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.

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.

RESPIRATORY AND CHEST WALL MECHANICS IN VERY PRETERM INFANTS.

Data on static compliance of the chest wall (Ccw) in preterm infants are scarce. We characterised 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 weeks' 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, lung resistance (Rl) 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 weeks' gestational age (GA) were studied at 36.6 ± 0.6 weeks' PMA. Median (IQR) Crs/kg is 0.69 (0.6), CL 0.95 (1.0) and Ccw 3.0 (2.4). Infants with BPD (n=11) had lower Crs (p=0.013), CL (p=0.019), and Ccw (p=0.027) compared to 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 lung and chest wall. Decreased Crs, CL and Ccw in infants with BPD explains the lower FRC and IC seen in these infants.

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

BACKGROUND: 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. METHODS: Preterm lambs (~129d; equivalent to human lung development at ~28w gestation) were exposed to antenatal steroids, surfactant, caffeine citrate, and supported by mechanical ventilation for 6-7d. Lambs were randomized to blinded treatment with either MSC-sEVs (human bone marrow MSC-derived; 2x1011 particles iv; n=8; 4F/4M) or vehicle control (saline iv; 4F/4M). Treatment was at 6 and 78 hours post-delivery. Physiological targets were pulse oximetry O2 saturation 90-94% (PaO2 60-90 mmHg), PaCO2 45-60 mmHg (pH 7.25-7.35), and tidal volume 5-7 mL/Kg. RESULTS: MSC-sEVs-treated preterm lambs tolerated enteral feedings and maintained weight compared to the vehicle control group. Respiratory severity score, oxygenation index, A-a gradient, distal airspace wall thickness, and smooth muscle thickness around terminal bronchioles and pulmonary arterioles were lower (*) for the MSC-sEVs group versus the vehicle controls. S/F ratio, radial alveolar count, secondary septal volume density, alveolar capillary surface density, and protein abundance of VEGF-R2 were higher (*) for the MSC-sEVs versus the vehicle control group. CONCLUSIONS: 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.

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.

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.

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.

Diagnostic Potential of Oscillometry: A Population-based Approach.

Rationale: Respiratory resistance (Rrs) and reactance (Xrs) as measured by oscillometry and their intrabreath changes have emerged as sensitive parameters for detecting early pathological impairments during tidal breathing. Objectives: This study evaluates the prevalence and association of abnormal oscillometry parameters with respiratory symptoms and respiratory diseases in a general adult population. Methods: A total of 7,560 subjects in the Austrian LEAD (Lung, hEart, sociAl, boDy) Study with oscillometry measurements (computed with the Resmon Pro FULL; Restech Srl) were included in this study. The presence of respiratory symptoms and doctor-diagnosed respiratory diseases was assessed using an interview-based questionnaire. Rrs and Xrs at 5 Hz, their inspiratory and expiratory components, the area above the Xrs curve, and the presence of tidal expiratory flow limitation were analyzed. Normality ranges for oscillometry parameters were defined. Measurements and Main Results: The overall prevalence of abnormal oscillometry parameters was 20%. The incidence of abnormal oscillometry increased in the presence of symptoms or diagnoses: 17% (16-18%) versus 27% (25-29%), P < 0.0001. All abnormal oscillometry parameters except Rrs at 5 Hz were significantly associated with respiratory symptoms/diseases. Significant associations were found, even in subjects with normal spirometry, with abnormal oscillometry incidence rates increasing by 6% (4-8%; P < 0.0001) in subjects with symptoms or diagnoses. Conclusions: Abnormal oscillometry parameters are present in one-fifth of this adult population and are significantly associated with respiratory symptoms and disease. Our findings underscore the potential of oscillometry as a tool for detecting and evaluating respiratory impairments, even in individuals with normal spirometry.

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.

Surfactant status assessment and personalized therapy for surfactant deficiency or dysfunction.

Surfactant is a pivotal neonatal drug used both for respiratory distress syndrome due to surfactant deficiency and for more complex surfactant dysfunctions (such as in case of neonatal acute respiratory distress syndrome). Despite its importance, indications for surfactant therapy are often based on oversimplified criteria. Lung biology and modern monitoring provide several diagnostic tools to assess the patient surfactant status and they can be used for a personalized surfactant therapy. This is desirable to improve the efficacy of surfactant treatment and reduce associated costs and side effects. In this review we will discuss these diagnostic tools from a pathophysiological and multi-disciplinary perspective, focusing on the quantitative or qualitative surfactant assays, lung mechanics or aeration measurements, and gas exchange metrics. Their biological and technical characteristics are described with practical information for clinicians. Finally, available evidence-based data are reviewed, and the diagnostic accuracy of the different tools is compared. Lung ultrasound seems the most suitable tool for assessing the surfactant status, while some other promising tests require further research and/or development.

Oscillatory mechanics trajectory in very preterm infants: a cohort study.

BACKGROUND: The aim of this study was to describe the trajectory of oscillatory mechanics from the first week of life to term equivalent and evaluate whether oscillatory mechanics are associated with simultaneous lung disease in infants ≤32 weeks gestation. METHODS: In this observational, longitudinal study, we enrolled 66 infants. Forced oscillations were applied using a neonatal mechanical ventilator (Fabian HFOi) that superimposed oscillations (10 Hz, amplitude 2.5 cmH2O) on a positive end-expiratory pressure (PEEP). Measurements were performed at 5-7-9 cmH2O of PEEP or the clinical pressure ±2 cmH2O; they were repeated at 7, 14, 28 post-natal days, and 36 and 40 weeks post-menstrual age (PMA). RESULTS: The mean (range) gestational age of study participants was 29.2 (22.9-31.9) weeks. Nineteen infants (29%) developed bronchopulmonary dysplasia (BPD). Respiratory system reactance was significantly lower (lower compliance), and respiratory system resistance was significantly higher in infants with developing BPD from 7 post-natal days to 36 weeks PMA. All oscillatory mechanics parameters were significantly associated with the simultaneous respiratory severity score (p < 0.001 for all). CONCLUSIONS: Serial measurements of oscillatory mechanics allow differentiating lung function trajectory in infants with and without evolving BPD. Oscillatory mechanics significantly correlate with the severity of simultaneous lung disease. IMPACT: The results of the present study suggest that respiratory system reactance, as assessed by respiratory oscillometry, allows the longitudinal monitoring of the progression of lung disease in very premature infants. This paper describes for the first time the trajectory of oscillatory mechanics in very preterm infants with and without evolving bronchopulmonary dysplasia from the first week of life to term equivalent. Serial respiratory oscillometry measurements allow the identification of early markers of evolving bronchopulmonary dysplasia and may help personalizing the respiratory management strategy.

Home monitoring of lung mechanics by oscillometry before, during and after severe COVID-19 disease: a case study.

A patient regularly self-performing home oscillometry developed severe COVID-19 pneumonia and continued testing during and after the disease. COVID-19 suddenly worsened oscillatory reactance, which took almost 1 year to recover to pre-COVID-19 values. https://bit.ly/3WCpWC0.

Ventilatory response and stability of oxygen saturation during a hypoxic challenge in very preterm infants.

BACKGROUND: Preterm infants have immature control of breathing and impaired pulmonary gas exchange. We hypothesized that infants with bronchopulmonary dysplasia (BPD) have a blunted ventilatory response and peripheral oxygen saturation (SpO2 ) instability during a hypoxic challenge. METHODS: We evaluated the response to hypoxia in 57 very preterm infants (38 no BPD, 10 mild BPD, 9 moderate-to-severe BPD) at 36 weeks' postmenstrual age. The fraction of inspired oxygen (FI O2 ) was reduced stepwise at 5-min intervals to achieve peripheral SpO2 between 86% and 95%. The lowest permissible FI O2 and SpO2 were 0.14% and 86%. We recorded SpO2 , FI O2 , and the respiratory signal (respiratory inductive plethysmography). We calculated respiratory rate (RR), tidal volume (VT ), minute ventilation (VE ), and respiratory drive (ratio between VT and inspiratory time, VT /TI ). SpO2 variability was expressed as the interquartile range (IQR). RESULTS: FI O2 was reduced from a median (Q1, Q3) of 0.21 (0.21, 0.21) to 0.17 (0.17, 0.18). We observed a marked individual variability in the ventilatory response to the hypoxic challenge, regardless of BPD severity. At the lowest permissible FI O2 , 37 (65%) infants reduced their VE , and 20 (35%) increased minute ventilation; 20 infants (35%) developed periodic breathing associated with increased SpO2 IQR and lower SpO2 minima, and 16 (28%) exhibited an oscillatory pattern in VE and SpO2 without end-expiratory pauses, regardless of BPD severity. CONCLUSION: In very preterm infants, a mild hypoxic challenge reduced ventilation, increased SpO2 variability and periodic breathing regardless of BPD severity.

Influence of neonatal endotracheal tube dimensions on oscillometry-acquired reactance: a bench study.

Objective.To examine the influence of the endotracheal tube (ETT) on respiratory reactance (Xrs) measured with the forced oscillation technique (FOT) and develop a correction method for it.Approach.In a bench study, the reactance of ETTs (Xtube) with different dimensions was measured on a breathing test lung in various respiratory settings.Main results.Xtubecan be accurately predicted by a fitted formula, with an R2of 0.97, with negligible effects due to changes in respiratory pattern and lung volume.Significance.The developed formula offers the ability to measure ETT-independent Xrsvalues of patients, improving the potential of FOT for lung function testing in mechanically ventilated newborns.

Oscillatory mechanics in very preterm infants on continuous positive airway pressure support: Reference values.

OBJECTIVE: To create reference values for respiratory system resistance (Rrs) and reactance (Xrs) measured by the forced oscillation technique (FOT) in nonintubated very preterm infants. DESIGN: Retrospective analysis of data collected as part of prospective observational studies in two centers. SETTING: Tertiary neonatal intensive care units. PATIENTS: Non-intubated infants below 32 weeks' gestation age who did not develop bronchopulmonary dysplasia. INTERVENTIONS: We applied FOT using a mechanical ventilator (Fabian HFOi; Vyaire) that superimposed small-amplitude oscillations (10 Hz) on a continuous positive airway pressure of 3 and 5 cmH2 O. Measurements were performed during regular tidal breathing using a face mask. MAIN OUTCOME MEASURES: We analyzed 198 measurements performed between 7 postnatal days and 40 weeks postmenstrual age (PMA) in 85 infants, with a median (Q1, Q3) gestational age of 30.43 (29.14, 31.18) weeks. Logarithmic transformations were applied to Rrs and Xrs, and the relationship between transformed impedance values and demographic factors was examined by backwards stepwise linear regression. RESULTS: In univariable analysis, transformed Xrs was significantly associated with PMA, postnatal age, weight, and length, while Rrs was not. The best multivariable regression model estimating transformed Xrs (cmH2 O*s/L) at continuous positive airway pressure (CPAP) = 5 cmH2 O was: Ln(50 - Xrs) = 4.536 - 0.009 x PMA - 0.014 x weight z-score. SEE = 0.053, R2 = 0.36. The mean (SD) Rrs at CPAP = 5 cmH2 O was 33.63 (5.28) cmH2 O*s/L. CONCLUSION: We have established reference values for Rrs and Xrs at 10 Hz in nonintubated preterm neonates on continuous positive airway pressure support.

TwinEDA: a sustainable deep-learning approach for limb-position estimation in preterm infants' depth images.

Early diagnosis of neurodevelopmental impairments in preterm infants is currently based on the visual analysis of newborns' motion patterns by trained operators. To help automatize this time-consuming and qualitative procedure, we propose a sustainable deep-learning algorithm for accurate limb-pose estimation from depth images. The algorithm consists of a convolutional neural network (TwinEDA) relying on architectural blocks that require limited computation while ensuring high performance in prediction. To ascertain its low computational costs and assess its application in on-the-edge computing, TwinEDA was additionally deployed on a cost-effective single-board computer. The network was validated on a dataset of 27,000 depth video frames collected during the actual clinical practice from 27 preterm infants. When compared to the main state-of-the-art competitor, TwinEDA is twice as fast to predict a single depth frame and four times as light in terms of memory, while performing similarly in terms of Dice similarity coefficient (0.88). This result suggests that the pursuit of efficiency does not imply the detriment of performance. This work is among the first to propose an automatic and sustainable limb-position estimation approach for preterm infants. This represents a significant step towards the development of broadly accessible clinical monitoring applications.

Bubble CPAP respiratory support devices for infants in low-resource settings.

Approximately 46% of the 5.2 million annual under-5 deaths derive from neonatal conditions commonly associated with hypoxemia or acute respiratory distress. It has been estimated that 98% of these deaths occur in low- and middle-income countries (LMICs). Effective implementation of noninvasive respiratory support at all levels of healthcare could significantly reduce neonatal mortality. Several factors limit the widespread and effective implementation of noninvasive respiratory support in LMICs, including inadequate infrastructure, lack of proper instrumentation, shortage of skilled staff, costly disposables, and difficulties in the supply of consumables and spare parts. The aim of this state-of-the-art paper is to provide a detailed evaluation of the commercially available devices providing noninvasive respiratory support in LMICs, focusing on bubblecontinuous positive airway pressure (bCPAP). bCPAP might be administrated using a variety of different commercial devices, including devices specifically designed for LMICs, as well as using self-made systems. We described all the equipment required for safe and effective implementation of bCPAP, including air and oxygen sourced, pressure-reducing valves and flowmeters, air-oxygen blending systems, humidifiers, respiratory support devices, patient circuits, and airway interfaces. Specifically, we critically evaluated the advantages and disadvantages of various existing solutions within the context of low-resource settings.