Mechanism of reduced maximum expiratory flow in dogs with compensatory lung growth

We examined the mechanism of the reduced maximum expiratory flow rates (Vmax) in a dog model of postpneumonectomy compensatory lung growth. During forced expiration, a Pitot-static tube was used to locate the airway site of flow limitation, or choke point, and to measure dynamic intrabronchial pressures. The factors determining Vmax were calculated and the results analyzed in terms of the wave-speed theory of flow limitation. Measurements were made at multiple lung volumes and during ventilation both with air and with HeO2. Five of the puppies had undergone a left pneumonectomy at 10 wk of age, and 5 littermate controls had undergone a sham operation. All dogs were studied at 26 wk of age, at which time compensatory lung growth had occurred in the postpneumonectomy group. Vmax was markedly decreased in the postpneumonectomy group compared with control, averaging 42% of the control flow rates from 58 to 35% of the vital capacity (VC). At 23% of the VC, Vmax was 15% less than control. Choke points were more peripheral in the postpneumonectomy dogs compared with controls at all volumes. The total airway pressure was the same at the choke-point airway in the postpneumonectomy dogs as that in the same airway in the control dogs, suggesting that the airways of the postpneumonectomy dogs displayed different bronchial area-pressure behavior from the control dogs. Despite the decreased Vmax on both air and HeO2, the density dependence of flow was high in the postpneumonectomy dogs and the same as controls at all lung volumes examined.     

Positive effort dependence of maximal expiratory flow

The maximal expiratory-flow volume (MEFV) curve in normal subjects is thought to be relatively effort independent over most of the vital capacity (VC). We studied seven normal males and found positive effort dependence of maximal expiratory flow between 50 and 80% VC in five of them, as demonstrated by standard isovolume pressure-flow (IVPF) curves. We then attempted to distinguish the effects of chest wall conformational changes from possible mechanisms intrinsic to the lungs as an explanation for positive effort dependence. IVPF curves were repeated in four of the subjects who had demonstrated positive effort dependence. Transpulmonary pressure was varied by introducing varied resistances at the mouth but effort, as defined by pleural pressure, was maintained constant. By this method, chest wall conformation at a given volume would be expected to remain the same despite changing transpulmonary pressures. When these four subjects were retested in this way, no increases in flow with increasing transpulmonary pressure were found. In further studies, voluntarily altering the chest wall pattern of emptying (as defined by respiratory inductive plethysmography) did however alter maximal expiratory flows, with transpulmonary pressure maintained constant. We conclude that maximal expiratory flow can increase with effort over a larger portion of the vital capacity than is commonly recognized, and this effort dependence may be the result of changes in central airway mechanical properties that occur in relation to changes in chest wall shape during forced expiration.     

Smooth muscle dynamics and maximal expiratory flow in asthma.

A computational model for maximal expiratory flow in constricted lungs is presented. The model was constructed by combining a previous computational model for maximal expiratory flow in normal lungs and a previous mathematical model for smooth muscle dynamics. Maximal expiratory flow-volume curves were computed for different levels of smooth muscle activation. The computed maximal expiratory flow-volume curves agree with data in the literature on flow in constricted nonasthmatic subjects. In the model, muscle force during expiration depends on the balance between the decrease in force that accompanies muscle shortening and the recovery of force that occurs during the time course of expiration, and the computed increase in residual volume (RV) depends on the magnitude of force recovery. The model was also used to calculate RV for a vital capacity maneuver with a slow rate of expiration, and RV was found to be further increased for this maneuver. We propose that the measurement of RV for a vital capacity maneuver with a slow rate of expiration would provide a more sensitive test of smooth muscle activation than the measurement of maximal expiratory flow.     

Respiratory mechanics and maximal expiratory flow in the anesthetized mouse.

Mice have been widely used in immunologic and other research to study the influence of different diseases on the lungs. However, the respiratory mechanical properties of the mouse are not clear. This study extended the methodology of measuring respiratory mechanics of anesthetized rats and guinea pigs and applied it to the mouse. First, we performed static pressure-volume and maximal expiratory flow-volume curves in 10 anesthetized paralyzed C57BL/6 mice. Second, in 10 mice, we measured dynamic respiratory compliance, forced expiratory volume in 0.1 s, and maximal expiratory flow before and after methacholine challenge. Averaged total lung capacity and functional residual capacity were 1.05 +/- 0.04 and 0.25 +/- 0.01 ml, respectively, in 20 mice weighing 22.2 +/- 0.4 g. The chest wall was very compliant. In terms of vital capacity (VC) per second, maximal expiratory flow values were 13.5, 8.0, and 2.8 VC/s at 75, 50, and 25% VC, respectively. Maximal flow-static pressure curves were relatively linear up to pressure equal to 9 cm H(2)O. In addition, methacholine challenge caused significant decreases in respiratory compliance, forced expiratory volume in 0.1 s, and maximal expiratory flow, indicating marked airway constriction. We conclude that respiratory mechanical parameters of mice (after normalization with body weight) are similar to those of guinea pigs and rats and that forced expiratory maneuver is a useful technique to detect airway constriction in this species.     

Airway dynamics in transition between peak and maximal expiratory flow

Expiratory flow-volume curves with periodic interruption of flow showed flow transients exceeding maximal flow (Vmax) measured on the maximum expiratory flow-volume (MEFV) curve in a mechanical lung model and in five tracheotomized, vagotomized, open-chest, anesthetized dogs. Direct measurement of flow from the collapsing model airway showed that the volume of the flow transients in excess of the MEFV envelope was greater than that from the collapsing airway. Determination of wave-speed flows from local airway transmural pressure-area curves (J. Appl. Physiol. 52: 357-369, 1982) and photography of the airway led to the following conclusions. Flow transients exceeding Vmax are wave-speed flows determined by an initial and unstable configuration of the flow-limiting segment (FLS) with maximum compression in the midportion. The drop in flow from the peak to the following plateau is due to development of a more stable airway configuration with maximum compression at the mouthward end with a smaller area and a smaller maximal flow. When FLS jumps to a more peripheral position, the more distal airways may pass through similar configurational changes that are responsible for the sudden decrease of flow (the "knee") seen on most MEFV curves from dogs.     

Analysis of bronchial mechanics and density dependence of maximal expiratory flow

The computational model for expiratory flow in humans of Lambert and associates (J. Appl. Physiol. Respirat. Environ. Exercise Physiol. 52: 44-56, 1982) was used to investigate the effect of bronchial constrictions in three airway zones on the density dependence of maximal expiratory flow. It was found that constriction of the peripheral airways (less than 2 mm diam) reduced density dependence and increased the volume of isoflow. Constriction of the larger intraparenchymal airways resulted in increased density dependence at low lung volumes and essentially normal values at other volumes. The volume of isoflow was reduced. Extraparenchymal (but intrathoracic) airway constriction caused no change in the volume of isoflow but caused increased density dependence at the higher lung volumes. It was shown that in these model simulations the addition of extraparenchymal constriction to intraparenchymal constriction causes essentially no changes in density dependence. An increased volume of isoflow and significantly decreased density dependence at 50 and 25% vital capacity were produced by simulated constrictions only in the peripheral airways.     

Sensitivity and specificity of the computational model for maximal expiratory flow

The computational model for forced expiratory flow from human lungs of Lambert and associates (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 52: 44-56, 1982) was used to investigate the sensitivity of maximal expiratory flow to lung properties. It was found that maximal flow is very sensitive to recoil pressure and airway areas but not very sensitive to lung volume, airway compliance, and airway length. Linear programming was used to show that a given air flow-pressure curves was compatible with a fairly wide range of airway properties. Additional data for maximal flow with a He-O2 mixture narrowed the range somewhat. It was shown that the flow-pressure curve contains more information about central than peripheral airways and that information about the latter is obtainable only from flows at recoils less than 2 cmH2O. Parameter ranges compatible with individual flow-pressure curves showed differences that demonstrated that such curves give some indication of individual central airway properties.     

Properties of steady maximal expiratory flow within excised canine central airways

Using our transistor model of the lung during forced expiration (J. Appl. Physiol. 62: 2013-2025, 1987), we recently predicted that 1) axially arranged choke points can exist simultaneously during forced expiration with sufficient effort, and 2) overall maximal expiratory flow may be relatively insensitive to nonuniform airways obstruction because of flow interdependence between parallel upstream branches. We tested these hypotheses in excised central airways obtained from five canine lungs. Steady expiratory flow was induced by supplying constant upstream pressure (Pupstream = 0-16 cmH2O) to the bronchi of both lungs while lowering pressure at the tracheal airway opening (16 to -140 cmH2O). Intra-airway pressure profiles obtained during steady maximal expiratory flow disclosed a single choke point in the midtrachea when Pupstream was high (2-16 cmH2O). However, when Pupstream was low (0 cmH2O), two choke sites were evident: the tracheal site persisted, but another upstream choke point (main carina or both main bronchi) was added. Flow interdependence was studied by comparing maximal expiratory flow through each lung before and after introduction of a unilateral external resistance upstream of the bronchi of one lung. When this unilateral resistance was added, ipsilateral flow always fell, but changes in flow through the contralateral lung depended on the site of the most upstream choke. When a single choke existed in the trachea, addition of the external resistance increased contralateral flow by 38 +/- 28% (SD, P less than 0.003). In contrast, when the most upstream choke existed at the main carina or in the bronchi, addition of the external resistance had no effect on contralateral maximal expiratory flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of pulmonary resistance and maximal expiratory flow measurements during exercise in humans.

To evaluate methods used to document changes in airway function during and after exercise, we studied nine subjects with exercise-induced asthma and five subjects without asthma. Airway function was assessed from measurements of pulmonary resistance (RL) and forced expiratory vital capacity maneuvers. In the asthmatic subjects, forced expiratory volume in 1 s (FEV1) fell 24 +/- 14% and RL increased 176 +/- 153% after exercise, whereas normal subjects experienced no change in airway function (RL -3 +/- 8% and FEV1 -4 +/- 5%). During exercise, there was a tendency for FEV1 to increase in the asthmatic subjects but not in the normal subjects. RL, however, showed a slight increase during exercise in both groups. Changes in lung volumes encountered during exercise were small and had no consistent effect on RL. The small increases in RL during exercise could be explained by the nonlinearity of the pressure-flow relationship and the increased tidal breathing flows associated with exercise. In the asthmatic subjects, a deep inspiration (DI) caused a small, significant, transient decrease in RL 15 min after exercise. There was no change in RL in response to DI during exercise in either asthmatic or nonasthmatic subjects. When percent changes in RL and FEV1 during and after exercise were compared, there was close agreement between the two measurements of change in airway function. In the groups of normal and mildly asthmatic subjects, we conclude that changes in lung volume and DIs had no influence on RL during exercise. Increases in tidal breathing flows had only minor influence on measurements of RL during exercise. Furthermore, changes in RL and in FEV1 produce equivalent indexes of the variations in airway function during and after exercise.     

Effects of airway tone and volume history on maximal expiratory flow in asthma

We assessed the difference between isovolumic maximal expiratory flows (Vmax) using maneuvers begun at mid-lung volumes, so-called partial expiratory flow-volume curves (P), vs. those begun at full inflation, so-called maximal expiratory flow-volume curves (M), in 10 asthmatic subjects before and following obstruction induced by isocapnic hyperpnea with cold air and before and after bronchodilation with a beta-agonist or antimuscarinic agent. Volume history effects were quantitated as an M-to-P ratio of Vmax at 30% vital capacity (M/P V30). Although M/P V30 was variable among patients at base line, there was a uniform increase in M/P V30 during constriction and a consistent decrease below base line after dilation. Blunting of induced obstruction with beta-agonists also diminished the increase in M/P V30. Antimuscarinics, despite equivalent bronchodilation, failed to alter the degree of obstruction induced by cold air or the increase in M/P V30 seen during obstruction. The level of airway tone, as indicated by specific resistance, related directly to the M/P V30. We conclude that the response of the asthmatic lung to a deep inhalation is relatively predictable when acute changes in airway tone are produced.     

Density dependence of maximal expiratory flow before and during tracheal constriction in dogs

The effect of carbachol-induced central bronchoconstriction on density dependence of maximal expiratory flow (MEF) was assessed in five dogs. MEFs were measured on air and an 80% He-20% O2 mixture before and after local application of carbachol to the trachea. Airway pressures were measured using a pitot-static probe, from which central airway areas were estimated. At lower concentrations of carbachol the flow-limiting site remained in the trachea over most of the vital capacity (VC), and tracheal area and compliance decreased in all five dogs. In four dogs, decreases in choke point area predominated and produced decreases in flows. In one dog the increase in airway "stiffness" apparently offset the fall in area to account for an increase in MEF. Density dependence measured as the ratio of MEF on HeO2 to MEF on air at 50% of VC increased in all five dogs. Increases in density dependence appeared to be related to increases in airway stiffness at the choke point rather than decreases in gas-related airway pressure differences. Lower concentrations produced a localized decrease in tracheal area and extended the plateau of the flow-volume curve to lower lung volumes. Higher concentrations caused further reductions in tracheal area and greater longitudinal extension of bronchoconstriction, resulting in upstream movement of the site of flow limitation at higher lung volumes. Density dependence increased if the flow-limiting sites remained in the trachea at mid-VC but fell if the flow-limiting site had moved upstream by that volume.     

Influence of expiratory flow on closing capacity at low expiratory flow rates.

Single-breath oxygen (SBO2) tests at expiratory flow rates of 0.2, 0.5, and 1.01/s were performed by 10 normal subjects in a body plethysmograph. Closing capacity (CC)--the absolute lung volume at which phase IV began--increased significantly with increases in flow. Five subjects were restudied with a 200-ml bolus of 100% N2 inspired from residual volume after N2 washout by breathing 100% O2 and similar results were obtained. An additional five subjects performed SBO2 tests in the standing, supine, and prone positions; closing volume (CV)--the lung volume above residual volume at which phase IV began--also increased with increases of expiratory flow. The observed increase in CC with increasing flow did not appear to result from dependent lung regions reaching some critical "closing volume" at a higher overall lung volume. In normal subjects, the phase IV increase in NI concentration may be caused by the asynchronous onset of flow limitation occurring initially in dependent regions.     

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.