Quantification of thoracic volumes by three-dimensional imaging

End-expiratory thoracic cavity volume (Vthx) was measured in eight volunteers lying supine by three-dimensional X-ray computed tomography using the Dynamic Spatial Reconstructor. Untrapped end-expiratory pulmonary gas volume at functional residual capacity (FRC) was determined by nitrogen clearance. Both measurements were done before and after induction of anesthesia-paralysis. After induction of anesthesia-paralysis, Vthx and FRC were consistently and significantly (P less than 0.01) reduced by 0.28 +/- 0.22 (SD) and 0.59 +/- 0.24 liter, respectively. The reduction of FRC was larger than the reduction of Vthx (delta Vthx) in six of the eight subjects, a finding suggesting that intrathoracic fluid (blood) plus trapped gas volume (Vtt) increased. Changes in Vthx were partitioned into volume changes from the thoracic rib cage (delta Vrc) and from shape and/or position changes of the diaphragm (delta Vdi). delta Vrc contributed significantly (0.17 +/- 0.15 liter, P less than 0.02) to delta Vthx, whereas delta Vdi contributed only in four of the eight subjects. We conclude that delta Vrc, delta Vdi, and delta Vtt contribute to the reduction of FRC after induction of anesthesia-paralysis in humans; the relative contribution of them varies among subjects.     

Lung elastic recoil during breathing at increased lung volume.

During dynamic hyperinflation with induced bronchoconstriction, there is a reduction in lung elastic recoil at constant lung volume (R. Pellegrino, O. Wilson, G. Jenouri, and J. R. Rodarte. J. Appl. Physiol. 81: 964-975, 1996). In the present study, lung elastic recoil at control end inspiration was measured in normal subjects in a volume displacement plethysmograph before and after voluntary increases in mean lung volume, which were achieved by one tidal volume increase in functional residual capacity (FRC) with constant tidal volume and by doubling tidal volume with constant FRC. Lung elastic recoil at control end inspiration was significantly decreased by approximately 10% within four breaths of increasing FRC. When tidal volume was doubled, the decrease in computed lung recoil at control end inspiration was not significant. Because voluntary increases of lung volume should not produce airway closure, we conclude that stress relaxation was responsible for the decrease in lung recoil.     

Effects of acute pleural effusion on respiratory system mechanics in dogs

We determined regional (Vr) and overall lung volumes in six head-up anesthetized dogs before and after the stepwise introduction of saline into the right pleural space. Functional residual capacity (FRC), as determined by He dilution, and total lung capacity (TLC) decreased by one-third and chest wall volume increased by two-thirds the saline volume added. Pressure-volume curves showed an apparent increase in lung elastic recoil and a decrease in chest wall elastic recoil with added saline, but the validity of esophageal pressure measurements in these head-up dogs is questionable. Vr was determined from the positions of intraparenchymal markers. Lower lobe TLC and FRC decreased with added saline. The decrease in upper lobe volume was less than that of lower lobe volume at FRC and was minimal at TLC. Saline increased the normal Vr gradient at FRC and created a gradient at TLC. During deflation from TLC to FRC before saline was added, the decrease in lung volume was accompanied by a shape change of the lung, with greatest distortion in the transverse (ribs to mediastinum) direction. After saline additions, deflation was associated with deformation of the lung in the cephalocaudal and transverse directions. The deformation with saline may be a result of upward displacement of the lungs into a smaller cross-sectional area of the thoracic cavity.     

Hyperinflation: control of functional residual lung capacity

Hyperinflation is the consequence of a dysbalance of static forces (determining the relaxation volume) and/or of the dynamic components. The relaxation volume is determined by an equilibrium between the elastic recoil of the lungs and of the chest walls. The dynamic components include the pattern of breathing, upper airway resistance and postinspiratory activity of inspiratory muscles. The respiratory and laryngeal muscles are under control and thus both static and dynamic hyperinflation can be secured. Our knowledge of the mechanism of increased FRC is based on clinical observations and on experiments. The most frequent stimuli leading to a dynamic increase of functional residual lung capacity (FRC) include hypoxia and vagus afferentation. Regulation of FRC is still and undetermined concept. The controlled increase of FRC, hyperinflation, participates in a number of lung diseases.     

Influence of sleep on lung volume in asthmatic patients and normal subjects

To assess the effect of sleep on functional residual capacity (FRC) in normal subjects and asthmatic patients, 10 adult subjects (5 asthmatic patients with nocturnal worsening, 5 normal controls) were monitored overnight in a horizontal volume-displacement body plethysmograph. With the use of a single inspiratory occlusion technique, we determined that when supine and awake, asthmatic patients were hyperinflated relative to normal controls (FRC = 3.46 +/- 0.18 and 2.95 +/- 0.13 liters, respectively; P less than 0.05). During sleep FRC decreased in both groups, but the decrease was significantly greater in asthmatic patients such that during rapid-eye-movement (REM) sleep FRC was equivalent between the asthmatic and normal groups (FRC = 2.46 +/- 0.23 and 2.45 +/- 0.09 liters, respectively). Specific pulmonary conductance decreased progressively and significantly in the asthmatic patients during the night, falling from 0.047 +/- 0.007 to 0.018 +/- 0.002 cmH2O-1.s-1 (P less than 0.01). There was a significant linear relationship through the night between FRC and pulmonary conductance in only two of the five asthmatic patients (r = 0.55 and 0.65, respectively). We conclude that 1) FRC falls during sleep in both normal subjects and asthmatic patients, 2) the hyperinflation observed in awake asthmatic patients is diminished during non-REM sleep and eliminated during REM sleep, and 3) sleep-associated reductions in FRC may contribute to but do not account for all the nocturnal increase in airflow resistance observed in asthmatic patients with nocturnal worsening.     

Decrease in functional residual capacity during inspiratory loading and the sensation of dyspnea.

The purposes of the present study were to determine the changes in functional residual capacity (FRC) during inspiratory loading and to examine their mechanisms. We studied seven normal subjects seated in a body plethysmograph. In both graded inspiratory elastic (35, 48, and 68 cmH2O/l) and resistive (21, 86, and 192 cmH2O.l-1.s) loading, FRC invariably decreased from control FRC and phasic expiratory activity increased. The reduction in FRC was greater with greater loads. A single inspiratory effort against an inspiratory occlusion at three different target mouth pressures (-25, -50, and -75 cmH2O) and durations (1, 2, and 5 s) also resulted in a decrease in FRC with an increase in expiratory electromyogram activity in the following expiration. The decrease in FRC was greater with greater target pressure and duration. This decrease in FRC is qualitatively similar to that during inspiratory loaded breathing, and we suspect that the same mechanisms are at work. Because neither vagal nor chemoreceptor reflex can account for these responses, we suspect conscious awareness of breathing or behavioral control to be responsible. In an additional study, the sensation of discomfort of breathing during elastic loading decreased with a decrease in FRC. These results suggest that the reduced FRC may be due to behavioral control of breathing to reduce the sensation of dyspnea during inspiratory loading.     

Effect of chest strapping on regional lung function.

We studied lung mechanics and regional lung function in five young men during restrictive chest strapping. The effects on lung mechanics were similar to those noted by others in that lung elastic recoil increased as did maximum expiratory flow at low lung volumes. Chest strapping reduced the maximum expiratory flow observed at a given elastic recoil pressure. Breathing helium increased maximum expiratory flow less when subjects were strapped than when they were not. These findings indicated that strapping decreased the caliber of airways upstream from the equal pressure point. Regional lung volumes from apex to base were measured with xenon 133 while subjects were seated. The distribution of regional volumes was measured at RV, and at volumes equal to strapped FRC and strapped TLC; no change due to chest strapping was observed. Similarly, the regional distribution of 133Xe boluses inhaled at RV and strapped TLC was unaffected by chest strapping. Closing capacity decreased with chest strapping. We concluded that airway closure decreased during chest strapping and that airway closure was not the cause of the observed increase in elastic recoil of the lung. The combination of decreased slope of the static pressure-volume curve and unchanged regional volumes suggested that strapping increased the apex-to-base pleural pressure gradient.     

In vivo length-force relationship of canine diaphragm

Diaphragmatic length was measured by sonomicrometry and transdiaphragmatic pressure (Pdi) by conventional latex balloons in eight dogs anesthetized with pentobarbital sodium under passive conditions and during supramaximal phrenic stimulation. The passive length-pressure relationship indicates that the crural part of the diaphragm is more compliant than the costal part. With supramaximal stimulation the costal diaphragm showed a length-pressure relationship similar in shape to in vitro length-tension curves previously described for the canine diaphragm. The crural part has a smaller pressure-length slope than the costal part in the length range from 80% of optimum muscle length (Lo) to Lo. At supine functional residual capacity (FRC) the resting length (LFRC) of the costal and crural diaphragms are not at Lo. The costal part is distended to 105% of Lo, and crural is shortened to 92% of Lo. Tidal shortening will increase the force output of costal while decreasing that of the crural diaphragm. The major forces setting the passive supine LFRC are the abdominal weight (pressure) and the elastic recoil of the lungs. The equilibrium length (resting length of excised diaphragmatic strips) was 79 +/- 3.6% LFRC for the costal diaphragm and 87 +/- 3.9% LFRC for the crural diaphragm. Similar shortening was obtained in the upright position, indicating passive diaphragmatic stretch at supine LFRC.     

Airway constriction measured from tantalum bronchograms in conscious mice in response to methacholine

A single-projection X-ray technique showed an increase in functional residual capacity (FRC) in conscious mice in response to aerosolized methacholine (MCh) with little change in airway resistance (Raw) measured using barometric plethysmography (Lai-Fook SJ, Houtz PK, Lai Y-L. J Appl Physiol 104: 521-533, 2008). The increase in FRC presumably prevented airway constriction by offsetting airway contractility. We sought a more direct measure of airway constriction. Anesthetized Balb/c mice were intubated with a 22-G catheter, and tantalum dust was insufflated into the lungs to produce a well-defined bronchogram. After overnight recovery, the conscious mouse was placed in a sealed box, and bronchograms were taken at maximum and minimum points of the box pressure cycle before (control) and after 1-min exposures to 25, 50, and 100 mg/ml MCh aerosol. After overnight recovery, each mouse was studied under both room and body temperature box air conditions to correct for gas compression effects on the control tidal volume (Vt) and to determine Vt and Raw with MCh. Airway diameter (D), FRC, and Vt were measured from the X-ray images. Compared with control, D decreased by 24%, frequency decreased by 35%, FRC increased by 120%, and Raw doubled, to reach limiting values with 100 mg/ml MCh. Vt was unchanged with MCh. The limiting D occurred near zero airway elastic recoil, where the maximal contractility was relatively small. The conscious mouse adapted to MCh by breathing at a higher lung volume and reduced frequency to reach a limit in constriction.     

Effects of continuous positive airway pressure on upper airway and respiratory muscle activity

To study the effects of continuous positive airway pressure (CPAP) on lung volume, and upper airway and respiratory muscle activity, we quantitated the CPAP-induced changes in diaphragmatic and genioglossal electromyograms, esophageal and transdiaphragmatic pressures (Pes and Pdi), and functional residual capacity (FRC) in six normal awake subjects in the supine position. CPAP resulted in increased FRC, increased peak and rate of rise of diaphragmatic activity (EMGdi and EMGdi/TI), decreased peak genioglossal activity (EMGge), decreased inspiratory time and inspiratory duty cycle (P less than 0.001 for all comparisons). Inspiratory changes in Pes and Pdi, as well as Pes/EMGdi and Pdi/EMGdi also decreased (P less than 0.001 for all comparisons), but mean inspiratory airflow for a given Pes increased (P less than 0.001) on CPAP. The increase in mean inspiratory airflow for a given Pes despite the decrease in upper airway muscle activity suggests that CPAP mechanically splints the upper airway. The changes in EMGge and EMGdi after CPAP application most likely reflect the effects of CPAP and the associated changes in respiratory system mechanics on the afferent input from receptors distributed throughout the intact respiratory system.     

Respiratory mechanics and breathing pattern during and following maximal exercise

We looked for evidence of changes in lung elastic recoil and of inspiratory muscle fatigue at maximal exercise in seven normal subjects. Esophageal pressure, flow, and volume were measured during spontaneous breathing at increasing levels of cycle exercise to maximum. Total lung capacity (TLC) was determined at rest and immediately before exercise termination using a N2-washout technique. Maximal inspiratory pressure and inspiratory capacity were measured at 1-min intervals. The time course of instantaneous dynamic pressure of respiratory muscles (Pmus) was calculated for the spontaneous breaths immediately preceding exercise termination. TLC volume and lung elastic recoil at TLC were the same at the end of exercise as at rest. Maximum static inspiratory pressures at exercise termination were not reduced. However, mean Pmus of spontaneous breaths at end exercise exceeded 15% of maximum inspiratory pressure in five of the subjects. We conclude that lung elastic recoil is unchanged even at maximal exercise and that, while inspiratory muscles operate within a potentially fatiguing range, the high levels of ventilation observed during maximal exercise are not maintained for a sufficient time to result in mechanical fatigue.     

Respiratory load compensation in chronic airway obstruction

To assess respiratory neuromuscular function and load compensating ability in patients with chronic airway obstruction (CAO), we studied eight stable patients with irreversible airway obstruction during hyperoxic CO2 rebreathing with and without a 17 cmH2O X l-1 X s flow-resistive inspiratory load (IRL). Minute ventilation (VE), transdiaphragmatic pressure (Pdi), and diaphragmatic electromyogram (EMGdi) were monitored. Pdi and EMGdi were obtained via a single gastroesophageal catheter with EMGdi being quantitated as the average rate of rise of inspiratory (moving average) activity. Based on the effects of IRL on the Pdi response to CO2 [delta Pdi/delta arterial CO2 tension (PaCO2)] and the change in Pdi for a given change in EMGdi (delta Pdi/delta EMGdi) during rebreathing, two groups could be clearly identified. Four patients (group A) were able to increase delta Pdi/delta PaCO2 and delta Pdi/delta EMGdi, whereas in the other four (group B) the IRL responses decreased. All group B patients were hyperinflated having significantly greater functional residual capacity (FRC) and residual volume than group A. In addition the IRL induced percent change in delta Pdi/delta PaCO2, and delta VE/delta PaCO2 was negatively correlated with lung volume so that in the hyperinflated group B the higher the FRC the greater was the decrease in Pdi response due to IRL. In both groups the greater the FRC the greater was the decrease in the ventilatory response to loading. Patients with CAO, even with severe airways obstruction, can effect load compensation by increasing diaphragmatic force output, but the presence of increased lung volume with the associated shortened diaphragm prevents such load compensation.     

Partial forced expiratory flow-volume curves in young children during ketamine anesthesia

Maximal flows at functional residual capacity (VmaxFRC) from partial forced expiratory flow-volume (PEFV) curves were obtained in 14 normal preschool children (8 boys, 6 girls) of average age 44 mo, under general anesthesia before elective surgery. PEFV curves were generated from end inspiration by rapid compression of the chest wall with an inflatable jacket. VmaxFRC, expressed in milliliter per second, correlated linearly with height, weight, age, and FRC in milliliter and milliliters per kilogram. The best correlation of VmaxFRC (ml/s) was to height to the power of 2.47, which agrees with the results predicted by wave-speed theory. Mean FRC-corrected VmaxFRC was 2.42 +/- 0.50 (SD) FRC's/s with no significant difference between boys (2.35 FRC's/s) and girls (2.51 FRC's/s). There was no correlation between lung-size corrected VmaxFRC and height, weight, or age, but it tended to decrease with increasing FRC. The intersubject variability for VmaxFRC was reduced by normalizing for FRC, and was significantly better than that reported for awake children. This can be attributed to the greater control over volume history and more reliable maximal flow generation during anesthesia. The intrasubject coefficient of variation (CV) for VmaxFRC was 12.2%, and the intersubject CV was 20.0%. The difference may represent the variability due to dysanapsis. It is concluded that dysanapsis is not a prominent factor in children of this age group. In addition, the similarity of the regression equation for VmaxFRC vs. height to that of FRC vs. height supports the concept of equidimensional growth of the airways and lung parenchyma.     

Shape of the chest wall in the prone and supine anesthetized dog

The shape of the passive chest wall of six anesthetized dogs was determined at total lung capacity (TLC) and functional residual capacity (FRC) in the prone and supine body positions by use of volumetric-computed tomographic images. The transverse cross-sectional areas of the rib cage, mediastinum, and diaphragm were calculated every 1.6 mm along the length of the thorax. The changes in the volume and the axial distribution of transverse area of the three chest wall components with lung volume and body position were evaluated. The decrease of the transverse area within the rib cage between TLC and FRC, as a fraction of the area at TLC, was uniform from the apex of the thorax to the base. The volume of the mediastinum increased slightly between TLC and FRC (14% of its TLC volume supine and 20% prone), squeezing the lung between it and the rib cage. In the transverse plane, the heart was positioned in the midthorax and moved little between TLC and FRC. The shape, position, and displacement of the diaphragm were described by contour plots. In both postures, the diaphragm was flatter at FRC than at TLC, because of larger displacements in the dorsal than in the ventral region of the diaphragm. Rotation from the prone to supine body position produced a lever motion of the diaphragm, displacing the dorsal portion of the diaphragm cephalad and the ventral portion caudad. In five of the six dogs, bilateral isovolume pneumothorax was induced in the supine body position while intrathoracic gas volume was held constant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of platelet-activating factor-receptor antagonism on endotoxin-induced lung dysfunction in sheep

To further define the role ofplatelet-activating factor (PAF) in endotoxin-induced lung dysfunction,we examined the effect of ABT-299, a specific and potent PAF-receptorantagonist, on the response to endotoxemia in six chronicallyinstrumented awake sheep. We administered Escherichiacoli endotoxin (0.5 µg/kg) intravenously with orwithout pretreatment with ABT-299 while monitoring mean pulmonaryarterial pressure (Ppa), mean systemic arterial pressure (Psa), dynamiccompliance of the lungs (Cdyn), and functional residual capacity (FRC).Endotoxin administration caused pulmonary hypertension, reduced Cdyn,leukopenia, and hypoxemia while having no significant effect on Psa orFRC. Administration of ABT-299 did not affect any of the measuredvariables at baseline. Pretreatment with ABT-299 attenuated the peakPpa seen after endotoxin administration but had minimal effects onendotoxin-induced changes in Cdyn, white blood cell count, oralveolar-to-arterial oxygen difference. ABT-299 was shown to completelyblock the pulmonary hypertension and reduction in Cdyn seen afterintravenous administration of exogenous PAF. We conclude that PAF doesnot play an essential role in the sheep's response to endotoxin.

     

Regional lung strain in dogs during deflation from total lung capacity

Regional lung distortion during deflation from total lung capacity to functional residual capacity (FRC) in intact supine and prone anesthetized dogs was determined from the displacement of multiple metallic markers embedded in the lung parenchyma. Distortion was expressed as strain (epsilon), which is related to fractional length changes. In the supine position, transverse strain (epsilon yy) was larger than vertical strain (epsilon xx) and cephalocaudal strain (epsilon zz) in the upper lobe. The FRC of the lower lobe was smaller than FRC of the upper lobe and all strains were larger, but epsilon zz increased most and became equal to epsilon yy. In the prone position, epsilon yy was largest in all upper lobes and in three of four lower lobes. Strains and volumes of the upper and lower lobes were similar. The upper and lower lobes rotated slightly around different axes, indicating that interpleural fissures allow additional degrees of freedom for the lungs to conform to the thoracic cavity. In the prone position, there were no consistent gradients of strain or volume. These results indicate that, in determining the regional distribution of FRC in the recumbent dog, in addition to the effect of gravity on the lung, there are important interactions between lung and thoracic cavity shapes.     

Effects of swim training on lung volumes and inspiratory muscle conditioning

Lung volumes and inspiratory muscle (IM) function tests were measured in 16 competitive female swimmers (age 19 +/- 1 yr) before and after 12 wk of swim training. Eight underwent additional IM training; the remaining eight were controls. Vital capacity (VC) increased 0.25 +/- 0.25 liters (P less than 0.01), functional residual capacity (FRC) increased 0.39 +/- 0.29 liters (P less than 0.001), and total lung capacity (TLC) increased 0.35 +/- 0.47 (P less than 0.025) in swimmers, irrespective of IM training. Residual volume (RV) did not change. Maximum inspiratory mouth pressure (PImax) measured at FRC changed -43 +/- 18 cmH2O (P less than 0.005) in swimmers undergoing IM conditioning and -29 +/- 25 (P less than 0.05) in controls. The time that 65% of prestudy PImax could be endured increased in IM trainers (P less than 0.001) and controls (P less than 0.05). All results were compared with similar IM training in normal females (age 21.1 +/- 0.8 yr) in which significant increases in PImax and endurance were observed in IM trainers only with no changes in VC, FRC, or TLC (Clanton et al., Chest 87: 62-66, 1985). We conclude that 1) swim training in mature females increases VC, TLC, and FRC with no effect on RV, and 2) swim training increases IM strength and endurance measured near FRC.     

Regional correlation of emphysematous changes in lung function and structure: a comparison between pulmonary function testing and hyperpolarized MRI metrics

Regional and global relationships of lung function and structure were studied using hyperpolarized 3He MRI in a rat elastase-induced model of emphysema (n = 4) and healthy controls (n = 5). Fractional ventilation (r) and apparent diffusion coefficient (ADC) of 3He were measured at a submillimeter planar resolution in ventral, middle, and dorsal slices 6 mo after model induction. Pulmonary function testing (PFT) was performed before MRI to yield forced expiratory volume in 50 ms (FEV??), airway resistance (R(I)), and dynamic compliance (C(dyn)). Cutoff threshold values of ventilation and diffusion, r* and ADC*, were computed corresponding to 80% population of pixels falling above or below each threshold value, respectively. For correlation analysis, r* was compared with FEV??/functional residual capacity (FRC), R(I) and C(dyn), whereas ADC* was compared with FEV??/FRC, total lung capacity (TLC), and C(dyn). Regional correlation of r and ADC was evaluated by dividing each of the three lung slices into four quadrants. C(dyn) was significantly larger in elastase rats (0.92 ± 0.16 vs. 0.61 ± 0.12 ml/cmH?O). The difference of R(I) and FEV?? was insignificant between the two groups. The r* of healthy rats was significantly larger than the elastase group (0.42 ± 0.03 vs. 0.28 ± 0.06), whereas ADC* was significantly smaller in healthy animals (0.27 ± 0.04 vs. 0.36 ± 0.01 cm2/s). No systematic difference in these quantities was observed between the three lung slices. A significant 33% increase in ADC* and a significant 31% decline in r* for elastase rats was observed compared with a significant 51% increase in C(dyn) and a nonsignificant 26% decline in FEV??/FRC. Correlation of imaging and PFT metrics revealed that r and ADC divide the rats into two separate clusters in the sample space.     

Effect of lung volume on ventilation distribution

To examine the effect of preinspiratory lung volume (PILV) on ventilation distribution, we performed multiple-breath N2 washouts (MBNW) in seven normal subjects breathing 1-liter tidal volumes over a wide range of PILV above closing capacity. We measured the following two independent indexes of ventilation distribution from the MBNW: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency during that portion of the washout where 80-90% of the lung N2 had been cleared. Three of the subjects also performed single-breath N2 washouts (SBNW) by inspiring 1-liter breaths and expiring to residual volume at PILV = functional residual capacity (FRC), FRC + 1.0, and FRC - 0.5, respectively. From the SBNW we measured the phase III slope over the expired volume ranges of 0.75-1.0, 1.0-1.6, and 1.6-2.2 liters (S0.75, S1.0, and S1.6, respectively). Between a PILV of 0.92 +/- 0.09 (SE) liter above FRC and a PILV of 1.17 +/- 0.43 liter below FRC, Snf decreased by 61% (P less than 0.001) and alveolar mixing efficiency increased from 80 to 85% (P = 0.05). In addition, Snf and alveolar mixing efficiency were negatively correlated (r = 0.74). In contrast, over a similar volume range, S1.0 and S1.6 were greater at lower PILV. We conclude that, during tidal breathing in normal subjects, ventilation distribution becomes progressively more inhomogeneous at higher lung volumes over a range of volumes above closing capacity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship of end-expiratory pressure, lung volume, and 99mTc-DTPA clearance

We investigated the dose-response effect of positive end-expiratory pressure (PEEP) and increased lung volume on the pulmonary clearance rate of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). Clearance of lung radioactivity was expressed as percent decrease per minute. Base-line clearance was measured while anesthetized sheep (n = 20) were ventilated with 0 cmH2O end-expiratory pressure. Clearance was remeasured during ventilation at 2.5, 5, 10, 15, or 20 cmH2O PEEP. Further studies showed stepwise increases in functional residual capacity (FRC) (P less than 0.05) measured at 0, 2.5, 5, 10, 15, and 20 cmH2O PEEP. At 2.5 cmH2O PEEP, the clearance rate was not different from that at base line (P less than 0.05), although FRC was increased from base line. Clearance rate increased progressively with increasing PEEP at 5, 10, and 15 cmH2O (P less than 0.05). Between 15 and 20 cmH2O PEEP, clearance rate was again unchanged, despite an increase in FRC. The pulmonary clearance of aerosolized 99mTc-DTPA shows a sigmoidal response to increasing FRC and PEEP, having both threshold and maximal effects. This relationship is most consistent with the hypothesis that alveolar epithelial permeability is increased by lung inflation.