Effects of increasing tidal volume and end-expiratory lung volume on induced bronchoconstriction in healthy humans.

BACKGROUND: Increasing functional residual capacity (FRC) or tidal volume (VT) reduces airway resistance and attenuates the response to bronchoconstrictor stimuli in animals and humans. What is unknown is which one of the above mechanisms is more effective in modulating airway caliber and whether their combination yields additive or synergistic effects. To address this question, we investigated the effects of increased FRC and increased VT in attenuating the bronchoconstriction induced by inhaled methacholine (MCh) in healthy humans. METHODS: Nineteen healthy volunteers were challenged with a single-dose of MCh and forced oscillation was used to measure inspiratory resistance at 5 and 19 Hz (R5 and R19), their difference (R5-19), and reactance at 5 Hz (X5) during spontaneous breathing and during imposed breathing patterns with increased FRC, or VT, or both. Importantly, in our experimental design we held the product of VT and breathing frequency (BF), i.e, minute ventilation (VE) fixed so as to better isolate the effects of changes in VT alone. RESULTS: Tripling VT from baseline FRC significantly attenuated the effects of MCh on R5, R19, R5-19 and X5. Doubling VT while halving BF had insignificant effects. Increasing FRC by either one or two VT significantly attenuated the effects of MCh on R5, R19, R5-19 and X5. Increasing both VT and FRC had additive effects on R5, R19, R5-19 and X5, but the effect of increasing FRC was more consistent than increasing VT thus suggesting larger bronchodilation. When compared at iso-volume, there were no differences among breathing patterns with the exception of when VT was three times larger than during spontaneous breathing. CONCLUSIONS: These data show that increasing FRC and VT can attenuate induced bronchoconstriction in healthy humans by additive effects that are mainly related to an increase of mean operational lung volume. We suggest that static stretching as with increasing FRC is more effective than tidal stretching at constant VE, possibly through a combination of effects on airway geometry and airway smooth muscle dynamics.

Differences in pulmonary function measured by oscillometry between horses with mild-moderate equine asthma and healthy controls.

BACKGROUND: The diagnosis of mild-moderate equine asthma (MEA) can be confirmed by airway endoscopy, bronchoalveolar lavage fluid (BALf) cytology, and lung function evaluation by indirect pleural pressure measurement. Oscillometry is a promising pulmonary function test method, but its ability to detect subclinical airway obstruction has been questioned. OBJECTIVES: To evaluate the differences in lung function measured by oscillometry between healthy and MEA-affected horses. STUDY DESIGN: Prospective case-control clinical study. METHODS: Thirty-seven horses were divided into healthy and MEA groups, based on history and clinical score; the diagnosis of MEA was confirmed by airway endoscopy and BALf cytology. Horses underwent oscillometry at frequencies ranging from 2 to 6 Hz. Obtained parameters included whole-breath, inspiratory, expiratory, and the difference between inspiratory and expiratory resistance (Rrs) and reactance (Xrs). Differences between oscillometry parameters at different frequencies were evaluated within and between groups by repeated-measures two-way ANOVA and post hoc tests with Bonferroni correction. Frequency dependence was compared between groups by t test. For significant parameters, a receiver operating characteristics curve was designed, cut-off values were identified and their sensitivity and specificity were calculated. Statistical significance was set at p < 0.05. RESULTS: No significant differences in Xrs and Rrs were observed between groups. The frequency dependence of whole-breath and inspiratory Xrs significantly differed between healthy (respectively, -0.03 ± 0.02 and -0.05 ± 0.02 cmH2O/L/s) and MEA (-0.1 ± 0.03 and -0.2 ± 0.02 cmH2O/L/s) groups (p < 0.05 and p < 0.01). For inspiratory Xrs frequency dependence, a cut-off value of -0.06 cmH2O/L/s was identified, with 86.4% (95% CI: 66.7%-95.3%) sensitivity and 66.7% (95% CI: 41.7%-84.8%) specificity. MAIN LIMITATIONS: Sample size, no BALf cytology in some healthy horses. CONCLUSIONS: Oscillometry can represent a useful non-invasive tool for the diagnosis of MEA. Specifically, the evaluation of the frequency dependence of Xrs may be of special interest.

Recapitulating COVID-19 detection methods: RT-PCR, sniffer dogs and electronic nose.

In December 2019, a number of subjects presenting with an unexplained pneumonia-like illness were suspected to have a link to a seafood market in Wuhan, China. Subsequently, this illness was identified as the 2019-novel coronavirus (2019-nCoV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the World Committee on Virus Classification. Since its initial identification, the virus has rapidly sperad across the globe, posing an extraordinary challenge for the medical community. Currently, the Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is considered the most reliable method for diagnosing SARS-CoV-2. This procedure involves collecting oro-pharyngeal or nasopharyngeal swabs from individuals. Nevertheless, for the early detection of low viral loads, a more sensitive technique, such as droplet digital PCR (ddPCR), has been suggested. Despite the high effectiveness of RT-PCR, there is increasing interest in utilizing highly trained dogs and electronic noses (eNoses) as alternative methods for screening asymptomatic individuals for SARS-CoV-2. These dogs and eNoses have demonstrated high sensitivity and can detect volatile organic compounds (VOCs), enabling them to distinguish between COVID-19 positive and negative individuals. This manuscript recapitulates the potential, advantages, and limitations of employing trained dogs and eNoses for the screening and control of SARS-CoV-2.

Early respiratory system reactance predicts respiratory outcomes in preterm infants: a retrospective, multicentre study.

OBJECTIVE: This multicenter, international, retrospective study aims to investigate whether respiratory system reactance (Xrs) assessed by respiratory oscillometry on the 7th day of life is associated with respiratory outcomes in preterm infants below 32 weeks' gestation. METHODS: Sinusoidal pressure oscillations (2-5 cmH2O peak-to-peak, 10 Hz) were superimposed on the positive end-expiratory pressure (PEEP). We assessed the association of Xrs z-score with the duration of respiratory support using linear regression and with bronchopulmonary dysplasia (BPD, according to Jensen et al. 2019) using logistic regression. We used the likelihood ratio test to evaluate whether Xrs z-score adds significantly to clinical predictors, including gestational age (GA), birth weight (BW) and the National Institute of Child Health and Human Development (NICHD) BPD prediction model. RESULTS: One hundred and thirty-seven infants (median (Q1, Q3) GA=28.43 (26.11, 30.29) weeks) were included; 44 (32%) developed BPD. Xrs z-score was significantly associated with the duration of respiratory support (R2=0.35). Xrs z-score was significantly higher in infants who developed BPD (p<0.001); the optimal cut-off value was 2.6, associated with 77% sensitivity and 80% specificity. In univariable analysis, per z-score increase in Xrs, the OR for BPD increased by 60% and the respiratory support by eight days. In multivariable analysis, Xrs z-score added significantly to the NICHD model and to GA and BW z-score to predict respiratory support duration (p=0.016 and p=0.014, respectively) and BPD development (p=0.003 and p<0.001, respectively). CONCLUSION: Xrs z-score on the 7th day after birth improves the prediction of respiratory outcome in preterm infants.

A Novel CPAP Device With an Integrated Oxygen Concentrator for Low Resource Countries: In Vitro Validation and Usability Test in Field.

Goal: To develop and validatea novel neonatal non-invasive respiratory support device prototype designed to operate in low-resource settings. Methods: The device integrates a blower-based ventilator and a portable oxygen concentrator. A novel control algorithm was designed to achieve the desired fraction of inspired oxygen (FiO2) while minimizing power consumption. The accuracy of the delivered FiO2 and the device power consumption were evaluated in vitro, and a formative usability test was conducted in a rural hospital in Uganda. Results: The agreement between the set and delivered FiO2 was high (limit of agreement:-5.6 ÷ 3.8%). For FiO2 below 60%, the control algorithm reduced the power drain by 50%. The device was also appreciated by intended users. Conclusion: The prototype proved effective in delivering oxygen-enriched continuous positive airway pressure in the absence of compressed air and oxygen, holding promise for a sustainable and effective implementation of neonatal respiratory support in low-resource settings.

Reference Equations for Within-Breath Respiratory Oscillometry in White Adults.

BACKGROUND: Within-breath analysis of oscillometry parameters is a growing research area since it increases sensitivity and specificity to respiratory pathologies and conditions. However, reference equations for these parameters in White adults are lacking and devices using multiple sinusoids or pseudorandom forcing stimuli have been underrepresented in previous studies deriving reference equations. The current study aimed to establish reference ranges for oscillometry parameters, including also the within-breath ones in White adults using multi-sinusoidal oscillations. METHODS: White adults with normal spirometry, BMI ≤30 kg/m2, without a smoking history, respiratory symptoms, pulmonary or cardiac disease, neurological or neuromuscular disorders, and respiratory tract infections in the previous 4 weeks were eligible for the study. Study subjects underwent oscillometry (multifrequency waveform at 5-11-19 Hz, Resmon PRO FULL, RESTECH Srl, Italy) in 5 centers in Europe and the USA according to international standards. The within-breath and total resistance (R) and reactance (X), the resonance frequency, the area under the X curve, the frequency dependence of R (R5-19), and within-breath changes of X (ΔX) were submitted to lambda-mu-sigma models for deriving reference equations. For each output parameter, an AIC-based stepwise input variable selection procedure was applied. RESULTS: A total of 144 subjects (age 20.8-86.3 years; height 146-193 cm; BMI 17.42-29.98 kg/m2; 56% females) were included. We derived reference equations for 29 oscillatory parameters. Predicted values for inspiratory and expiratory parameters were similar, while differences were observed for their limits of normality. CONCLUSIONS: We derived reference equations with narrow confidence intervals for within-breath and whole-breath oscillatory parameters for White adults.

Relationship between oscillatory volume and oscillatory pressure in neonatal high-frequency oscillatory ventilators: an in vitro study.

OBJECTIVE: We analysed the relationship between oscillatory volume (VOSC) and pressure amplitude (ΔP) in six neonatal high-frequency oscillatory (HFO) ventilators and related it to (1) the accuracy of VOSC and ΔP measurements and (2) the maximal delivered ΔP. DESIGN: In vitro study. SETTING: Neonatal intensive care unit. INTERVENTIONS: Ventilators tested were VN800 (Dräger), Servo-n (Maquet Getinge), SensorMedics 3100A (Vyaire Medical), Fabian HFOi (Vyaire Medical), SLE6000 (SLE UK) and Humming Vue (Metran). We changed various settings and mechanical characteristics of the test lung to mimic preterm and term conditions. MAIN OUTCOME MEASURES: For each condition, we measured VOSC and ΔP. We assessed the accuracy of the VOSC and ΔP measurements versus a reference measurement system using linear regression and Bland-Altman analysis. We evaluated the maximum delivered ΔP at different oscillatory frequencies. RESULTS: We observed large variability between machines in the ΔP displayed at any target VOSC. Most ventilators over-read ΔP with errors up to 30 cmH2O or 60%. The error in the measurement of VOSC was up to ±2 mL or ±30%. We observed high variability in the accuracy of ΔP and VOSC measurements; the SLE6000 committed the lowest errors in ΔP measurements and the Fabian HFOi in VOSC. The maximum delivered ΔP varied depending on the ventilator, being maximal for the Humming Vue, followed by the SLE6000 and SensorMedics 3100A. CONCLUSIONS: The variability in the relationship between VOSC and ΔP among HFO ventilators is largely explained by the variable accuracy in ΔP and VOSC measurement. Different ventilators also exhibit important differences in the maximal generated ΔP.

Impact of neonatal noninvasive resuscitation strategies on lung mechanics, tracheal pressure, and tidal volume in preterm lambs.

This study investigated the relationship between three respiratory support approaches on lung volume recruitment during the first 2 h of postnatal life in preterm lambs. We estimated changes in lung aeration, measuring respiratory resistance and reactance by oscillometry at 5 Hz. We also measured intratracheal pressure in subsets of lambs. The first main finding is that sustained inflation (SI) applied noninvasively (Mask SI; n = 7) or invasively [endotracheal tube (ETT) SI; n = 6] led to similar rapid lung volume recruitment (∼6 min). In contrast, Mask continuous positive airway pressure (CPAP) without SI (n = 6) resuscitation took longer (∼30-45 min) to reach similar lung volume recruitment. The second main finding is that, in the first 15 min of postnatal life, the Mask CPAP without SI group closed their larynx during custom ventilator-driven expiration, leading to intratracheal positive end-expiratory pressure of ∼17 cmH2O (instead of 8 cmH2O provided by the ventilator). In contrast, the Mask SI group used the larynx to limit inspiratory pressure to ∼26 cmH2O (instead of 30 cmH2O provided by the ventilator). These different responses affected tidal volume, being larger in the Mask CPAP without SI group [8.4 mL/kg; 6.7-9.3 interquartile range (IQR)] compared to the Mask SI (5.0 mL/kg; 4.4-5.2 IQR) and ETT SI groups (3.3 mL/kg; 2.6-3.7 IQR). Distinct physiological responses suggest that spontaneous respiratory activity of the larynx of preterm lambs at birth can uncouple pressure applied by the ventilator to that applied to the lung, leading to unpredictable lung pressure and tidal volume delivery independently from the ventilator settings.NEW & NOTEWORTHY We compared invasive and noninvasive resuscitation on lambs at birth, including or not sustained inflation (SI). Lung volume recruitment was faster in those receiving SI. During noninvasive resuscitation, larynx modulation reduced tracheal pressure from that applied to the mask in lambs receiving SI, while it led to increased auto-positive end-expiratory pressure and very large tidal volumes in lambs not receiving SI. Our results highlight the need for individualizing pressures and monitoring tidal volumes during resuscitation at birth.

Effect of different lung recruitment strategies and airway device on oscillatory mechanics in children under general anaesthesia.

BACKGROUND: Atelectasis has been reported in 68 to 100% of children undergoing general anaesthesia, a phenomenon that persists into the recovery period. Children receiving recruitment manoeuvres have less atelectasis and fewer episodes of oxygen desaturation during emergence. The optimal type of recruitment manoeuvre is unclear and may be influenced by the airway device chosen. OBJECTIVE: We aimed to investigate the different effects on lung mechanics as assessed by the forced oscillation technique (FOT) utilising different recruitment strategies: repeated inflations vs. one sustained inflation and different airway devices, a supraglottic airway device vs. a cuffed tracheal tube. DESIGN: Pragmatic enrolment with randomisation to the recruitment strategy. SETTING: We conducted this single-centre trial between February 2020 and March 2022. PARTICIPANTS: Seventy healthy patients (53 boys) aged between 2 and 16 years undergoing general anaesthesia were included. INTERVENTIONS: Forced oscillations (5 Hz) were superimposed on the ventilator waveform using a customised system connected to the anaesthesia machine. Pressure and flow were measured at the inlet of the airway device and used to compute respiratory system resistance and reactance. Measurements were taken before and after recruitment, and again at the end of surgery. MAIN OUTCOME MEASURES: The primary endpoint measured is the change in respiratory reactance. RESULTS: Statistical analysis (linear model with recruitment strategy and airway device as factors) did not show any significant difference in resistance and reactance between before and after recruitment. Baseline reactance was the strongest predictor for a change in reactance after recruitment: prerecruitment Xrs decreased by mean (standard error) of 0.25 (0.068) cmH 2 O s l -1 per  1 cmH 2 O -1  s l -1 increase in baseline Xrs ( P  < 0.001). After correcting for baseline reactance, the change in reactance after recruitment was significantly lower for sustained inflation compared with repeated inflation by mean (standard error) 0.25 (0.101) cmH 2 O ( P  = 0.0166). CONCLUSION: Although there was no significant difference between airway devices, this study demonstrated more effective recruitment via repeated inflations than sustained inflation in anaesthetised children. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12619001434189.

Respiratory and chest wall mechanics in very preterm infants.

Data on static compliance of the chest wall (Ccw) in preterm infants are scarce. We characterized the static compliance of the lung (CL) and Ccw to determine their relative contribution to static compliance of the respiratory system (Crs) in very preterm infants at 36 wk postmenstrual age (PMA). We also aimed to investigate how these compliances were influenced by the presence of bronchopulmonary dysplasia (BPD) and impacted breathing variables. Airway opening pressure, esophageal pressure, and tidal volume (VT) were measured simultaneously during a short apnea evoked by the Hering-Breuer reflex. We computed tidal breathing variables, airway resistance (R), and dynamic lung compliance (CL,dyn), inspiratory capacity (IC), and Crs, CL, and Ccw. Functional residual capacity was assessed by the multiple breath washout technique (FRCmbw). Breathing variables, compliances, and lung volumes were adjusted for body weight. Twenty-three preterm infants born at 27.2 ± 2.0 wk gestational age (GA) were studied at 36.6 ± 0.6 wk PMA. Median and interquartile range (IQR) Crs/kg is 0.69 (0.6), CL/kg 0.95 (1.0), and Ccw/kg 3.0 (2.4). Infants with BPD (n = 11) had lower Crs/kg (P = 0.013), CL/kg (P = 0.019), and Ccw/kg (P = 0.027) compared with infants without BPD. Ccw/CL ratio was equal between groups. FRCmbw/kg (P = 0.044) and IC/kg (P = 0.005) were decreased in infants with BPD. Infants with BPD have reduced static compliance of the respiratory system, the lungs, and chest wall. Decreased Crs, CL, and Ccw in infants with BPD explain the lower FRC and IC seen in these infants.NEW & NOTEWORTHY Data on chest wall compliance in very preterm infants in the postsurfactant era are scarce. To our knowledge, we are the first group to report data on static respiratory system compliance (Crs), lung compliance (CL), and chest wall compliance (Ccw) in preterm infants with and without bronchopulmonary dysplasia (BPD) in the postsurfactant era.

Mesenchymal stromal cell extracellular vesicles improve lung development in mechanically ventilated preterm lambs.

Novel therapies are needed for bronchopulmonary dysplasia (BPD) because no effective treatment exists. Mesenchymal stromal cell extracellular vesicles (MSC-sEVs) have therapeutic efficacy in a mouse pup neonatal hyperoxia BPD model. We tested the hypothesis that MSC-sEVs will improve lung functional and structural development in mechanically ventilated preterm lambs. Preterm lambs (∼129 days; equivalent to human lung development at ∼28 wk gestation) were exposed to antenatal steroids, surfactant, caffeine, and supported by mechanical ventilation for 6-7 days. Lambs were randomized to blinded treatment with either MSC-sEVs (human bone marrow MSC-derived; 2 × 1011 particles iv; n = 8; 4 F/4 M) or vehicle control (saline iv; 4 F/4 M) at 6 and 78 h post delivery. Physiological targets were pulse oximetry O2 saturation 90-94% ([Formula: see text] 60-90 mmHg), [Formula: see text] 45-60 mmHg (pH 7.25-7.35), and tidal volume 5-7 mL/kg. MSC-sEVs-treated preterm lambs tolerated enteral feedings compared with vehicle control preterm lambs. Differences in weight patterns were statistically significant. Respiratory severity score, oxygenation index, A-a gradient, distal airspace wall thickness, and smooth muscle thickness around terminal bronchioles and pulmonary arterioles were significantly lower for the MSC-sEVs group. S/F ratio, radial alveolar count, secondary septal volume density, alveolar capillary surface density, and protein abundance of VEGF-R2 were significantly higher for the MSC-sEVs group. MSC-sEVs improved respiratory system physiology and alveolar formation in mechanically ventilated preterm lambs. MSC-sEVs may be an effective and safe therapy for appropriate functional and structural development of the lung in preterm infants who require mechanical ventilation and are at risk of developing BPD.NEW & NOTEWORTHY This study focused on potential treatment of preterm infants at risk of developing bronchopulmonary dysplasia (BPD), for which no effective treatment exists. We tested treatment of mechanically ventilated preterm lambs with human mesenchymal stromal cell extracellular vesicles (MSC-sEVs). The results show improved respiratory gas exchange and parenchymal growth of capillaries and epithelium that are necessary for alveolar formation. Our study provides new mechanistic insight into potential efficacy of MSC-sEVs for preterm infants at risk of developing BPD.

Global and regional heterogeneity of lung aeration in neonates with different respiratory disorders: a physiological, observational study.

BACKGROUND.: Aeration heterogeneity affects lung stress and influences outcomes in adults with acute respiratory distress syndrome (ARDS). We hypothesize that aeration heterogeneity may differ between neonatal respiratory disorders and is associated with oxygenation, so its evaluation may be relevant in managing respiratory support. METHODS.: Observational, prospective study. Neonates with respiratory distress syndrome (RDS), transient tachypnea (TTN), evolving bronchopulmonary dysplasia (BPD) and neonatal ARDS (NARDS) were enrolled. Quantitative lung ultrasound and transcutaneous blood gas measurements were simultaneously performed. Global aeration heterogeneity (with its intra- and inter-patient components) and regional aeration heterogeneity were primary outcomes; oxygenation metrics were the secondary outcomes. RESULTS.: 230 (50 RDS, TTN or evolving BPD and 80 NARDS) patients were studied. Intra-patient aeration heterogeneity was higher in TTN (mean: 61% [standard deviation: 33%]) and evolving BPD (mean: 57% [standard deviation: 20%], p<0.001), with distinctive aeration distributions. Inter-patient aeration heterogeneity was high for all disorders (Gini-Simpson index: between 0.6 and 0.72) except RDS (Gini-Simpson index: 0.5) whose heterogeneity was significantly lower than all others (p<0.001). NARDS and evolving BPD had the most diffuse injury and worst gas exchange metrics. Regional aeration heterogeneity was mostly localized in upper anterior and posterior zones. Aeration heterogeneity and total lung aeration had an exponential relationship (p<0.001; adj-R 2=0.62). Aeration heterogeneity is associated with greater total lung aeration (i.e., higher heterogeneity means a relatively higher proportion of normally aerated lung zones, thus greater aeration; p<0.001; adj-R 2=0.83) and better oxygenation metrics upon multivariable analyses. CONCLUSIONS.: Global aeration heterogeneity and regional aeration heterogeneity differ amongst neonatal respiratory disorders. TTN and evolving BPD have the highest intra-patient aeration heterogeneity. TTN, evolving BPD and NARDS have the highest inter-patient aeration heterogeneity, but the latter two have the most diffuse injury and worst gas exchange. Higher aeration heterogeneity is associated with better total lung aeration and oxygenation.

Oscillometry Longitudinal Data on COVID-19 Acute Respiratory Syndrome Treated with Non-Invasive Respiratory Support.

Background: Oscillometry allows for the non-invasive measurements of lung mechanics. In COVID-19 ARDS patients treated with Non-Invasive Oxygen Support (NI-OS), we aimed to (1) observe lung mechanics at the patients' admission and their subsequent changes, (2) compare lung mechanics with clinical and imaging data, and (3) evaluate whether lung mechanics helps to predict clinical outcomes. Methods: We retrospectively analyzed the data from 37 consecutive patients with moderate-severe COVID-19 ARDS. Oscillometry was performed on their 1st, 4th, and 7th day of hospitalization. Resistance (R5), reactance (X5), within-breath reactance changes (ΔX5), and the frequency dependence of the resistance (R5-R19) were considered. Twenty-seven patients underwent computed tomographic pulmonary angiography (CTPA): collapsed, poorly aerated, and normally inflated areas were quantified. Adverse outcomes were defined as intubation or death. Results: Thirty-two patients were included in this study. At the first measurement, only 44% of them had an abnormal R5 or X5. In total, 23 patients had measurements performed on their 3rd day and 7 on their 7th day of hospitalization. In general, their R5, R5-R19, and ΔX decreased with time, while their X5 increased. Collapsed areas on the CTPA correlated with the X5 z-score (ρ = -0.38; p = 0.046), while poorly aerated areas did not. Seven patients had adverse outcomes but did not present different oscillometry parameters on their 1st day of hospitalization. Conclusions: Our study confirms the feasibility of oscillometry in critically ill patients with COVID-19 pneumonia undergoing NI-OS. The X5 z-scores indicates collapsed but not poorly aerated lung areas in COVID-19 pneumonia. Our data, which show a severe impairment of gas exchange despite normal reactance in most patients with COVID-19 ARDS, support the hypothesis of a composite COVID-19 ARDS physiopathology.

Benefits of intratracheal and extrathoracic high-frequency percussive ventilation in a model of capnoperitoneum.

Abdominal inflation with CO2 is used to facilitate laparoscopic surgeries, however, providing adequate mechanical ventilation in this scenario is of major importance during anesthesia management. We characterized high-frequency percussive ventilation (HFPV) in protecting from the gas exchange and respiratory mechanical impairments during capnoperitoneum. In addition, we aimed to assess the difference between conventional pressure-controlled mechanical ventilation (CMV) and HFPV modalities generating the high-frequency signal intratracheally (HFPVi) or extrathoracally (HFPVe). Anesthetized rabbits (n = 16) were mechanically ventilated by random sequences of CMV, HFPVi, and HFPVe. The ventilator superimposed the conventional waveform with two high-frequency signals (5 Hz and 10 Hz) during intratracheal HFPV (HFPVi) and HFPV with extrathoracic application of oscillatory signals through a sealed chest cuirass (HFPVe). Lung oxygenation index ([Formula: see text]/[Formula: see text]), arterial partial pressure of carbon dioxide ([Formula: see text]), intrapulmonary shunt (Qs/Qt), and respiratory mechanics were assessed before abdominal inflation, during capnoperitoneum, and after abdominal deflation. Compared with CMV, HFPVi with additional 5-Hz oscillations during capnoperitoneum resulted in higher [Formula: see text]/[Formula: see text], lower [Formula: see text], and decreased Qs/Qt. These improvements were smaller but remained significant during HFPVi with 10 Hz and HFPVe with either 5 or 10 Hz. The ventilation modes did not protect against capnoperitoneum-induced deteriorations in respiratory tissue mechanics. These findings suggest that high-frequency oscillations combined with conventional pressure-controlled ventilation improved lung oxygenation and CO2 removal in a model of capnoperitoneum. Compared with extrathoracic pressure oscillations, intratracheal generation of oscillatory pressure bursts appeared more effective. These findings may contribute to the optimization of mechanical ventilation during laparoscopic surgery.NEW & NOTEWORTHY The present study examines an alternative and innovative mechanical ventilation modality in improving oxygen delivery, CO2 clearance, and respiratory mechanical abnormalities in a clinically relevant experimental model of capnoperitoneum. Our data reveal that high-frequency oscillations combined with conventional ventilation improve gas exchange, with intratracheal oscillations being more effective than extrathoracic oscillations in this clinically relevant translational model.

Cytokine mRNA expression in the bronchoalveolar lavage cells from horses affected by different equine asthma subtypes.

Equine asthma (EA) is a respiratory syndrome associated with the increase of different leukocyte populations in the bronchoalveolar lavage fluid (BALF). Its pathogenetic mechanisms remain unclear. This study aimed to evaluate the associations between the mRNA expression of different cytokines in the BALF, different EA subtypes and lung function. Fifteen horses underwent physical examination, airway endoscopy, BALF cytology and lung function testing (8/15). One horse did not have evidence of EA and was used as healthy reference, while the others were classified as affected by neutrophilic or mixed granulocytic EA. Cells isolated from the residual BALF were used for IL-1ß, IL-2, IFN-γ, IL-4, IL-17A genes expression by quantitative RT-PCR., Cytokine expression was compared between groups, and their correlations with BALF leukocyte and lung function were evaluated. IL-1ß expression was positively correlated with BALF neutrophils count (p=0.038, r=0.56) and with increased expiratory resistance (p=0.047, r=0.76). IFN-γ was correlated with BALF mast cells (p=0.029, r=0.58). IL-4 was higher in horses with mixed granulocytic EA than neutrophilic (p=0.008), positively correlated with BALF mast cells (p=0.028, r=0.59) and inversely with whole-breath (p=0.046, r=-0.76) and expiratory reactance (p=0.003, r=-0.93). Finally, IL-17A was inversely correlated with expiratory reactance (p=0.009, r=-0.92). These results support that multiple immune responses are involved in EA pathogenesis; innate, Th2, and Th17 responses. Innate immunity appeared associated with neutrophilic inflammation, and Th2 response with increased mast cells. The role of Th1 response in EA remains questionable.

A Survey of the Union of European Neonatal and Perinatal Societies on Neonatal Respiratory Care in Neonatal Intensive Care Units.

(1) Background: Our survey aimed to gather information on respiratory care in Neonatal Intensive Care Units (NICUs) in the European and Mediterranean region. (2) Methods: Cross-sectional electronic survey. An 89-item questionnaire focusing on the current modes, devices, and strategies employed in neonatal units in the domain of respiratory care was sent to directors/heads of 528 NICUs. The adherence to the "European consensus guidelines on the management of respiratory distress syndrome" was assessed for comparison. (3) Results: The response rate was 75% (397/528 units). In most Delivery Rooms (DRs), full resuscitation is given from 22 to 23 weeks gestational age. A T-piece device with facial masks or short binasal prongs are commonly used for respiratory stabilization. Initial FiO2 is set as per guidelines. Most units use heated humidified gases to prevent heat loss. SpO2 and ECG monitoring are largely performed. Surfactant in the DR is preferentially given through Intubation-Surfactant-Extubation (INSURE) or Less-Invasive-Surfactant-Administration (LISA) techniques. DR caffeine is widespread. In the NICUs, most of the non-invasive modes used are nasal CPAP and nasal intermittent positive-pressure ventilation. Volume-targeted, synchronized intermittent positive-pressure ventilation is the preferred invasive mode to treat acute respiratory distress. Pulmonary recruitment maneuvers are common approaches. During NICU stay, surfactant administration is primarily guided by FiO2 and SpO2/FiO2 ratio, and it is mostly performed through LISA or INSURE. Steroids are used to facilitate extubation and prevent bronchopulmonary dysplasia. (4) Conclusions: Overall, clinical practices are in line with the 2022 European Guidelines, but there are some divergences. These data will allow stakeholders to make comparisons and to identify opportunities for improvement.

Oscillometry for personalizing continuous distending pressure maneuvers: an observational study in extremely preterm infants.

RATIONALE: Lung recruitment and continuous distending pressure (CDP) titration are critical for assuring the efficacy of high-frequency ventilation (HFOV) in preterm infants. The limitation of oxygenation (peripheral oxygen saturation, SpO2) in optimizing CDP calls for evaluating other non-invasive bedside measurements. Respiratory reactance (Xrs) at 10 Hz measured by oscillometry reflects lung volume recruitment and tissue strain. In particular, lung volume recruitment and decreased tissue strain result in increased Xrs values. OBJECTIVES: In extremely preterm infants treated with HFOV as first intention, we aimed to measure the relationship between CDP and Xrs during SpO2-driven CDP optimization. METHODS: In this prospective observational study, extremely preterm infants born before 28 weeks of gestation undergoing SpO2-guided lung recruitment maneuvers were included in the study. SpO2 and Xrs were recorded at each CDP step. The optimal CDP identified by oxygenation (CDPOpt_SpO2) was compared to the CDP providing maximal Xrs on the deflation limb of the recruitment maneuver (CDPXrs). RESULTS: We studied 40 infants (gestational age at birth = 22+ 6-27+ 5 wk; postnatal age = 1-23 days). Measurements were well tolerated and provided reliable results in 96% of cases. On average, Xrs decreased during the inflation limb and increased during the deflation limb. Xrs changes were heterogeneous among the infants for the amount of decrease with increasing CDP, the decrease at the lowest CDP of the deflation limb, and the hysteresis of the Xrs vs. CDP curve. In all but five infants, the hysteresis of the Xrs vs. CDP curve suggested effective lung recruitment. CDPOpt_SpO2 and CDPXrs were highly correlated (ρ = 0.71, p < 0.001) and not statistically different (median difference [range] = -1 [-3; 9] cmH2O). However, CDPXrs were equal to CDPOpt_SpO2 in only 6 infants, greater than CDPOpt_SpO2 in 10, and lower in 24 infants. CONCLUSIONS: The Xrs changes described provide complementary information to oxygenation. Further investigation is warranted to refine recruitment maneuvers and CPD settings in preterm infants.

Respiratory oscillometry testing in relation to exercise in healthy and asthmatic Thoroughbreds.

BACKGROUND: Racehorses may experience exercise-induced bronchodilation or bronchoconstriction, with potential differences between healthy and asthmatic individuals. OBJECTIVES: To identify exercise-related lung function variations by oscillometry in racehorses, compare lung function between healthy and mild equine asthma (MEA) horses, assess oscillometry's potential as a predictor of racing fitness. STUDY DESIGN: Prospective case-control clinical study. METHODS: Fourteen Thoroughbred racehorses (5 healthy, 9 MEA) underwent a protocol including respiratory oscillometry at rest, exercise with fitness monitoring, oscillometry at 15 and 45 min post-exercise, and bronchoalveolar lavage fluid (BALf) cytology. Oscillometry parameters (resistance [Rrs] and reactance [Xrs]) were compared within and between healthy and MEA groups at different timepoints. Associations between Rrs and Xrs at rest and 15 min post-exercise and BALf cytology and fitness indices were evaluated. RESULTS: MEA horses showed higher Rrs at 15 min post-exercise (0.6 ± 0.2 cmH2 O/L/s) than healthy horses (0.3 ± 0.1 cmH2 O/L/s) (p < 0.01). In healthy horses, Rrs decreased at 15 min post-exercise compared with resting values (0.5 ± 0.1 cmH2 O/L/s) (p = 0.04). In MEA horses, oscillometry parameters did not vary with time. Post-exercise Xrs inversely correlated with total haemosiderin score (p < 0.01, r2 = 0.51). Resting Rrs inversely correlated with speed at 200 bpm (p = 0.03, r2 = -0.61), and Xrs with maximum heart rate (HR) during exercise (p = 0.02, r2 = -0.62). Post-exercise Rrs inversely correlated with mean (p = 0.04, r2 = -0.60) and maximum speed (p = 0.04, r2 = -0.60), and HR variability (p < 0.01, r2 = -0.74). MAIN LIMITATIONS: Small sample size, oscillometry repeatability not assessed, potential interference of upper airway obstructions, external variables influencing fitness indices. CONCLUSIONS: Oscillometry identified lung function differences between healthy and MEA horses at 15 min post-exercise. Only healthy horses exhibited exercise-induced bronchodilation. Oscillometry showed potential in predicting subclinical airway obstruction.

Combining lung ultrasound and oscillatory mechanics for assessing lung disease in very preterm infants.

BACKGROUND: We investigated whether combining lung ultrasound scores (LUSs) and respiratory system reactance (Xrs) measured by respiratory oscillometry explains the severity of lung disease better than individual parameters alone. METHODS: We performed a prospective observational study in very preterm infants. Forced oscillations (10 Hz) were applied using a neonatal mechanical ventilator (Fabian HFOi, Vyaire). We used the simultaneous respiratory severity score (RSS = mean airway pressure × FIO2) as a primary outcome. We built linear mixed-effect models to assess the relationship between Xrs z-score, LUS and RSS and compared nested models using the likelihood ratio test (LRT). RESULTS: We enrolled 61 infants (median (Q1, Q3) gestational age = 30.00 (26.86, 31.00) weeks) and performed 243 measurements at a postnatal age of 26 (13, 41) days and postmenstrual age of 33.14 (30.46, 35.86) weeks. Xrs z-score and LUS were independently associated with simultaneous RSS (p < 0.001 for both). The model including Xrs and LUS explained the RSS significantly better than Xrs (p value LRT < 0.001) or LUS alone (p value LRT < 0.001). CONCLUSIONS: Combining LUS and Xrs z-score explains the severity of lung disease better than each parameter alone and has the potential to improve the understanding of the underlying pathophysiology. IMPACT: Combining respiratory system reactance by oscillometry and lung ultrasound score explains the respiratory support requirement (e.g., proxy of the severity of lung disease) significantly better than each parameter alone. We assessed the relationship between lung ultrasound and respiratory system reactance in very preterm infants for the first time. Combining respiratory oscillometry and lung ultrasound has the potential to improve the understanding of respiratory pathophysiology.