Impact of airway closure and lung collapse on inhaled nitric oxide effect in acute lung injury: an experimental study.

BACKGROUND: Efficacy of inhaled therapy such as Nitric Oxide (iNO) during mechanical ventilation may depend on airway patency. We hypothesized that airway closure and lung collapse, countered by positive end-expiratory pressure (PEEP), influence iNO efficacy. This could support the role of an adequate PEEP titration for inhalation therapy. The main aim of this study was to assess the effect of iNO with PEEP set above or below the airway opening pressure (AOP) generated by airway closure, on hemodynamics and gas exchange in swine models of acute respiratory distress syndrome. Fourteen pigs randomly underwent either bilateral or asymmetrical two-hit model of lung injury. Airway closure and lung collapse were measured with electrical impedance tomography as well as ventilation/perfusion ratio (V/Q). After AOP detection, the effect of iNO (10ppm) was studied with PEEP set randomly above or below regional AOP. Respiratory mechanics, hemodynamics, and gas-exchange were recorded. RESULTS: All pigs presented airway closure (AOP > 0.5cmH2O) after injury. In bilateral injury, iNO was associated with an improved mean pulmonary pressure from 49 ± 8 to 42 ± 7mmHg; (p = 0.003), and ventilation/perfusion matching, caused by a reduction in pixels with low V/Q and shunt from 16%[IQR:13-19] to 9%[IQR:4-12] (p = 0.03) only at PEEP set above AOP. iNO had no effect on hemodynamics or gas exchange for PEEP below AOP (low V/Q 25%[IQR:16-30] to 23%[IQR:14-27]; p = 0.68). In asymmetrical injury, iNO improved pulmonary hemodynamics and ventilation/perfusion matching independently from the PEEP set. iNO was associated with improved oxygenation in all cases. CONCLUSIONS: In an animal model of bilateral lung injury, PEEP level relative to AOP markedly influences iNO efficacy on pulmonary hemodynamics and ventilation/perfusion match, independently of oxygenation.

Effects of Kinematic Hardening of Mucus Polymers in an Airway Closure Model.

The formation of a liquid plug inside a human airway, known as airway closure, is computationally studied by considering the elastoviscoplastic (EVP) properties of the pulmonary mucus covering the airway walls for a range of liquid film thicknesses and Laplace numbers. The airway is modeled as a rigid tube lined with a single layer of an EVP liquid. The Saramito-Herschel-Bulkley (Saramito-HB) model is coupled with an Isotropic Kinematic Hardening model (Saramito-HB-IKH) to allow energy dissipation at low strain rates. The rheological model is fitted to the experimental data under healthy and cystic fibrosis (CF) conditions. Yielded/unyielded regions and stresses on the airway wall are examined throughout the closure process. Yielding is found to begin near the closure in the Saramito-HB model, whereas it occurs noticeably earlier in the Saramito-HB-IKH model. The kinematic hardening is seen to have a notable effect on the closure time, especially for the CF case, with the effect being more pronounced at low Laplace numbers and initial film thicknesses. Finally, standalone effects of rheological properties on wall stresses are examined considering their physiological values as baseline.

Prone-position decreases airway closure in a patient with ARDS undergoing venovenous extracorporeal membrane oxygenation.

PURPOSE: Airway closure is a interruption of communication between larger and smaller airways. The presence of airway closure during mechanical ventilation may lead to the overestimation of driving pressure (DP), introducing errors in the assessment of respiratory mechanics and in positive end-expiratory pressure (PEEP) setting on the ventilator. Patients with severe acute respiratory distress syndrome (ARDS) may exhibit the airway closure phenomenon, which can be easily diagnosed with a low-flow inflation. Prone positioning is a therapeutic manoeuver proven to reduce mortality in ARDS patients, and has been widely implemented also in patients requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO). To date, the impact of prone positioning on changes in airway closure has not been described. METHODS: We present an image analysis of the pressure waveform during volume-controlled ventilation and low-flow inflations before and after prone positioning in an ARDS patient on VV ECMO. RESULTS: A high airway opening pressure level (23 cmH2O) was detected in the supine position during tidal ventilation. Airway closure was confirmed by using a low-flow inflation. Prone positioning significantly attenuated airway closure, with the airway opening pressure decreasing to 13 cmH2O. After re-supination, airway closure was lower as compared with supine position at baseline (17 cmH2O). CONCLUSION: Prone positioning reduced airway closure in an ARDS patient on VV ECMO support.

A new physiological manikin to test and compare ventilation devices during cardiopulmonary resuscitation.

Background: There is a lack of bench systems permitting to evaluate ventilation devices in the specific context of cardiac arrest. Objectives: The objective of the study is to assess if a new physiological manikin may permit to evaluate the performances of medical devices dedicated to ventilation during cardiopulmonary resuscitation (CPR). Methods: Specific CPR-related features required to reproduce realistic ventilation were implemented into the SAM (Sarthe Anjou Mayenne) manikin. In the first place, the manikin ability to mimic ventilation during CPR was assessed and compared to real-life tracings of airway pressure, flow and capnogram from three out of hospital cardiac arrest (OHCA) patients. In addition, to illustrate the interest of this manikin, ventilation was evaluated during mechanical continuous chest compressions with two devices dedicated to CPR: the Boussignac cardiac arrest device (B-card - Vygon; Ecouen France) and the Impedance Threshold Device (ITD - Zoll; Chelmsford, MA). Results: The SAM manikin enabled precise replication of ventilation tracings as observed in three OHCA patients during CPR, and it allowed for comparison between two distinct ventilation devices. B-card generated a mean, maximum and minimum intrathoracic pressure of 6.3 (±0.1) cmH2O, 18.9 (±1.1) cmH2O and -0.3 (±0.2) cmH2O respectively; while ITD generated a mean, maximum and minimum intrathoracic pressure of -1.6 (±0.0) cmH2O, 5.7 (±0.1) cmH2O and -4.8 (±0.1) cmH2O respectively during CPR. B-card allowed to increase passive ventilation compared to the ITD which resulted in a dramatic limitation of passive ventilation. Conclusion: The SAM manikin is an innovative model integrating specific physiological features that permit to accurately evaluate and compare ventilation devices during CPR.

Explorative study on lower inflection point dynamics during cardiopulmonary resuscitation: Potential implications for airway management.

INTRODUCTION: In patients undergoing cardiopulmonary resuscitation (CPR) after an Out-of-Hospital Cardiac Arrest (OHCA), intrathoracic airway closure can impede ventilation, adversely affecting patient outcomes. This explorative study investigates the evolution of intrathoracic airway closure by analyzing the lower inflection point (LIP) during the inspiration phase of CPR, aiming to identify the potential thresholds for alveolar recruitment. METHODS AND MATERIALS: Eleven OHCA patients undergoing CPR with endotracheal intubation and manual bag ventilation were included. Flow and pressure measurements were obtained using Sensirion SFM3200AW and Wika CPT2500 sensors attached to the endotracheal tube, connected to a Surface Go Tablet for data collection. Flow data was analyzed in Microsoft Excel, while pressure data was processed using the Wika USBsoft2500 application. Analysis focused on the inspiration phase of the first 6-8 breaths, with an additional 2 breaths recorded and analyzed at the end of CPR. RESULTS: Across the cohort, the median tidal volume was 870.00 milliliter (mL), average flow was 31.90 standard liters per minute (slm), and average pressure was 17.21 cmH2O. The calculated average LIP was 31.47 cmH2O. Most cases (72.7%) exhibited a negative trajectory in LIP evolution during CPR, with 2 cases (18.2%) showing a positive trajectory and 1 case remaining inconclusive. The average LIP in the first 8 breaths was significantly higher than in the last 2 breaths (p = 0.018). No significant correlation was found between average LIP and return of spontaneous circulation (ROSC), compression depth, frequency, or end-tidal CO2 (EtCO2). However, a significant negative correlation was observed between the average LIP of the last 2 breaths and CPR duration (p = 0.023). VALIDATION: LIP calculation in low-flow ventilations using the novel mathematical method yielded values consistent with those reported in the literature. DISCUSSION/CONCLUSION: These explorative data demonstrate a predominantly negative trajectory in LIP evolution during CPR, suggesting potential challenges in maintaining airway patency. Limitations include a small sample size and sensor recording issues. Further research is warranted to explore the evolution of LIP and its implications for personalized ventilation strategies in CPR.

Airway opening pressure maneuver to detect airway closure in mechanically ventilated pediatric patients.

Background: Airway closure, which refers to the complete collapse of the airway, has been described under mechanical ventilation during anesthesia and more recently in adult patients with acute respiratory distress syndrome (ARDS). A ventilator maneuver can be used to identify airway closure and measure the pressure required for the airway to reopen, known as the airway opening pressure (AOP). Without that maneuver, AOP is unknown to clinicians. Objective: This study aims to demonstrate the technical adaptation of the adult maneuver for children and illustrate its application in two cases of pediatric ARDS (p-ARDS). Methods: A bench study was performed to adapt the maneuver for 3-50 kg patients. Four maneuvers were performed for each simulated patient, with 1, 2, 3, and 4 s of insufflation time to deliver a tidal volume (Vt) of 6 ml/kg by a continuous flow. Results: Airway closure was simulated, and AOP was visible at 15 cmH2O with a clear inflection point, except for the 3 kg simulated patient. Regarding insufflation time, a 4 s maneuver exhibited a better performance in 30 and 50 kg simulated patients since shorter insufflation times had excessive flowrates (>10 L/min). Below 20 kg, the difference in resistive pressure between a 3 s and a 4 sec maneuver was negligible; therefore, prolonging the maneuver beyond 3 s was not useful. Airway closure was identified in two p-ARDS patients, with the pediatric maneuver being employed in the 28 kg patient. Conclusions: We propose a pediatric AOP maneuver delivering 6 ml/kg of Vt at a continuous low-flow inflation for 3 s for patients weighing up to 20 kg and for 4 s for patients weighing beyond 20 kg.

Airway Closure in Patients With Cardiogenic Pulmonary Edema as a Cause of Driving Pressure Overestimation: The "Uncorking Effect".

Airway closure is an underestimated phenomenon reported in hypoxemic respiratory failure under mechanical ventilation, during cardiac arrest, and in patients who are obese. Because airway and alveolar pressure are not communicating, it leads to an overestimation of driving pressure and an underestimation of respiratory system compliance. Airway closure also favors denitrogenation atelectasis. To date, it has been described mainly in patients with ARDS and those with obesity. We describe three cases of airway closure in patients with hydrostatic pulmonary edema caused by cardiogenic shock, highlighting its resolution in a limited period of time (24 h) as pulmonary edema resolved. The waveforms show a biphasic reopening that we refer to as the "uncorking effect". The detection of airway closure may require setting positive end-expiratory pressure at or above the airway opening pressure to avoid the overestimation of driving pressure.

Advanced respiratory mechanics assessment in mechanically ventilated obese and non-obese patients with or without acute respiratory distress syndrome.

BACKGROUND: Respiratory mechanics is a key element to monitor mechanically ventilated patients and guide ventilator settings. Besides the usual basic assessments, some more complex explorations may allow to better characterize patients' respiratory mechanics and individualize ventilation strategies. These advanced respiratory mechanics assessments including esophageal pressure measurements and complete airway closure detection may be particularly relevant in critically ill obese patients. This study aimed to comprehensively assess respiratory mechanics in obese and non-obese ICU patients with or without ARDS and evaluate the contribution of advanced respiratory mechanics assessments compared to basic assessments in these patients. METHODS: All intubated patients admitted in two ICUs for any cause were prospectively included. Gas exchange and respiratory mechanics including esophageal pressure and end-expiratory lung volume (EELV) measurements and low-flow insufflation to detect complete airway closure were assessed in standardized conditions (tidal volume of 6 mL kg-1 predicted body weight (PBW), positive end-expiratory pressure (PEEP) of 5 cmH2O) within 24 h after intubation. RESULTS: Among the 149 analyzed patients, 52 (34.9%) were obese and 90 (60.4%) had ARDS (65.4% and 57.8% of obese and non-obese patients, respectively, p = 0.385). A complete airway closure was found in 23.5% of the patients. It was more frequent in obese than in non-obese patients (40.4% vs 14.4%, p < 0.001) and in ARDS than in non-ARDS patients (30% vs. 13.6%, p = 0.029). Respiratory system and lung compliances and EELV/PBW were similarly decreased in obese patients without ARDS and obese or non-obese patients with ARDS. Chest wall compliance was not impacted by obesity or ARDS, but end-expiratory esophageal pressure was higher in obese than in non-obese patients. Chest wall contribution to respiratory system compliance differed widely between patients but was not predictable by their general characteristics. CONCLUSIONS: Most respiratory mechanics features are similar in obese non-ARDS and non-obese ARDS patients, but end-expiratory esophageal pressure is higher in obese patients. A complete airway closure can be found in around 25% of critically ill patients ventilated with a PEEP of 5 cmH2O. Advanced explorations may allow to better characterize individual respiratory mechanics and adjust ventilation strategies in some patients. Trial registration NCT03420417 ClinicalTrials.gov (February 5, 2018).

Lung de-recruitment in the allergic asthma of obesity: evidence from an anatomically based inverse model.

The increase in asthma associated with the obesity epidemic cannot simply be due to airway hyperresponsiveness from chronic lung compression because chronic lung compression is a feature of obesity in general. We therefore sought to investigate what other factors might be at play in the impaired lung function seen in obese individuals with asthma. We measured respiratory system impedance in four groups-Lean Control, Lean Allergic Asthma, Obese Control, and Obese Allergic Asthma-before and after administration of albuterol. Impedance measurements were fit with an anatomically based computational model of lung mechanics that represents the airway tree as a branching structure with a uniform degree of asymmetry and a fixed radius scaling ratio, γ, between branches of sequential order. The two model parameters that define the airway tree, γ and tracheal radius, varied only modestly between the four study groups, indicating relatively minor differences in airway caliber. In contrast, respiratory system elastance was 57, 34, 143, and 271 cmH2O/L, respectively, for the four groups, suggesting that obesity induced significant lung de-recruitment that was exacerbated by allergic asthma. In addition, when the radii of the individual branches of the airway tree were varied randomly, we found that roughly half the terminal airways had to be closed to have the model fit the data well. We conclude that de-recruitment of small airways is a particular feature of Obese Allergic Asthma, and this can be inferred from respiratory system impedance fit with an anatomically based computational model.NEW & NOTEWORTHY Using a novel anatomically based computational model to interpret oscillometry measurements of impedance, we show that respiratory system elastance is increased in obesity and is increased dramatically in individuals with obese allergic asthma. A significant component of this increased elastance in obese allergic asthma appears to be due to closure of small airways rather than alveolar atelectasis, and this closure is partially mitigated by albuterol. These findings potentially point to nonpharmacological therapies in obese allergic asthma aimed at recruiting closed airways.

A novel capnogram analysis to guide ventilation during cardiopulmonary resuscitation: clinical and experimental observations.

BACKGROUND: Cardiopulmonary resuscitation (CPR) decreases lung volume below the functional residual capacity and can generate intrathoracic airway closure. Conversely, large insufflations can induce thoracic distension and jeopardize circulation. The capnogram (CO2 signal) obtained during continuous chest compressions can reflect intrathoracic airway closure, and we hypothesized here that it can also indicate thoracic distension. OBJECTIVES: To test whether a specific capnogram may identify thoracic distension during CPR and to assess the impact of thoracic distension on gas exchange and hemodynamics. METHODS: (1) In out-of-hospital cardiac arrest patients, we identified on capnograms three patterns: intrathoracic airway closure, thoracic distension or regular pattern. An algorithm was designed to identify them automatically. (2) To link CO2 patterns with ventilation, we conducted three experiments: (i) reproducing the CO2 patterns in human cadavers, (ii) assessing the influence of tidal volume and respiratory mechanics on thoracic distension using a mechanical lung model and (iii) exploring the impact of thoracic distension patterns on different circulation parameters during CPR on a pig model. MEASUREMENTS AND MAIN RESULTS: (1) Clinical data: 202 capnograms were collected. Intrathoracic airway closure was present in 35%, thoracic distension in 22% and regular pattern in 43%. (2) Experiments: (i) Higher insufflated volumes reproduced thoracic distension CO2 patterns in 5 cadavers. (ii) In the mechanical lung model, thoracic distension patterns were associated with higher volumes and longer time constants. (iii) In six pigs during CPR with various tidal volumes, a CO2 pattern of thoracic distension, but not tidal volume per se, was associated with a significant decrease in blood pressure and cerebral perfusion. CONCLUSIONS: During CPR, capnograms reflecting intrathoracic airway closure, thoracic distension or regular pattern can be identified. In the animal experiment, a thoracic distension pattern on the capnogram is associated with a negative impact of ventilation on blood pressure and cerebral perfusion during CPR, not predicted by tidal volume per se.

Airway closing index in school-age children during exercise bronchoprovocation.

OBJECTIVE: Airway Closing Index (ACI), the ratio of % change in FVC to % change in FEV1 with bronchoprovocation, may represent changes in airflow due to airway closure, as opposed to airway narrowing. The objective of this study was to evaluate ACI during exercise bronchoprovocation (EB) in children. METHODS: Children, 6 to 18 years of age, who underwent EB using a stationary bicycle ergometer over a 6-year period were reviewed. Pulmonary function, including ACI, in patients with a positive exercise challenge, defined as ≥10% decrease in FEV1 following exercise, were compared to patients with a negative challenge. RESULTS: A total of 1030 children with a median age of 13 (IQR 11-15) underwent EB, of which 376 (37%) had a positive exercise challenge. There was wide variability in ACI, with a median of 0.75 (0.28-1.21). Median ACI in those with a positive test was 0.68 (IQR 0.41-0.93) compared to 0.84 (IQR 0.09-1.06) for those with a negative test, p = 0.017. Median ACI was higher in older children (p < 0.001) and females (p < 0.0001). Median percent change in FEV1 following bronchodilator for children in the highest quintile for ACI was 4.5 (IQR 1.3-8.1) compared to 5.5 (IQR 2-9.2) for children in the lowest quintile, p = 0.04. CONCLUSIONS: There is wide variability in the ACI in children undergoing EB. ACI was lower in children with a positive challenge, the significance is unknown. Children with higher ACI may have increased airway closure with bronchoprovocation, and less response to bronchodilators.

Reversibility of total airway closure and alveolar consolidation in a COVID-19 patient: A case study.

Coronavirus disease 2019 (COVID-19) may be complicated by life-threatening pneumonia requiring tracheal intubation, mechanical ventilation and veno-venous extracorporeal membrane oxygenation (vvECMO). It is not yet clear to what extent and after which delay the most severe cases of COVID-19 pneumonia are reversible. Here, we present a 39-year-old patient who developed a severe COVID-19-attributed acute respiratory distress syndrome (ARDS) resulting in complete alveolar consolidation and airway closure for several weeks. His remarkable ventilatory pattern was established using ventilator airway pressure curve analysis and computed tomography imaging. The patient was managed with supportive care, mechanical ventilation and vvECMO. He received dexamethasone and tocilizumab as immunomodulatory drugs. Despite multiple complications, he recovered and was weaned from vvECMO, ventilator and oxygen on days 75, 95 and 99 post-intubation, respectively. He was discharged from hospital on day 113. This case study strongly supports the remarkable potential for reversibility of ARDS in COVID-19 patients and discusses the implications for critical care nursing regarding mechanical ventilation and ECMO device management in patients who may become entirely dependent on vvECMO for oxygenation and carbon dioxide elimination.

Positive end-expiratory pressure in COVID-19-related ARDS: Do not forget the airway closure.

Airway closure is a physiological phenomenon in which the distal airways are obstructed when the airway pressure drops below the airway opening pressure. We assessed this phenomenon in 27 patients with coronavirus disease 2019-related acute respiratory distress syndrome. Twelve (44%) patients had an airway opening pressure above 5 cmH2O. The median airway opening pressure was 8 cmH2O (interquartile range, 7-10), with a maximum value of 17 cmH2O. Three patients had a baseline positive end-expiratory pressure lower than the airway opening pressure.

Closing volume detection by single-breath gas washout and forced oscillation technique.

Closing volume (CV) is commonly measured by single-breath nitrogen washout (CVSBW). A method based on the forced oscillation technique was recently introduced to detect a surrogate CV (CVFOT). As the two approaches are based on different physiological mechanisms, we aim to investigate CVFOT and CVSBW relationship at different degrees and patterns of airway obstruction. A mathematical model was developed to evaluate the CVSBW and CVFOT sensitivity to different patterns of airway obstruction, either located in a specific lung region or equally distributed throughout the lung. The two CVs were also assessed during slow vital capacity (VC) maneuvers in triplicate in 13 healthy subjects and pre- and postmethacholine challenge (Mch) in 12 subjects with mild-moderate asthma. Model simulations suggest that CVSBW is more sensitive than CVFOT to the presence of few flow-limited or closed airways that modify the contribution of tracer-poor and tracer-rich lung regions to the overall exhaled gas. Conversely, CVFOT occurs only when at least ∼65% of lung units are flow limited or closed, regardless of their regional distribution. CVSBW did not differ between healthy subjects and those with asthma (17 ± 9% VC vs. 22 ± 10% VC), whereas CVFOT did (16 ± 5% VC vs. 23 ± 6% VC, P < 0.01). In patients with asthma, both CVSBW and CVFOT increased post-Mch (33 ± 7% VC P < 0.001 and 43 ± 12% VC P < 0.001, respectively). CVSBW weakly correlated with CVFOT (r = 0.45, P < 0.01). The closing capacities (CV + residual volume) were correlated (r = 0.74, P < 0.001), but the changes with Mch in both CVs and closing capacities did not correlate. CVFOT is easy to measure and provides a reproducible parameter useful for describing airway impairment in obstructive respiratory diseases.NEW & NOTEWORTHY The forced oscillation technique can identify a surrogate of closing volume (CVFOT). We investigated its relationship with the one measured by single-breath washout (CVSBW). CVFOT weakly correlates with CVSBW. The respective closing capacities were correlated, but their increases after methacholine challenge in asthmatics did not. Our results suggest that CVFOT is less sensitive than CVSBW to few flow-limited/closed airways but more specific in detecting increases in flow-limited/closed airways involving the majority of the lung.

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.

Breath Hold Facilitates Targeted Deposition of Aerosolized Droplets in a 3D Printed Bifurcating Airway Tree.

The lungs have long been considered a desired route for drug delivery but, there is still a lack of strategies to rationally target delivery sites especially in the presence of heterogeneous airway disease. Furthermore, no standardized system has been proposed to rapidly test different ventilation strategies and how they alter the overall and regional deposition pattern in the airways. In this study, a 3D printed symmetric bifurcating tree model mimicking part of the human airway tree was developed that can be used to quantify the regional deposition patterns of different delivery methodologies. The model is constructed in a novel way that allows for repeated measurements of regional deposition using reusable parts. During ventilation, nebulized ~3-micron-sized fluid droplets were delivered into the model. Regional delivery, quantified by precision weighing individual airways, was highly reproducible. A successful strategy to control regional deposition was achieved by combining an inspiratory wave form with a "breath hold" pause after each inspiration. Specifically, the second generation of the tree was successfully targeted, and deposition was increased by up to four times in generation 2 when compared to a ventilation without the breath hold (p < 0.0001). Breath hold was also demonstrated to facilitate deposition into blocked regions of the model, which mimic airway closure during an asthma that receive no flow during inhalation. Additionally, visualization experiments demonstrated that in the absence of fluid flow, the deposition of 3-micron water droplets is dominated by gravity, which, to our knowledge, has not been confirmed under standard laboratory conditions.

Forced expiratory time: a composite of airway narrowing and airway closure.

Forced expiratory time (FET) is a spirometrically derived variable thought to reflect lung function, but its physiological basis remains poorly understood. We developed a mathematical theory of FET assuming a linear forced expiratory flow-volume profile that terminates when expiratory flow falls below a defined detection threshold. FET is predicted to correlate negatively with both FEV1 and FVC if variations in the rate of lung emptying (relative to normal) among individuals in a population exceed variations in the amount of lung emptying. We retrospectively determined FET pre- and postmethacholine challenge in 1,241 patients (818 had normal lung function, 137 were obstructed, and 229 were restricted) and examined its relationships to spirometric and demographic variables in both hyperresponsive and normoresponsive individuals. Mean FET was 9.6 ± 2.2 s in the normal group, 12.3 ± 3.0 s in those with obstruction, and 8.8 ± 1.9 s in those with restriction. FET was inversely related to FEV1/FVC in all groups, negatively related to FEV1 in the obstructed patients, and positively related to FVC in both the normal and restricted patients. There was no relationship with methacholine responsiveness. Overall, our theory of the relationship between FET to the spirometric indices is supported by these findings and potentially explains how FET is affected by sex, age, smoking status, and possibly body mass index.NEW & NOTEWORTHY Forced expiratory time (FET) has long been felt to reflect important physiological information about lung function but exactly how has never been clear. Here, we use a model analysis to assess the contributions of airway narrowing versus airway closure to FET in a population of individuals and find support for the theory that FET correlates positively with FEV1 if the amounts of lung emptying over a forced expiration vary from predicted values more than variations in the rates of lung emptying, whereas the correlation is negative in the opposite case.

Lung and chest wall mechanics in patients with acute respiratory distress syndrome, expiratory flow limitation, and airway closure.

Tidal expiratory flow limitation (EFL), which may herald airway closure (AC), is a mechanism of loss of aeration in ARDS. In this prospective, short-term, two-center study, we measured static and dynamic chest wall (Est,cw and Edyn,cw) and lung (Est,L and Edyn,L) elastance with esophageal pressure, EFL, and AC at 5 cmH2O positive end-expiratory pressure (PEEP) in intubated, sedated, and paralyzed ARDS patients. For EFL determination, we used the atmospheric method and a new device allowing comparison of tidal flow during expiration to PEEP and to atmosphere. AC was validated when airway opening pressure (AOP) assessed from volume-pressure curve was found greater than PEEP by at least 1 cmH2O. EFL was defined whenever flow did not increase between exhalation to PEEP and to atmosphere over all or part of expiration. Elastance values were expressed as percentage of normal predicted values (%N). Among the 25 patients included, eight had EFL (32%) and 13 AOP (52%). Between patients with and without EFL Edyn,cw [median (1st to 3rd quartiles)] was 70 (16-127) and 102 (70-142) %N (P = 0.32) and Edyn,L338 (332-763) and 224 (160-275) %N (P < 0.001). The corresponding values for Est,cw and Est,L were 70 (56-88) and 85 (64-103) %N (P = 0.35) and 248 (206-348) and 170 (144-195) (P = 0.02), respectively. Dynamic EL had an area receiver operating characteristic curve of 0.88 [95% confidence intervals 0.83-0.92] for EFL and 0.74[0.68-0.79] for AOP. Higher Edyn,L was accurate to predict EFL in ARDS patients; AC can occur independently of EFL, and both should be assessed concurrently in ARDS patients.NEW & NOTEWORTHY Expiratory flow limitation (EFL) and airway closure (AC) were observed in 32% and 52%, respectively, of 25 patients with ARDS investigated during mechanical ventilation in supine position with a positive end-expiratory pressure of 5 cmH2O. The performance of dynamic lung elastance to detect expiratory flow limitation was good and better than that to detect airway closure. The vast majority of patients with EFL also had AC; however, AC can occur in the absence of EFL.

Ventilation During Cardiopulmonary Resuscitation: What Have We Learned From Models?

The optimization of ventilation during cardiopulmonary resuscitation (CPR) is a broad field of research. Recent physiological observations in this field challenge the current understanding of respiratory and circulatory interactions. Thanks to different models available (bench, animal, human), the understanding of physiological phenomena occurring during CPR has progressed. In this review, we describe the clinical observations that have led to the emerging concept of lung volume reduction and associated thoracic airway closure. We summarize the clinical and animal observations supporting these concepts. We then discuss the different contributions of bench, animal, and human models to the understanding of airway closure and their impact on intrathoracic pressure, airway closure, and hemodynamics generated by chest compression. The limitation of airway pressure and ventilation, resulting from airway closure reproducible in models, may play a major role in ventilation and gas exchange impairment observed during prolonged resuscitation.

Older age and obesity are associated with increased airway closure in response to methacholine in patients with asthma.

BACKGROUND AND OBJECTIVE: The reduction of forced expiratory volume in 1 s (FEV1 ) in response to methacholine challenge in asthma may reflect two components: airway narrowing, assessed by the change in FEV1 /forced vital capacity (FVC), and airway closure, assessed by the change in FVC. The purpose of this study was to determine the degree and determinants of airway closure in response to methacholine in a large group of asthmatic patients participating in studies conducted by the American Lung Association-Airways Clinical Research Centers (ALA-ACRC). METHODS: We used the methacholine challenge data from participants in five studies of the ALA-ACRC to determine the closing index, defined as the contribution of airway closure to the decrease in FEV1 , and calculated as %ΔFVC/%ΔFEV1 . RESULTS: There were a total of 936 participants with asthma, among whom the median closing index was 0.67 relative to that of a published healthy population of 0.54. A higher closing index was associated with increased age (10-year increments) (0.04, 95% CI = 0.02, 0.05, P < 0.005) and obesity (0.07, 95% CI = 0.03, 0.10, P < 0.001). There was no association between the closing index and asthma control. CONCLUSION: Our findings confirm that airway closure in response to methacholine occurs in a large, diverse population of asthmatic participants, and that increased airway closure is associated with older age and obesity. These findings suggest that therapies targeting airway closure may be important in patients with a high closing index.