Changes In Lung Mechanics Research Articles

Recruitment-to-inflation ratio to assess response to PEEP during laparoscopic surgery: A physiologic study

Study objectiveDuring laparoscopic surgery, the role of PEEP to improve outcome is controversial. Mechanistically, PEEP benefits depend on the extent of alveolar recruitment, which prevents ventilator-induced lung injury by reducing lung dynamic strain. The hypotheses of this study were that pneumoperitoneum-induced aeration loss and PEEP-induced recruitment are inter-individually variable, and that the recruitment-to-inflation ratio (R/I) can identify patients who benefit from PEEP in terms of strain reduction. DesignSequential study. SettingOperating room. PatientsSeventeen ASA I-III patients receiving robot-assisted prostatectomy during Trendelenburg pneumoperitoneum. Interventions and measurementsPatients underwent end-expiratory lung volume (EELV) and respiratory/lung/chest wall mechanics (esophageal manometry and inspiratory/expiratory occlusions) assessment at PEEP = 0 cmH2O before and after pneumoperitoneum, at PEEP = 4 and 12 cmH2O during pneumoperitoneum. Pneumoperitoneum-induced derecruitment and PEEP-induced recruitment were assessed through a simplified method based on multiple pressure-volume curve. Dynamic and static strain changes were evaluated. R/I between 12 and 4 cmH2O was assessed from EELV. Inter-individual variability was rated with the ratio of standard deviation to mean (CoV). Main resultsPneumoperitoneum reduced EELV by (median [IqR]) 410 mL [80–770] (p < 0.001) and increased dynamic strain by 0.04 [0.01–0.07] (p < 0.001), with high inter-individual variability (CoV = 70% and 88%, respectively). Compared to PEEP = 4 cmH2O, PEEP = 12 cmH2O yielded variable amount of recruitment (139 mL [96–366] CoV = 101%), causing different extent of dynamic strain reduction (median decrease 0.02 [0.01–0.04], p = 0.002; CoV = 86%) and static strain increases (median increase 0.05 [0.04–0.07], p = 0.01, CoV = 33%). R/I (1.73 [0.58–3.35]) estimated the decrease in dynamic strain (p ≤0.001, r = −0.90) and the increase in static strain (p = 0.009, r = −0.73) induced by PEEP, while PEEP-induced changes in respiratory and lung mechanics did not. ConclusionsTrendelenburg pneumoperitoneum yields variable derecruitment: PEEP capability to revert these phenomena varies significantly among individuals. High R/I identifies patients in whom higher PEEP mostly reduces dynamic strain with limited static strain increases, potentially allowing individualized settings.

Breath-by-breath assessment of acute pulmonary edema using electrical impedance tomography, spirometry and volumetric capnography in a sheep (Ovis Aries) model.

The bedside diagnosis of acute pulmonary edema is challenging. This study evaluated the breath-by-breath information from electrical impedance tomography (EIT), respiratory mechanics and volumetric capnography (VCap) to assess acute pulmonary edema induced by xylazine administration in anesthetized sheep. To determine the ability and efficiency of each monitoring modality in detecting changes in lung function associated with onset of pulmonary edema. Twenty healthy ewes were anesthetized, positioned in sternal (prone) recumbency and instrumented. Synchronized recordings of EIT, spirometry and VCap were performed for 60 s prior to start of injection, during xylazine injection over 60 s (0-60 s) and continuously for 1 min (60-120 s) after the end of injection. After visual assessment of the recorded mean variables, statistical analysis was performed using a mixed effect model for repeated measures with Bonferroni's correction for multiple comparisons, to determine at which breath after start of injection the variable was significantly different from baseline. A significant change over time was defined as an adjusted p < 0.05. All statistics were performed using GraphPad Prism 0.1.0. Electrical impedance tomography showed significant changes from baseline in all but two variables. These changes were observed simultaneously during xylazine injection at 48 s and were consistent with development of edema in dependent lung (decreased end-expiratory lung impedance, ventilation in centro-ventral and ventral lung region) and shift of ventilation into non-dependent lung (decreased non-dependent silent spaces and increased center of ventilation ventral to dorsal and increased ventilation in centro-dorsal and dorsal lung region). All changes in lung mechanics also occurred during injection, including decreased dynamic respiratory system compliance and increased peak expiratory flow, peak inspiratory pressure and airway resistance at 48, 54 and 60 s, respectively. Changes in VCap variables were delayed with all occurring after completion of the injection. In this model of pulmonary edema, EIT detected significant and rapid change in all assessed variables of lung function with changes in regional ventilation indicative of pulmonary edema. Volumetric capnography complemented the EIT findings, while respiratory mechanics were not specific to lung edema. Thus, EIT offers the most comprehensive method for pulmonary edema evaluation, including the assessment of ventilation distribution, thereby enhancing diagnostic capabilities.

Changes in lung mechanics and ventilation-perfusion match: comparison of pulmonary air- and thromboembolism in rats

BackgroundPulmonary air embolism (AE) and thromboembolism lead to severe ventilation-perfusion defects. The spatial distribution of pulmonary perfusion dysfunctions differs substantially in the two pulmonary embolism pathologies, and the effects on respiratory mechanics, gas exchange, and ventilation-perfusion match have not been compared within a study. Therefore, we compared changes in indices reflecting airway and respiratory tissue mechanics, gas exchange, and capnography when pulmonary embolism was induced by venous injection of air as a model of gas embolism or by clamping the main pulmonary artery to mimic severe thromboembolism.MethodsAnesthetized and mechanically ventilated rats (n = 9) were measured under baseline conditions after inducing pulmonary AE by injecting 0.1 mL air into the femoral vein and after occluding the left pulmonary artery (LPAO). Changes in mechanical parameters were assessed by forced oscillations to measure airway resistance, lung tissue damping, and elastance. The arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were determined by blood gas analyses. Gas exchange indices were also assessed by measuring end-tidal CO2 concentration (ETCO2), shape factors, and dead space parameters by volumetric capnography.ResultsIn the presence of a uniform decrease in ETCO2 in the two embolism models, marked elevations in the bronchial tone and compromised lung tissue mechanics were noted after LPAO, whereas AE did not affect lung mechanics. Conversely, only AE deteriorated PaO2, and PaCO2, while LPAO did not affect these outcomes. Neither AE nor LPAO caused changes in the anatomical or physiological dead space, while both embolism models resulted in elevated alveolar dead space indices incorporating intrapulmonary shunting.ConclusionsOur findings indicate that severe focal hypocapnia following LPAO triggers bronchoconstriction redirecting airflow to well-perfused lung areas, thereby maintaining normal oxygenation, and the CO2 elimination ability of the lungs. However, hypocapnia in diffuse pulmonary perfusion after AE may not reach the threshold level to induce lung mechanical changes; thus, the compensatory mechanisms to match ventilation to perfusion are activated less effectively.

Bedside test for estimating stiff index in mechanically ventilated ARDS patient: a pilot study

Stiff index is defined as the proportion of lung tissue elasticity in relation to chest wall elasticity to pertain to its cyclic tidal volume. It is meant to reflect the risk of overloading lung pressure. Introducing the Stiff index into bedside management determines the pressure needed to keep the lung open with no risk of barotrauma.Aim of the work The primary endpoint was to highlight the stiff index in ARDS patients as a potential surrogate for detecting the changes in lung mechanics and the assumptions underlying the estimation of relevant respiratory parameters. Secondly, we aimed to assess intrathoracic pressure ITP in view of chest wall elastance Ecw in relation to respiratory system elastance Ers within the same population.Subjects and methods Data were collected from forty ARDS patients, diagnosed according to Berlin definition, who were admitted to ICUS Ain Shams University hospitals during the period between December 2022 and April 2023. These populations were patients’ purposive samples who underwent volume‐controlled ventilation at least 2 days prior to study enrollment. Their mean age was 64.68 ± 15.01 years with males (N = 22) to females (N = 18) ratio 55%. Measurements of peak airway pressure, plateau pressure, and delta airway pressure change ∆Paw measured three times on end-expiratory (ee) and on end-inspiratory (ei) occlusion tests, and the higher of the three readings were reported.Results The calculated mean Stiff index was (0.66 ± 0.159) which was correlated with Peak pressure (r = − 0.377, P = 0.017) and with trans-pulmonary end inspiration TPPei (r = 0.312, P = 0.05). The stiff index was also found to be correlated with intra-thoracic pressure ITP (r = 0.769, P 0.001), but is not statistically significant with inspiratory tidal volume (r = 0.132, P 0.416).Conclusion Lung pressure loading in ARDS could be recognized by estimating an increase in stiff index. The cut point of stiff factor that limited the plateau at or below 30 cmH2o was 0.75 with 71% sensitivity and 0.63% specificity, respectively. The more the Stiff index the more was the ITP, and it had no relation to TV.

Automated evaluation of typical patient–ventilator asynchronies based on lung hysteretic responses

BackgroundPatient–ventilator asynchrony is common during mechanical ventilation (MV) in intensive care unit (ICU), leading to worse MV care outcome. Identification of asynchrony is critical for optimizing MV settings to reduce or eliminate asynchrony, whilst current clinical visual inspection of all typical types of asynchronous breaths is difficult and inefficient. Patient asynchronies create a unique pattern of distortions in hysteresis respiratory behaviours presented in pressure–volume (PV) loop.MethodsIdentification method based on hysteretic lung mechanics and hysteresis loop analysis is proposed to delineate the resulted changes of lung mechanics in PV loop during asynchronous breathing, offering detection of both its incidence and 7 major types. Performance is tested against clinical patient data with comparison to visual inspection conducted by clinical doctors.ResultsThe identification sensitivity and specificity of 11 patients with 500 breaths for each patient are above 89.5% and 96.8% for all 7 types, respectively. The average sensitivity and specificity across all cases are 94.6% and 99.3%, indicating a very good accuracy. The comparison of statistical analysis between identification and human inspection yields the essential same clinical judgement on patient asynchrony status for each patient, potentially leading to the same clinical decision for setting adjustment.ConclusionsThe overall results validate the accuracy and robustness of the identification method for a bedside monitoring, as well as its ability to provide a quantified metric for clinical decision of ventilator setting. Hence, the method shows its potential to assist a more consistent and objective assessment of asynchrony without undermining the efficacy of the current clinical practice.

Effect of bronchial thermoplasty on static and dynamic lung compliance and resistance in patients with severe persistent asthma

RationaleBronchial thermoplasty (BT) reduces severity and frequency of bronchoconstriction and symptoms in severe, persistent asthmatics although it is usually not associated with change in spirometric variables. Other than spirometry. there are almost no data on changes in lung mechanics following BT. ObjectiveTo assess lung static and dynamic lung compliance (Cst,L and Cdyn,L, respectively) and static and dynamic lung resistance (Rst,L and Rdyn,L, respectively) before and after BT in severe asthmatics using the esophageal balloon technique. MethodsRdyn,L and Cdyn,L were measured at respiratory frequencies up to 145 breaths/min, using the esophageal balloon technique in 7 patients immediately before and 12–50 weeks after completing a series of 3 BT sessions. ResultsAll patients experienced improved symptoms within a few weeks following completion of BT. Pre-BT, all patients exhibited frequency dependency of lung compliance, with mean Cdyn,L decreasing to 63% of Cst,L at maximum respiratory rates. Post-BT, Cst,L did not change significantly from pre-thermoplasty values, while Cdyn,L diminished to 62%% of Cst,L. In 4 of 7 patients, post-BT values of Cdyn,L were consistently higher than pre-BT over the range of respiratory rates. RL in 4 of 7 patients during quiet breathing and at higher respiratory frequencies decreased following BT. ConclusionsPatients with severe persistent asthma exhibit increased resting lung resistance and frequency dependence of compliance, the magnitudes of which are ameliorated in some patients following bronchial thermoplasty and associated with variable change in frequency dependence of lung resistance. These findings are related to asthma severity and may be related to the heterogeneous and variable nature of airway smooth muscle modeling and its response to BT.

A Longitudinal Study of Respiratory Mechanics in Pregnant Women with Obesity and Overweight.

Respiratory mechanics and the role of sex hormones in pregnancy are not well elucidated. We examined longitudinal and positional changes in lung mechanics in pregnancy and investigated the role of sex hormones. A longitudinal study enrolled 135 women with obesity in early pregnancy. Fifty-nine percent of women identified as White; median body mass index at enrollment was 34.4kg/m2. Women with respiratory disease were excluded. We obtained measurements of airway resistance and respiratory system reactance in various positions using impedance oscillometry and sex hormones in early and late pregnancy. With pregnancy progression, there was a significant increase in resonant frequency (Fres) (p = 0.012), integrated area of low frequency reactance (AX) (p = 0.0012) and R5-R20Hz (p = 0.038) in the seated position,and a significant increase in R5Hz (p = 0.000), Fres (p = 0.001), AX (p < 0.001 = 0.000), and R5-R20Hz (p = 0.014) in the supine position. Compared to the seated position, the supine position was associated with a significant increase in R5Hz, R20Hz, X5Hz, Fres, and AX in early (p-values < 0.026) and late pregnancy (p-values ≤ 0.001). Changes in progesterone levels between early and late pregnancy predicted the change in R5, Fres, and AX (p-values ≤ 0.043). Resistive and elastic loads increase with pregnancy progression and a change in body position from seated to supine increases resistive and elastic loads in both early and late pregnancies. The increase in airway resistance is primarily related to an increase in peripheral rather than central airways resistance. There was an association between the change in progesterone levels and airway resistance.

Effect of Obesity on Airway Mechanics.

Obesity is known to induce lung function impairment. Previous studies of decline in lung function associated with obesity are well established. In this cross-sectional study, to evaluate the effects of different obesity indices on lung mechanics, healthy subjects (males-23 and females-22) were recruited. Anthropometric parameters like body mass index (BMI), waist circumference (WC), hip circumference (HC) and neck circumference (NC) were measured and waist-hip ratio (WHR) was derived. Spirometry, impulse oscillometry (IOS) and fractional exhaled nitric oxide (FeNO) measurements were performed to assess lung function. Subgroups were divided and analysed. In males, increased WHR is associated with increased total airway resistance (R5). BMI correlates positively with R5, R5% predicted, resistance at 20 Hz (R20) and R20% predicted; likewise, WHR shows a positive correlation with R5. In females, increased WHR has significantly higher R5, R5% predicted, R20, R20% predicted, area of reactance (Ax), resonant frequency (Fres) and decreased reactance at 5 Hz (X5), reactance at 20 Hz (X20), X20% predicted. The female group with higher WC shows significantly increased R5, R5% predicted, R20, R20% predicted, Ax, Fres and lower fixed ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC), X5, X20, X20% predicted. The group with higher NC has a lower FEV1/FVC ratio. WHR positively correlated with R5% predicted and Fres while WC correlated positively with R5, R5% predicted, Ax and Fres; same way, NC with X5% predicted. Obesity/overweight causes significant changes in lung volumes, capacity and airway mechanics, Higher WC and WHR are associated with significant changes in lung mechanics, which are more prominent in females than in males. NC is not associated with changes in lung mechanics.

Contribution of Carotid Bodies on Pulmonary Function During Normoxia and Acute Hypoxia.

Carotid bodies (CBs) are main peripheral chemoreceptors involved in breathing regulation. Despite the well-known role played by CBs on breathing control, the precise contribution of CBs on the regulation of lung mechanics remains controversial. Accordingly, we study changes in lung mechanics in normoxia (FiO2 21%) and hypoxia (FiO2 8%) in mice with or without functional CBs. For this, we used adult male mice that underwent sham or CB denervation (CBD) surgery. Compared to sham-operated mice, we found that CBD induced an increase in lung resistance (RL) while breathing normoxic air (sham vs. CBD, p<0.05). Importantly, changes in RL were accompanied by an approximately threefold reduction in dynamic compliance (Cdyn). Additionally, end-expiratory work (EEW) was increased in normoxia in the CBD group. Contrarily, we found that CBD has no effect on lung mechanics during hypoxic stimulation. Indeed, RL, Cdyn, and EEW values in CBD mice were undistinguishable from the ones obtained in sham mice. Finally, we found that CBD induces lung parenchyma morphological alterations characterized by reduced alveoli space. Together our results showed that CBD progressively increases lung resistance at normoxic conditions and suggest that CB tonic afferent discharges are needed for the proper regulation of lung mechanics at rest.

Lung mechanics during video-assisted abdominal surgery in Trendelenburg position: a cross-sectional propensity-matched comparison between classic laparoscopy and robotic-assisted surgery

BackgroundVideo-assisted surgery has become an increasingly used surgical technique in patients undergoing major thoracic and abdominal surgery and is associated with significant perioperative respiratory and cardiovascular changes. The aim of this study was to investigate the effect of intraoperative pneumoperitoneum during video-assisted surgery on respiratory physiology in patients undergoing robotic-assisted surgery compared to patients undergoing classic laparoscopy in Trendelenburg position.MethodsTwenty-five patients undergoing robotic-assisted surgery (RAS) were compared with twenty patients undergoing classic laparoscopy (LAS). Intraoperative ventilatory parameters (lung compliance and plateau airway pressure) were recorded at five specific timepoints: after induction of anesthesia, after carbon dioxide (CO2) insufflation, one-hour, and two-hours into surgery and at the end of surgery. At the same time, arterial and end-tidal CO2 values were noted and arterial to end-tidal CO2 gradient was calculated.ResultsWe observed a statistically significant difference in plateau pressure between RAS and LAS at one-hour (26.2 ± 4.5 cmH2O vs. 20.2 ± 3.5 cmH2O, p = 0.05) and two-hour intervals (25.2 ± 5.7 cmH2O vs. 17.9 ± 3.1 cmH2O, p = 0.01) during surgery and at the end of surgery (19.9 ± 5.0 cmH2O vs. 17.0 ± 2.7 cmH2O, p = 0.02). Significant changes in lung compliance were also observed between groups at one-hour (28.2 ± 8.5 mL/cmH2O vs. 40.5 ± 13.9 mL/cmH2O, p = 0.01) and two-hour intervals (26.2 ± 7.8 mL/cmH2O vs. 54.6 ± 16.9 mL/cmH2O, p = 0.01) and at the end of surgery (36.3 ± 9.9 mL/cmH2O vs. 58.2 ± 21.3 mL/cmH2O, p = 0.01). At the end of surgery, plateau pressures remained higher than preoperative values in both groups, but lung compliance remained significantly lower than preoperative values only in patients undergoing RAS with a mean 24% change compared to 1.7% change in the LAS group (p = 0.01). We also noted a more significant arterial to end-tidal CO2 gradient in the RAS group compared to LAS group at one-hour (12.9 ± 4.5 mmHg vs. 7.4 ± 4.4 mmHg, p = 0.02) and two-hours interval (15.2 ± 4.5 mmHg vs. 7.7 ± 4.9 mmHg, p = 0.02), as well as at the end of surgery (11.0 ± 6.6 mmHg vs. 7.0 ± 4.6 mmHg, p = 0.03).ConclusionVideo-assisted surgery is associated with significant changes in lung mechanics after induction of pneumoperitoneum. The observed changes are more severe and longer-lasting in patients undergoing robotic-assisted surgery compared to classic laparoscopy.

Pneumothorax in Intubated Patients With COVID-19: A Case Series.

Pneumothorax is a rare complication among mechanically ventilated patients since low tidal volumes are used nowadays instead of traditional high tidal volumes, but the incidence is slightly higher in patients with high positive end-expiratory pressure (PEEP). Herein we describe a case series of nine patients who were on mechanical ventilation due to acute respiratory distress syndrome (ARDS) secondary to coronavirus disease 2019 (COVID-19) and developed pneumothorax in due course. A retrospective analysis was done on COVID-19 intubated patients from March 2020 to June 2020 in a community hospital in Central New Jersey, which was one of the early hit states in the United States at the beginning of the pandemic. Outcomes were studied. The demographics of patients like age, gender, and body mass index (BMI); risk factors like smoking, comorbidities especially chronic lung disease, and the treatment they received were compared. We compared the total number of days on the ventilator, the highest PEEP they received, and the ventilator day when pneumothorax developed. All the patients who developed pneumothorax had a chest tube inserted to treat it. The mortality was noted to be 100% indicating that pneumothorax is a life-threatening complication of COVID-19and COVID-19 by itself is a risk factor for pneumothorax likely due to a change in lung mechanics. There is a need for large-scale studies to confirm that these outcomes are related to COVID-19.

217.9: Activation of Angiotensin-converting Enzyme 2 (ACE2) Modulates Lung Mechanics in a Brain Death Model and Attenuates Pulmonary Edema After Rat Lung Transplantation

Introduction: Lung transplantation is a therapeutic option established worldwide for end-stage lung diseases. However, as most donors evolve with brain death (BD), the donated lung may have been compromised. In view of the participation of the renin angiotensin system (RAS) and the use of angiotensin-converting enzyme 2 (ACE2) activators in several pathological processes, it was investigated how diminazene aceturate (DIZE), an ACE2 activator, modulates hemodynamic and blood gas changes, as well as lung function following transplantation in rats. Method: Male Lewis rats were randomly distributed in the following experimental groups: intact, brain death (BD) and BD + diminazene aceturate (BD+DIZE). The last two groups were submitted to brain death process, treated with saline (0.9%) or DIZE (15 mg/kg-1) and kept on mechanical ventilation for 6 hours (donor). After this period, cardiopulmonary block extraction and left unilateral transplantation (LTx) with independent graft ventilation was performed, followed by 2h reperfusion. Hemodynamics (mean arterial pressure - MAP), blood gas analysis, lung mechanics, and pulmonary edema were evaluated. Results are presented as S.E.M. (ANOVA; Tukey; p<0.05). (Approval # CEUA/FMUSP - 1630/2021). Results: The administration of DIZE, 3 hours after BD, prevented the increase in the MAP (210’ after BD-induction: BD – 110 ± 12 mmHg; n=5; BD+DIZE – 40 ± 12 mmHg; n=4/ p=0.0001) without associated blood gas and metabolic alterations. Changes in lung mechanics, such as decreased tissue damping (G) and histeresivity (n) followed by increased respiratory system compliance (Crs), were associated with BD+DIZE (G - 0,25 ± 0,03 cmH2O/mL; Crs - 0,71 ± 0,03 mL/cmH2O; n – 0,14 ± 0,008) compared to intact (G - 0,40 ± 0,02 cmH2O/mL, p = 0.01; Crs – 0,64 ± 0,01 mL/cmH2O, p = 0.02; n - 0,26 ± 0,01, p = 0.004) and BD groups (G – 0,41± 0,05 cmH2O/mL, p = 0.02; Crs – 0,61 ± 0,01 mL/cmH2O, p = 0.01; n - 0,25 ± 0,008, p = 0.01) (Figure 1). After LTx, MAP, gas exchange function, and lung mechanical parameters, were not different among the 3 groups (p>0.05). On the other hand, the DIZE treatment was capable to reduce wet-to-dry weight ratio (INTACT – 1,87 ± 0,13; BD – 2,59 ± 0,14; BD+DIZE – 1,93 ± 0,15/ p=0.01) (Figure 2). Conclusion: Our data suggests that activation of ACE2 is able to modulate donor hemodynamic and lung mechanical parameters, probably reducing tissue resistance and improving airflow in the peripheral airways, converging to a decrease in ventilation heterogeneity in the sudden onset model of brain death. Our data also indicates that DIZE attenuates pulmonary edema on grafts from BD donors after lung transplantation. Keywords: Diminazene aceturate. Renin-angiotensin system. Brain death. Lung mechanics. Lung transplantation.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico.

Oscillatory Mechanics Response to Inhaled Bronchodilators in Very Preterm Infants: A Retrospective Study

To identify short-term repeatability of forced oscillation technique (FOT) measurement of lung function, assess the lung function response to bronchodilators (BDs) by FOT, and prove the concept that only some very preterm infants manifest a change in lung mechanics in response to BD. We retrospectively analyzed respiratory system resistance and respiratory system reactance measured by FOT (Fabian HFOi). The measurement short-term repeatability was assessed in 43 patients on 60 occasions; BD responsiveness was assessed using a different data set, including 38 measurements in 18 infants. The coefficient of repeatability was calculated as twice the SD of differences between measurements performed 15minutes apart. We assessed BD responsiveness by measuring respiratory system resistance and respiratory system reactance before and 15minutes after administering 200 mcg/kg of nebulized salbutamol. A positive response was defined as an improvement in respiratory system resistance or respiratory system reactance greater than the identified coefficient of repeatability. The coefficient of repeatability was 7.5 cmH2O∗s/L (21%) for respiratory system resistance and 6.3 cmH2O∗s/L (21%) for respiratory system reactance. On average, respiratory system resistance did not change significantly following BD administration, though respiratory system reactance increased significantly (from -32.0 [-50.2, -24.4] to -27.9 [-38.1, -22.0] cmH2O∗s/L, P<.001). Changes in respiratory system resistance or respiratory system reactance after BD were greater than the identified coefficient of repeatability in 8 infants (44%) on 13 (34%) occasions. We identified a threshold to assess BD responsiveness by FOT in preterm infants. We speculate that FOT could be used to assess and personalize treatment with BD.

Kisspeptin Reduces Airway Hyperreactivity and Remodeling in Asthmatic Ovariectomized Mice

RationaleEpidemiological data show changes in asthma occurrence with age and sex. After puberty, increased severity in women shows sex‐skewed occurrence of asthma in females vs. males. This implies the importance of female sex‐steroids, particularly estrogen in asthma pathophysiology. Greater asthma in women may represent detrimental mechanisms upstream to or independent of estrogen. Moreover, data from CNS studies show kisspeptin (Kp) signaling is modulated by estrogen. Our recent in vitro studies show Kp via its receptor, KISS1R regulates airway smooth muscle (ASM) cell proliferation. However, the relevance of endogenous estrogen on Kp/KISS1R signaling and their effect on regulating airway hyperresponsiveness (AHR) and remodeling is not yet explored. Accordingly, in this present study, we utilized intact female vs. ovariectomized (OVX) mice to isolate estrogen influence from the Kp effect in regulating AHR and remodeling in a murine model of allergic asthma.MethodsWild Type C57BL/6J intact female and OVX mice were procured from Jackson Laboratory, USA, and challenged intranasally with a mixed‐allergen (MA) for 28 days. On alternate days, animals from the treatment group received intranasal Kp‐10 (1.2mg/kg), vehicle group received PBS alone. On day 29, mice were anesthetized and subjected to SCIREQ flexiVent to measure lung mechanics like airway resistance (Rrs), elastance (Ers), compliance (Crs), tissue damping (G), and tissue‐elasticity (H). Following this, bronchoalveolar lavage (BAL) was performed for differential leukocyte count (DLC) and lung tissues were processed for histology using hematoxylin and eosin (H&amp;E) and trichrome staining. Additionally, laser‐capture microdissection (LCM) assisted qRT‐PCR analysis in ASM cells was performed for genes relevant to airway remodeling.ResultsMA‐challenged intact female and OVX mice showed a significant increase in Rrs, Ers, G, H, and reduced Crs compared to PBS, more pronounced effects were observed in intact females. Kp‐10 treatment significantly reversed the MA‐induced changes with a decrease in Rrs, Ers, G, H, and increased Crs. Interestingly, in OVX mice we observed significant effects of Kp‐10 to improve the lung mechanics compared to intact females. Notably, Kp‐10 alone exposed group did not show any changes in lung mechanics compared to PBS. DLC in BAL showed Kp‐10 treatment significantly reduced MA‐induced inflammatory cell infiltration. Futhermore, histology studies showed Kp‐10 treatment significantly reduced MA‐induced smooth muscle mass and collagen deposition in airways.ConclusionOverall, this study shows the modulatory role of estrogen in regulating kisspeptin signaling, thereby AHR and remodeling. Thus, providing the relevance to higher asthma incidence and severity in women compared to men.

The Impact of Mechanical Ventilation Modes on Complications of Fiberoptic Bronchoscopy in Critically Ill Patients.

OBJECTIVEThe effects of fiberoptic bronchoscopy are not elucidated in different mechanical ventilation modes. The present study aimed to evaluate the effects of fiberoptic bronchoscopy on lung mechanics, ventilation parameters, and gas exchange in 2 often-used modes, volume control and pressure control, in invasively ventilated patients followed up in the intensive care unit.MATERIAL AND METHODSEligible patients were screened and included in the study after intensive care unit-fiberoptic bronchoscopy database search. Patients who underwent fiberoptic bronchoscopy under volume control and pressure control mechanical ventilation modes were compared. The primary outcome was the occurrence of any complication within the first 24 hours after the procedure, and secondary outcomes were changes in lung mechanics (dynamic lung compliance and airway resistance) and gas exchange (arterial partial pressures of oxygen and carbon dioxide).ResultsA total of 61 patients (median age: 69 years, 60.7% male) were included. Twenty-nine (47.5%) patients were ventilated in volume control mode and 32 (52.5%) in pressure control mode during the fiberoptic bronchoscopy procedure, and the median (interquartile range) duration of the procedure was 9 [8-11] minutes. Baseline dynamic lung compliance, airway resistance, arterial partial pressures of oxygen and carbon dioxide, and the fraction of inspired O2 were similar in both groups. After fiberoptic bronchoscopy, dynamic lung compliance decreased in both groups, and airway resistance and peak airway pressures increased but reached pre-fiberoptic bronchoscopy values at the 1st hour after the procedure. No significant differences were detected in both groups in terms of blood gas values and lung mechanics in the 1st and 24th hours after the procedure. In both groups, the 24th hour fraction of inspired O2 was the same as the pre-fiberoptic bronchoscopy values, but the ratio of arterial partial pressure of oxygen and the fraction of inspired O2 improved. No complications developed in patients within 24 hours after the procedure.ConclusionNo differences were detected in terms of gas exchange and pulmonary mechanics, and complications in volume control and pressure control modes in critically ill intubated patients.

Mechanisms Involved in the Stimulatory and Inhibitory Effects of 5-Hydroxytryptamine on Vagal Mechanosensitive Afferents in Rat Lung.

Mechanosensitive vagal afferents in the lung, rapidly and slowly adapting receptors (RARs and SARs, respectively), play an important role in eliciting the reflexes that regulate the normal airway function. A profound bronchoconstrictive effect of 5-hydroxytryptamine (5-HT) has been extensively reported in various animal species, but its influence on the SAR and RAR activity is not known. This study investigated the effect of 5-HT on these receptors, and the possible mechanisms involved. Single-fiber activities of these afferents were measured in anesthetized, open-chest, and mechanically ventilated rats. Our results showed that intravenous injection of 5-HT evoked a consistent and pronounced stimulation of phasic RARs. In contrast, 5-HT generated an inconsistent and paradoxical action on SARs: no effect in 29% (5 of 17) of the SARs; stimulation in 35% (6 of 17); and inhibition in the remainder. These responses of both RARs and SARs to 5-HT were reproducible and dose-dependent. After the injection of a high dose of 5-HT (16 μg/kg), the receptor responses slowly reached a peak (after ∼8 s) and returned toward the baseline in ∼20 s, accompanied by a consistent increase in total pulmonary resistance and a decrease in dynamic lung compliance in a temporal pattern very similar to the increased receptor activity. When these changes in lung mechanics induced by 5-HT were prevented by pretreatment with salbutamol, a β2 adrenergic receptor agonist, the delayed responses of both RARs and SARs to 5-HT were also abolished, except that the immediate stimulatory effect on a subset of RARs, the silent RARs, was not affected. In conclusion, 5-HT generated a delayed stimulatory effect on RARs and a paradoxical effect on SARs, which resulted primarily from the 5-HT-induced changes in mechanical properties of the lung.

Respiratory effects of lung recruitment maneuvers depend on the recruitment-to-inflation ratio in patients with COVID-19-related acute respiratory distress syndrome

BackgroundIn the context of acute respiratory distress syndrome (ARDS), the response to lung recruitment maneuvers (LRMs) varies considerably from one patient to another and so is difficult to predict. The aim of the study was to determine whether or not the recruitment-to-inflation (R/I) ratio could differentiate between patients according to the change in lung mechanics during the LRM.MethodsWe evaluated the changes in gas exchange and respiratory mechanics induced by a stepwise LRM at a constant driving pressure of 15 cmH2O during pressure-controlled ventilation. We assessed lung recruitability by measuring the R/I ratio. Patients were dichotomized with regard to the median R/I ratio.ResultsWe included 30 patients with moderate-to-severe ARDS and a median [interquartile range] R/I ratio of 0.62 [0.42–0.83]. After the LRM, patients with high recruitability (R/I ratio ≥ 0.62) presented an improvement in the PaO2/FiO2 ratio, due to significant increase in respiratory system compliance (33 [27–42] vs. 42 [35–60] mL/cmH2O; p < 0.001). In low recruitability patients (R/I < 0.62), the increase in PaO2/FiO2 ratio was associated with a significant decrease in pulse pressure as a surrogate of cardiac output (70 [55–85] vs. 50 [51–67] mmHg; p = 0.01) but not with a significant change in respiratory system compliance (33 [24–47] vs. 35 [25–47] mL/cmH2O; p = 0.74).ConclusionAfter the LRM, patients with high recruitability presented a significant increase in respiratory system compliance (indicating a gain in ventilated area), while those with low recruitability presented a decrease in pulse pressure suggesting a drop in cardiac output and therefore in intrapulmonary shunt.

The physiological basis of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare dyspnoea-fatigue syndrome caused by a progressive increase in pulmonary vascular resistance and eventual right ventricular (RV) failure. In spite of extensive pulmonary vascular remodelling, lung function in PAH is generally well preserved, with hyperventilation and increased physiological dead space, but minimal changes in lung mechanics and only mild to moderate hypoxaemia and hypocapnia. Hypoxaemia is mainly caused by a low mixed venous oxygen tension from a decreased cardiac output. Hypocapnia is mainly caused by an increased chemosensitivity. Exercise limitation in PAH is cardiovascular rather than ventilatory or muscular. The extent of pulmonary vascular disease in PAH is defined by multipoint pulmonary vascular pressure–flow relationships with a correction for haematocrit. Pulsatile pulmonary vascular pressure–flow relationships in PAH allow for the assessment of RV hydraulic load. This analysis is possible either in the frequency domain or in the time domain. The RV in PAH adapts to increased afterload by an increased contractility to preserve its coupling to the pulmonary circulation. When this homeometric mechanism is exhausted, the RV dilates to preserve flow output by an additional heterometric mechanism. Right heart failure is then diagnosed by imaging of increased right heart dimensions and clinical systemic congestion signs and symptoms. The coupling of the RV to the pulmonary circulation is assessed by the ratio of end-systolic to arterial elastances, but these measurements are difficult. Simplified estimates of RV–pulmonary artery coupling can be obtained by magnetic resonance or echocardiographic imaging of ejection fraction.

Dopamine Reverses Lung Function Deterioration After Cardiopulmonary Bypass Without Affecting Gas Exchange

To investigate the effects of dopamine on the adverse pulmonary changes after cardiopulmonary bypass. A prospective, nonrandomized clinical investigation. A university hospital. One hundred fifty-seven patients who underwent elective cardiac surgery that required cardiopulmonary bypass. Fifty-two patients were administered intravenous infusion of dopamine (3 µg/kg/min) for five minutes after weaning from cardiopulmonary bypass; no intervention was applied in the other 105 patients. Measurements were performed under general anesthesia and mechanical ventilation before cardiopulmonary bypass, after cardiopulmonary bypass, and after the intervention. In each protocol stage, forced oscillatory lung impedance was measured to assess airway and tissue mechanical changes. Mainstream capnography was performed to assess ventilation- and/or perfusion-matching by calculating the normalized phase-3 slopes of the time and volumetric capnograms and the physiologic deadspace. Arterial and central venous blood samples were analyzed to characterize lung oxygenation and intrapulmonary shunt. After cardiopulmonary bypass, dopamineinduced marked improvements in airway resistance and tissue damping, with relatively small decreases in lung tissue elastance. These changes were associated with decreases in the normalized phase-3 slopes of the time and volumetric capnograms. The inotrope had no effect on physiologic deadspace, intrapulmonary shunt, or lung oxygenation. Dopamine reversed the complex detrimental lung mechanical changes induced by cardiopulmonary bypass and alleviated ventilation heterogeneities without affecting the physiologic deadspace or intrapulmonary shunt. Therefore, dopamine has a potential benefit on the gas exchange abnormalities after weaning from cardiopulmonary bypass.

Postnatal diuretics, weight gain and home oxygen requirement in extremely preterm infants.

Diuretics are often given to infants with evolving/established bronchopulmonary dysplasia (BPD) with the hope of improving their pulmonary outcomes. We aimed to determine if diuretic use in preterm infants was associated with improved pulmonary outcomes, but poorer weight gain. An observational study over a 5year period was undertaken of all infants born at less than 29weeks of gestation and alive at discharge in all neonatal units in England who received consecutive diuretic use for at least 7days. Postnatal weight gain and home supplementary oxygen requirement were the outcomes. A literature review of randomised controlled trials (RCTs) and crossover studies was undertaken to determine if diuretic usage wasassociated with changes in lung mechanics and oxygenation, duration of supplementary oxygen and requirement for home supplementary oxygen. In the observational study, 9,457 infants survived to discharge, 44.6% received diuretics for at least 7days. Diuretic use was associated with an increased probability of supplementary home oxygen of 0.14 and an increase in weight gain of 2.5g/week. In the review, seven of the 10 studies reported improvements only in short term lung mechanics. There was conflicting evidence regarding whether diuretics resulted in short term improvements in oxygenation. Diuretic use was not associated with a reduction in requirement for supplemental oxygen on discharge. The literature review highlighted a lack of RCTs assessing meaningful long-term clinical outcomes. Randomised trials are needed to determine the long-term risk benefit ratio of chronic diuretic use.