Modeling expiratory flow from excised tracheal tube laws.

Flow limitation during forced exhalation and gas trapping during high-frequency ventilation are affected by upstream viscous losses and by the relationship between transmural pressure (Ptm) and cross-sectional area (A(tr)) of the airways, i.e., tube law (TL). Our objective was to test the validity of a simple lumped-parameter model of expiratory flow limitation, including the measured TL, static pressure recovery, and upstream viscous losses. To accomplish this objective, we assessed the TLs of various excised animal tracheae in controlled conditions of quasi-static (no flow) and steady forced expiratory flow. A(tr) was measured from digitized images of inner tracheal walls delineated by transillumination at an axial location defining the minimal area during forced expiratory flow. Tracheal TLs followed closely the exponential form proposed by Shapiro (A. H. Shapiro. J. Biomech. Eng. 99: 126-147, 1977) for elastic tubes: Ptm = K(p) [(A(tr)/A(tr0))(-n) - 1], where A(tr0) is A(tr) at Ptm = 0 and K(p) is a parametric factor related to the stiffness of the tube wall. Using these TLs, we found that the simple model of expiratory flow limitation described well the experimental data. Independent of upstream resistance, all tracheae with an exponent n < 2 experienced flow limitation, whereas a trachea with n > 2 did not. Upstream viscous losses, as expected, reduced maximal expiratory flow. The TL measured under steady-flow conditions was stiffer than that measured under expiratory no-flow conditions, only if a significant static pressure recovery from the choke point to atmosphere was assumed in the measurement.     

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)     

Acoustic and spirometry parameters of forced expiratory sounds during a five-day dry immersion

The dynamic studies of the parameters of forced expiration under the conditions of a five-day dry immersion involved seven healthy male subjects aged 20 to 25 years. During forced expiration, spirometry tests were performed simultaneously with tracheal sounds being recorded by a microphone. A number of parameters, including the acoustic duration of the forced-expiration tracheal sounds, the lungs’ forced vital capacity, the 1-s forced expiration volume, the peak expiratory flow, and time of achieving the peak expiratory flow, were recorded before dry immersion, on days 1 and 4 of immersion, and the next day after the termination of immersion. There was a significant decrease (by 8.4%) in the peak expiratory flow on day 1 of immersion; however, by day 4 of immersion, the peak expiratory flow increased by 8.9%, reaching its baseline values. The lungs’ forced vital capacity and the forced expiration volume during 1 second, on the average, did not change throughout the experiment. There was a significant increase (by 17%) in the duration of the forced expiration tracheal sounds after the immersion, which suggests an increase in respiratory resistance and needs further studies. A moderate negative correlation between the duration of the forced expiration tracheal sounds and Gensler’s index (r = ?0.63) was found, whereas the correlation with other spirometry parameters was weak or absent.     

Changes in regional emptying sequence need not change maximum expiratory flow

Nine normal young men inhaled boluses of He at the onset of slow vital capacity (VC) inspirations. During the subsequent VC expirations, we measured expired flow, volume, and He concentrations. Expirations consisted of full or partial maximum expiratory flow-volume (MEFV) maneuvers. Full maneuvers were forced expirations from total lung capacity (TLC). Partial maneuvers were accomplished by expiring slowly from TLC to 70, 60, 50, and 40% VC and then initiating forced expiration. Expired He concentrations from full and partial maneuvers were compared with each other and with those resulting from slow expirations. At comparable volumes less than 50% VC, flow during partial and full MEFV maneuvers did not differ. Expired He concentrations were higher during partial maneuvers than during full ones; at the onset of partial maneuvers upper zone emptying predominated, whereas this was not the case at the same lung volumes during maneuvers initiated at TLC. We observed substantial differences in regional emptying sequence that did not influence maximum expiratory flow.     

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.     

Model of forced expiratory flows and airway geometry in infants.

Early measurements of autopsied lungs from infants, children, and adults suggested that the ratio of peripheral to central airway resistance was higher in infants than older children and adults. Recent measurements of forced expiration suggest that infants have high flows relative to lung volume. We employed a computational model of forced expiratory flow along with physiological and anatomic data to evaluate whether the infant lung is a uniformly scaled-down version of the adult lung. First, we uniformly scaled an existing computational model of adult forced expiration to estimate forced expiratory flows (FEF) and density dependence for an 18-mo-old infant. The values obtained for FEF and density dependence were significantly lower than those reported for healthy 18-mo-old infants. Next, we modified the model for the infant lung to reproduce standard indexes of expiratory flow [forced expiratory volume in 0.5 s (FEV(0.5)), FEFs after exhalation of 50 and 75% forced vital capacity, FEF between 25 and 75% expired volume] for this age group. The airway sizes obtained for the infant lung model that produced accurate physiological measurements were similar to anatomic data available for this age and larger than those in the scaled model. Our findings indicate that the airways in the infant lung model differ from those in the scaled model, i.e., middle and peripheral airway sizes are larger than result from uniform downscaling of the adult lung model. We show that the infant lung model can be made to reproduce individual flow-volume curves by adjusting lumen area generation by generation.     

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.     

Maximum airflow through the nose in humans

Inspiratory and expiratory flow via the nose and via the mouth during maximum-effort vital capacity (VC) maneuvers have been compared in 10 healthy subjects. Under baseline conditions maximum flow via the nose was lower than that via the mouth in the upper 50-60% of the VC on expiration and throughout the VC on inspiration. The mean ratio of maximum inspiratory to maximum expiratory flow at mid-VC was 1.38 during mouth breathing and 0.62 during nasal breathing. Inspiratory flow limitation with no increase in flow through the nose as driving pressure was increased above a critical value (usually between 12 and 30 cmH2O) was found in all six subjects studied. Stenting the alae nasi in seven subjects increased peak flow via the nose from a mean of 3.49 to 4.32 l/s on inspiration and from 4.83 to 5.61 l/s on expiration. Topical application of an alpha-adrenergic agonist in seven subjects increased mean peak nasal flow on inspiration from 3.25 to 3.89 l/s and on expiration from 5.03 to 7.09 l/s. Further increases in peak flow occurred with subsequent alan stenting. With the combination of stenting and topical mucosal vasoconstriction, nasal peak flow on expiration reached 81% and, on inspiration, 79% of corresponding peak flows via the mouth. The results demonstrate that narrowing of the alar vestibule and the state of the mucosal vasculature both influence maximum flow through the nose; under optimal conditions, nasal flow capacity is close to that via the mouth.     

Measuring peak expiratory flow in general practice: comparison of mini Wright peak flow meter and turbine spirometer.

OBJECTIVE--To compare measurements of the peak expiratory flow rate taken by the mini Wright peak flow meter and the turbine spirometer. DESIGN--Pragmatic study with randomised order of use of recording instruments. Phase 1 compared a peak expiratory flow type expiration recorded by the mini Wright peak flow meter with an expiration to forced vital capacity recorded by the turbine spirometer. Phase 2 compared peak expiratory flow type expirations recorded by both meters. Reproducibility was assessed separately. SETTING--Routine surgeries at Aldermoor Health Centre, Southampton. SUBJECTS--212 Patients aged 4 to 78 presenting with asthma or obstructive airways disease. Each patient contributed only once to each phase (105 in phase 1, 107 in phase 2), but some entered both phases on separate occasions. Reproducibility was tested on a further 31 patients. MAIN OUTCOME MEASURE--95% Limits of agreement between measurements on the two meters. RESULTS--208 (98%) Of the readings taken by the mini Wright meter were higher than the corresponding readings taken by the turbine spirometer, but the 95% limits of agreement (mean difference (2 SD] were wide (1 to 173 l/min). Differences due to errors in reproducibility were not sufficient to predict this level of disagreement. Analysis by age, sex, order of use, and the type of expiration did not detect any significant differences. CONCLUSIONS--The two methods of measuring peak expiratory flow rate were not comparable. The mini Wright meter is likely to remain the preferred instrument in general practice.     

Lung hyperinflation in isolated dog lungs during high-frequency oscillation

To study the phenomenon of lung hyperinflation (LHI), i.e., an increase in lung volume without a concomitant rise in airway pressure, we measured lung volume changes in isolated dog lungs during high-frequency oscillation (HFO) with air, He, and SF6 and with mean tracheal pressure controlled at 2.5, 5.0, and 7.5 cmH2O. The tidal volume and frequency used were 1.5 ml/kg body wt and 20 Hz, respectively. LHI was observed during HFO in all cases except for a few trials with He. The degree of LHI was inversely related to mean tracheal pressure and varied directly with gas density. Maximum expiratory flow rate (Vmax) was measured during forced expiration induced by a vacuum source (-150 cmH2O) at the trachea. Vmax was consistently higher than the peak oscillatory flow rate (Vosc) during HFO, demonstrating that overall expiratory flow limitation did not cause LHI in isolated dog lungs. Asymmetry of inspiratory and expiratory impedances seems to be one cause of LHI, although other factors are involved.     

Lung mechanics in papain-treated rabbits

To further investigate the effects of airway cartilage softening on static and dynamic lung mechanics, 11 rabbits were treated with 100 mg/kg iv papain, whereas 9 control animals received no pretreatment. Lung mechanics were studied 24 h after papain injection. There was no significant difference in lung volumes, lung pressure-volume curves, or chest wall compliance. Papain-treated rabbits showed increased lung resistance: 91 +/- 63 vs. 39 +/- 22 cmH2O X l-1 X s (mean +/- SD; P less than 0.05), decreased maximal expiratory flows at all lung volumes, and preserved density dependence of maximal expiratory flows. We conclude that increased airway wall compliance is probably the mechanism that limited maximal expiratory flow in this animal model. In addition the increased lung resistance suggests that airway cartilage plays a role in the regulation of airway caliber during quiet tidal breathing.     

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.     

Novel method for measuring effects of gas compression on expiratory flow

During forced vital capacity maneuvers in subjects with expiratory flow limitation, lung volume decreases during expiration both by air flowing out of the lung (i.e., exhaled volume) and by compression of gas within the thorax. As a result, a flow-volume loop generated by using exhaled volume is not representative of the actual flow-volume relationship. We present a novel method to take into account the effects of gas compression on flow and volume in the first second of a forced expiratory maneuver (FEV(1)). In addition to oral and esophageal pressures, we measured flow and volume simultaneously using a volume-displacement plethysmograph and a pneumotachograph in normal subjects and patients with expiratory flow limitation. Expiratory flow vs. plethysmograph volume signals was used to generate a flow-volume loop. Specialized software was developed to estimate FEV(1) corrected for gas compression (NFEV(1)). We measured reproducibility of NFEV(1) in repeated maneuvers within the same session and over a 6-mo interval in patients with chronic obstructive pulmonary disease. Our results demonstrate that NFEV(1) significantly correlated with FEV(1), peak expiratory flow, lung expiratory resistance, and total lung capacity. During intrasession, maneuvers with the highest and lowest FEV(1) showed significant statistical difference in mean FEV(1) (P < 0.005), whereas NFEV(1) from the same maneuvers were not significantly different from each other (P > 0.05). Furthermore, variability of NFEV(1) measurements over 6 mo was <5%. We concluded that our method reliably measures the effect of gas compression on expiratory flow.     

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.     

Exercise flow-volume loops in prepubescent aerobically trained children.

We studied mechanical ventilatory constraints in 13 aerobically trained (Tr) and 11 untrained (UT) prepubescent children by plotting the exercise flow-volume (F-V) loops within the maximal F-V loop (MFVL) measured at rest. The MFVL allowed to determine forced vital capacity (FVC) and maximal expiratory flows. Expiratory and inspiratory reserve volumes relative to FVC (ERV/FVC and IRV/FVC, respectively) were measured during a progressive exercise test until exhaustion. Breathing reserve (BR) and expiratory flow limitation (expFL), expressed in percentage of tidal volume (V(T)) and defined as the part of the tidal breath meeting the boundary of the MFVL, were measured. Higher FVC and maximal expiratory flows were found in Tr than UT (P < 0.05) at rest. Our results have shown that during exercise, excepting one subject, all Tr regulated their V(T) within FVC similarly during exercise, by breathing at low lung volume at the beginning of exercise followed breathing at high lung volume at strenuous exercise. In UT, ERV/FVC and IRV/FVC were regulated during exercise in many ways. The proportion of children who presented an expFL was nearly the same in both groups (approximately 70% with a range of 14 to 65% of V(T)), and no significant difference was found during exercise concerning expFL. However, higher ventilation (V(E)), ERV/FVC, and dyspnea associated with lower BR, IRV/FVC, and SaO2 were reported at peak power in Tr than UT (P < 0.05). These results suggest that, because of their higher Ve level, trained children presented higher ventilatory constraints than untrained. These may influence negatively the SaO2 level and dyspnea during strenuous exercise.     

Posterior cricoarytenoid activity and glottic size during hyperpnea in humans.

We measured the electromyographic activity of the posterior cricoarytenoid (PCA) muscle simultaneously with glottic width (dg) in five normal human subjects during hyperpnea induced by hypoxia (7% CO2 in N2) or hypercapnia (9% CO2 in 50% O2). The glottic aperture was measured during inspiration at the time corresponding to peak inspiratory PCA activity and during expiration at the time corresponding to the minimum tonic activity. During hyperpnea, peak and tonic PCA activity increased simultaneously with widening of the vocal cords in both phases of the respiratory cycle. The PCA activity during both inspiration and expiration showed a single curvilinear relationship with dg of the form dg = A - Be-k.PCA (where A, B, and k are constants) in three of the five subjects. At 50% of maximum PCA activity, dg already reached 95% of its maximum value, which was less than that recorded during a voluntary forced expiratory maneuver. The single curvilinear relationship between PCA activity and dg could be due to the length-tension relationship of the PCA muscle and/or changes in its mechanical coupling, as well as simultaneous agonist and antagonist laryngeal muscle activity during progressive chemical stimulation. Also, further widening of the glottis during forced expiration suggests recruitment of additional muscles, e.g., the arytenoideus.     

Forced expiratory wheezes are a manifestation of airway flow limitation

To study the mechanism of generation of respiratory wheezes we examined the relationships between forced expiratory wheezes (FEW) and flow limitation in the lung. Tracheal lung sounds were measured in six healthy subjects during forced expiration through a flow-limiting valve in series with a high-impedance suction pump. Mouth pressure, esophageal pressure, transpulmonary pressure (Ptp), flow (V), and volume were also measured. For any flow rate, V was constant until the subject became flow limited. The onset of flow limitation was documented by a small change in V and a sudden change in Ptp, which was previously found by Olafsson and Hyatt to correspond to the beginning of the flow plateau of the isovolume pressure-flow curve (J. Clin. Invest. 48: 564-573, 1969). FEW started 107 +/- 45 ml (SD) after the onset of flow limitation. Additional 79 +/- 65 ml were exhaled between the onset of FEW to the final sharp drop in V. The frequency spectra of FEW were the same as those of respiratory wheezes found in obstructive airway diseases. Administration of inhaled bronchodilator (isoproterenol) did not eliminate the FEW, nor did it change their relationship to flow limitation. The sequence of events around the onset of FEW, and the tight correlation with the onset of flow limitation correspond well to recent experimental observations on the onset of flutter in collapsible, thick-walled latex tubes.     

Dynamic characteristics of the external respiratory function in young male residents of the north during the annual cycle

The following aspects were studied during the annual cycle in young men (aged 19.0 ± 0.9 years) living in northern European Russia (62°N): the peak and instantaneous volumetric flow rates (PVFR and IVFR, respectively) at the moments of expiration of 25, 50, and 75% of the forced vital capacity of the lungs (FVC); the average volumetric expiratory flow rate in the process of expiration from 25 to 75% of FVC; the respiratory rate; and the time of attainment of PVFR and FVC. The pulmonary function parameters were determined using an SPM-01-R-D microprocessor spirograph. It was found that only the velocity characteristics of the external respiratory function significantly (the F test) changed in young men during the annual cycle; the time functions were not significantly different. A greater variation in the velocity parameters of the external respiratory function was found during the annual cycle compared to those for the inhabitants of temperate latitudes, which is indicative of adaptive reactions of the external respiratory function and a slightly restricted bronchial patency at the level of mediumand, especially, small-caliber bronchi. The PVFR and IVFR at the moments of expiration of 25, 50, and 75% of FVC and the average volumetric expiratory flow rate in the 25–75% range of the FVC in the male residents of the North are higher during the cold season and lower in the warm season.     

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.     

Ozone exposure decreases the effect of a deep inhalation on forced expiratory flow in normal subjects.

Sixteen healthy nonsmoking subjects (7 women), 21-49 yr old, were exposed in a climate chamber to either clean air or 300 parts/billion ozone on 4 days for 5 h each day. Before each exposure, the subjects had been pretreated with either oxidants (fish oil) or antioxidants (multivitamins). The study design was double-blind crossover with randomized allocation to the exposure regime. Full and partial flow-volume curves were recorded in the morning and before and during a histamine provocation at the end of the day. Nasal cavity volume and inflammatory markers in nasal lavage fluid were also measured. Compared with air, ozone exposure decreased peak expiratory flow, forced expiratory volume in 1 s, and forced vital capacity (FVC), with no significant effect from the pretreatment regimens. Ozone decreased the ratio of maximal to partial flow at 40% FVC by 0.08 +/- 0.03 (mean +/- SE, analysis of variance: P = 0.018) and at 30% FVC by 0.10 +/- 0.05 (P = 0.070). Ozone exposure did not significantly increase bronchial responsiveness, but, after treatment with fish oil, partial flows decreased more than after vitamins during the histamine test, without changing the maximal-to-partial flow ratio. The decreased effect of a deep inhalation after ozone exposure can be explained by changes in airway hysteresis relative to parenchymal hysteresis, due either to ozone-induced airway inflammation or to less deep inspiration after ozone, not significantly influenced by multivitamins or fish oil.