Airway Closure and Expiratory Flow Limitation in Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is mostly characterized by the loss of aerated lung volume associated with an increase in lung tissue and intense and complex lung inflammation. ARDS has long been associated with the histological pattern of diffuse alveolar damage (DAD). However, DAD is not the unique pathological figure in ARDS and it can also be observed in settings other than ARDS. In the coronavirus disease 2019 (COVID-19) related ARDS, the impairment of lung microvasculature has been pointed out. The airways, and of notice the small peripheral airways, may contribute to the loss of aeration observed in ARDS. High-resolution lung imaging techniques found that in specific experimental conditions small airway closure was a reality. Furthermore, low-volume ventilator-induced lung injury, also called as atelectrauma, should involve the airways. Atelectrauma is one of the basic tenet subtending the use of positive end-expiratory pressure (PEEP) set at the ventilator in ARDS. Recent data revisited the role of airways in humans with ARDS and provided findings consistent with the expiratory flow limitation and airway closure in a substantial number of patients with ARDS. We discussed the pattern of airway opening pressure disclosed in the inspiratory volume-pressure curves in COVID-19 and in non-COVID-19 related ARDS. In addition, we discussed the functional interplay between airway opening pressure and expiratory flow limitation displayed in the flow-volume curves. We discussed the individualization of the PEEP setting based on these findings.

Hybrid extracorporeal membrane oxygenation (ECMO) cannulation following traumatic pneumonectomy: A case report

A 28-year-old man presented in extremis after a motorcycle crash. Following traumatic pneumonectomy, he developed right heart failure and was placed on veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) only to transition to veno-arteriovenous (VAV) ECMO due to persistent hypoxemia. Resulting flow limitation caused distal ischemia of his left leg, requiring thrombectomy and fasciotomy. Potential loss of limb necessitated transitioning to veno-venous (VV) ECMO from which he was successfully decannulated thereafter. ECMO can bridge recovery following the most dire injuries, and hybrid strategies can ameliorate post-operative complications; however, ECMO itself carries significant risks that must be weighed against intended benefit.

Within-Breath Oscillatory Mechanics in Horses Affected by Severe Equine Asthma in Exacerbation and in Remission of the Disease

Oscillometry is a technique that measures the resistance (R) and the reactance (X) of the respiratory system. In humans, analysis of inspiratory and expiratory R and X allows to identify the presence of tidal expiratory flow limitation (EFLt). The aim of this study was to describe inspiratory and expiratory R and X measured by impulse oscillometry system (IOS) in horses with severe asthma (SEA) when in clinical remission (n = 7) or in exacerbation (n = 7) of the condition. Seven healthy, age-matched control horses were also studied. Data at 3, 5, and 7 Hz with coherence > 0.85 at 3 Hz and >0.9 at 5 and 7 Hz were considered. The mean, inspiratory and expiratory R and X and the difference between inspiratory and expiratory X (ΔX) were calculated at each frequency. The data from the three groups were statistically compared. Results indicated that in horses during exacerbation of severe asthma, X during expiratory phase is more negative than during inspiration, such as in humans in presence of EFLt. The evaluation of X during inspiration is promising in discriminating between horses with SEA in remission and control horses.

Quantifying tidal expiratory flow limitation using a vector-based analysis technique

Objective: Tidal expiratory flow limitation (EFLT) is commonly identified by tidal breaths exceeding the forced vital capacity (FVC) loop. This technique, known as the Hyatt method, is limited by the difficulties in defining the FVC and tidal flow-volume (TV) loops. The vector-based analysis (VBA) technique described and piloted in this manuscript identifies and quantifies EFLT as tidal breaths that conform to the contour of the FVC loop. Approach: The FVC and TV loops are interpolated to generate uniformly spaced plots. VBA is performed to determine the smallest vector difference between each point on the FVC and TV curves, termed the flow reserve vector (FRV). From the FVC point yielding the lowest FRV, the tangential angles of the FVC and TV segments are recorded. If the TV and FVC loops become parallel, the difference between the tangential angles tends towards zero. We infer EFLT as parallel TV and FVC segments where the FRV is <0.1 and the tangential angle is within ±18 degrees for ≥5% of TV. EFLT is quantified by the percent of TV loop fulfilling these criteria. We compared the presence and degree of EFLT at rest and during peak exercise using the Hyatt method and our VBA technique in 25 healthy subjects and 20 subjects with moderate-severe airflow obstruction. Main results: Compared to the Hyatt method, our VBA technique reported a significantly lower degree of EFLT in healthy subjects during peak exercise, and in obstructed subjects at rest and during peak exercise. In contrast to the Hyatt method, our VBA technique re-classified five subjects (one in the healthy group and four in the obstructed group) as demonstrating EFLT. Significance: Our VBA technique provides an alternative approach to determine and quantify EFLT which may reduce the overestimation of the degree EFLT and more accurately identify subjects experiencing EFLT.

Overnight variation in tidal expiratory flow limitation in COPD patients and its correction: an observational study

Background Tidal expiratory flow limitation (EFLT) is common among COPD patients. Whether EFLT changes during sleep and can be abolished during home ventilation is not known. Methods COPD patients considered for noninvasive ventilation used a ventilator which measured within-breath reactance change at 5 Hz (∆Xrs) and adjusted EPAP settings to abolish EFLT. Participants flow limited (∆Xrs > 2.8) when supine underwent polysomnography (PSG) and were offered home ventilation for 2 weeks. The EPAP pressure that abolished EFLT was measured and compared to that during supine wakefulness. Ventilator adherence and subjective patient perceptions were obtained after home use. Results Of 26 patients with supine EFLT, 15 completed overnight PSG and 10 the home study. In single night and 2-week home studies, EFLT within and between participants was highly variable. This was unrelated to sleep stage or body position with only 14.6% of sleep time spent within 1 cmH2O of the awake screening pressure. Over 2 weeks, mean EPAP was almost half the mean maximum EPAP (11.7 vs 6.4 cmH2O respectively). Group mean ∆Xrs was ≤ 2.8 for 77.3% of their home use with a mean time to abolish new EFLT of 5.91 min. Adherence to the ventilator varied between 71 and 100% in prior NIV users and 36–100% for naïve users with most users rating therapy as comfortable. Conclusions Tidal expiratory flow limitation varies significant during sleep in COPD patients. This can be controlled by auto-titrating the amount of EPAP delivered. This approach appears to be practical and well tolerated by patients. Trial registration: The trial was retrospectively registered at CT.gov NCT04725500.

Simulated Ventilation of Two Patients With a Single Ventilator in a Pandemic Setting

Background: Simultaneous ventilation of two patients, e.g., due to a shortage of ventilators in a pandemic, may result in hypoventilation in one patient and hyperinflation in the other patient. Methods: In a simulation of double patient ventilation using artificial lungs with equal compliances (70mL∙mbar-1), we tried to voluntarily direct gas flow to one patient by using 3D-printed y-adapters and stenosis adapters during volume-, and pressure-controlled ventilation. Subsequently, we modified the model using a special one-way valve on the limited flow side and measured in pressure-controlled ventilation with the flow sensor adjusted on either side in a second and third setup. In the last setup, we also measured with different lung compliances.Results: Volume- or pressure-controlled ventilation using standard connection tubes with the same compliance in each lung resulted in comparable minute volumes in both lungs, even if one side was obstructed to 3mm (6.6±0.2vs.6.5±0.1L for volume-controlled ventilation, p=.25 continuous severe alarm and 7.4±0.1vs.6.1±0.1L for pressure-controlled ventilation, p=.02 no alarm). In the second setup, pressure-controlled ventilation resulted at a 3mm flow limitation in minute ventilation of 9.4±0.3vs3.5±0.1L∙min-1, p=.001. In a third setup using the special one-way valve and the flow sensor on the unobstructed side, pressure-controlled ventilation resulted at a 3mm flow limitation in minute ventilation of 7.4±0.2vs3±0L∙min-1, at the compliance of 70mL∙mbar-1 for both lungs, 7.2±0vs4.1±0L∙ min-1, at the compliances of 50 vs. 70mL∙mbar-1, and 7.2±0.2vs5.7±0L∙ min-1, at the compliance of 30 vs. 70mL∙mbar-1 (all p=.001).Conclusions: Overriding a modern intensive care ventilator's safety features are possible, thereby ventilating two lungs with one ventilator simultaneously in a laboratory simulation using 3D-printed y-adapters. Directing tidal volumes in different pulmonary conditions towards one lung using 3D-printed flow limiters with diameters <6mm was also possible. While this ventilation setting was technically feasible in a bench model, it would be volatile, if not dangerous in a clinical situation.

P088 Presence versus absence of flow limitation during stable breathing in patients with obstructive sleep apnoea

Introduction Flow limitation is the distinguishing characteristic of obstructive sleep apnoea. Critically, periods of flow limitation can occur without overt reductions in airflow (e.g. disproportionate increase in ventilatory drive vs. achieved ventilation), however, such periods are ignored by clinical scoring. Here we investigate flow limitation during so-called “stable breathing”, i.e. periods of sleep without scored events, by applying our recently-validated model to estimate flow limitation from the airflow signal. Methods Flow limitation was visually-scored (N=117,871 breaths) from N=40 participants attending an overnight sleep study for suspected sleep apnoea. Scoring was aided by physiological signals (e.g. intra-oesophageal diaphragm EMG). Model flow limitation classification used features extracted from the pneumotach signal (cross-validated accuracy=92.4%). We applied this method to investigate the occurrence of flow limitation during stable breathing, defined as periods of sleep &gt;3 min duration without scored arousals or respiratory events. Results Model predicted flow limitation frequency was strongly correlated with visual scoring (R²=0.84 p&lt;0.001). The median flow limitation frequency during stable breathing ranged from 8–91%, with an overall median of 59% (IQR 37%-75%). Flow limitation frequency during stable breathing was only modestly associated with the apnoea-hypopnea index (R²=0.12 p&lt;0.05). Discussion Flow limitation occurs surprisingly frequently during stable breathing. While some individuals achieve stable breathing with minimal flow limitation, others demonstrate substantial flow limitation. Heterogeneity in frequency of flow limitation (within and between individuals) may provide further insights into emergent phenotypic variability within sleep disordered breathing. Finally, this model performed similarly in nasal pressure (88.2% accuracy), indicating potential application to clinical studies.

Frequency of flow limitation using airflow shape

Study Objectives The presence of flow limitation during sleep is associated with adverse health consequences independent of obstructive sleep apnea (OSA) severity (apnea-hypopnea index, AHI), but remains extremely challenging to quantify. Here we present a unique library and an accompanying automated method that we apply to investigate flow limitation during sleep. Methods A library of 117,871 breaths (N=40 participants) were visually classified (certain flow limitation, possible flow limitation, normal) using airflow shape and physiological signals (ventilatory drive per intra-esophageal diaphragm EMG). An ordinal regression model was developed to quantify flow limitation certainty using flow-shape features (e.g. flattening, scooping); breath-by-breath agreement (Cohen’s ƙ) and overnight flow limitation frequency (R 2, %breaths in certain or possible categories during sleep) were compared against visual scoring. Subsequent application examined flow limitation frequency during arousals and stable breathing, and associations with ventilatory drive. Results The model (23 features) assessed flow limitation with good agreement (breath-by-breath ƙ=0.572, p&lt;0.001) and minimal error (overnight flow limitation frequency R 2=0.86, error=7.2%). Flow limitation frequency was largely independent of AHI (R 2=0.16) and varied widely within individuals with OSA (74[32-95]%breaths, mean[range], AHI&gt;15/hr, N=22). Flow limitation was unexpectedly frequent but variable during arousals (40[5-85]%breaths) and stable breathing (58[12-91]%breaths), and was associated with elevated ventilatory drive (R 2=0.26-0.29; R 2&lt;0.01 AHI v. drive). Conclusions Our method enables quantification of flow limitation frequency, a key aspect of obstructive sleep-disordered breathing that is independent of the AHI and often unavailable. Flow limitation frequency varies widely between individuals, is prevalent during arousals and stable breathing, and reveals elevated ventilatory drive.