Distribution of inhaled 99mtechnetium labelled ultrafine carbon particle aerosol (Technegas) in human lungs

Using a gamma camera, we quantified the topographical intrapulmonary distribution of inhaled 100 ml boluses of Technegas (TG), an ultrafine dispersion of carbon aggregates labelled with 99mTc, and 133Xenon (Xe) in six seated, normal subjects, inhaling from residual volume (RV) and from within a 1 l volume range above functional residual capacity (FRC) at a flow less than 0.5 l.s-1. Following inspiration of air to total lung capacity (TLC) counts were recorded during a 20 s breathhold. Twenty min after administration of the final TG bolus (TGF) counts were again recorded (TG20). Upper (U), middle (M) and lower (L) zones, as well as central (C) and peripheral (P) regions were identified in each lung. The relative fractional concentration (Fr) of TG and Xe was calculated for all zones after RV and FRC boluses, using counts obtained during Xe equilibration. The U/M or U/L ratios for XeFr did not differ significantly from those for TGFr (paired t-test; p greater than 0.1). The P/C count ratio constitutes a penetration index, which for TG was 1.07 +/- 0.13 (mean +/- SD) that of Xe. After correction for radioactive decay, TG20 counts were no different from TGF counts. The results suggest that the intrapulmonary distribution and penetration of TG in normal lungs is no different from Xe and that stable deposition in the lung periphery makes TG suitable for multiple-view imaging of ventilation distribution.     

Intrapulmonary distribution of 99mtechnetium labelled ultrafine carbon aerosol (Technegas) in severe airflow obstruction

Technegas (TG), an ultrafine dispersion of carbon aggregates labelled with 99mTechnetium (99mTc), has been recently introduced for clinical imaging of lung ventilation. In 12 selected subjects with severe chronic airflow limitation (FEV1 = 0.89 +/- 0.22; mean +/- SD, l) we have studied the regional intrapulmonary distribution of TG and compared it quantitatively with that of 133Xenon (133Xe). A 133Xe equilibration image was acquired for 10-15 s during a breathhold at total lung capacity (TLC). Six subjects (Group 1) inspired 100 ml boli of TG or 133Xe from functional residual capacity (FRC) and another 6 subjects (Group 2) inspired 1.0 l of labelled gas from FRC followed by air to TLC at a constant flow rate less than 0.5 l.s-1. Lung images were then acquired with the chest position rigorously controlled. From the equilibration image, upper, middle, lower, central and peripheral regions were defined. Relative regional fractional concentrations (RFC) were then calculated using the equilibration image to correct for ventilated lung volume. In addition, in four of the Group 2 subjects, each lung image was divided into multiple regions (12-17 per lung). The RFC were then calculated as above (RFCM). The highest and lowest RFC were not significantly different between 133Xe and TG in either Group 1 or Group 2 subjects. Similarly the RFCM analysis showed no systematic difference between 133Xe and TG. The ratio of peripheral to central RFC constitutes a penetration index which for TG was 0.99 +/- 0.23 that of 133Xe. Our results indicate that even in the presence of severe airflow limitation the radiolabelled tracer TG mimics the regional distribution of a real gas.     

Pulmonary function with acute loss of excess lung water by hemodialysis in patients with chronic uremia

We studied lung function in six patients with advanced renal failure who were on a chronic hemodialysis program. With the patients in the seated position, both before and after hemodialysis, we measured lung volumes, maximal mid-expiratory flow rates (MMFR) and alveolar arterial oxygen differences (A-a DO₂). Using xenon 133 (¹³³Xe) we also studied regional lung function and the volume at which “airway closure” began (“closing capacity”). Before dialysis a restrictive pattern was observed, with normal MMFR and reduced lung volumes. With removal of body fluid the residual volume decreased further with a concomitant increase in vital capacity and in MMFR. Before dialysis the majority of patients had an increased residual volume in basal lung regions which decreased after dialysis. In five of six patients the “closing capacities” decreased with dialysis. These results reflected reversible premature airway closure and gas trapping at the lung bases perhaps due to accumulation of edema around small airways.In addition, most of the patients had decreased ventilation and perfusion at the lung bases which improved with dialysis. Little change occurred, however, in the A-a DO₂ with dialysis.     

Regional lung function in chronic pulmonary congestion with and without mitral stenosis.

Relative regional ventilation and perfusion were measured with xenon-133 in 16 seated patients with pure or predominant mitral stenosis (group 1) and in 12 patients with chronic pulmonary congestion due to left-sided heart disease without mitral stenosis (group 2). The apex-base perfusion gradient was abnormally reduced and often reversed in group 1 patients. There was a significant negative correlation between perfusion gradient and mean pulmonary capillary pressure in both groups, but for a given elevation of pulmonary capillary pressure the perfusion gradient tended to be greater (i.e., less abnormal) in group 2. The regression line of perfusion gradient on pulmonary capillary pressure indicated that perfusion gradient had a value of zero (indicating reversal of the perfusion gradient) at a mean pulmonary capillary pressure of 26 mm Hg in group 2 but at only 18 mm Hg in group 1. Relative lower zone ventilation was abnormally reduced in group 1 and there was a significant negative correlation between ventilation gradient and pulmonary capillary pressure in group 1 but not group 2 patients. Comparison of the distribution of slowly inhaled small volume boluses, large volume boluses, and inspiratory capacity breaths of 133Xe suggested that the lower zone hypoventilation was due mainly to closure of peripheral airways but that selectively increased resistance and reduced compliance in the lower zones may contribute in some patients. Both ventilation and perfusion were reduced at the lung bases in group 1 patients, and between regions nonuniformity of relative ventilation/perfusion was significantly less than normal. Although ventilation distribution was relatively normal in group 2 patients, they also had significantly less regional ventilation/perfusion nonuniformity than normal subjects.     

Factors influencing the measurement of closing volume.

The various factors influencing closing volume were studied by performing the single-breath N2 test on 9 healthy nonsmokers. Time of day, day of the week, and preceding volume history had no effect on either closing volume or alveolar plateau. Slow inspiratory flow resulted in larger ratio of closing volume to vital capacity, ratio of closing capacity to total lung capacity, and change in N2 concentration than fast inspiratory flow. Voluntary regulation of the expiratory flow resulted in smaller ratios of closing volume to vital capacity and closing capacity to total lung capacity than when flow was regulated by a resistance. Prolonged breath holding of the inspired O2 led to larger ratio of closing volume to vital capacity and ratio of closing capacity to total lung capacity. To obtain uniform, comparable closing volumes, it is suggested that the subject inspire slowly, control expiratory flow (preferably voluntarily), and not pause between inspiration and expiration.     

Maximal static pressures and lung volumes in young female swimmers

The postulate that lung volumes are increased in swimmers because of a training effect that increases maximal static pressures (Pmax) thus augmenting the ability to inflate and deflate the lung was examined by comparing 38 competitively trained female swimmers to 59 controls between 7 and 13 years of age. Maximal static pressures on inspiration and expiration were generated near residual volume (RV), at functional residual capacity (FRC) and near total lung capacity (TLC). Lung volumes were measured by body plethysmography. The expected increase in lung volumes was present in the swimmers and was most marked in the oldest subjects. However, training did not have the anticipated effect on Pmax. In the younger swimmers training was associated with an increase in Pmax, but in the older swimmers Pmax was actually decreased in comparison to controls. These findings suggest that training may directly enhance lung growth, since the changes in lung volume cannot be accounted for by increases in respiratory muscle strength.     

Influence of lung volume and rib cage configuration on transdiaphragmatic pressure during phrenic nerve stimulation in man

Transdiaphragmatic pressure was recorded during bilateral supramaximal percutaneous phrenic nerve stimulation at 1 Hz (twitch Pdi) to investigate the effect of lung volume and rib cage configuration on diaphragm contractility in man. Stimulations were performed in 5 normal supine subjects at resting end expiration (FRC) and at lung volumes above and below FRC, during relaxation against a closed airway and during isovolume manoeuvres. Twitch Pdi at FRC was 24.4 cm H2O. At lung volumes above FRC, twitch Pdi decreased by 7.04 +/- 3.2 cm H2O per litre of volume change. At lung volumes below FRC, twitch Pdi increased by 12.4 +/- 8.6 cm H2O per litre of volume change. When the diaphragm was lengthened during an isovolume manoeuvre at FRC, twitch Pdi increased. A similar relationship between lung volume and twitch Pdi was obtained during stimulations performed with abdominal binding. These results demonstrate that the pressure developed by the diaphragm during phrenic nerve stimulation is significantly affected both by increases and decreases in lung volume and by the rib cage configuration at which stimulation is performed.     

Limitation of RI imaging in evaluating lung function test--development of new methods

We developed two methods for determining the regional distribution of (1) RV/TLC and air trapping during forced expiration and (2) the ratio or pulmonary blood volume to blood flow. 1) The regional distributions of RV/TLC and air trapping ratio: A.T.R. (air trapping caused by forced expiration) were measured in respiratory disease cases and normal subjects using Xe-133 gas. In normal subjects, RV/TLC gradually decreased from the apex to the base of the lung. A.T.R. was very low in all lung fields. In chronic emphysema (CPE), both RV/TLC and A.T.R. were much higher than the value in normal subjects at the highly diseased areas. In contrast, in case of diffuse panbronchiolitis (DPB), RV/TLC remained within the normal range and A.T.R. was increased considerably in the diseased regions. These results suggest that airway obstruction occurs only during the forced expiration in DPB. 2) The regional distribution of the ratio of pulmonary blood volume to blood flow (tau p) were measured in a normal subject and a case of mitral regurgitation. In both subjects, the distribution of 1/tau p consisted of three zones: upper, middle and lower. The distribution of 1/tau p was constant in the middle zone, but, in the upper and lower zones, it decreased in proportion to the distance from the middle zone. In the case of mitral regurgitation, the middle zone shifted to the apex. Applying the results to the lung perfusion model proposed by West, it was suggested that these phenomena might reflect the increase of the pulmonary venous pressure and the perfusion disorder in the lower lung.     

The effect of airway pressure and oscillation amplitude on ventilation in pre-term infants

We determined the effect of lung recruitment and oscillation amplitude on regional oscillation volume and functional residual capacity (FRC) in high-frequency oscillatory ventilation (HFOV) used in pre-term infants with respiratory distress syndrome (RDS). Changes in lung volume, oscillation volume and carbon dioxide levels were recorded in 10 infants during a stepwise recruitment procedure, and an increase in pressure amplitude of 5 cmH(2)O was measured using electrical impedance tomography and transcutaneous monitoring. The pressures at maximal respiratory system compliance, maximal oscillation volume and minimal carbon dioxide levels were determined. Impedance data were analysed for the chest cross-section and predefined regions of interest. Despite the fixed pressure amplitude, the oscillation volume changed during the incremental pressure steps following a parabolic pattern, with an inverse relationship to the carbon dioxide pressures. The pressures corresponding with maximal compliance, maximal oscillation volume and minimal carbon dioxide were similar and highly correlated. Regional analysis showed similar findings. The increase in pressure amplitude resulted in increased oscillation volumes and decreased carbon dioxide levels, while FRC remained unchanged. In HFV pre-term infants with RDS, oscillation volumes are closely related to the position of ventilation in the pressure-volume envelope and the applied pressure amplitude. Changes in pressure amplitude do not seem to affect FRC.     

Control of the larynx in patients with obstructive and restrictive pulmonary impairment

To study changes in glottic movements associated with pulmonary functional abnormalities, we measured changes in glottic resistance (Rgl) during quiet tidal breathing in normal subjects (N), patients with chronic obstructive pulmonary disease (COPD) and patients with idiopathic pulmonary fibrosis (IPF). Changes in Rgl were measured with a non-invasive method using low frequency sound. Changes in Rgl were tightly coupled to changes in tidal volume and were reproducible in all subjects. Rgl was higher during expiration than during inspiration in N and COPD. COPD showed greater changes in Rgl between inspiration and expiration than did N. However, Rgl did not differ between inspiration and expiration in three of six IPF, and was lower during expiration than during inspiration in two of six IPF. We suggest that glottic movements during quiet tidal breathing change in association with the functional abnormalities of pulmonary diseases.     

Ventilation asymmetry after transplantation for emphysema: role of chest wall and mediastinum

After single-lung transplantation for emphysema, the hyperinflated native lung and the graft have different extents and rates of inflation and emptying. This requires that breathing produces asymmetrical expansion of the chest wall, displacement of the mediastinum, or both. In a first study in four seated transplant recipients, we measured the volumes of the two hemithoraces with optoelectronic plethysmography. Functional residual capacity and total lung capacity were identical on the native and transplanted sides, and changes in chest wall volume during CO(2)-induced hyperpnea and FVC maneuvers were similar on both sides. Studies with computerized tomography in three of these patients and in four additional patients in supine posture indicated that the mediastinum was shifted toward the graft at functional residual capacity and total lung capacity. The mediastinum moved toward the native lung during tidal and full inspiration and toward the graft during tidal and forced expiration; additional studies with fluoroscopy showed qualitatively similar changes in upright posture. In summary, the two hemithoraces assume identical static volumes and show similar volume changes during CO(2)-induced hyperpnea and FVC maneuvers in patients with single-lung transplantation for emphysema; displacement of the mediastinum accommodates part, if not all, of the unequal lung volumes and asymmetrical ventilation.     

Der Nachweis des Verschlusses kleiner Luftwege mit Hilfe einer modifizierten133Xenon-Bolustechnik

A modified bolus technique for the measurement of “closing volume” is described; it involves the use of¹³³Xe as tracer, a pneumotachograph in an open system for control of flow and volume, and a gamma camera for direct registration of the radioactivity over the lung. The results obtained in a group of 11 normal subjects are in good agreement with the predicted values obtained with the original¹³³Xe bolus technique. The disadvantages of the method described are the expensive apparatus and the rather large amounts of radioactivity needed. The advantages are: easy handling of the open system, no dead-space effect compared to methods in which the tracer gas is recorded at the mouth, and regional location of airway closure.     

Influence of lung volume on sympathetic nerve discharge in normal humans

The purpose of this study was to determine the influence of tidal volume, breathing pattern, and beginning lung volume on the modulation of efferent, muscle sympathetic nerve activity (MSNA) in humans. In seven supine, healthy subjects, we measured MSNA (microneurography of the right peroneal nerve) and beat to beat arterial blood pressure during 1) low-frequency breathing (fb = 12 breaths/min) at tidal volumes (VT) of 30% (control), 50%, and 70% of inspiratory capacity and with inspiratory time-to-total breath time ratios (TI/TTOT) of 0.3-0.5 (control), less than 0.3, and greater than 0.5; and 2) simulated exercise hyperpnea (fb = 40 breaths/min; VT = 60-70% inspiratory capacity; minute ventilation, approximately 90 1). To optimize our ability to discern modulatory effects, breathing was performed during three conditions of heightened MSNA: nonhypotensive (less than 20 mm Hg) lower-body negative pressure, isometric handgrip exercise, and posthandgrip vascular occlusion (ischemia). PETCO2 was maintained at normal levels by adjusting the FICO2. Within-breath modulation of MSNA was observed during control tidal breathing with approximately 65% of the burst frequency occurring during the expiratory phase. Deep, low-frequency breathing potentiated this modulatory influence (p less than 0.05 versus control) and produced near-complete sympathoinhibition from onset-mid inspiration to early-mid expiration. Increasing (slow inspiration) and decreasing (fast inspiration) TI/TTOT shifted the onset of sympathoinhibition occurring later (greater change in volume) and earlier (less change in volume) during inspiration, respectively. In two subjects who performed deep breathing from an elevated beginning lung volume, the sympathoinhibition was observed earlier in the inspiratory period and with less change in volume compared with control. These within-breath modulatory effects did not appear to be due solely to changes in arterial pressure. Sustained low- or high ("exerciselike")-frequency deep breathing did not alter total minute MSNA compared with control breathing. These results demonstrate that the depth and pattern of breathing, and possibly the starting lung volume, exert marked influences on the within-breath modulation of MSNA in humans. Our findings also suggest that these modulatory effects may be mediated, at least in part, by pulmonary stretch reflexes.     

The Hering–Breuer deflationary reflex in the newborn infant

Initial observations on healthy term infants using the forced partial expiratory flow-volume technique with an inflatable jacket suggested that this technique was stimulating the Hering-Breuer deflationary reflex,¹ a reflex which has not been systematically studied in man. To investigate this fully, esophageal pressure, jacket pressure, flow and volume at the mouth were recorded during the forced partial expiratory flow-volume maneuver on 10 infants (mean age, 3.1 days; birth weight, 3533 g; gestation, 39.8 weeks). A total of 186 measurements were performed at different points in the respiratory cycle. In 159 (85%) recordings inspiratory effort was evident with a fall in esophageal pressure within 166 msec; in some cases this occurred before the jacket was fully inflated. This was associated with a reduction of 23.4 cm H₂O in mean intrathoracic pressure, which was 2.5 times that occurring during normal tidal breathing. In the remaining 27 measurements a plateau pressure was associated with closure of the upper airway. When the squeeze was applied at low lung volumes (end-expiration) the inspiratory effort occurred significantly earlier (133 msec) and stronger (reducing peak intrathoracic pressure to 15.8 cm H₂O) than when applied at end-inspiration (181 msec with a reduction in intrathoracic pressure to 25.2 cm H₂O). The observed inspiratory response was highly consistent, representing the deflationary reflex as described by Hering and Breuer in 1868.^2,3 The stronger and more rapid onset of inspiration at low lung volume supports the claim made by Breuer that it has a protective role on functional residual capacity (FRC) in young infants. Pediatr Pulmonol. 1994;18:163–169. © 1994 Wiley-Liss, Inc.     

Interactions of regional respiratory mechanics and pulmonary ventilatory impairment in pulmonary emphysema: assessment with dynamic MRI and xenon-133 single-photon emission CT

STUDY OBJECTIVES: Dynamic MRI and (133)Xe single-photon emission CT (SPECT) were used to directly evaluate the interaction of regional respiratory mechanics and lung ventilatory function in pulmonary emphysema. METHODS: Respiratory diaphragmatic and chest wall (D/CW) motions were analyzed by sequential MRI of fast-gradient echo pulse sequences during two to three respiratory cycles in 28 patients with pulmonary emphysema, including 9 patients undergoing lung volume reduction surgery (LVRS). The extent of air trapping in the regional lung was quantified by the (133)Xe retention index (RI) on three-dimensional (133)Xe SPECT displays. RESULTS: By contrast to healthy subjects (n = 6) with regular, synchronous D/CW motions, pulmonary emphysema patients showed reduced, irregular, or asynchronous motions in the hemithorax or location with greater (133)Xe retention, with significant decreases in the maximal amplitude of D/CW motions (MADM and MACWM; p < 0.0001 and p < 0.05, respectively). The removal of (133)Xe retention sites by LVRS effectively and regionally improved D/CW motions in nine patients, with significant increases in MADM and MACWM (p < 0.01 and p < 0.001, respectively). In a total of 40 studies of the 28 patients including post-LVRS studies, normalized MADM and MACWM correlated with percent predicted FEV(1) (r = 0.881, p < 0.0001; and r = 0.906, p < 0.0001, respectively), and also with (133)Xe RI in each hemithorax (r = -0.871, p < 0 0.0001; and r = -0.901, p < 0 0.0001, respectively.) CONCLUSIONS: This direct comparison of regional respiratory mechanics with lung ventilation demonstrated a close interaction between these impairments in pulmonary emphysema. The present techniques provide additional sensitivity for evaluating pathophysiologic compromises in pulmonary emphysema, and may also be useful for selecting resection targets for LVRS and for monitoring the effects.     

Pleural pressure from abdominal to pulmonary rib cage: sweep of the lung border

Pleural pressure was measured by a capsule placed in the superior part of right 8th or 9th intercostal space of dogs in left lateral posture. Transit of lung border was observed through endothoracic fascia at sides of the capsule. During inspiration the capsule membrane faced sequentially: diaphragm, lung border, lung; vice versa during expiration. Pressure on the diaphragm at end expiration was -5.3 +/- 0.5 cm H2O, reflecting outward recoil of the rib cage. At transit of lung border during inspiration (bor. I) a marked negative pressure spike occurred; a smaller spike occurred at expiratory transit (bor. E). These spikes should reflect pleural liquid pressure at lung border. At bor. I lung volume and radial displacement of rib 9 or 10 were greater during active than passive ventilation, whereas at bor. E they were similar under both conditions. Hence, during spontaneous inspiration displacement of lung border lags behind lung and rib expansion. Speed of lung border (assessed from duration of negative spike) ranged from 0.8 to 2.3 cm/sec during spontaneous breathing. On average it was similar at bor. I and bor. E, while air flow was greater at bor. I.     

Regional distribution of a 133Xe labelled gas volume inspired at constant flow rates.

We measured the regional distribution of 480 ml of 133Xe labelled gases inspired from FRC at constant inspiratory flow rates ranging from 0.1 to 6 litres/s. The gases used were air and 20% O2 in helium. At low inspiratory flow rates the gas was preferentially delivered to the dependent region of the lung. At maximal inspiratory flows, all regions of the lung were more evenly ventilated. The rate of redistribution was found to be slower and more even than in previous studies using smaller volumes of inspired gas. Assuming equal and synchronous changes of pleural surface pressure, these results can be reasonably predicted by the mechanical time constant theory applied to a simple two-compartment lung model based on equal regional resistances. Breathing the HeO2 mixture did not significantly change ventilation distribution at any flow rate.     

Gas mixing in the human upper airways

The longitudinal dispersion of gas in the upper airways (oropharynx and larynx) was studied in 5 healthy subjects by measuring the response after injection of a bolus of 133Xe into the inspired airstream. The radioxenon concentration was measured during inspiration and expiration with two counter probes, one in front of the lips and one under the glottis. Assuming that the output tracer concentration follows a Gaussian distribution, the dispersion is expressed by the variance. The dispersion coefficient for the upper airways can then be readily computed with a simple mathematical model. This coefficient is found to be a function of the Peclet number.     

Single-breath, room-air method for measuring closing volume (phase 4) in the normal human lung.

The purpose of this study was to evaluate a new method to measure closing volume (CV). This new method does not require oxygen or inert gases to be inhaled to obtain the onset of phase 4. Because there are regional differences in the concentrations of the resident alveolar gases (O2, CO2, and N2), there should be an abrupt change in the concentration of these gases at the terminal portion of a prolonged expired vital capacity (VC) that marks the onset of phase 4. Nine normal healthy subjects, 30 to 65 years of age, inspired room air from residual volume (to mimic the maneuver of the standard single breath N2 (SBN2) washout test) to total lung capacity. During the expiration (flow constant at 250 ml.s-1) following a 10-s breath hold at total lung capacity, the exhaled gas was analyzed with a mass spectrometer for fractions of O2, CO2, and N2. Although the onset of phase 4 can be shown as the change in concentration of any of the three alveolar resident gases, oxygen was selected because (1) it demonstrates a greater apex to base concentration gradient than that found with CO2 and N2, and (2) a clear identification of the onset of phase 4 (minimum value of O2 fraction). With this method, the mean +/- SEM of CV was 16.8 +/- 1.52 percent (CV x 100/VC). No significant difference was found among the room air method, SBN2 method, and the helium bolus technique.     

Glottic dimensions in healthy men and women

Glottic aperture is important in modulating respiratory system resistance. Male patients with obstructive sleep apnea (OSA) have a smaller glottic cross-sectional area compared to controls. Since OSA has a strong male predominance, we reasoned that glottic dimensions may differ between healthy men and women. Therefore, we utilized the acoustic reflection to measure glottic cross-sectional area in 44 non-smoking, non-obese, healthy subjects, 25 men and 19 women. Glottic area was measured during a continuous slow expiration from total lung capacity (TLC) to residual volume (RV). We compared glottic areas in men and women at three lung volumes: TLC, 50% of vital capacity (VC), and RV. We found that in all but 2 subjects, glottic areas at TLC was greater than at 50% VC or RV. At any given lung volume, there was no significant difference in glottic area between men and women. The reduction in glottic area between TLC and RV was also similar between men and women (36 +/- 24% and 33 +/- 21%, respectively). However, this reduction in glottic area occurred mainly at low lung volumes in women, and more uniformly throughout the vital capacity range in men. We conclude that changes in glottic dimensions are dependent on lung volume, that healthy men and women have similar glottic areas, and that the glottic aperture shows similar variation with lung volume among both sexes.