals with C-SCI.

Physiological and Pathophysiological Consequences of Mechanical Ventilation.

Mechanical ventilation is a life-support system used to ensure blood gas exchange and to assist the respiratory muscles in ventilating the lung during the acute phase of lung disease or following surgery. Positive-pressure mechanical ventilation differs considerably from normal physiologic breathing. This may lead to several negative physiological consequences, both on the lungs and on peripheral organs. First, hemodynamic changes can affect cardiovascular performance, cerebral perfusion pressure (CPP), and drainage of renal veins. Second, the negative effect of mechanical ventilation (compression stress) on the alveolar-capillary membrane and extracellular matrix may cause local and systemic inflammation, promoting lung and peripheral-organ injury. Third, intra-abdominal hypertension may further impair lung and peripheral-organ function during controlled and assisted ventilation. Mechanical ventilation should be optimized and personalized in each patient according to individual clinical needs. Multiple parameters must be adjusted appropriately to minimize ventilator-induced lung injury (VILI), including: inspiratory stress (the respiratory system inspiratory plateau pressure); dynamic strain (the ratio between tidal volume and the end-expiratory lung volume, or inspiratory capacity); static strain (the end-expiratory lung volume determined by positive end-expiratory pressure [PEEP]); driving pressure (the difference between the respiratory system inspiratory plateau pressure and PEEP); and mechanical power (the amount of mechanical energy imparted as a function of respiratory rate). More recently, patient self-inflicted lung injury (P-SILI) has been proposed as a potential mechanism promoting VILI. In the present chapter, we will discuss the physiological and pathophysiological consequences of mechanical ventilation and how to personalize mechanical ventilation parameters.

Predictors of Expiratory Flow Limitation during Exercise in Healthy Males and Females

It is unclear whether the frequency and mechanisms of expiratory flow limitation (EFL) during exercise differ between males and females. This study aimed to determine which factors predispose individuals to EFL during exercise and whether these factors differ based on sex. We hypothesized that i) EFL frequency would be similar in males and females and ii) in females, EFL would be associated with indices of low ventilatory capacity, whereas in males, EFL would be associated with indices of high ventilatory demand. Data from n = 126 healthy adults (20-45 y, n = 60 males, n = 66 females) with a wide range of cardiorespiratory fitness (81%-182% predicted maximal oxygen uptake) were included in the study. Participants performed spirometry and an incremental cycle exercise test to exhaustion. Standard cardiorespiratory variables were assessed throughout exercise. The tidal flow-volume overlap method was used to assess EFL based on a minimum threshold of 5% overlap between the tidal and the maximum expiratory flow-volume curves. Predictors of EFL during exercise were determined via multiple logistical regression using anthropometric, pulmonary function, and peak exercise data. During exercise, EFL occurred in 49% of participants and was similar between the sexes (females = 45%, males = 53%; P = 0.48). In males, low forced expired flow between 25% and 75% of forced vital capacity and high slope ratio as well as low end-expiratory lung volume, high breathing frequency, and high relative tidal volume at peak exercise were associated with EFL ( P < 0.001; Nagelkerke R2 = 0.73). In females, high slope ratio, high breathing frequency, and tidal volume at peak exercise were associated with EFL ( P < 0.001; Nagelkerke R2 = 0.61). Despite sex differences in respiratory system morphology, the frequency and the predictors of EFL during exercise do not substantially differ between the sexes.

Are alveolar recruitment maneuvers and peep ventilation effective in the intraoperative period of laparoscopic bariatric surgery? A systematic review

The purpose of the study is to systematically review about alveolar recruitment maneuvers followed by mechanical ventilation with PEEP guided by electrical impedance tomography (EIT) in laparoscopic bariatric surgery. Metodology: The primary outcomes were: regional pulmonary ventilation (regional impedance variation), end-expiratory lung impedance, and end-expiratory lung volume. Results: The survey identified three eligible studies. The sample consisted of 136 participants of both genders. The alveolar recruitment maneuver (ARM) was performed through the mechanical ventilator and using the EIT in the patient’s chest. The studies showed moderate to high risk of bias, and the quality of the evidence was classified as very low quality due to the methodological limitations found and absence of directionality. Conclusion: ARM with PEEP guided by EIT does not significantly improve the respiratory system mechanics in the intraoperative period in obese patients undergoing laparoscopic bariatric surgery.

High-Flow Nasal Cannula Reduces Effort of Breathing But Not Consistently via Positive End-Expiratory Pressure

High-flow nasal cannula (HFNC) therapy reduces the effort of breathing in patients with bronchiolitis, but the mechanisms are not understood. Theorized mechanisms include dead space washout and positive end-expiratory pressure (PEEP) application. What are the mechanisms of action of HFNC therapy in patients with bronchiolitis? Prospective, single-center study of children 3 years of age or younger with bronchiolitis from January 2020 through March 2021. Flow was titrated between 0.5 and 2 L/kg/min. Electrical impedance tomography measured end-expiratory lung impedance (EELZ) change as an end-expiratory lung volume (EELV) change surrogate and change in tidal impedance difference (ΔZ) as a tidal volume (VT) surrogate. A subset showed manometry measuring esophageal pressure change (ΔPes; transpulmonary pressure surrogate) and pressure rate product (PRP; effort of breathing metric). We hypothesized that EELV and VT would not change and that effort would reduce via respiratory rate (not ΔPes). Measurements were reported as the difference from 0.5 L/kg/min. We studied 22 patients in total, 10 with esophageal manometry. Median EELZ increased by 0.36 arbitrary unit (AU), 2.42 AU, and 4.8 AU at 1 L/kg/min, 1.5 L/kg/min, and 2 L/kg/min (P= .01, 2 L/kg/min vs0.5 L/kg/min), which corresponded to a median increase in EELV of 1.8mL/kg between 0.5 and 2 L/kg/min. Seven patients showed an increase in EELZ of > 5 AU, 12 showed no change in EELZ (± 5 AU), and three showed a decrease in EELZ of > 5 AU. ΔZ (ie, VT) did not change from 0.5 L/kg/min to 2 L/kg/min (median change, 0.29 AU; P= .48). Median PRP decreased by 78cm H2O/min from 0.5 L/kg/min to 2 L/kg/min (P= .02), with all patients demonstrating a reduction in PRP, with a nonsignificant change in ΔPes (P= .68). Increasing HFNC in children with bronchiolitis reduces the effort of breathing, but no consistent increase occurs in end-expiratory lung volume and no significant change occurs in VT or transpulmonary pressure. This suggests that PEEP application is not the primary mechanism of action of HFNC in children with bronchiolitis.

Distribution and Magnitude of Regional Volumetric Lung Strain and Its Modification by PEEP in Healthy Anesthetized and Mechanically Ventilated Dogs.

The present study describes the magnitude and spatial distribution of lung strain in healthy anesthetized, mechanically ventilated dogs with and without positive end-expiratory pressure (PEEP). Total lung strain (LSTOTAL) has a dynamic (LSDYNAMIC) and a static (LSSTATIC) component. Due to lung heterogeneity, global lung strain may not accurately represent regional total tissue lung strain (TSTOTAL), which may also be described by a regional dynamic (TSDYNAMIC) and static (TSSTATIC) component. Six healthy anesthetized beagles (12.4 ± 1.4 kg body weight) were placed in dorsal recumbency and ventilated with a tidal volume of 15 ml/kg, respiratory rate of 15 bpm, and zero end-expiratory pressure (ZEEP). Respiratory system mechanics and full thoracic end-expiratory and end-inspiratory CT scan images were obtained at ZEEP. Thereafter, a PEEP of 5 cmH2O was set and respiratory system mechanics measurements and end-expiratory and end-inspiratory images were repeated. Computed lung volumes from CT scans were used to evaluate the global LSTOTAL, LSDYNAMIC, and LSSTATIC during PEEP. During ZEEP, LSSTATIC was assumed zero; therefore, LSTOTAL was the same as LSDYNAMIC. Image segmentation was applied to CT images to obtain maps of regional TSTOTAL, TSDYNAMIC, and TSSTATIC during PEEP, and TSDYNAMIC during ZEEP. Compliance increased (p = 0.013) and driving pressure decreased (p = 0.043) during PEEP. PEEP increased the end-expiratory lung volume (p < 0.001) and significantly reduced global LSDYNAMIC (33.4 ± 6.4% during ZEEP, 24.0 ± 4.6% during PEEP, p = 0.032). LSSTATIC by PEEP was larger than the reduction in LSDYNAMIC; therefore, LSTOTAL at PEEP was larger than LSDYNAMIC at ZEEP (p = 0.005). There was marked topographic heterogeneity of regional strains. PEEP induced a significant reduction in TSDYNAMIC in all lung regions (p < 0.05). Similar to global findings, PEEP-induced TSSTATIC was larger than the reduction in TSDYNAMIC; therefore, PEEP-induced TSTOTAL was larger than TSDYNAMIC at ZEEP. In conclusion, PEEP reduced both global and regional estimates of dynamic strain, but induced a large static strain. Given that lung injury has been mostly associated with tidal deformation, limiting dynamic strain may be an important clinical target in healthy and diseased lungs, but this requires further study.

Physiologically variable ventilation prevents lung function deterioration in a model of pulmonary fibrosis.

Positive pressure ventilation exerts an increased stress and strain in the presence of pulmonary fibrosis. Thus, ventilation strategies that avoid high pressures while maintaining lung aeration are of paramount importance. Although physiologically variable ventilation (PVV) has proven beneficial in various models of pulmonary disease, its potential advantages in pulmonary fibrosis have not been investigated. Therefore, we assessed the benefit of PVV over conventional pressure-controlled ventilation (PCV) in a model of pulmonary fibrosis. Lung fibrosis was induced with intratracheal bleomycin in rabbits. Fifty days later, the animals were randomized to receive 6 h of either PCV (n = 10) or PVV (n = 11). The PVV pattern was prerecorded in spontaneously breathing, healthy rabbits. Respiratory mechanics and gas exchange were assessed hourly; end-expiratory lung volume and intrapulmonary shunt fraction were measured at hours 0 and 6. Histological and cellular analyses were performed. Fifty days after bleomycin treatment, the rabbits presented elevated specific airway resistance [69 ± 26% (mean ± 95% confidence interval)], specific tissue damping (38 ± 15%), and specific elastance (47 ± 16%) along with histological evidence of fibrosis. Six hours of PCV led to increased respiratory airway resistance (Raw, 111 ± 30%), tissue damping (G, 36 ± 13%) and elastance (H, 58 ± 14%), and decreased end-expiratory lung volume (EELV, -26 ± 7%) and oxygenation ([Formula: see text]/[Formula: see text], -14 ± 5%). The time-matched changes in the PVV group were significantly lower for G (22 ± 9%), H (41 ± 6%), EELV (-13 ± 6%), and [Formula: see text]/[Formula: see text] ratio (-3 ± 5%, P < 0.05 for all). There was no difference in histopathology between the ventilation modes. Thus, prolonged application of PVV prevented the deterioration of gas exchange by reducing atelectasis development in bleomycin-induced lung fibrosis.NEW & NOTEWORTHY The superposition of physiological breathing variability onto a conventional pressure signal during prolonged mechanical ventilation prevents atelectasis development in bleomycin-induced lung fibrosis. This advantage is evidenced by reduced deterioration in tissue mechanics, end-expiratory lung volume, ventilation homogeneity, and gas exchange.

Phenotyping Cardiopulmonary Exercise Limitations in Chronic Obstructive Pulmonary Disease.

BackgroundExercise limitation in chronic obstructive pulmonary disease (COPD) is commonly attributed to abnormal ventilatory mechanics and/or skeletal muscle function, while cardiovascular contributions remain relatively understudied. To date, the integrative exercise responses associated with different cardiopulmonary exercise limitation phenotypes in COPD have not been explored but may provide novel therapeutic utility. This study determined the ventilatory, cardiovascular, and metabolic responses to incremental exercise in patients with COPD with different exercise limitation phenotypes.MethodsPatients with COPD (n = 95, FEV1:23–113%pred) performed a pulmonary function test and incremental cardiopulmonary exercise test. Exercise limitation phenotypes were classified as: ventilatory [peak ventilation (VEpeak)/maximal ventilatory capacity (MVC) ≥ 85% or MVC-VEpeak ≤ 11 L/min, and peak heart rate (HRpeak) < 90%pred], cardiovascular (VEpeak/MVC < 85% or MVC-VEpeak > 11 L/min, and HRpeak ≥ 90%pred), or combined (VEpeak/MVC ≥ 85% or MVC-VEpeak ≤ 11 L/min, and HRpeak ≥ 90%pred).ResultsFEV1 varied within phenotype: ventilatory (23–75%pred), combined (28–90%pred), and cardiovascular (68–113%pred). The cardiovascular phenotype had less static hyperinflation, a lower end-expiratory lung volume and larger tidal volume at peak exercise compared to both other phenotypes (p < 0.01 for all). The cardiovascular phenotype reached a higher VEpeak (60.8 ± 11.5 L/min vs. 45.3 ± 15.5 L/min, p = 0.002), cardiopulmonary fitness (VO2peak: 20.6 ± 4.0 ml/kg/min vs. 15.2 ± 3.3 ml/kg/min, p < 0.001), and maximum workload (103 ± 34 W vs. 72 ± 27 W, p < 0.01) vs. the ventilatory phenotype, but was similar to the combined phenotype.ConclusionDistinct exercise limitation phenotypes were identified in COPD that were not solely dependent upon airflow limitation severity. Approximately 50% of patients reached maximal heart rate, indicating that peak cardiac output and convective O2 delivery contributed to exercise limitation. Categorizing patients with COPD phenotypically may aid in optimizing exercise prescription for rehabilitative purposes.

Lung Ultrasound and Electrical Impedance Tomography During Ventilator-Induced Lung Injury.

Lung damage during mechanical ventilation involves lung volume and alveolar water content, and lung ultrasound (LUS) and electrical impedance tomography changes are related to these variables. We investigated whether these techniques may detect any signal modification during the development of ventilator-induced lung injury (VILI). Experimental animal study. Experimental Department of a University Hospital. Forty-two female pigs (24.2 ± 2.0 kg). The animals were randomized into three groups (n = 14): high tidal volume (TV) (mean TV, 803.0 ± 121.7 mL), high respiratory rate (RR) (mean RR, 40.3 ± 1.1 beats/min), and high positive-end-expiratory pressure (PEEP) (mean PEEP, 24.0 ± 1.1 cm H2O). The study lasted 48 hours. At baseline and at 30 minutes, and subsequently every 6 hours, we recorded extravascular lung water, end-expiratory lung volume, lung strain, respiratory mechanics, hemodynamics, and gas exchange. At the same time-point, end-expiratory impedance was recorded relatively to the baseline. LUS was assessed every 12 hours in 12 fields, each scoring from 0 (presence of A-lines) to 3 (consolidation). In a multiple regression model, the ratio between extravascular lung water and end-expiratory lung volume was significantly associated with the LUS total score (p < 0.002; adjusted R2, 0.21). The variables independently associated with the end-expiratory difference in lung impedance were lung strain (p < 0.001; adjusted R2, 0.18) and extravascular lung water (p < 0.001; adjusted R2, 0.11). Data suggest as follows. First, what determines the LUS score is the ratio between water and gas and not water alone. Therefore, caution is needed when an improvement of LUS score follows a variation of the lung gas content, as after a PEEP increase. Second, what determines the end-expiratory difference in lung impedance is the strain level that may disrupt the intercellular junction, therefore altering lung impedance. In addition, the increase in extravascular lung water during VILI development contributed to the observed decrease in impedance.

Lung volume distribution in preterm infants on non-invasive high-frequency ventilation

IntroductionNon-invasive high-frequency oscillatory ventilation (nHFOV) is an extension of nasal continuous positive airway pressure (nCPAP) support in neonates. We aimed to compare global and regional distribution of lung volumes during...

Individualized positive end-expiratory pressure guided by end-expiratory lung volume in early acute respiratory distress syndrome: study protocol for the multicenter, randomized IPERPEEP trial

BackgroundIn acute respiratory distress syndrome (ARDS), response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP based on patients’ individual response is warranted.End-expiratory lung volume (EELV) assessment by nitrogen washin-washout aids bedside estimation of PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient’s individual recruitability.We designed a randomized trial to test whether an individualized PEEP setting protocol driven by EELV measurement may improve a composite clinical outcome in patients with moderate-to-severe ARDS (IPERPEEP trial).MethodsIPERPEEP is an open-label, multicenter, randomized trial that will be conducted in 10 intensive care units in Italy and will enroll 132 ARDS patients showing PaO2/FiO2 ratio ≤ 150 mmHg within 24 h from endotracheal intubation while on mechanical ventilation with PEEP 5 cmH2O.To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume of 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH2O for 30 min (EXPRESS PEEP).Afterwards, a 5-step decremental PEEP trial will be conducted (EXPRESS PEEP to PEEP 5 cmH2O), and EELV will be measured at each step. Recruitment-to-inflation ratio will be calculated for each PEEP range from EELV difference. Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or to achieve a plateau pressure of 28–30 cmH2O (control arm, EXPRESS strategy). In both groups, tidal volume size, use of prone positioning and neuromuscular blocking agents, and weaning from PEEP and from mechanical ventilation will be standardized.The primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator-free days, and serum interleukin-6 concentration over the course of the initial 72 h of treatment.DiscussionThe IPERPEEP study is a randomized trial powered to elucidate whether an individualized PEEP setting protocol based on bedside assessment of lung recruitability can improve a composite clinical outcome during moderate-to-severe ARDS.Trial registrationClinicalTrials.govNCT04012073. Registered 9 July 2019.