Static end-expiratory and dynamic forced expiratory tracheal collapse in COPD.

AIM: To determine the range of tracheal collapse at end-expiration among chronic obstructive pulmonary disease (COPD) patients and to compare the extent of tracheal collapse between static end-expiratory and dynamic forced-expiratory multidetector-row computed tomography (MDCT). MATERIALS AND METHODS: After institutional review board approval and obtaining informed consent, 67 patients meeting the National Heart, Lung, and Blood Institute (NHLBI)/World Health Organization (WHO) Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD were sequentially imaged using a 64-detector-row CT machine at end-inspiration, during forced expiration, and at end-expiration. Standardized respiratory coaching and spirometric monitoring were employed. Mean percentage tracheal collapse at end-expiration and forced expiration were compared using correlation analysis, and the power of end-expiratory cross-sectional area to predict excessive forced-expiratory tracheal collapse was computed following construction of receiver operating characteristic (ROC) curves. RESULTS: Mean percentage expiratory collapse among COPD patients was 17 ± 18% at end-expiration compared to 62 ± 16% during forced expiration. Over the observed range of end-expiratory tracheal collapse (approximately 10-50%), the positive predictive value of end-expiratory collapse to predict excessive (≥80%) forced expiratory tracheal collapse was <0.3. CONCLUSION: COPD patients demonstrate a wide range of end-expiratory tracheal collapse. The magnitude of static end-expiratory tracheal collapse does not predict excessive dynamic expiratory tracheal collapse.

Effective pulmonary ventilation with small-volume oscillations at high frequency.

At high oscillation frequencies (4 to 30 hertz), effective alveolar ventilation can be achieved with tidal volumes much smaller than the anatomic dead space. An explanation of this phenomenon is given in terms of the combined effects of diffusion and convection and in terms of data consistent with the hypothesis. Theory and experimental results both show that the significant variable determining the effectiveness of gas exchange is the amplitude of the oscillatory flow rate independent of the individual values of frequency and stroke volume.

Esophageal pressure: research or clinical tool?

Esophageal manometry has traditionally been utilized for respiratory physiology research, but clinicians have recently found numerous applications within the intensive care unit. Esophageal pressure (PEs) is a surrogate for pleural pressures (PPl), and the difference between airway pressure (PAO) and PEs provides a good estimate for the pressure across the lung also known as the transpulmonary pressure (PL). Differentiating the effects of mechanical ventilation and spontaneous breathing on the respiratory system, chest wall, and across the lung allows for improved personalization in clinical decision making. Measuring PL in acute respiratory distress syndrome (ARDS) may help set positive end expiratory pressure (PEEP) to prevent derecruitment and atelectrauma, while assuring peak pressures do not cause over distension during tidal breathing and recruitment maneuvers. Monitoring PEs allows improved insight into patient-ventilator interactions and may help in decisions to adjust sedation and paralytics to correct dyssynchrony. Intrinsic PEEP (auto-PEEP) may be monitored using esophageal manometry, which may also improve patient comfort and synchrony with the ventilator. Finally, during weaning, PEs may be used to better predict weaning success and allow for rapid intervention during failure. Improved consistency in definition and terminology and further outcomes research is needed to encourage more widespread adoption; however, with clear clinical benefit and increased ease of use, it appears time to reintroduce basic physiology into personalized ventilator management in the intensive care unit.

Effects of frequency, tidal volume, and lung volume on CO2 elimination in dogs by high frequency (2-30 Hz), low tidal volume ventilation.

Recent studies have shown that effective pulmonary ventilation is possible with tidal volumes (VT) less than the anatomic dead-space if the oscillatory frequency (f) is sufficiently large. We systematically studied the effect on pulmonary CO2 elimination (VCO2) of varying f (2-30 Hz) and VT (1-7 ml/kg) as well as lung volume (VL) in 13 anesthetized, paralyzed dogs in order to examine the contribution of those variables that are thought to be important in determining gas exchange by high frequency ventilation. All experiments were performed when the alveolar PCO2 was 40 +/- 1.5 mm Hg. In all studies, VCO2 increased monotonically with f at constant VT. We quantitated the effects of f and VT on VCO2 by using the dimensionless equation VCO2/VOSC = a(VT/VTo)b(f/fo)c where: VOSC = f X VT, VTo = mean VT, fo = mean f and a, b, c, are constants obtained by multiple regression. The mean values of a, b, and c for all dogs were 2.12 X 10(-3), 0.49, and 0.08, respectively. The most important variable in determining VCO2 was VOSC; however, there was considerable variability among dogs in the independent effect of VT and f on VCO2, with a doubling of VT at a constant VOSC causing changes in VCO2 ranging from -13 to +110% (mean = +35%). Increasing VL from functional residual capacity (FRC) to the lung volume at an airway opening minus body surface pressure of 25 cm H2O had no significant effect on VCO2.

Cardiovascular aspects of glossopharyngeal insufflation and exsufflation.

Breath-hold divers use glossopharyngeal breathing to inhale above total lung capacity (glossopharyngeal insufflation, GI) or exhale below residual volume (glossopharyngeal exsufflation, GE). In these maneuvers, air is moved using glossopharyngeal rather than respiratory muscle activity. Four competitive divers performed several GI and GE maneuvers in sitting or standing position, while cardiovascular parameters were measured with a photoplethysmographic method; echocardiography was also performed during GE. During GI, the divers showed a 48% drop in mean arterial pressure (MAP) to 50 mmHg, with a 88% decrease in pulse pressure (PP), while heart rate (HR) increased by 36% to 103 beats/min and cardiac output (CO) dropped by 79% to 1.3 l/min. The increase in intrathoracic pressure during GI, measured in separate experiments, is probably responsible for these hemodynamic changes, by impeding venous return into the chest. Associated with the drop in MAP during GI were various neurological signs and symptoms, including dizziness, tunnel vision, involuntary twitching of facial muscles and one brief episode of loss of consciousness. During GE, initially MAP and PP increased by 36% and 61%, to 149 and 95 mmHg respectively; later HR decreased by 37% to 45 beats/min and CO dropped by 37% to 4.3 l/min. The early cardiovascular changes of GE may be related to a decrease in intrathoracic pressure, enhancing venous return, as shown by a 6 to 15% increase in end-diastolic diameter; later changes are similar to the responses to apnea at low lung volumes. Because of their hemodynamic effects, these breathing maneuvers should be performed with caution, particularly in the case of GI.

Pneumomediastinum after lung packing.

Lung packing (glossopharyngeal insufflation) consists of forcing air into the lungs, using glossopharyngeal muscle contractions similar to swallowing. Breath-hold divers perform this technique after a maximal inhalation prior to diving, thus increasing initial lung volume. However, as suggested by previous authors, this breathing maneuver could theoretically lead to lung rupture. Here we report a pneumomediastinum found on chest CT scan in a diver during a physiological study, when glossopharyngeal insufflation increased the volume of gas in the lungs by 1,040 ml (over his total lung capacity); at the same time, his transpulmonary pressures increased up to 4.1 kPa. We discuss the possibility that the very high transpulmonary pressures during lung packing caused this pneumomediastinum.

Diaphragmatic excursion after pleural sclerosis.

Chemical sclerosis of the pleural space is used to prevent recurrence of spontaneous pneumothorax. To test whether sclerosis restricts diaphragmatic excursion, we measured diaphragmatic excursion by ultrasonography in subjects with unilateral pleural sclerosis and compared it with diaphragmatic excursions in normal subjects, in subjects with cystic fibrosis (a diffuse bilateral lung disease), and in those who underwent surgical procedures that obliterate the pleural space. In five subjects with unilateral chemical sclerosis, diaphragmatic excursion was significantly less on the sclerosed side than on the contralateral side (10.7 +/- 1.3 vs 17.3 +/- 1.7 mm, mean +/- SEM; p less than .01). Compared with those of normal subjects, the side-to-side differences in excursion were increased by pulmonary disease (p less than .03) and additionally by unilateral sclerosis (p less than .015). There was no significant difference between diaphragmatic excursions on left and right sides of subjects without history of pleural disease. These data suggest that chemical pleural sclerosis causes a measurable reduction in diaphragmatic excursion on the affected side. The physiologic significance of this effect is not known.

Causes of allograft dysfunction after single lung transplantation for emphysema: extrinsic restriction versus intrinsic obstruction. Brigham and Women's Hospital Lung Transplantation Group.

BACKGROUND: A subset of patients with emphysema who have undergone single lung transplantation (SLT) may subsequently present with dyspnea, worsening airways obstruction, hypoxemia, and progressive chronic native lung hyperinflation. The leading cause of late allograft dysfunction is bronchiolitis obliterans syndrome (BOS). However, extrinsic restriction manifests with a similar clinical presentation and is an additional mechanism to consider. We describe the use of the inspiratory lung resistance (RLi) to distinguish a decline in respiratory status due predominantly to either extrinsic restriction or BOS. METHODS: We studied five patients who underwent SLT for emphysema between 1992 and 1995, in whom the diagnoses of BOS and extrinsic restriction were subsequently entertained. Forced expiratory volume in 1 second (FEV1), RLi, static lung compliance, elastic recoil pressure at total lung capacity (TLC), and the slope of the maximum flow static recoil (MFSR) plot were measured. RESULTS: All patients had severe airflow obstruction, with mean FEV1 0.98 +/- 0.24 liter (26 +/- 5% predicted), elevated static lung compliance, reduced elastic recoil pressure at TLC, and reduced slope of the MFSR plot. Three patients had "low" RLi (9.3-12.8 cm H20/L/sec). Obstruction was attributed predominantly to extrinsic restriction. These patients underwent lung volume reduction surgery (LVRS) on the native lung; improvements in pulmonary mechanics were observed at 6 months. In contrast, two patients had markedly elevated RLi (17.3 and 17.4 cm H2O/L/sec). Obstruction was attributed predominantly to intrinsic airway disease from BOS that was subsequently documented at autopsy. CONCLUSIONS: The RLi appears to be a useful adjunct to the clinical history in distinguishing a decline in respiratory status due predominantly to either BOS or extrinsic restriction in patients who have undergone SLT for emphysema. Determination of the mechanism of allograft dysfunction may allow the selection of an appropriate subset of patients who would benefit from LVRS.

Action of human respiratory muscles inferred from finite element analysis of rib cage.

The actions of several human respiratory muscles have been inferred from finite element analysis of the rib cage. The human model is based on anatomic and mechanical measurements in dogs and human cadavers. As in an earlier canine model, the external and internal (interosseous) intercostal muscles were found to cause, respectively, inspiratory and expiratory displacements of the rib cage, in agreement with the two-dimensional geometric analysis of Hamberger. When extended to three dimensions, Hamberger's analysis helps explain why muscles at the side of the rib cage produce changes in the anteroposterior diameter, whereas muscles at the front and back of the rib cage cause changes in the transverse diameter.

Intercostal muscle action inferred from finite-element analysis.

The external and internal intercostal muscles are important respiratory muscles in humans, but their mechanical actions have been controversial. We used finite-element analysis based on anatomic and mechanical measurements in dogs to assess the action of the intercostal and other rib cage muscles in a model of an isolated canine rib cage. When intercostal muscle forces of either the internal or the external layer were applied in a single interspace, they pulled the adjacent ribs together, consistent with published observations in dogs. However, when the forces were applied in all interspaces, the external layer caused an inspiratory motion and the internal layer caused an expiratory motion, consistent with conventional understanding of intercostal muscle actions. Parasternal intercostal, levator costae, and transversus thoracis (triangularis sterni) muscle actions were also simulated. These muscles caused expected movements of the ribs and sternum. We conclude that the actions of intercostal muscles depend on the spatial extent of their activation. Their actions in a single interspace and in multiple interspaces can be observed and explained with three-dimensional finite-element models.

Effects of series compliance on twitches superimposed on voluntary contractions.

The activation of skeletal muscle during voluntary isometric contraction has been assessed by measuring the increase in force caused by a superimposed maximal shock to the motor nerve (the twitch-interpolation technique). When the muscle is held isometric, the increase in force with stimulation (superimposed twitch force) decreases with increasing voluntary force, and a line fit through the data can be extrapolated to maximal voluntary force at the zero twitch force axis. In a previous paper we questioned the applicability of this technique in situations where a high series compliance allows the muscle to shorten during the superimposed twitch. To explore effects of series compliance, we measured force of the adductor pollicis during voluntary isometric contractions with noncompliant and compliant loading devices. With the compliant loading device, superimposed twitch force was systematically less than with the noncompliant device, and the plot of superimposed twitch force vs. voluntary force was often concave upward, preventing easy extrapolation to maximal voluntary force. These findings are consistent with force-velocity characteristics of muscle and suggest that twitch-interpolation data must be interpreted with caution when the muscle is not held isometric during the superimposed twitch.

Lung volume and effectiveness of inspiratory muscles.

We related inspiratory muscle activity to inspiratory pressure generation (Pmus) at different lung volumes in five seated normal subjects. Integrated electromyograms were recorded from diaphragmatic crura (Edi), parasternals (PS), and lateral external intercostals (EI). At 20% increments in the vital capacity (VC) subjects relaxed and then made graded and maximal inspiratory efforts against an occluded airway. At any given level of pressure generation, Edi, PS, and EI increased with increasing lung volume. The Pmus generated at total lung capacity as a fraction of that at a low lung volume (between residual volume and 40% VC) was 0.39 +/- 0.15 (SD) for the diaphragm, 0.20 +/- 0.06 for PS, and 0.22 +/- 0.04 for the lateral EI muscles. Our results indicate a lesser volume dependence of the Pmus-EMG relationship for the diaphragm than for PS and EI muscles. This difference in muscle effectiveness with lung volume may reflect differences in length-tension and/or geometric mechanical advantage between the rib cage muscles and the diaphragm.

Dynamic behavior of excised dog rib cage: dependence on muscle.

To assess the contribution of the rib cage to chest wall elastance and hysteresis, we measured force-displacement behavior of the isolated canine rib cage during sinusoidal forcing of the sternum in the midsagittal plane at low frequencies (0.02-2.0 Hz). Elastance of the rib cage was nearly invariant with frequency of forcing from 0.02 to 1.0 Hz and decreased with increasing amplitude. Hysteresis, the width of the force-displacement loop at middisplacement (zero displacement), was nearly constant with frequency below 1.0 Hz and increased with increasing amplitude of forcing. Removal of muscle reduced elastance and hysteresis of the rib cage substantially. The data suggest that the excised dog rib cage shows dynamic behavior similar to that of the intact human rib cage and chest wall and that respiratory muscle is responsible for a major part of the behavior of the passive chest wall. We also calculated the major and minor stiffnesses in the sagittal plane, which differed by a factor of 3-11, and their directions lay close to the dorsoventral and cephalocaudal axes, respectively. Removal of muscle reduced the stiffnesses but did not change their directions. Thus, although respiratory muscles impede motion in the sagittal plane, they do not alter its pattern.

Measurement of gastric and diaphragmatic height during slow breathing maneuvers.

Changes in height of the gastric air bubble can be inferred, in theory, from the difference between gastric pressures measured with water- and air-filled balloon-catheter systems. We describe an apparatus that satisfactorily measures changes in height of gastric balloons in vitro. During slow breathing maneuvers in standing subjects, the apparatus measured changes in height of the balloons in the stomach that were consistent with expected changes in height of the diaphragmatic dome. In four subjects, balloon movements were nearly always less than movements of the costal margin of the diaphragmatic dome observed by ultrasonography; the average ratio of height changes was 0.73. We conclude that changes in height of the diaphragmatic dome can be measured with this method during slow breathing maneuvers in upright subjects.

Relative strengths of the chest wall muscles.

We hypothesized that during maximal respiratory efforts involving the simultaneous activation of two or more chest wall muscles (or muscle groups), differences in muscle strength require that the activity of the stronger muscle be submaximal to prevent changes in thoracoabdominal configuration. Furthermore we predicted that maximal respiratory pressures are limited by the strength of the weaker muscle involved. To test these hypotheses, we measured the pleural pressure, abdominal pressure (Pab), and transdiaphragmatic pressure (Pdi) generated during maximal inspiratory, open-glottis and closed-glottis expulsive, and combined inspiratory and expulsive maneuvers in four adults. We then determined the activation of the diaphragm and abdominal muscles during selected maximal respiratory maneuvers, using electromyography and phrenic nerve stimulation. In all subjects, the Pdi generated during maximal inspiratory efforts was significantly lower than the Pdi generated during open-glottis expulsive or combined efforts, suggesting that rib cage, not diaphragm, strength limits maximal inspiratory pressure. Similarly, at high lung volumes, the Pab generated during closed-glottis expulsive efforts was significantly greater than that generated during open-glottis efforts, suggesting that the latter pressure is limited by diaphragm, not abdominal muscle, strength. As predicted, diaphragm activation was submaximal during maximal inspiratory efforts, and abdominal muscle activation was submaximal during open-glottis expulsive efforts at midlung volume. Additionally, assisting the inspiratory muscles of the rib cage with negative body-surface pressure significantly increased maximal inspiratory pressure, whereas loading the rib cage muscles with rib cage compression decreased maximal inspiratory pressure. We conclude that activation of the chest wall muscles during static respiratory efforts is determined by the relative strengths and mechanical advantage of the muscles involved.

Rib cage distortion during voluntary and involuntary breathing acts.

We examined chest wall and rib cage configuration in seven normal subjects during a variety of breathing maneuvers. Magnetometers were used to measure lower rib cage anteroposterior, lower rib cage transverse, upper rib cage anteroposterior, and abdomen anteroposterior diameters. Changes of these diameters were recorded during voluntary maneuvers, rebreathing, reading, and "natural" breathing. Relative motion of the rib cage and abdomen was displayed with the rib cage represented by the product of its lower anteroposterior and transverse diameters. During spontaneous breathing the rib cage and chest wall are near their relaxation configuration. During chemically driven ventilation the chest wall and rib cage progressively depart from this configuration. Much greater distortions of the chest wall and rib cage occurred during some voluntary maneuvers. Additionally, esophageal pressure and gastric pressure were measured during voluntary distortion of the rib cage. Substantial changes in lower rib cage shape occurred during voluntary maneuvers when compared with spontaneous breaths at the same transmural pressure. We conclude that the unitary behavior of the rib cage in normal subjects requires muscle coordination.

Dependence of diaphragmatic length on lung volume and thoracoabdominal configuration.

Changes in lung volume can be partitioned into volume displacements of the rib cage and abdomen. Abdominal displacements are often used as estimates of diaphragmatic displacements and changes in lengthening of diaphragmatic muscle. We used X-rays, ultrasound, and linear measurements of thoracic and abdominal diameters to estimate relationships among lung volume, thoracoabdominal configuration and diaphragmatic length, and we found that diaphragmatic length was strongly dependent on rib cage as well as abdominal displacement. In three subjects, the diaphragm shortened 57-85% as much during a breath made without abdominal displacement as during a normal breath in which the abdominal wall moved outward with the rib cage. We conclude that changes in diaphragmatic length can be estimated from surface measurements without radiation and that the length of the diaphragm cannot be estimated from displacements of the abdominal wall alone.

Gravitational and shear-associated pressure gradients in the abdomen.

The abdomen has been variously characterized as a hydrostatic system, in which pressures exhibit a gravitational gradient and pressure fluctuations are spatially uniform, and as a compartment, in which pressure gradients are not simply gravitational and pressure fluctuations differ markedly from place to place. To characterize the pressures acting on the ventral abdominal wall, we used saline-filled catheters and air-filled balloons in anesthetized dogs in various body positions during spontaneous breathing and mechanical ventilation. Pressures were measured in the stomach and at multiple sites next to the abdominal wall. Under most circumstances, measurements next to the abdominal wall exhibited a hydrostatic gravitational gradient of approximately 0.89 cmH2O/cm height and pressure fluctuations were spatially homogeneous. Deviations from this hydrostatic behavior were seen when abdominal pressures were compared with gastric pressures, when measurements were made with a balloon catheter, and when the lower abdomen was constricted with a binder. Analysis of these and previously published data suggests that the abdomen does, at times, behave like a hydraulic system but can deviate from simple hydrostatic behavior to the extent that shape-stable abdominal viscera are deformed.

Influence of posterior cricoarytenoid muscle activity on pressure-flow relationship of the larynx.

We examined the effect of posterior cricoarytenoid (PCA) muscle activity on the pressure-flow (PV) relationship of the larynx in five anesthetized tracheostomized dogs. The PCA activity was recorded using bipolar fine-wire electrodes, expressed as a percentage of the quiet breathing level and altered by mechanical ventilation, changes in lung volume, and chest wall compression. Subglottic pressure was recorded while a constant flow of air was passed through the upper airway. In the absence of PCA activity the PV relationship was alinear and could be described by a power function (P = K0Va, where K0 and a are constants). The slope of the log P-log V plots in the absence of PCA and thyroarytenoid activity was 1.83 +/- 0.02 (SD), whereas with increasing PCA activity it was 1.88 +/- 0.11. An effective hydraulic diameter (DH) was calculated for 20% increments of PCA activity, and in two dogs glottic diameter (Dg) was calculated from glottic area measurements obtained by fiber-optic laryngoscopy. Both DH and Dg increased linearly with increasing PCA activity. Denervation of the cricothyroid muscle had no systematic effect on laryngeal resistance. The results indicate that the PV relationship of the larynx may be described by a power function with a single exponent, the magnitude of which is independent of glottic dilator muscle activity and consistent with orifice flow. However, laryngeal diameter increases linearly with PCA activity in the range studied.

Forced expiratory wheezes are a manifestation of airway flow limitation.

To study the mechanism of generation of respiratory wheezes we examined the relationships between forced expiratory wheezes (FEW) and flow limitation in the lung. Tracheal lung sounds were measured in six healthy subjects during forced expiration through a flow-limiting valve in series with a high-impedance suction pump. Mouth pressure, esophageal pressure, transpulmonary pressure (Ptp), flow (V), and volume were also measured. For any flow rate, V was constant until the subject became flow limited. The onset of flow limitation was documented by a small change in V and a sudden change in Ptp, which was previously found by Olafsson and Hyatt to correspond to the beginning of the flow plateau of the isovolume pressure-flow curve (J. Clin. Invest. 48: 564-573, 1969). FEW started 107 +/- 45 ml (SD) after the onset of flow limitation. Additional 79 +/- 65 ml were exhaled between the onset of FEW to the final sharp drop in V. The frequency spectra of FEW were the same as those of respiratory wheezes found in obstructive airway diseases. Administration of inhaled bronchodilator (isoproterenol) did not eliminate the FEW, nor did it change their relationship to flow limitation. The sequence of events around the onset of FEW, and the tight correlation with the onset of flow limitation correspond well to recent experimental observations on the onset of flutter in collapsible, thick-walled latex tubes.