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.     

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.     

Does inhalation of pentamidine in the supine position increase deposition in the upper part of the lung?

To assess the effect of posture on the distribution of nebulized pentamidine isethionate deposition in the lung, ten patients with AIDS were studied. Two nebulizer systems, System 22 Mizer (MedicAid) and Respirgard II (Marquest) were modified by adding 40 cm of corrugated tubing (volume 150 ml) to allow the patients to be studied in both the sitting and supine posture. Modification of the nebulizers caused a reduction in lung deposition in the sitting position for the System 22 Mizer but increased deposition in the Respirgard II compared with the unmodified apparatus. The ratio of upper to lower zone deposition (corrected for 133Xe distribution) was increased in the supine position for both devices (p less than 0.01). The best upper zone deposition was achieved with the unmodified System 22 Mizer in the sitting position. Respirgard II had the lowest nonpulmonary deposition and the lowest incidence of adverse effects. The supine position was associated with a redistribution of deposition to the upper zones. To attempt to reduce upper zone recurrence of Pneumocystis carinii pneumonia, the supine posture is suggested for less efficient nebulizer devices, ie, the Respirgard II, but for more efficient systems, ie, System 22 Mizer, the sitting position is probably suitable. This postulate needs to be confirmed by a clinical trial.     

Effect of prone position on regional shunt, aeration, and perfusion in experimental acute lung injury

RATIONALE: The prone position is used to improve gas exchange in patients with acute respiratory distress syndrome. However, the regional mechanism by which the prone position improves gas exchange in acutely injured lungs is still incompletely defined. METHODS: We used positron emission tomography imaging of [(13)N]nitrogen to assess the regional distribution of pulmonary shunt, aeration, perfusion, and ventilation in seven surfactant-depleted sheep in supine and prone positions. RESULTS: In the supine position, the dorsal lung regions had a high shunt fraction, high perfusion, and poor aeration. The prone position was associated with an increase in lung gas content and with a more uniform distribution of aeration, as the increase in aeration in dorsal lung regions was not offset by loss of aeration in ventral regions. Consequently, the shunt fraction decreased in dorsal regions in the prone position without a concomitant impairment of gas exchange in ventral regions, thus leading to a significant increase in the fraction of pulmonary perfusion participating in gas exchange. In addition, the vertical distribution of specific alveolar ventilation became more uniform in the prone position. A biphasic relation between regional shunt fraction and gas fraction showed low shunt for values of gas fraction higher than a threshold, and a steep linear increase in shunt for lower values of gas fraction. CONCLUSION: In a surfactant-deficient model of lung injury, the prone position improved gas exchange by restoring aeration and decreasing shunt while preserving perfusion in dorsal lung regions, and by making the distribution of ventilation more uniform.     

Assessment of continuous skeletal muscle blood flow during exercise in humans

The ability to measure regional blood flow from exercising skeletal muscles is of great interest. However, noninvasive techniques such as venous occlusion plethysmography and pulsed Doppler duplex ultrasonography only allow determination of blood flow at rest. The aim of our study was to investigate the influence of position on continuous measured skeletal muscle blood flow response in the upright and supine positions during graded maximal exercise by means of the local (133)Xenon washout technique with portable CdTe(Cl) detectors. Fifteen healthy subjects (8 women and 7 men, mean age 46 +/- 11 years) performed graded maximal bicycle exercise in both supine and upright positions in random order on 2 subsequent days. Blood flow in the musculus tibialis anterior was measured using the local (133)Xenon washout technique. A total of 55-110 MBq of (133)Xenon dissolved in isotonic saline was injected intramuscularly and the gamma emission was registered by light-weight portable CdTe(Cl) detectors. During supine exercise skeletal muscle blood flow increased continuously with increasing work load. However, during upright exercise blood flow increased only at the initial three work loads, then it decreased gradually. Immediately after exercise blood flow returned to preexercise values for both positions. The skeletal muscle blood flow at maximum work load for each subject was 74% (relative flow values) (P < 0.05) higher in the supine compared with the upright position. There was no significant difference in absolute or relative blood flow values at similar time points. Exercise time was longer in the supine (1345 +/- 548 s) compared with the upright position (1148 +/- 453 s) (P < 0.005). The local (133)Xenon washout technique with portable CdTe(Cl) detectors allows continuous determination of skeletal muscle blood flow during graded bicycle exercise in supine and upright positions. Furthermore, blood flow at maximum work load and exercise time was increased in supine compared with upright exercise.     

Impaired left lower lobe ventilation in patients with cardiomegaly. An isotope study of mechanisms.

Reduced left lower lobe ventilation (V) in patients with enlarged hearts has been commonly observed on routine isotope ventilation-perfusion lung scanning, and there is evidence to show that this reduction is dependent on posture. Clinically, it may have a role in posture-dependent dyspnea and postoperative left lower lobe changes in cardiomegaly. Previous studies have shown improvement in left lower lobe V in the prone compared with the supine position. In 11 patients showing this phenomenon in krypton 81m V scanning, a mean relative reduction in V of 53 percent occurred at the left base. No significant change in perfusion or in the signal from preinjected technetium 99m macroaggregated albumin was observed between the two positions. No significant change in ventilatory turnover (measured with intravenous xenon 133) was seen either, suggesting that no air trapping takes place. By combining the data from the intravenous 133Xe (which gives the ratio, V/lung volume) and continuously inhaled 81mKr (which reflects regional V), an index of relative volume between the two sides was derived and shown to be significantly reduced at the left base on moving from the prone to supine positions (a mean reduction of 40 percent; p less than 0.02 by Wilcoxon signed rank test). Thus, the mechanism of postural left lower lobe hypoventilation in cardiomegaly is predominantly a regional loss of alveolar volume.     

Regional differences in gas trapping (airway closure) between apex and base of excised rat lungs

Excised rat lungs were ventilated with air under three conditions: (a) while suspendend by the trachea and surrounded by air, (b) while inverted and surrounded by saline, and (c)_while upright and surrounded by saline. The distribution of transpulmonary pressures over which gas trapping occurred in the lung for each of the three conditions was found by a method previously described by Frazer et al. A distribution having a small standard deviation (SD) indicates more uniform gas trapping in the lung while a larger SD indicates less uniform gas trapping. Results showed that the SD was 0.63 for the inverted lung in saline, 1.10 for the lung in air, and 1.57 for the upright lung in saline.We conclude that gas trapping in lungs inverted in saline occurs more uniformly than gas trapping in lungs in air or upright in saline. The results obtained in saline in the upright and inverted position also imply that as the lung is deflated surrounded by air, gas trapping initially occurs in the base of the lung before it occurs in the apex. Since gas trapping and airway closure are related, there could also be intrinsic dissimilarities in airway closure between the apex and base of excised rat lungs suspended by the trachea in air.     

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.     

Distribution of local repolarization changes produced by efferent vagal stimulation in the canine ventricles

The purpose of this study was to compare the distribution of effects of right and left efferent vagal stimulation on ventricular recovery properties in the in situ heart. To measure these effects in many areas simultaneously, local repolarization changes (local QT intervals) were recorded with bipolar electrodes in nine ventricular sites from 38 anesthetized dogs. In initial experiments, this method was shown to correlate with effective refractory period changes measured in the same test site after QT recording; vagal nerve stimulation prolonged the local QT interval by 1 ms for each 0.82 ms prolongation in effective refractory period (r = 0.87). Simultaneous local QT recordings during vagal nerve stimulation demonstrated uniform prolongation with two exceptions. First, left vagal efferent stimulation prolonged local QT interval in the posterior left ventricular base more than did right vagal stimulation (5.9 +/- 1.0 mean +/- standard error of the mean versus 3.7 +/- 0.9%, p less than 0.05). This probably resulted from an interaction with the left sympathetic nerves because left stellate ganglionectomy or norepinephrine infusion eliminated differences between effects of right and left vagal stimulation. Second, it was also found that vagal stimulation from either side did not prolong local QT interval time in the anterior right ventricle despite attempts to augment vagal effects with bilateral vagal stimulation alone or during isoproterenol or physostigmine administration. These regional differences in ventricular repolarization exhibited in response to efferent vagal nerve stimulation in the dog may provide a basis for understanding how autonomic influences could contribute to the genesis of ventricular arrhythmias.     

Position as a variable for cardiovascular responses during exercise

Twenty-one normal young male subjects underwent resting and exercise (bicycle) radionuclide angiography in the full supine and 70 degrees upright tilt positions in order to examine the effects of position on left ventricular size and performance, hemodynamics, and exercise duration. All subjects also underwent full (90 degrees) upright bicycle ergometry with respiratory gas analysis to establish the level of maximal exercise capacity for each. Body position significantly (p less than 0.05) affected resting and exercise cardiovascular parameters. End-diastolic and endsystolic left ventricular volumes and stroke volume were larger in the supine position, both at rest and during exercise. The cardiac output at rest and during exercise were comparable for the two positions; an increase in resting and exercise heart rate in the 70 degrees tilt position compensated for the reduced stroke volume of this posture. At maximal exercise, the 70 degrees upright position was associated with a greater response in left ventricular ejection fraction, otherwise this parameter was not position related. Exercise capacity, in terms of duration and workload, was significantly higher in the supine (1870 +/- 390 s) and full upright (1830 +/- 250 s) positions than in the 70 degrees tilt position (1730 +/- 260 s). Changes in body position significantly alter parameters of ventricular, cardiovascular, and exercise performance.     

Regional pulmonary function in patients with mitral stenosis in relation to haemodynamic data

Central haemodynamics in 23 patients with mitral stenosis and 7 control subjects were compared with the results of regional lung perfusion studied by (133)Xe, pulmonary scintigraphy with (99)mTc-labelled macro-aggregates of albumin, and regional ventilation by (133)Xe.A close correlation was found between both methods assessing regional pulmonary perfusion, i.e. pulmonary scintigraphy and (133)Xe.The results show that lower lung zones, when compared with upper zones, have both worse perfusion and worse ventilation.The changed distribution of perfusion and the changed distribution of ventilation correlated significantly with central haemodynamics in these patients. The ventilation gradient can be a valuable diagnostic tool for evaluating the severity of mitral stenosis, especially in long and repeated studies, due to its simplicity for the patient.     

Predominantly unilateral asthma studied with 133Xe-radiospirometry.

Regional lung function in the supine position was studied with 133Xe-radiospirometry in 10 asthmatic subjects in remission, before and after inhalation of specific allergens in the right lateral decubitus position. Regional ventilation and regional lung volume showed a significant decrease in the right lung. The decrease in ventilation was most pronounced in the diaphragmatic half of the lung. The regional perfusion of the right lung decreased less than the ventilation. The change in perfusion, however, became greater with time, whereas the decrease in ventilation remained the same as shortly after the provocation. Predominantly regional asthma could thus be provoked in the regions that receive most of the allergen in the right lateral position. The asthma was easily controlled and caused little discomfort.     

The hemodynamic and metabolic basis for decreased aerobic capacity in the supine exercise compared with the upright exercise in coronary artery disease

To elucidate the mechanism of reduced exercise tolerance in the supine position, 14 patients with coronary artery disease were studied by both supine ergometer exercise and upright treadmill exercise. Maximal oxygen consumption in the supine position amounted to 80% of that in the upright position (1110 +/- 453 vs 1387 +/- 470 ml/min; p less than 0.001). Maximal cardiac output was identical in both positions (12.07 +/- 4.44 vs 12.55 +/- 4.49 l/min; ns). Maximal arteriovenous oxygen difference in the supine position amounted to 83% of that in the upright position (9.22 +/- 1.92 vs 11.14 +/- 1.88 vol%; p less than 0.01). Thus, the lower maximal oxygen consumption in the supine position was not caused by the decreased cardiac output but by the impaired augmentation of arteriovenous oxygen difference. Lactate concentration at the same oxygen consumption was higher in the supine position, which means early augmentation of anaerobic metabolism. We concluded that the aerobic capacity in the supine position was significantly lower than that in the upright position in patients with coronary artery disease, and the impaired utilization of transported oxygen was considered to be one of the mechanisms of the decreased aerobic capacity in the supine position.     

Regional esophageal distribution and clearance of refluxed gastric acid

Regional differences in the esophageal distribution and clearance of refluxed gastric acid was studied in seven asymptomatic volunteers and seven patients with reflux esophagitis. Intraluminal pH was recorded for 3 postprandial hours from the distal, middle, and proximal esophagus on two separate occasions (with subjects in upright and supine positions). With the subjects in a supine position, about half of the acid reflux episodes reached the proximal esophagus in patients as well as in controls. This percentage decreased to 25% in patients and 29% in controls when they were upright. In both groups, the pH drops in the distal esophagus were significantly greater than in the proximal esophagus for both the supine and upright positions. In both patients and controls, a 4-5-fold greater acid exposure occurred in the distal esophagus, than in the proximal esophagus. In both patient and control groups, acid exposure time, as well as the number of reflux episodes in the distal esophagus, were significantly greater than that of the proximal esophagus (P less than 0.05). Spontaneous acid clearance time in the distal esophagus was significantly longer than that of the proximal esophagus in both positions (P less than 0.05) for both subject groups. In conclusion, regional differences exist in the exposure of the esophageal mucosa to refluxed gastric acid. These regional differences are more pronounced when subjects are upright than supine. Regional differences also exist in esophageal acid clearance, with clearance taking longer in the distal esophagus than in the proximal esophagus. The net effect of these phenomena is that acid exposure time in the distal esophagus is greater than that in the remainder of the esophagus.     

Influence of body posture on intestinal transit of gas

BACKGROUND: Patients describe that body posture may affect their abdominal bloating, distension, and flatulence, but whether changes in position have objectively demonstrable effects, either beneficial or deleterious, has not been investigated. Aim: To determine the effect of body posture, upright versus supine, on intestinal transit of gas loads. SUBJECTS: Eight healthy subjects without gastrointestinal symptoms. METHODS: In each subject a gas mixture was continuously infused into the jejunum (12 ml/min) for three hours, and gas evacuation, clearance of a non- absorbable gaseous marker, perception, and abdominal girth were measured. Paired studies were randomly performed in each subject on separate days in the upright and supine positions. RESULTS: In the upright position, intestinal gas retention was much smaller than when supine (13 (52) ml v 146 (75) ml retention at 60 minutes, respectively; p<0.05), and clearance of the gas marker was expedited (72 (10)% clearance v 49 (16)% at 60 minutes, respectively; p<0.05). The gas challenge test was well tolerated both in the upright and supine positions without abdominal distension. CONCLUSION: Body posture has a significant influence on intestinal gas propulsion: transit is faster in the upright position than when supine.     

Autonomic modulation of the atrial cycle length by the head up tilt test: non-invasive evaluation in patients with chronic atrial fibrillation

Objective—To determine the effects of upright posture compared with supine position on the dominant atrial cycle length (DACL) in patients with chronic atrial fibrillation.
Design—The power/frequency spectrum of QRST suppressed lead V1 ECG was studied in 14 patients in the supine position and during the head up tilt table test. The DACL changes were compared with changes in heart rate and blood pressure.
Results—Compared with the supine position, the upright position reduced the DACL from 160 to 150 ms (p < 0.01). The DACL was increased after returning to the supine position from the upright position, from 147 to 154 ms (p < 0.01). Heart rate increased from 91 beats/min in the supine position to 106 in the upright position (p < 0.01). There was a decrease in heart rate from 109 beats/min in the upright position to 93 after returning to the supine position (p < 0.01). No significant changes were seen in systolic or diastolic blood pressure. There were indications of an inverse relation between DACL and heart rate when comparing the supine position before and after tilt with the upright position (p < 0.001).
Conclusions—The sympathetic stimulation and vagal withdrawal induced by rising to upright body position are associated with a decrease in DACL during chronic atrial fibrillation. Thus a reflex increase in sympathetic discharge after induction of atrial fibrillation could favour the persistence of the arrhythmia.

Keywords: atrial fibrillation;  autonomic nervous system;  atrial cycle length;  heart rate     

Normal esophageal high‐resolution manometry and impedance values in the supine and sitting positions in the population of Northern China

The aim of this study was to investigate the normal high‐resolution manometry and impedance (HRiM) values in the supine and sitting positions in the population of Northern China, and to investigate the influence of different body positions and bolus consistency on esophageal HRiM findings. In this study, healthy volunteers in the supine position underwent esophageal HRiM examination of 10 swallows of 5 mL normal saline solution and 10 swallows of 5 mL synthetic gel of known viscosity, and in the sitting position of an additional five swallows of a synthetic gel of known viscosity. Total bolus transit time (TBTT), complete bolus transit rate (CBTR), distal contractile integral (DCI), distal esophageal amplitude (DEA), and integrated relaxation pressure (IRP) were measured. Sixty‐two healthy volunteers were examined in the supine position and 45 of these performed additional swallows of the viscous gel in the sitting position. In the supine position, normal values for swallowing the liquid and viscous boli were as follows: TBTT 6.9 ± 0.9 and 8.0 ± 1.2 s (P < 0.001), CBTR 90.3 ± 14.0 and 77.9 ± 20.3% (P < 0.001), DCI 1891.5 ± 1131.9 and 1967.8 ± 1140.1 mmHg.s.cm (P = 0.227), DEA 95.3 ± 35.4 and 98.7 ± 37.5 mmHg (P = 0.148), and IRP 10.4 ± 4.9 and 9.0 ± 4.2 mmHg (P < 0.001), respectively. For swallows of the viscous boli in the sitting position, TBTT, DCI, DEA, and IRP were significantly decreased, while CBTR was unchanged (P = 0.075). Normal HRiM values of the population of Northern China were established. Esophageal transit times of viscous boli were significantly slower, more often incomplete and produced less normal peristalsis in the supine position than swallows of liquid boli. Independent reference values for different manometric systems, body positions, and population need to be established before clinical application.     

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.     

High-frequency oscillatory ventilation may increase airway closure

In five seated, normal subjects, we measured closing volumes using 133Xe boluses inhaled at residual volume. High frequency oscillatory ventilation (HFOV) (15 Hz, 2 cc/kg) was applied during either inspiration to total lung capacity or the subsequent expiration. Closing volume was increased (P less than 0.001) when HFOV was applied during the latter half of expiration, but not when HFOV was applied during inspiration or the first half of expiration. Subsequently, in seven subjects, we measured the regional distributions of 133Xe boluses delivered during open-glottis breath-hold at 14% vital capacity after equilibration with N2O. HFOV was applied during bolus delivery for about 16 sec. These distributions were compared with those achieved by intravenous injections of 133Xe in saline. Regional perfusion (injected isotope) exceeded regional N2O uptake at the lung bases and this was significantly accentuated by HFOV, compatible with increased basal closure. We conclude that in normal subjects at low lung volumes, HFOV may enhance airway closure, though other explanations are possible.     

Regional distribution of ventilation in chronic obstructive lung disease and the effect of salbutamol

Regional distribution of ventilation was assessed in 5 normal volunteers, and 19 patients with symptomatic chronic obstructive lung disease (COAD) using the technique of gated lung ventilation imaging with 127Xe. The results of this technique were compared with the more conventional assessment of regional ventilation by analysis of 127Xe wash-out curves. Both techniques demonstrate loss of the normal gravitational distribution of ventilation in patients with severe COAD which is significantly reduced from normals in upper, middle and lower zones of each lung, being most marked in the lower zones (p less than 0.01). Gated lung imaging also shows a significant reduction of regional ventilation in patients with mild to moderate COAD compared to normals but only in the lower zones (p less than 0.05). Gated lung imaging provides a better quantitative method of assessing regional lung function than wash-out analysis and confirms loss of the normal gravitational distribution of ventilation in patients with obstructive lung disease and relates this to severity of disease. The distribution of ventilation was also assessed in 6 patients with severe COAD before and after placebo or salbutamol. There was a significant improvement of the distribution of ventilation to the lung bases after salbutamol (p less than 0.05).