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Rationale: Body habitus is a major determinant of obstructive sleep apnea (OSA). However, many individuals do not have OSA despite being overweight/obese (body mass index > 25 kg/m(2)) for reasons that are not fully elucidated., Objectives: To determine the key physiologic traits (upper-airway anatomy/collapsibility, upper-airway muscle responsiveness, chemoreflex control of ventilation, arousability from sleep) responsible for the absence of OSA in overweight/obese individuals., Methods: We compared key physiologic traits in 18 overweight/obese subjects without apnea (apnea-hypopnea index < 15 events per hour) with 25 overweight/obese matched patients with OSA (apnea-hypopnea index ≥ 15 events per hour) and 11 normal-weight nonapneic control subjects. Traits were measured by repeatedly lowering continuous positive airway pressure to subtherapeutic levels for 3 minutes during non-REM sleep., Measurements and Main Results: Overweight/obese subjects without apnea exhibited a less collapsible airway than overweight/obese patients with apnea (critical closing pressure: -3.7 ± 1.9 vs. 0.6 ± 1.2 cm H2O; P = 0.003; mean ± 95% confidence interval), but a more collapsible airway relative to normal-weight control subjects (-8.8 ± 3.1 cm H2O; P < 0.001). Notably, overweight/obese subjects without apnea exhibited a threefold greater upper-airway muscle responsiveness than both overweight/obese patients with apnea (Δgenioglossus EMG/Δepiglottic pressure: -0.49 [-0.22 to -0.79] vs. -0.15 [-0.09 to -0.22] %max/cm H2O; P = 0.008; mean [95% confidence interval]) and normal-weight control subjects (-0.16 [-0.04 to -0.30] %max/cm H2O; P = 0.02). Loop gain was elevated (more negative) in both overweight/obese groups and normal-weight control subjects (P = 0.02). Model-based analysis demonstrated that overweight/obese individuals without apnea rely on both more favorable anatomy and collapsibility and enhanced upper-airway dilator muscle responses to avoid OSA., Conclusions: Overweight/obese individuals without apnea have a moderately compromised upper-airway structure that is mitigated by highly responsive upper-airway dilator muscles to avoid OSA. Elucidating the mechanisms underlying enhanced muscle responses in this population may provide clues for novel OSA interventions.

Purpose: Prone 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., Methods: Studies 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., Results: Seven 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., Conclusions: Prone 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.

This report summarizes current physiological and technical knowledge on esophageal pressure (Pes) measurements in patients receiving mechanical ventilation. The respiratory changes in Pes are representative of changes in pleural pressure. The difference between airway pressure (Paw) and Pes is a valid estimate of transpulmonary pressure. Pes helps determine what fraction of Paw is applied to overcome lung and chest wall elastance. Pes is usually measured via a catheter with an air-filled thin-walled latex balloon inserted nasally or orally. To validate Pes measurement, a dynamic occlusion test measures the ratio of change in Pes to change in Paw during inspiratory efforts against a closed airway. A ratio close to unity indicates that the system provides a valid measurement. Provided transpulmonary pressure is the lung-distending pressure, and that chest wall elastance may vary among individuals, a physiologically based ventilator strategy should take the transpulmonary pressure into account. For monitoring purposes, clinicians rely mostly on Paw and flow waveforms. However, these measurements may mask profound patient-ventilator asynchrony and do not allow respiratory muscle effort assessment. Pes also permits the measurement of transmural vascular pressures during both passive and active breathing. Pes measurements have enhanced our understanding of the pathophysiology of acute lung injury, patient-ventilator interaction, and weaning failure. The use of Pes for positive end-expiratory pressure titration may help improve oxygenation and compliance. Pes measurements make it feasible to individualize the level of muscle effort during mechanical ventilation and weaning. The time is now right to apply the knowledge obtained with Pes to improve the management of critically ill and ventilator-dependent patients.

Purpose: Comparisons of negative versus positive pressure ventilation have imperfectly matched the pressure-time profile or the lung volume history, or have incompletely applied in vivo negative pressure to include the complete thoracic wall and abdomen., Hypothesis: Negative pressure exerts the same pattern of lung distension as positive pressure when the pressure-time and volume history profiles are identical and the application of negative pressure is over the whole lung., Methods: (1) In isolated (ex vivo) and (2) intact (in vivo) mouse lungs (n = 4/group) (sealed chamber enclosing either the whole lung or whole mouse except for external airway opening), identical and inverse-tidal, square-wave pressure-time profiles were obtained with positive and negative pressure ventilation. (3) Following an identical volume history, surfactant-depleted rabbits (n = 7) were randomly assigned to sustained, static equivalent positive versus negative pressures. (4) Surfactant-depleted anesthetized rabbits (n = 10) with identical volume histories were randomized to positive versus negative ventilation with identical pressure-time characteristics., Results: Matched positive and negative pressure time profiles in ex vivo and in vivo mice resulted in identical tidal volumes. Identical (negative vs. positive) sustained static pressures resulted in similar PaO(2) and end expiratory lung volumes. Positive and negative ventilation with identical volume histories and pressure time characteristics showed no difference in oxygenation or lung volumes. Historical comparisons suggested better oxygenation with negative pressure when the volume history was not identical., Conclusions: These data do not support major biological differences between negative and positive pressure ventilation when waveforms and lung volume history are matched.

Rationale and Objectives: To assess the reproducibility of multidetector-row computed tomography (MDCT)-measured forced expiratory tracheal collapse in healthy volunteers., Methods and Materials: Fourteen healthy, nonsmoking volunteers (6 males, 8 females, mean age 48.7 +/- 13.8 years) underwent repeat imaging 1 year after baseline imaging of tracheal dynamics employing the same scanner and technique (64-MDCT, 40 mAs, 120 kVp, and 0.625 mm detector collimation) with spirometric monitoring of total lung capacity and forced exhalation. Cross-sectional area (CSA) of the trachea was measured 1 cm above the aortic arch at end-inspiration and dynamic expiration, and percentage (%) expiratory reduction in tracheal lumen was calculated. Measurements were compared between baseline (Yr1) and repeat imaging (Yr2) using correlation coefficients and Bland-Altman plots., Results: Mean end-inspiratory CSA was 255.3 +/- 56 mm(2) at Yr1 and 255.1 +/- 52 mm(2) at Yr2; mean dynamic expiratory CSA was 125.6 +/- 60 mm(2) at Yr1 and 132.1 +/- 58 mm(2) at Yr2; and mean % expiratory reduction was 51.7 +/- 18% at Yr1 and 48.7 +/- 19% at Yr2. Mean differences between Yr1 and Yr2 values were 0.2 mm(2) for end-inspiratory CSA, 6.5 mm(2) for dynamic expiratory CSA, and 3.0% for percentage expiratory reduction. There was excellent correlation between the Yr1 and Yr2 measures of end-inspiratory CSA (r(2) = 0.97, P < .001), dynamic expiratory CSA (r(2) = 0.89, P < .001), and % expiratory reduction (r(2) = 0.86, P < .001)., Conclusion: MDCT measurements of forced expiratory tracheal collapse in healthy volunteers are highly reproducible over time., (Copyright 2010 AUR. Published by Elsevier Inc. All rights reserved.)

Rationale: Previous investigations have identified several potential predictors of outcomes from lung volume reduction surgery (LVRS). A concern regarding these studies has been their small sample size, which may limit generalizability. We therefore sought to examine radiographic and physiologic predictors of surgical outcomes in a large, multicenter clinical investigation, the National Emphysema Treatment Trial., Objectives: To identify objective radiographic and physiological indices of lung disease that have prognostic value in subjects with chronic obstructive pulmonary disease being evaluated for LVRS., Methods: A subset of the subjects undergoing LVRS in the National Emphysema Treatment Trial underwent preoperative high-resolution computed tomographic (CT) scanning of the chest and measures of static lung recoil at total lung capacity (SRtlc) and inspiratory resistance (Ri). The relationship between CT measures of emphysema, the ratio of upper to lower zone emphysema, CT measures of airway disease, SRtlc, Ri, the ratio of residual volume to total lung capacity (RV/TLC), and both 6-month postoperative changes in FEV(1) and maximal exercise capacity were assessed., Measurements and Main Results: Physiological measures of lung elastic recoil and inspiratory resistance were not correlated with improvement in either the FEV(1) (R = -0.03, P = 0.78 and R = -0.17, P = 0.16, respectively) or maximal exercise capacity (R = -0.02, P = 0.83 and R = 0.08, P = 0.53, respectively). The RV/TLC ratio and CT measures of emphysema and its upper to lower zone ratio were only weakly predictive of postoperative changes in both the FEV(1) (R = 0.11, P = 0.01; R = 0.2, P < 0.0001; and R = 0.23, P < 0.0001, respectively) and maximal exercise capacity (R = 0.17, P = 0.0001; R = 0.15, P = 0.002; and R = 0.15, P = 0.002, respectively). CT assessments of airway disease were not predictive of change in FEV(1) or exercise capacity in this cohort., Conclusions: The RV/TLC ratio and CT measures of emphysema and its distribution are weak but statistically significant predictors of outcome after LVRS.

BACKGROUND: During normal breathing, the mesothelial surfaces of the lung and chest wall slide relative to one another. Experimentally, the shear stresses induced by such reciprocal sliding motion are very small, consistent with hydrodynamic lubrication, and relatively insensitive to sliding velocity, similar to Coulomb-type dry friction. Here we explore the possibility that shear-induced deformation of surface roughness in such tissues could result in bidirectional load supporting behavior, in the absence of solid-solid contact, with shear stresses relatively insensitive to sliding velocity. METHOD OF APPROACH: We consider a lubrication problem with elastic blocks (including the rigid limit) over a planar surface sliding with velocity U , where the normal force is fixed (hence the channel thickness is a dependent variable). One block shape is continuous piecewise linear (V block), the other continuous piecewise smoothly quadratic (Q block). The undeformed elastic blocks are spatially symmetric; their elastic deformation is simplified by taking it to be affine, with the degree of shape asymmetry linearly increasing with shear stress. RESULTS: We find that the V block exhibits nonzero Coulomb-type starting friction in both the rigid and elastic case, and that the smooth Q block exhibits approximate Coulomb friction in the sense that the rate of change of shear force with U is unbounded as U → 0 ; shear force ∝U(1/ 2) in the rigid asymmetric case and ∝U(1/ 3) in the (symmetric when undeformed) elastic case. Shear-induced deformation of the elastic blocks results in load supporting behavior for both directions of sliding. CONCLUSIONS: This mechanism could explain load-supporting behavior of deformable surfaces that are symmetrical when undeformed, and may be the source of the weak velocity dependence of friction seen in the sliding of lubricated, but rough, surfaces of elastic media such as the visceral and parietal pleural surfaces of the lung and chest wall.

Objective: After single lung transplantation for emphysema, the volume of the graft at total lung capacity is usually less than its predicted volume in the donor. We sought to determine the contributions of donor-recipient size matching, postoperative native lung hyperinflation, and postoperative chest wall volume reduction to graft restriction after transplantation., Methods: In 19 patients, we estimated individual lung volumes from thoracic computed tomographs taken near total lung capacity before and after single lung transplantation for emphysema to analyze sources of graft restriction. Pulmonary function was assessed by spirometry, and in 5 patients, inspiratory function was assessed with esophageal manometry., Results: Graft volumes after transplantation were 54% +/- 17% of those predicted for the donors (mean +/- SD, P < .0001), and pulmonary function after transplantation was significantly correlated with graft volume. The greatest contribution to graft restriction was the decrease in chest wall volume after transplantation, which was -0.87 L (-31% +/- 29% of the graft's predicted volume; P < .0001). Volume expansion of the contralateral lung contributed -0.44 L (-18% +/- 24%; P = .0018). Other effects, including donor-patient size matching, were not significant. In 5 patients, the maximum negative inspiratory esophageal pressure at total lung capacity was low (-6 +/- 2 cm H2O, normal range approximately -17 to -29 cm H2O)., Conclusions: After single lung transplantation for emphysema, decreased volume of the chest wall was more important than increased volume of the native lung in causing restriction of the graft and decreased pulmonary function. Chest wall restriction is likely due to diminished inspiratory muscle function.

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.

Patients in acute respiratory distress require rapid assessment of the cause of dyspnea. We have observed that many of those patients who are in congestive heart failure (CHF) exhibit rounding of the abdominal cross-section during expiration. We sought to evaluate the diagnostic utility of this breathing pattern in dyspneic patients presenting to an emergency department. Twenty-six subjects with dyspnea due to a variety of conditions were recruited from the emergency department at Beth Israel Deaconess Medical Center. Subjects ranged in age from 21 to 94 years and 81% were female. We measured variation in the anteroposterior and transverse diameters of the rib cage and abdomen using respiratory magnetometers and determined phase of respiration with a pneumotachometer. Investigators blinded to the subjects' identities and diagnoses interpreted measurements as indicating normal respiratory movement without expiratory abdominal rounding, slight expiratory rounding, or pronounced expiratory rounding. The likely cause of dyspnea was determined from discharge diagnoses in the medical record. Expiratory rounding was observed in 12/14 subjects with CHF and 5/12 subjects without CHF (p = 0.0186), and pronounced expiratory rounding was present in 11/14 patients with CHF and 2/12 patients without CHF (p = 0.0016). Test characteristics for the association of CHF with pronounced expiratory rounding were sensitivity 79%, specificity 83%, and predictive accuracy 81%. In patients with acute respiratory distress, expiratory abdominal rounding suggests CHF as the primary cause of dyspnea; a greater degree of rounding suggests a greater likelihood of CHF. The clinical utility of this diagnostic sign remains to be determined in a prospective study.

To function normally, the lungs, heart, and other organs must undergo changes in shape and size, sliding against surrounding body walls. It is not known whether the delicate mesothelial surfaces covering these organs and body wall are in contact during sliding, or if hydrodynamic pressure in the lubricating liquid increases separation between their surfaces. To address this question, we measured the coefficient of friction (mu) of the mesothelial surface of nine rat-abdominal walls sliding in saline on a smooth glass surface. Sliding at physiological velocities of 0.0123-6.14 cm/s with normal stresses of 50-200 Pa, mu varied with velocity (P<0.001). On average, mu was relatively high at low speeds (0.078 at 0.041 cm/s), decreased to a minimum at intermediate speeds (0.034 at 1.23 cm/s), and increased slightly again at higher speeds (0.045 at 6.14 cm/s), consistent with a mixed lubrication regime in which there is at least partial hydrodynamic separation of surfaces. We conclude that mesothelial surfaces, sliding under physiological conditions, are protected from excessive shear by hydrodynamic pressures that increase separation of surfaces.

The frictional behaviour of rabbit's visceral pleura sliding against parietal pleura was assessed in vitro while oscillating at physiological velocities and amplitudes under physiological normal forces. For sliding velocities up to 3 cm s(-1) and normal compressive loads up to 12 cm H2O, the average value of the coefficient of kinetic friction (mu) was constant at 0.019 +/- 0.002 (S.E.) with pleural liquid as lubricant. With Ringer-bicarbonate solution, mu was still constant, but significantly increased (Deltamu = 0.008 +/- 0.001; P < 0.001). Under these conditions, no damage of the sliding pleural surfaces was found on light and electron microscopy. Additional measurements, performed also on peritoneum, showed that changes in nominal contact area or strain of the mesothelia, temperature in the range 19-39 degrees C, and prolonged sliding did not affect mu. Gentle application of filter paper increased mu approximately 10-fold and irreversibly, suggesting alteration of the mesothelia. With packed the red blood cells (RBC) between the sliding mesothelia, mu increased appreciably but reversibly on removal of RBC suspension, whilst no ruptures of RBC occurred. In conclusion, the results indicate a low value of sliding friction in pleural tissues, partly related to the characteristics of the pleural liquid, and show that friction is independent of velocity, normal load, and nominal contact area, consistent with boundary lubrication.