Parenchymal Hysteresis Research Articles

Lung hysteresis: a morphological view.

The lung is an imperfect elastic body and for this reason dissipates energy. The energy applied to the lung in inspiration is not recovered in expiration. The property of dissipating energy receives the name of hysteresis. Lung hysteresis can be quantified because it applies to the area between the ascending and descending portions of the pressure-volume curve. Lung hysteresis comprises parenchymal hysteresis and bronchial hysteresis. Each point on the pressure-volume applies to a different morphology of the lung parenchyma. The changes that take place in the lung architecture during expiration are related to alveolar recruitment: in inspiration the lung volume increases by the opening of distal air units. In expiration the lung volume decreases due to derecruitment. The energy is dissipated mainly in the alveolar recruitment process, in which forces of molecular adhesion, such as surface tension, are at work. Bronchial hysteresis involves the dead space and the bronchial wall being greater in expiration.

Effects of endothelin-1 on airway and parenchymal mechanics in guinea-pigs

The contributions of the airways and the parenchyma to the overall lung mechanical response to endothelin-1 (ET-1) have not been systematically studied. In this investigation, the ET-1 induced changes on lung mechanics in guinea-pigs were separated into airway and parenchymal components. Pulmonary impedance (ZL) data were collected between 0.5 and 21 Hz in six anaesthetized, paralysed, open-chest animals by introducing small-amplitude pseudorandom oscillations into the trachea through a wave tube. ZL was calculated before and following intravenous boluses of ET-1, with doses doubled from 0.125-2 microg x kg of body weight(-1). A model containing an airway resistance (Raw) and inertance (Iaw) and tissue damping (G) and elastance (H) was fitted to the ZL spectra in each condition. Parenchymal hysteresis (eta) was calculated as G/H. After each dose, ET-1 induced significant increases in Raw (at peak response mean+/-SEM: 424+/-129%), G (400+/-80%), H (95+/-22%) and eta (156+/-33%), whereas Iaw decreased following the two highest doses (-291+/-77%). These data suggest that the parenchymal constriction was accompanied by inhomogeneous constriction of the peripheral airways.

Effects of endothelin-1 on airway and parenchymal mechanics in guinea-pigs.

The contributions of the airways and the parenchyma to the overall lung mechanical response to endothelin-1 (ET-1) have not been systematically studied. In this investigation, the ET-1 induced changes on lung mechanics in guinea-pigs were separated into airway and parenchymal components. Pulmonary impedance (ZL) data were collected between 0.5 and 21 Hz in six anaesthetized, paralysed, open-chest animals by introducing small-amplitude pseudorandom oscillations into the trachea through a wave tube. ZL was calculated before and following intravenous boluses of ET-1, with doses doubled from 0.125-2 microg x kg of body weight(-1). A model containing an airway resistance (Raw) and inertance (Iaw) and tissue damping (G) and elastance (H) was fitted to the ZL spectra in each condition. Parenchymal hysteresis (eta) was calculated as G/H. After each dose, ET-1 induced significant increases in Raw (at peak response mean+/-SEM: 424+/-129%), G (400+/-80%), H (95+/-22%) and eta (156+/-33%), whereas Iaw decreased following the two highest doses (-291+/-77%). These data suggest that the parenchymal constriction was accompanied by inhomogeneous constriction of the peripheral airways.

Hyperpnea-induced changes in parenchymal lung mechanics in normal subjects and in asthmatics.

The effects of hyperpnea on parenchymal lung mechanics are unknown, but they may contribute to the resultant airflow limitation commonly seen in asthma. To investigate these effects, we measured the following parameters in seven asthmatic and six normal subjects before and after 5 min of hyperpnea: specific conductance, upstream resistance, static compliance, the coefficient of retraction, lung volumes, lung hysteresis, and the ratio of maximal to partial flow rates (the M:P ratio, an indicator of the effect of deep inhalation on airflow, and a measure of relative airway and parenchymal hysteresis). In addition to a central effect on the airways, as shown by significant falls in specific conductance, hyperpnea in asthmatics, but not in normal subjects, resulted in significant increases in residual volume and pressure-volume hysteresis, suggestive of changes in parenchymal lung mechanics. The M:P ratio also increased in the asthmatics, consistent with greater increases in airway than in parenchymal hysteresis after hyperpnea. We conclude that hyperpnea has significant effects on the lung parenchyma that contribute to airflow limitation in asthmatics, and we hypothesize that these effects may be due to alterations in peripheral airway smooth muscle tone and surfactant function.

Peripheral Lung Mechanics May Account for the Rise in the Maximal:Partial Ratio Which Follows Hyperpnea-Induced Bronchospasm

A deep inhalation (DI) increases airflow following hyperpnea-induced bronchospasm in asthmatics. 1 Pichurko BM Ingram RH Effects of airway tone and volume history on maximal expiratory flow in asthma. J Appl Physiol. 1987; 62: 1133-1140 Crossref PubMed Scopus (28) Google Scholar This effect is thought to be due to an increase in airways hysteresis relative to parenchymal hysteresis, brought about by large airway constriction induced by hyperpnea.

Volume history response of airway resistance.

Airways exhibit pressure volume hysteresis. The degree of airway hysteresis is directly proportional to smooth muscle tone. The lung parenchyma also exhibits similar pressure volume hysteresis. The effect on airway size depends on the relative difference between parenchymal and airway hysteresis as demonstrated by Froeb and Mead [1]. Hysteretic behaviour of airways and lung can be demonstrated by an act of deep inhalation, which is called a volume history (VH) manoeuvre. The model of Mead and Froeb has been analysed by Burns and Taylor [2]. These authors have shown that if airway volume represented by dead space (VD) is plotted against lung volume and the subject is asked to breath in from FRC to TLC and back, three different pattern of responses emerge. First, an anticlockwise loop represents bronchodilation in response to VH; second, a clockwise loop will indicate bronchoconstriction; third, no loop will show absence of VH response. When airway hysteresis exceed parenchymal hysteresis, airway size is greater on the deflation limb than it is at any given lung volume along the inflation limb. Airway hysteresis less than parenchymal hysteresis leads to the opposite volume history response Finally, if airway and parenchymal hysteresis are equal, volume history has no effect on airway size. It has been shown that this volume history response is maximal almost immediately after a deep inhalation, decays rapidly during the first minute and usually is completely reversed within 2–3 minutes following inspiration in normal subjects.KeywordsLung VolumeAirway ResistanceFunctional Residual CapacityTotal Lung CapacityConstrictor ResponseThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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.

Nonhomogeneous Lung Emptying in Cystic Fibrosis Patients: Volume History and Bronchodilator Effects

In spontaneous asthma after a deep inhalation (DI) obstruction occurs in direct proportion to disease severity. Since this has been associated with peripheral inflammation, which is present in cystic fibrosis (CF), we tested whether worsening obstruction after DI also occurs in CF in 12 patients. We assessed volume history effects by comparing isovolumic expiratory flows (Vmax) during forced exhalation begun at the end of tidal inspiration (partial P) with those begun at TLC (maximal M) to obtain M/P. As in asthma there was a correlation between M/P and FEV1 (% predicted; r = 0.64, p less than or equal to 0.03, n = 12). To control for a time dependency effect due to preferential emptying of fast compartments early in both the P and M maneuvers, we compared Vmax obtained from a first partial (P1) with a second (P2) obtained after inspiration to TLC and slow exhalation to the same starting volume as P1 (P2/P1). In contrast to asthma the P2/P1 was greater than the M/P and not related to disease severity. A further index of nonhomogeneous lung emptying was the relationship between M/P and the slope ratio at 70% TLC (r = -0.67, p less than or equal to 0.03). After isoetharine inhalation the M/P decreased (-0.12 +/- 0.12, p less than or equal to 0.01) but no change was apparent in P2/P1, indicating further increases in the degree of nonhomogeneity. We conclude that although volume history effects on M/P are similar in asthma and CF, this is due to a predominance of parenchymal hysteresis in the former and nonhomogeneity in the latter, which worsens with bronchodilator use.

The acoustic reflection technique for non-invasive assessment of upper airway area

Non-invasive assessment of upper airway area by acoustic reflections has been developed in the last 12 yrs. The technique is based on the analysis of sound waves reflected from the airways. Measurement of the amplitudes of the reflections and their times of arrival at the sensing microphone permits construction of a plot of airway area vs distance from the microphone. We describe the theoretical foundations of the method and review the underlying assumptions. This is followed by a summary of the results of in vitro and in vivo validation studies, with particular attention to the reproducibility, accuracy and variability of the technique. The description of clinical and physiological applications of this technique includes detection of tracheal stenosis, demonstration of structural and functional abnormalities of the pharynx and glottis in patients with sleep apnoea, dichotomous response of the airway area to exercise, and airway vs parenchymal hysteresis. Finally, we comment on the future directions that might be investigated using this technique.

Effects of Deep Inhalation during Early and Late Asthmatic Reactions to Allergen

Eighteen asthmatic patients with a biphasic asthmatic reaction to house dust mite were studied. The effect of deep inhalation (DI) was quantitated by comparing the maximal expiratory flow at 40% (MEF40) of vital capacity from partial (P) and maximal (M) flow-volume curves, and specific airway conductance (SGaw) before and after DI (SGawDI). At baseline, the ratio MEF40M/P was significantly larger than unity (1.45 +/- 0.26 SD), whereas the ratio SGawDI/SGaw was not significantly different from unity (0.92 +/- 0.24). During early phase reaction, both MEF40M/P and SGawDI/SGaw were significantly increased to 2.66 +/- 0.97 and 1.96 +/- 0.47, respectively. During late phase reaction, when the FEV1 values were similar to those observed during early phase reaction, MEF40M/P and SGawDI/SGaw were 1.86 +/- 0.46 and 1.43 +/- 0.29, respectively, significantly higher than the values at baseline but significantly lower than those during early phase reaction. Similar results were obtained in a subgroup of nine patients when SGaw values during the late phase reaction were similar to those during the early phase reaction. We conclude that DI has a different effect during early and late asthmatic reactions, suggesting a different ratio of airway to parenchymal hysteresis. This may result from an increased parenchymal hysteresis (more peripherally located bronchial obstruction) or a decreased airway hysteresis (prominent airway inflammation) during the late phase reaction.

Effects of increasing doses of beta-agonists on airway and parenchymal hysteresis

We examined the effects of a deep inhalation on airway caliber before and after increasing doses of a beta-agonist in eight subjects, including one former and two current but mild asthmatics. With bronchodilation the increase in maximal flow on the partial flow-volume curve (P), initiated from functional residual capacity, exceeded that seen on the maximal curve (M), initiated from total lung capacity, such that isovolumic maximal flows diminished after a deep inhalation; i.e., M/P ratios fell with bronchodilation, as we and others have found. Five of eight reversed this downward trend in M/P ratios at higher cumulative doses. Quasistatic pressure-volume curves (QSPV) were simultaneously performed on two of these five and demonstrated a decrease in pressure-volume hysteresis (PVH) at the higher doses associated with a rising M/P ratio. Three of eight had continuing low and diminishing M/P ratio up to the highest dose given. QSPV were performed in two of these three and indicated no change in PVH at any of the doses. One of these two had a repeat study using a subcutaneous beta-agonist after the inhaled drug was given, and the M/P ratio rose as QSPV PVH fell. These data support the relative hysteresis analysis of airway and parenchyma as an explanation for volume history effects on airway caliber.

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.

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.

Time dependence of airways and lung parenchymal recoil hysteresis.

Hysteresis of airways and lung parenchymal recoil was examined in normal subjects by measuring specific conductance (sGaw) and lung elastic recoil (Pst,L) before and 5, 10, 15, and 30 s after deep inspiration (DI). Routine lung function tests were normal before and after inhaled metaproterenol. sGaw increased significantly for 10 s after DI. Also, sGaw(DI) was greater than sGaw in 11 of 12, 8 of 12, 7 of 12, and 6 of 12 subjects at 5, 10, 15, and 30 s, respectively, after DI. The response of sGaw to DI and metaproterenol correlated significantly with each other (r = 0.82, P less than 0.001). However, after metaproterenol, sGaw(DI) did not exceed sGaw. Pst,L decreased significantly for 15 s after DI, with the lowest measured Pst,L(DI) values occurring 5 s after DI (P less than 0.01-0.001). Both sGaw(DI) and Pst,L(DI) values returned to base line (preinspiration) in a time-dependent exponential manner, with time constants of 9.2 +/- 4.9 and 11.3 +/- 6.1 s, respectively; these time constants were not significantly different from each other. We conclude that airways hysteresis is the predominant finding in normal subjects (even without prior pharmacological bronchoconstriction) before but not after metaproterenol; Pst,L decreases after DI and, in normal individuals, returns to base line in a time-dependent manner; and the time-dependent behavior of airways and lung parenchymal hysteresis have opposite (and unequal) effects on airway caliber.

Effect of volume history on successive partial expiratory flow-volume maneuvers.

In normal subjects, the second of two successive partial expiratory flow-volume (PEFV 2) curves often had higher isovolume maximal expiratory flow rates (Vmax) than the first (PEFV 1) (mean increase 30.2 +/- 13%). The higher Vmax on PEFV 2 was present only when there was a greater lung elastic recoil pressure (Pst(L)). In eight subjects the Pst(L) derived from sequential partial quasi-static pressure-volume curves, from interruption of the flow-volume maneuvers and at the start of the PEFV curves showed that isovolume upstream resistance increased although Vmax also increased after going to residual volume (RV). In four subjects the RV volume history did not change the pressure flow relationship across the upstream airways. If airways dimensions were the sole determinant of Vmax, then Vmax on PEFV 2 would be the same or smaller than on PEFV 1. That the opposite was observed in our study indicates that the increase in Pst(L), which results from parenchymal hysteresis, offsets any dimensional decrease in upstream airways due to airways hysteresis.