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Study Objectives: Precision medicine for obstructive sleep apnea (OSA) requires noninvasive estimates of each patient's pathophysiological "traits." Here, we provide the first automated technique to quantify the respiratory arousal threshold-defined as the level of ventilatory drive triggering arousal from sleep-using diagnostic polysomnographic signals in patients with OSA., Methods: Ventilatory drive preceding clinically scored arousals was estimated from polysomnographic studies by fitting a respiratory control model (Terrill et al.) to the pattern of ventilation during spontaneous respiratory events. Conceptually, the magnitude of the airflow signal immediately after arousal onset reveals information on the underlying ventilatory drive that triggered the arousal. Polysomnographic arousal threshold measures were compared with gold standard values taken from esophageal pressure and intraoesophageal diaphragm electromyography recorded simultaneously (N = 29). Comparisons were also made to arousal threshold measures using continuous positive airway pressure (CPAP) dial-downs (N = 28). The validity of using (linearized) nasal pressure rather than pneumotachograph ventilation was also assessed (N = 11)., Results: Polysomnographic arousal threshold values were correlated with those measured using esophageal pressure and diaphragm EMG (R = 0.79, p < .0001; R = 0.73, p = .0001), as well as CPAP manipulation (R = 0.73, p < .0001). Arousal threshold estimates were similar using nasal pressure and pneumotachograph ventilation (R = 0.96, p < .0001)., Conclusions: The arousal threshold in patients with OSA can be estimated using polysomnographic signals and may enable more personalized therapeutic interventions for patients with a low arousal threshold., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: In principle, if metabolic rate were to fall during sleep in a patient with obstructive sleep apnea (OSA), ventilatory requirements could be met without increased respiratory effort thereby favoring stable breathing. Indeed, most patients achieve periods of stable flow-limited breathing without respiratory events for periods during the night for reasons that are unclear. Thus, we tested the hypothesis that in patients with OSA, periods of stable breathing occur when metabolic rate (VO2) declines., Methods: Twelve OSA patients (apnea-hypopnea index >15 events/h) completed overnight polysomnography including measurements of VO2 (using ventilation and intranasal PO2) and respiratory effort (esophageal pressure)., Results: Contrary to our hypothesis, VO2 did not differ between stable and unstable breathing periods in non-REM stage 2 (208 ± 20 vs. 213 ± 18 mL/min), despite elevated respiratory effort during stable breathing (26 ± 2 versus 23 ± 2 cmH2O, p = .03). However, VO2 was lowered during deeper sleep (244 to 179 mL/min from non-REM stages 1 to 3, p = .04) in conjunction with more stable breathing. Further analysis revealed that airflow obstruction curtailed metabolism in both stable and unstable periods, since CPAP increased VO2 by 14% in both cases (p = .02, .03, respectively). Patients whose VO2 fell most during sleep avoided an increase in PCO2 and respiratory effort., Conclusions: OSA patients typically convert from unstable to stable breathing without lowering metabolic rate. During sleep, OSA patients labor with increased respiratory effort but fail to satisfy metabolic demand even in the absence of overt respiratory events., (© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

The human pharyngeal airway during sleep is conventionally modeled as a Starling resistor. However, inspiratory flow often decreases with increasing effort (negative effort dependence, NED) rather than remaining fixed as predicted by the Starling resistor model. In this study, we tested a major prediction of the Starling resistor model--that the resistance of the airway upstream from the site of collapse remains fixed during flow limitation. During flow limitation in 24 patients with sleep apnea, resistance at several points along the pharyngeal airway was measured using a pressure catheter with multiple sensors. Resistance between the nose and the site of collapse (the upstream segment) was measured before and after the onset of flow limitation to determine whether the upstream dimensions remained fixed (as predicted by the Starling resistor model) or narrowed (a violation of the Starling resistor model). The upstream resistance from early to mid inspiration increased considerably during flow limitation (by 35 ± 41 cmH2O · liter(-1) · s(-1), P < 0.001). However, there was a wide range of variability between patients, and the increase in upstream resistance was strongly correlated with the amount of NED (r = 0.75, P < 0.001). Therefore, patients with little NED exhibited little upstream narrowing (consistent with the Starling model), and patients with large NED exhibited large upstream narrowing (inconsistent with the Starling model). These findings support the idea that there is not a single model of pharyngeal collapse, but rather that different mechanisms may dominate in different patients. These differences could potentially be exploited for treatment selection., (Copyright © 2014 the American Physiological Society.)

In a study visualizing ventilation with hyperpolarized (3)He magnetic resonance imaging (MRI) in elite breath hold divers, the dynamic MRI images in one subject exhibited an apparent alternation of the image intensity between left and right lung. We hypothesized that the alternation resulted from alternating variations in inspiratory flow rate to left and right lungs. Analysis showed that the alternation was not due to random uncorrelated temporal fluctuations of intensity (p<0.001). The frequency of alternation was approximately 56 min(-1), suggesting a cardiac origin. Similar alternation of ventilation was confirmed retrospectively in 4 of 6 additional subjects. These observations are consistent with previous studies showing cardiogenic mixing of gas in the lung. We speculate that cardiogenic pendelluft, possibly from ballistic lateral motion of the beating heart, could cause alternating variations of inspiratory flow to the lungs., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The objectives of this study were to assess the relationship between right and left hemidiaphragmatic motions during breathing in normal subjects and to investigate alterations in lung motion with changes in posture, using dynamic magnetic resonance (MR) imaging. Imaging was conducted with a 1.5-T MR scanner using fast imaging employing steady-state acquisition with a torso coil. Eight healthy subjects were instructed to breathe from end-inspiration to end-expiration as slowly and as deeply as possible. Imaging and breathing were started together to afford sequential images on the coronal plane. Imaging sequences were performed in supine, prone, left lateral decubitus and right lateral decubitus postures. The component of movement of the most cephalic point in the cephalocaudal axis was measured, and the diaphragmatic excursion (maximum hemidiaphragmatic displacement), synchrony and velocity of the right and left hemidiaphragmatic motions were calculated during the expiratory phase and the inspiratory phase, respectively. Excursion was greater in the right hemidiaphragm in most postures, except the left lateral decubitus. In supine and prone postures, both hemidiaphragms moved synchronously in both inspiratory and expiratory phases. In both lateral decubitus postures, the hemidiaphragms moved asynchronously with different velocities in the expiratory phase but with the same velocities in the inspiratory phase. The method described here allowed the assessment of diaphragmatic motions. Motions in the right and left hemidiaphragms changed with posture. In addition, diaphragmatic motion differed between expiratory and inspiratory phases. This study suggests the further potential of dynamic MR imaging for the evaluation of pulmonary functions or deficiencies.

To examine effects of lung motion on the separation of pleural surfaces during breathing, we modeled the pleural space in two dimensions as a thin layer of fluid separating a stationary elastic solid and a sliding flat solid surface. The undeformed elastic solid contained a series of bumps, to represent tissue surface features, introducing unevenness in fluid layer thickness. We computed the extent of deformation of the solid as a function of sliding velocity, solid elastic modulus, and bump geometry (wavelength and amplitude). For physiological values of the parameters, significant deformation occurs (i.e. bumps are 'flattened') promoting less variation in fluid thickness and decreased fluid shear stress. In addition, deformation is persistent; bumps of sufficient wavelength, once deformed, require a recovery time longer than a typical breath-to-breath interval to return near their undeformed configuration. These results suggest that in the pleural space during normal breathing, separation of pleural surfaces is promoted by the reciprocating sliding of lung and chest wall.

PurposeBreath stacking dyssynchrony generates higher tidal volumes than intended, potentially increasing lung injury risk in acute respiratory distress syndrome (ARDS). Lack of validated criteria to quantify breath stacking dyssynchrony contributes to its under-recognition. This study evaluates performance of novel, objective criteria for quantifying breath stacking dyssynchrony (BREATHE criteria) compared to existing definitions and tests if neuromuscular blockade eliminates high-volume breath stacking dyssynchrony in ARDS.MethodsAirway flow and pressure were recorded continuously for up to 72 h in 33 patients with ARDS receiving volume-preset assist-control ventilation. The flow-time waveform was integrated to calculate tidal volume breath-by-breath. The BREATHE criteria considered five domains in evaluating for breath stacking dyssynchrony: ventilator cycling, interval expiratory volume, cumulative inspiratory volume, expiratory time, and inspiratory time.ResultsThe observed tidal volume of BREATHE stacked breaths was 11.3 (9.7-13.3) mL/kg predicted body weight, significantly higher than the preset volume [6.3 (6.0-6.8) mL/kg; p

PurposeProne positioning for ARDS has been performed for decades without definitive evidence of clinical benefit. A recent multicenter trial demonstrated for the first time significantly reduced mortality with prone positioning. This meta-analysis was performed to integrate these findings with existing literature and test whether differences in tidal volume explain conflicting results among randomized trials.MethodsStudies were identified using MEDLINE, EMBASE, Cochrane Register of Controlled Trials, LILACS, and citation review. Included were randomized trials evaluating the effect on mortality of prone versus supine positioning during conventional ventilation for ARDS. The primary outcome was risk ratio of death at 60 days meta-analyzed using random effects models. Analysis stratified by high (>8 ml/kg predicted body weight) or low (≤ 8 ml/kg PBW) mean baseline tidal volume was planned a priori.ResultsSeven trials were identified including 2,119 patients, of whom 1,088 received prone positioning. Overall, prone positioning was not significantly associated with the risk ratio of death (RR 0.83; 95% CI 0.68-1.02; p = 0.073; I (2) = 64%). When stratified by high or low tidal volume, prone positioning was associated with a significant decrease in RR of death only among studies with low baseline tidal volume (RR 0.66; 95% CI 0.50-0.86; p = 0.002; I (2) = 25%). Stratification by tidal volume explained over half the between-study heterogeneity observed in the unstratified analysis.ConclusionsProne positioning is associated with significantly reduced mortality from ARDS in the low tidal volume era. Substantial heterogeneity across studies can be explained by differences in tidal volume.

Background: OSA results from the collapse of different pharyngeal structures (soft palate, tongue, lateral walls, and epiglottis). The structure involved in collapse has been shown to impact non-CPAP OSA treatment. Different inspiratory airflow shapes are also observed among patients with OSA. We hypothesized that inspiratory flow shape reflects the underlying pharyngeal structure involved in airway collapse.Methods: Subjects with OSA were studied with a pediatric endoscope and simultaneous nasal flow and pharyngeal pressure recordings during natural sleep. The mechanism causing collapse was classified as tongue-related, isolated palatal, lateral walls, or epiglottis. Flow shape was classified according to the degree of negative effort dependence (NED), defined as the percent reduction in inspiratory flow from peak to plateau.Results: Thirty-one subjects with OSA (mean apnea-hypopnea index score ± SD, 54 ± 27 events/h) who were 50 ± 9 years of age were studied. NED was associated with the structure causing collapse (P < .001). Tongue-related obstruction (n = 13) was associated with a small amount of NED (median, 19; interquartile range [IQR], 14%-25%). Moderate NED was found among subjects with isolated palatal collapse (median, 45; IQR, 39%-52%; n = 8) and lateral wall collapse (median, 50; IQR, 44%-64%; n = 8). The epiglottis was associated with severe NED (median, 89; IQR, 78%-91%) and abrupt discontinuities in inspiratory flow (n = 9).Conclusions: Inspiratory flow shape is influenced by the pharyngeal structure causing collapse. Flow shape analysis may be used as a noninvasive tool to help determine the pharyngeal structure causing collapse. [ABSTRACT FROM AUTHOR]

Purpose: Breath stacking dyssynchrony generates higher tidal volumes than intended, potentially increasing lung injury risk in acute respiratory distress syndrome (ARDS). Lack of validated criteria to quantify breath stacking dyssynchrony contributes to its under-recognition. This study evaluates performance of novel, objective criteria for quantifying breath stacking dyssynchrony (BREATHE criteria) compared to existing definitions and tests if neuromuscular blockade eliminates high-volume breath stacking dyssynchrony in ARDS.Methods: Airway flow and pressure were recorded continuously for up to 72 h in 33 patients with ARDS receiving volume-preset assist-control ventilation. The flow-time waveform was integrated to calculate tidal volume breath-by-breath. The BREATHE criteria considered five domains in evaluating for breath stacking dyssynchrony: ventilator cycling, interval expiratory volume, cumulative inspiratory volume, expiratory time, and inspiratory time.Results: The observed tidal volume of BREATHE stacked breaths was 11.3 (9.7-13.3) mL/kg predicted body weight, significantly higher than the preset volume [6.3 (6.0-6.8) mL/kg; p < 0.001]. BREATHE identified more high-volume breaths (≥2 mL/kg above intended volume) than the other existing objective criteria for breath stacking [27 (7-59) vs 19 (5-46) breaths/h; p < 0.001]. Agreement between BREATHE and visual waveform inspection was high (raw agreement 96.4-98.1 %; phi 0.80-0.92). Breath stacking dyssynchrony was near-completely eliminated during neuromuscular blockade [0 (0-1) breaths/h; p < 0.001].Conclusions: The BREATHE criteria provide an objective definition of breath stacking dyssynchrony emphasizing occult exposure to high tidal volumes. BREATHE identified high-volume breaths missed by other methods for quantifying this dyssynchrony. Neuromuscular blockade prevented breath stacking dyssynchrony, assuring provision of the intended lung-protective strategy. [ABSTRACT FROM AUTHOR]

The article highlights a study which examined the effect of age and sex on forced expiratory tracheal collapse in healthy people. Low-dose computed tomography (CT) scanning was performed on the healthy subjects at total lung capacity (TLC) and during force exhalation with spirometric monitoring and coaching. Results of the study revealed that men exhibited positive age dependence of forced central airway collapse.

Mechanical characteristics and gas exchange inefficiencies of the lungs contribute to increased work of ventilation in chronic obstructive pulmonary disease (COPD) at rest and exercise, and the energy cost of ventilation is increased in COPD at any external work level. Assuming typical ventilatory variables and respiratory characteristics, we estimated the relative contributions of inspiratory and expiratory resistance, dynamic elastance, intrinsic positive end-expiratory pressure, and gas exchange inefficiency to the work of breathing, finding that the last of these is likely to be of major importance. Dynamic hyperinflation can be seen as both an impediment to inspiratory muscle function and an essential component of adaptation to severe obstruction. Extrinsic restriction, in which the chest wall fails to achieve and maintain abnormally high lung volumes in COPD, can limit ventilatory function and contribute to disability. [ABSTRACT FROM AUTHOR]

Measures the stiffness of the parietal pleural surface of mammalian chest walls using microindentation. Role of the parietal pleura in the reduction of mesothelial stresses during breathing; Indentation of the pleural surface over the ribs; Caudal regions' demonstration of lower stiffness.

The article comments on the paper "Ventilatory and perceptual responses to cycle exercise in obese females," by D. Ofir and colleagues. The paper examines the mechanism of dyspnea due to obesity. The authors designed the study to isolate the respiratory impairment of obesity. The authors reported that the obese subjects could produce 17% less external work in the cycle, yet they achieved similar maximum oxygen uptake.

We measured esophageal pressures, respiratory flow rates, and expired O2 and CO2 in six adult bottlenose dolphins (Tursiops truncatus) during voluntary breaths and maximal (chuff) respiratory efforts. The data were used to estimate the dynamic specific lung compliance (sCL), the O2 consumption rate (VO2) and CO2 production rates (VO2) during rest. Our results indicate that bottlenose dolphins have the capacity to generate respiratory flow rates that exceed 130 l s-1 and 30 l s-1 during expiration and inspiration, respectively. The esophageal pressures indicated that expiration is passive during voluntary breaths, but active during maximal efforts, whereas inspiration is active for all breaths. The average sCL of dolphins was 0.31±0.04 cmH2O-1, which is considerably higher than that of humans (0.08 cmH2O-1) and that previously measured in a pilot whale (0.13 cmH2O-1). The average estimated VO2 and VCO2 using our breath-by-breath respirometry system ranged from 0.857 to 1.185 l O2 min-1 and 0.589 to 0.851 l CO2 min-1, respectively, which is similar to previously published metabolic measurements from the same animals using conventional flow-through respirometry. In addition, our custom-made system allows us to approximate end tidal gas composition. Our measurements provide novel data for respiratory physiology in cetaceans, which may be important for clinical medicine and conservation efforts. [ABSTRACT FROM AUTHOR]

Abstract: The pleural surfaces of the lung and chest wall slide against each other with low friction. Normal load support can be effected either by a combination of quasi-static fluid pressure and solid–solid contacts of relatively stiff asperities, or by shear-induced hydrodynamic pressures in the pleural fluid layer. To distinguish between these mechanisms, we measured surface topography and spatial distribution of stiffness of rat parietal pleura using atomic force microscopy. The topography of the pleural surface has unevenness at length scales smaller than the thickness of pleural fluid, similar to mesothelial cell diameters. The estimated maximum normal contact pressure that could be borne by asperities of the soft pleura is much less than that required to support a substantial difference between pleural fluid pressure and the pleural surface pressure. These results suggest that during sliding motion, unevenness of the pleural surface is smoothed by local hydrodynamic pressure, preventing any significant contribution of solid–solid contacts. [Copyright &y& Elsevier]

To explore mechanisms causing involuntary airflow synchronous with oscillatory axial whole body acceleration (oscillatory axial acceleration, OAA) such as that during locomotion, we monitored airflow, acceleration, and electromyograms (EMGs) of the rib cage and abdominal muscles in standing subjects undergoing OAA at 3, 6, and 9 Hz at accelerations of 0.1–0.95 g. Subjects relaxed or performed static respiratory maneuvers at constant lung volume with glottis open. Oscillatory airflows (0.01–3.0 l s-1) synchronous with OAA were not consistent with expectations for a passive respiratory system, and were larger during active respiratory efforts than during relaxation. Peak inspiratory airflow usually preceded peak upward acceleration by 90–180°. In 80% of runs with respiratory muscles voluntarily activated or relaxed, EMGs showed activity synchronous with OAA. Changes in periodic muscle activity coincided with changes in oscillatory airflow. We conclude that periodic muscle activity, probably a reflex response to body wall deformation during OAA, strongly influences the involuntary airflow synchronous with OAA. [Copyright &y& Elsevier]

Abstract: We measured regional ventilation at 1l above functional residual capacity (FRC+1L) and total lung capacity (TLC) in three normal subjects and four elite breath-hold divers, and above TLC after glossopharyngeal insufflation (TLC+GI) in the divers. Hyperpolarized 3He MRI was used to map the local ventilation per unit volume over the entire lung. At TLC and above, there was markedly increased regional ventilation of the lungs in the pericardial region compared with the relatively uniform ventilation throughout the rest of the lung. The distribution of fractional ventilation regionally was relatively uniform at FRC+1L, with a small non-gravitational cephalocaudal gradient of specific ventilation in the supine posture. Our observations at high lung volumes are consistent with the effect of high pleural tension in the concave pericardial region, which promotes expansion of the subjacent lung, leading to a higher local effective compliance and a higher specific ventilation. [Copyright &y& Elsevier]