Airway hysteresis in normal subjects and individuals with chronic airflow obstruction

Specific conductance (sGaw) was measured without prior pharmacological induction of bronchoconstriction before and 5-10 s after a total lung capacity (TLC) volume history in normal subjects and in individuals with chronic airflow obstruction (CAO); increased sGaw after inspiration to TLC was considered evidence of airway hysteresis. Lung elastic recoil [Pst(L)] was also measured before and after inspiration to TLC. In the normal subjects 1) prebronchodilator sGaw increased significantly, whereas Pst(L) decreased significantly after inspiration to TLC; 2) modulators of cyclooxygenase activity had no significant effects on sGaw responses to deep inspiration; and 3) airway hysteresis diminished after inhalation of atropine or metaproterenol. In the CAO group 1) prebronchodilator sGaw and Pst(L) decreased significantly after inspiration to TLC, and 2) bronchoconstriction after deep inspiration diminished after inhalation of atropine or metaproterenol. This study demonstrates that normal airways exhibit hysteresis even without alteration of resting airway tone and that airway hysteresis is impaired in CAO.     

Effects of deep inhalation in asthma: relative airway and parenchymal hysteresis

Asthmatic subjects were screened for the effects or volume history on the degree of induced airway obstruction with methacholine by comparing isovolumic maximal expiratory flows (Vmax) from partial expiratory flow-volume curves (P) begun near functional residual capacity (FRC) followed by maximal expiratory flow-volume (M) maneuvers begun from total lung capacity (TLC). The isovolumic Vmax values from M and P maneuvers defined two groups: one had a high M/P ratio (high group), indicating a large degree of reversal with deep inhalation, another had a low M/P ratio (low group), indicating minimal reversal. No differences were found between groups. A more complete study was later performed in which we measured specific airway conductance (sGaw) and anatomical dead space (VD) as indices of airway size and hysteresis before and after deep inhalation. The area of quasi-static transpulmonary pressure (Ptp) volume (V) curves from FRC to TLC and back to FRC was measured as an index of parenchymal hysteresis. At base line both groups showed a decrease in both sGaw and VD after a deep inhalation (DI). After constriction neither group changed VD after DI, whereas sGaw increased significantly in the high group after DI. This suggests that dilation of airways with DI occurred peripheral to those contributing to VD in the high group. The areas of the Ptp-V curves were equal at base line; yet the increase in areas with constriction in the low group was much greater.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lung inflation does not increase maximal expiratory flow during induced obstruction in the dog

A deep inflation (DI) reverses induced bronchoconstriction in normal human subjects whether assessed by airway resistance before and after a DI or by isovolumic maximal expiratory flows (Vmax) from partial expiratory flow-volume (PEFV) vs. maximum expiratory flow-volume (MEFV) maneuvers. These observations suggest that with induced constriction the hysteresis of airways exceeds that of the parenchyma. In contrast with humans, a previous study of ours on dogs indicated that induced increases in airway resistance were unaffected by DI, suggesting that hysteresis of airways and parenchyma were equal. We hypothesized therefore that in constricted dog lungs, any differences that might arise in isovolumic Vmax between PEFV and MEFV maneuvers would not be due to changes in airway caliber but rather would be wholly determined by isovolumic differences in deflational recoil pressures. Recoil pressures were dynamically measured using six separate alveolar capsules in each of six dogs. At base line there were no significant differences between isovolumic recoil pressures or maximal flows with volume history, suggesting equal degrees of airway and parenchymal hysteresis. After histamine-induced constriction there were also no isovolumic differences in flows, but due to striking nonhomogeneities in dynamic recoil pressure among alveolar capsules, it was not possible to express a single meaningful recoil pressure pertinent to the lungs as a whole. These findings are consistent with the idea that isovolumic comparisons of Vmax serve as a reasonable indicator of changes in the relative degree of airway and parenchymal hysteresis.     

Effect of age on changes in flow rates and airway conductance after a deep breath

The effects of aging on changes in maximal expiratory flow rates and specific airway conductance after a deep breath were evaluated in 64 normal subjects. Flow rates (Vp) on partial expiratory flow-volume curves (PEFV), initiated from 60-70% of the vital capacity (VC), were compared with those (Vc) on maximal flow-volume curves (MEFV), initiated from total lung capacity (TLC), at a lung volume corresponding to 25% of VC on the MEFV curves. Specific airway conductance was measured before (sGaw) and after a deep inspiration (sGawDI). Bronchodilation after inspiration to TLC was inferred by Vp/Vc less than 1 and sGaw/sGawDI less than 1. The mean Vp was less than Vc. However, the ratio Vp/Vc increased significantly with age (r = 0.75, P less than 0.001). Specific conductance also increased after a deep inspiration (sGaw less than sGawDI). The ratio sGaw/sGawDIj increased slightly but significantly with age (r = 0.28, P less than 0.02). Measurement of lung elastic recoil pressures before and after a deep breath in a subgroup of patients (n = 14) suggested that the age-related increase in Vp/Vc was secondary to a decrement in the ability of a deep breath to decrease the upstream airway resistance. These findings suggest that even though changes in airway size after a deep breath as measured by sGaw/sGawDI have minimal age dependence, aging diminishes expiratory flow rates of MEFV curves relative to PEFV curves because of a decrease in the ability of a deep breath to increase the size of the peripheral airways.     

Effect of increased static lung recoil on bronchial dimesions of excised lungs.

We measured bronchial diameters and lengths during static deflation and inflation in eight excised dog lobes before and after static lung recoil (Pst(L)) had been significantly increased by cooling the lobe for 48 h at 4 degrees C and ventilating it for 3 h. In control lobes, bronchial diameters were the same at any volume even though Pst(L) was different during inflation and deflation. These results agree with those of Hughes et al. (J. Appl. Physiol. 32: 25-35, 1972). However, when Pst(L) was increased, diameters at a given volume were significantly increased over control values; diameters at a given pressure were nearly the same as the controls. Therefore, under these conditions, bronchial diameter did not conform to lung volume. The ventilation process appeared to alter the circumferential elastic properties of the bronchi because diameters at all pressures were slightly larger after ventilation. Bronchial length-volume relationships were the same in both control and ventilated lobes. Thus, when Pst(L) was markedly increased, diameter corresponded best to lung recoil and length to lung volume.     

Responsiveness, inflammation, and effects of deep breaths on obstruction in mild asthma

Using cellular and biochemical characteristics of bronchoalveolar lavage (BAL) liquid as an index of inflammation, we examined the relationships between change of airway caliber after a deep inhalation (DI), degree of base-line airway hyperresponsiveness, and peripheral airway inflammation in a group of 16 atopic asymptomatic mild asthmatics and 6 normal subjects. Compared with normal subjects, asthmatics demonstrated 1) significantly higher BAL concentrations of histamine, total protein, the sulfidopeptide leukotrienes (SRS-A), and leukotiene B4; 2) a decrease in specific airway conductance (sGaw) with a DI at base line vs. an increase in normal subjects (before vs. after percent change in sGaw, -10 vs. 12, P less than 0.05); and 3) no significant difference in BAL total cell count or leukocyte differential. Significant correlations were demonstrated between 1) percent of BAL eosinophils vs. degree of airway hyperresponsiveness; 2) base-line level of airway obstruction vs. degree of hyperresponsiveness; 3) effects of a DI vs. BAL concentrations of eosinophils, total protein, and histamine; 4) base-line forced expired volume in 1 s vs. BAL concentrations of total protein and histamine; and 5) BAL concentrations of the various mediators with each other. These data support the notion that 1) the response to a DI in mild, stable asthmatics represents a physiological indicator of peripheral obstruction because of inflammation and 2) this inflammation is associated with increases in several known mediators of airway inflammation and hyperreactivity.     

Mechanism of reduced maximal expiratory flow with aging.

To investigate the determinants of maximal expiratory flow (MEF) with aging, 17 younger (7 men and 10 women, 39 +/- 4 yr, mean +/- SD) and 19 older (11 men and 8 women, 69 +/- 3 yr) subjects with normal pulmonary function were studied. For further comparison, we also studied 10 middle-aged men with normal lung function (54 +/- 6 yr) and 15 middle-aged men (54 +/- 7 yr) with mild chronic airflow limitation (CAL; i.e., forced expiratory volume in 1 s/forced vital capacity = 63 +/- 8%). MEF, static lung elastic recoil pressure (Pst), and the minimal pressure for maximal flow (Pcrit) were determined in a pressure-compensated, volume-displacement body plethysmograph. Values were compared at 60, 70, and 80% of total lung capacity. In the older subjects, decreases in MEF (P < 0.01) and Pcrit (P < 0.05), compared with the younger subjects, were explained mainly by loss of Pst (P < 0.05). In the CAL subjects, MEF and Pcrit were lower (P < 0.05) than in the older subjects, but Pst was similar. Thus decreases in MEF and Pcrit were greater than could be explained by the loss of Pst and appeared to be related to increased upstream resistance. These data indicate that the loss of lung recoil explains the decrease in MEF with aging subjects, but not in the mild CAL patients that we studied.     

The airway response to deep inspirations decreases with COPD severity and is associated with airway distensibility assessed by computed tomography.

In patients with mild chronic obstructive pulmonary disease (COPD), the effect of deep inspirations (DIs) to reverse methacholine-induced bronchoconstriction is largely attenuated. In this study, we tested the hypothesis that the effectiveness of DI is reduced with increasing disease severity and that this is associated with a reduction in the ability of DI to distend the airways. Fifteen subjects [Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I-II: n = 7; GOLD stage III-IV: n = 8] underwent methacholine bronchoprovocation in the absence of DI, followed by DI. The effectiveness of DI was assessed by their ability to improve inspiratory vital capacity and forced expiratory volume in 1 s (FEV(1)). To evaluate airway distensibility, two sets of high-resolution computed tomography scans [at residual volume (RV) and at total lung capacity] were obtained before the challenge. In addition, mean parenchymal density was calculated on the high-resolution computed tomography scans. We found a strong correlation between the response to DI and baseline FEV(1) %predicted (r(2) = 0.70, P < 0.0001) or baseline FEV(1)/forced vital capacity (r(2) = 0.57, P = 0.001). RV %predicted and functional residual capacity %predicted correlated inversely (r(2) = 0.33, P = 0.02 and r(2) = 0.32, P = 0.03, respectively), and parenchymal density at RV correlated directly (r(2) = 0.30, P = 0.03), with the response to DI. Finally, the effect of DI correlated to the change in large airway area from RV to total lung capacity (r(2) = 0.44, P = 0.01). We conclude that loss of the effects of DI is strongly associated with COPD severity and speculate that the reduction in the effectiveness of DI is due to the failure to expand the lungs because of the hyperinflated state and/or the parenchymal damage that prevents distension of the airways with lung inflation.     

Relative hysteresis of the airways and lung parenchyma in normal subjects

We evaluated the mechanical properties of the airways sequentially from the glottis toward the main bronchi in 10 normal subjects. Plots of airway cross-sectional area vs. lung volume, measured during inspiration and expiration, were used to determine the relative magnitude of the airways vs. parenchymal hysteresis. Airway cross-sectional area was measured by means of the acoustic reflection technique. We found that the hysteresis of the proximal part of the trachea was greater than that of the lung parenchyma, whereas the hysteresis of the distal trachea and subcarinal segments of the airways was smaller than that of the lung parenchyma. The transition zone between the proximal and the more distal airway properties occurred 8-26 cm distal to the glottis. This transition zone was reproducible in its location on repeated testing in each subject but varied among subjects. To the extent that relative hysteresis of the airways depends on bronchomotor tone, our findings suggest that the bronchomotor tone is inhomogeneous, being maximal at the proximal part of the trachea and gradually decreasing toward the more distal trachea and subcarinal airway segments.     

Selected contribution: airway caliber in healthy and asthmatic subjects: effects of bronchial challenge and deep inspirations.

In 9 healthy and 14 asthmatic subjects before and after a standard bronchial challenge and a modified [deep inspiration (DI), inhibited] bronchial challenge and after albuterol, we tracked airway caliber by synthesizing a method to measure airway resistance (Raw; i.e., lung resistance at 8 Hz) in real time. We determined the minimum Raw achievable during a DI to total lung capacity and the subsequent dynamics of Raw after exhalation and resumption of tidal breathing. Results showed that even after a bronchial challenge healthy subjects can dilate airways maximally, and the dilation caused by a single DI takes several breaths to return to baseline. In contrast, at baseline, asthmatic subjects cannot maximally dilate their airways, and this worsens considerably postconstriction. Moreover, after a DI, the dilation that does occur in airway caliber in asthmatic subjects constricts back to baseline much faster (often after a single breath). After albuterol, asthmatic subjects could dilate airways much closer to levels of those of healthy subjects. These data suggest that the asthmatic smooth muscle resides in a stiffer biological state compared with the stimulated healthy smooth muscle, and inhibiting a DI in healthy subjects cannot mimic this.     

Heterogeneous airway tone in asthmatic subjects.

We examined the effect of volume history on the dynamic relationship between airways and lung parenchyma (relative hysteresis) in 20 asthmatic subjects. The acoustic reflection technique was employed to evaluate changes in airway cross-sectional areas during a slow continuous expiration from total lung capacity to residual volume and inspiration back to total lung capacity. Lung volume was measured continuously during this quasi-static maneuver. We studied three anatomic airway segments: extra- and intrathoracic tracheal and main bronchial segments. Plots of airway area vs. lung volume were obtained for each segment to assess the relative magnitude and direction of the airway and parenchymal hysteresis. We also performed maximal expiratory flow-volume and partial expiratory flow-volume curves and calculated the ratio of maximal to partial flow rates (M/P) at 30% of the vital capacity. We found that 10 subjects (group I) showed a significant predominance of airway over parenchymal hysteresis (P < 0.005) at the extra- and intrathoracic tracheal and main bronchial segments; these subjects had high M/P ratios [1.53 +/- 0.27 (SD)]. The other 10 subjects (group II) showed similar airway and parenchymal hysteresis for all three segments and significantly lower M/P ratios (1.16 +/- 0.20, P < 0.01). We conclude that the effect of volume history on the relative hysteresis of airway and lung parenchyma and M/P ratio at 30% of vital capacity in nonprovoked asthmatic subjects is variable. We suggest that our findings may result from heterogeneous airway tone in asthmatic subjects.     

Signal Transduction in Smooth Muscle: Selected Contribution: Airway caliber in healthy and asthmatic subjects: effects of bronchial challenge and deep inspirations

In 9 healthy and 14 asthmatic subjects before and after astandard bronchial challenge and a modified [deep inspiration (DI), inhibited] bronchial challenge and after albuterol, we tracked airwaycaliber by synthesizing a method to measure airway resistance (Raw;i.e., lung resistance at 8 Hz) in real time. We determined the minimumRaw achievable during a DI to total lung capacity and the subsequentdynamics of Raw after exhalation and resumption of tidal breathing.Results showed that even after a bronchial challenge healthy subjectscan dilate airways maximally, and the dilation caused by a single DItakes several breaths to return to baseline. In contrast, at baseline,asthmatic subjects cannot maximally dilate their airways, and thisworsens considerably postconstriction. Moreover, after a DI, thedilation that does occur in airway caliber in asthmatic subjectsconstricts back to baseline much faster (often after a single breath).After albuterol, asthmatic subjects could dilate airways much closer tolevels of those of healthy subjects. These data suggest that theasthmatic smooth muscle resides in a stiffer biological state comparedwith the stimulated healthy smooth muscle, and inhibiting a DI inhealthy subjects cannot mimic this.

     

Evolution of intrathoracic airway mechanics during lung growth

Elastic recoil pressure of the lungs (Pst(L)), maximum expiratory flow rates (MEF), critical transmural pressure of the collapsible flow-limiting segment (Ptm'), and S-segment conductance (Gs) have been determined in 40 healthy subjects, 7-18 yr old. Pst(L), measured at different lung volumes (fractional) from the expiratory quasi-static pressure-volume curves, increases progressively with age. MEF's, at different lung volumes, are closely related to total lung capacity (TLC); the ratios MEF/TLC, at all lung volumes, are independent of age. Ptm' is also independence of age and body height, most values lying between 0 and -15 cmH2O; this finding suggests that the locus and the behavior of the collapsible segment do not change during growth. Gs, in absolute value, increases with growth but, when adjusted for lung size, Gs decreases steadily with age and body height. These relations suggest that, from childhood to adolescence, the air spaces grow disproportionately more than the airway system.     

Reassessment of the interruption technique for measuring flow resistance in humans

We have previously produced evidence that, in patients with obstructive lung disease, compliance of extrathoracic airways is responsible for lack of mouth-to-alveolar pressure equilibration during respiratory efforts against a closed airway. The flow interruption method for measuring respiratory resistance (Rint) is potentially faced with the same problems. We reassessed the merits of the interruption technique by rendering the extrathoracic airways more rigid and by using a rapid shutter. We measured airway resistance (Raw) with whole body plethysmography during panting (at 2 Hz) and Rint during quiet breathing. Rint and Raw were expressed as specific airway (sGaw) and interruptive conductance (sGint), respectively. In nine healthy subjects (cheeks supported), sGint (0.140 +/- 0.050 s-1.cmH2O-1) was lower (P less than 0.02) than sGaw (0.182 +/- 0.043 s-1.cmH2O-1). By contrast, in 12 patients with severe obstructive lung disease (forced expiratory volume in 1 s/vital capacity = 41.0 +/- 19.8%), sGint (0.058 +/- 0.012 s-1.cmH2O-1) was higher (P less than 0.05) than sGaw (0.047 +/- 0.007 s-1.cmH2O-1), when the cheeks were supported. When the mouth floor was also supported, average values of sGaw (0.048 +/- 0.008 s-1.cmH2O-1) and sGint (0.049 +/- 0.014 s-1.cmH2O-1) became similar. In conclusion, we confirm previous findings in healthy subjects of higher values of Rint, with respect to Raw, probably because of differences in glottis opening between quiet breathing and panting. In airflow obstruction, supporting both the cheeks and the mouth floor decreased sGint, which became similar to sGaw.     

Bronchoconstrictor and antibronchoconstrictor properties of inhaled prostacyclin in asthma

Prostacyclin (PGI2) is generated in appreciable amounts during allergic reactions in human lung tissue. To define its activity on human airways we have studied the effects of doubling concentrations of inhaled PGI2 and its hydrolysis product 6-oxoprostaglandin F1 alpha (6-oxo-PGF1 alpha) on specific airway conductance (sGaw), maximum expiratory flow at 30% vital capacity (Vmax30), forced expiratory volume in 1 s (FEV1), and static lung volumes in subjects with mild allergic asthma. In a second study the effect of inhaled PGI2 on bronchoconstriction provoked by increasing concentrations of inhaled prostaglandin (PG) D2 and methacholine was observed. Inhalation of PGI2 up to a concentration of 500 micrograms/ml had no significant effect on sGaw but produced a concentration-related decrease in FEV1 and Vmax30 in all subjects. In two of four subjects inhalation of PGI2 also increased residual volume and decreased vital capacity but had no effect on total lung capacity. PGI2, but not 6-oxo-PGF1 alpha, protected against bronchoconstriction provoked by either PGD2 or methacholine whether airway caliber was measured as sGaw, FEV1, or Vmax30. The apparent disparity between the bronchoconstrictor and antibronchoconstrictor effects of PGI2 might be explained by its potent vasodilator effect in causing airway narrowing through mucosal engorgement and reducing the spasmogenic effects of other inhaled mediators by increasing their clearance from the airways.     

Partitioning of pulmonary resistance during constriction in the dog: effects of volume history

We assessed the relative changes in airways and lung tissue with bronchoconstriction, and the changes in each during and following a deep inhalation (DI). We partitioned pulmonary resistance (RL) into airway (Raw) and tissue (Vtis) components using alveolar capsules in 10 anesthetized, paralyzed, and open-chested dogs ventilated sinusoidally with 350-ml breaths at 1 Hz. We made measurements before and during bronchoconstriction induced by vagal stimulation or inhalation of histamine or prostaglandin F2 alpha (PGF2 alpha), each of which decreased dynamic compliance by approximately 40%. With histamine and PGF2 alpha the rise in RL was predominantly due to Vtis. With vagal stimulation there was a relatively greater increase in Raw than Vtis. At higher lung volumes, Vtis increases offset falls in Raw, producing higher RL at these volumes before and during constriction with PGF2 alpha and histamine. During constriction with vagal stimulation, the fall in Raw with inflation overrode the rise in Vtis, resulting in a lower RL at the higher compared with the lower lung volume. The changes seen after a DI in the control and constricted states were due to alterations in tissue properties, both viscous and elastic. However, the relative hysteresis of the airways and parenchyma were equal, since Raw, our index of airway size, was unchanged after a DI.     

Transient mechanical benefits of a deep inflation in the injured mouse lung.

The lasting effects of a recruitment maneuver (RM) in the injured lung are not well characterized. We speculated that the reduction in respiratory elastance (H) after a deep inflation (DI) is transient in nature and should be sustained longer at higher positive end-expiratory pressure (PEEP). Thirteen ventilated mice were given 2 DIs at various levels of PEEP before and after saline lavage. Forced oscillations were used to measure H periodically over 7 min after the DIs. Time constants (tau) were estimated for the post-DI recovery in H. Values for tau before lavage (80-115 s) were reduced after lavage (13-30 s) at all levels of PEEP (P = 0.0001). PEEP did not significantly influence tau before or after lavage. The plateau level and total recovery in H after a DI were significantly influenced by PEEP and lavage (P < 0.0001). Our results suggest that for a DI to be beneficial in the injured mouse lung, it may have to be applied several times a minute.     

Effect of deep inspiration avoidance on ventilation heterogeneity and airway responsiveness in healthy adults

The mechanisms by which deep inspiration (DI) avoidance increases airway responsiveness in healthy subjects are not known. DI avoidance does not alter respiratory mechanics directly; however, computational modeling has predicted that DI avoidance would increase baseline ventilation heterogeneity. The aim was to determine if DI avoidance increased baseline ventilation heterogeneity and whether this correlated with the increase in airway responsiveness. Twelve healthy subjects had ventilation heterogeneity measured by multiple-breath nitrogen washout (MBNW) before and after 20 min of DI avoidance. This was followed by another 20-min period of DI avoidance before the inhalation of a single methacholine dose. The protocol was repeated on a separate day with the addition of five DIs at the end of each of the two periods of DI avoidance. Baseline ventilation heterogeneity in convection-dependent and diffusion-convection-dependent airways was calculated from MBNW. The response to methacholine was measured by the percent fall in forced expiratory volume in 1 s/forced vital capacity (FVC) (airway narrowing) and percent fall in FVC (airway closure). DI avoidance increased baseline diffusion-convection-dependent airways (P = 0.02) but did not affect convection-dependent airways (P = 0.9). DI avoidance increased both airway closure (P = 0.002) and airway narrowing (P = 0.02) during bronchial challenge. The increase in diffusion-convection-dependent airways due to DI avoidance did not correlate with the increase in either airway narrowing (r(s) = 0.14) or airway closure (r(s) = 0.12). These findings suggest that DI avoidance increases diffusion-convection-dependent ventilation heterogeneity that is not associated with the increase in airway responsiveness. We speculate that DI avoidance reduces surfactant release, which increases peripheral ventilation heterogeneity and also predisposes to peripheral airway closure.     

Maintenance of airway caliber in isolated airways by deep inspiration and tidal strains.

Deep inspirations (DIs) are large periodic breathing maneuvers that regulate airway caliber and prevent airway obstruction in vivo. This study characterized the intrinsic response of the intact airway to DI, isolated from parenchymal attachments and other in vivo interactions. Porcine isolated bronchial segments were constricted with carbachol and subjected to transmural pressures of 5-10 cmH2O at 0.25 Hz (tidal breathing) interspersed with single DIs of amplitude 5-20 cmH2O, 5-30 cmH2O, or 5-40 cmH2O (6-s duration) or DI of amplitude 5-30 cmH2O (30-s duration). Tidal breathing was ceased after DI in a subset of airways and in control airways in which no DI was performed. Luminal cross-sectional area was measured using a fiber-optic endoscope. Bronchodilation by DI was amplitude dependent; 5-20 cmH2O DIs produced less dilation than 5-30 cmH2O and 5-40 cmH2O DIs (P=0.003 and 0.012, respectively). Effects of DI duration were not significant (P=0.182). Renarrowing after DI followed a monoexponential decay function to pre-DI airway caliber with time constants between 27.4+/-4.3 and 36.3+/-6.9 s. However, when tidal breathing was ceased after DI, further bronchoconstriction occurred within 30s. This response was identical in both the presence and absence of DI (P=0.919). We conclude that the normal bronchodilatory response to DI occurs as a result of the direct mechanical effects of DI on activated ASM in the airway wall. Further bronchoconstriction occurs by altering the airway wall stress following DI, demonstrating the importance of continual transient strains in maintaining airway caliber.     

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.