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.

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.

The Clinical Utility of Forced Oscillation Technique (FOT) during Hospitalisation in patients with exacerbation of COPD

BackgroundForced Oscillation Technique (FOT) is an innovative tool to measure within-breath reactance at 5 Hz (ΔXrs5Hz) but its feasibility and utility in acute exacerbations of COPD (AECOPD) is understudied.MethodsA prospective observational study was conducted in 82 COPD patients admitted due to AECOPD. FOT indices were measured and the association between these indices and spirometry, peak inspiratory flow rate, blood inflammatory biomarkers and patient-reported outcomes including assessment of dyspnoea, quality of life; anxiety and depression and frailty at admission and discharge were explored.ResultsAll patients were able to perform FOT in both sitting and supine position. The prevalence of expiratory flow limitation (EFL) in the upright position was 39% (32/82) and increased to 50% (41/82) in the supine position. EFL (measured by ΔXrs5Hz) and resistance at 5 Hz (Rrs5Hz) negatively correlated with FEV1; those with EFL had lower FEV1 (0.74±0.30 versus 0.94±0.36 L, p=0.01) and FVC (1.7 ±0.55 versus 2.1 ±0.63 L, p= 0.009) and higher BMI [27 (21–36) versus 23 (19–26) kg/m2, p=0.03] compared to those without EFL. During recovery from AECOPD, changes in EFL was observed in association with improvement in breathlessness.ConclusionFOT was easily used to detect EFL during hospitalisation due to AECOPD. The prevalence of EFL increased when patients moved from a seated to a supine position and EFL was negatively correlated with airflow limitation. Improvements in EFL were associated with a reduction in breathlessness. FOT is of potential clinical value by providing a non-invasive, objective, and effort-independent technique to measure lung function parameters during AECOPD requiring hospital admission.

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.

Pulmonary function with expiratory resistive loading in healthy volunteers

Expiratory flow limitation is a key characteristic in obstructive pulmonary diseases. To study abnormal lung mechanics isolated from heterogeneities of obstructive disease, we measured pulmonary function in healthy adults with expiratory loading. Thirty-seven volunteers (25±5 yr) completed spirometry and body plethysmography under control and threshold expiratory loading of 7, 11 cmH2O, and a subset at 20 cmH2O (n = 11). We analyzed the shape of the flow-volume relationship with rectangular area ratio (RAR; Ma et al., Respir Med 2010). Airway resistance was increased (p<0.0001) with 7 and 11 cmH2O loading vs control (9.20±1.02 and 11.76±1.68 vs. 2.53± 0.80 cmH2O/L/s). RAR was reduced (p = 0.0319) in loading vs control (0.45±0.07 and 0.47±0.09L vs. 0.48±0.08). FEV1 was reduced (p<0.0001) in loading vs control (3.24±0.81 and 3.23±0.80 vs. 4.04±1.05 L). FVC was reduced (p<0.0001) in loading vs control (4.11±1.01 and 4.14±1.03 vs. 5.03±1.34 L). Peak expiratory flow (PEF) was reduced (p<0.0001) in loading vs control (6.03±1.67 and 6.02±1.84 vs. 8.50±2.81 L/s). FEV1/FVC (p<0.0068) was not clinically significant and FRC (p = 0.4) was not different in loading vs control. Supra-physiologic loading at 20 cmH2O did not result in further limitation. Expiratory loading reduced FEV1, FVC, PEF, but there were no clinically meaningful differences in FEV1/FVC, FRC, or RAR. Imposed expiratory loading likely leads to high airway pressures that resist dynamic airway compression. Thus, a concave expiratory flow-volume relationship was consistently absent–a key limitation for model comparison with pulmonary function in COPD. Threshold loading may be a useful strategy to increase work of breathing or induce dynamic hyperinflation.

Diagnostic Insights from Plethysmographic Alveolar Pressure Assessed during Spontaneous Breathing in COPD Patients

Since its introduction in the clinical practice, body plethysmography has assisted pneumologists in the diagnosis of respiratory diseases and patients’ follow-up, by providing easy assessment of absolute lung volumes and airway resistance. In the last decade, emerging evidence suggested that estimation of alveolar pressure by electronically-compensated plethysmographs may contain information concerning the mechanics of the respiratory system which goes beyond those provided by the simple value of airway resistance or conductance. Indeed, the systematic study of expiratory alveolar pressure-flow loops produced during spontaneous breathing at rest has shown that the marked expansion of expiratory loops in chronic obstructive pulmonary disease patients mainly reflects the presence of tidal expiratory flow-limitation. The presence of this phenomenon can be accurately predicted on the basis of loop-derived parameters. Finally, we present results suggesting that plethysmographic alveolar pressure may be used to estimate non-invasively intrinsic positive end-expiratory pressure (PEEPi) in spontaneously breathing patients, a task which previously could be only accomplished by introducing a balloon-tipped catheter in the esophagus.