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Biomedical subjects

K R Lutchen

Publications and source records attributed to K R Lutchen.

At least 19 recordsLinked to original sources
PubMed2001

Airway constriction pattern is a central component of asthma severity: the role of deep inspirations.

Measurements of lung resistance and elastance (RL and EL) from 0.1 to 8 Hz reflect both the mean level and pattern of lung constriction. The goal of this study was to establish a relation between a deep inspiration (DI) and the heterogeneity of constriction in healthy versus asthmatic subjects. Constriction pattern was assessed from measurements of the RL and EL from 0.1 to 8 Hz in seven healthy subjects and in 12 asthmatics. These data were acquired before and after a DI and before and after a standard methacholine challenge versus a modified challenge in which a DI is prohibited. Generally, avoidance of a DI increased responsiveness. In healthy subjects and in those with mild-to-moderate baseline asthma a bronchial challenge, especially during self-inhibited DI, produced a heterogenous pattern of constriction inclusive of randomly distributed airway closures or near closures. Nevertheless, such subjects were able to reopen their airways via a DI. In contrast, in subjects with severe baseline asthma, there is a more extreme heterogeneous constriction pattern with random airway closures even at baseline. Further, there is no residual bronchodilatory effect of a DI either before or after bronchial challenge. We conjecture that inflammation and wall-remodeling facilitate a dangerous degree of heterogeneous constriction inclusive of airway closures or near closures, and contribute to the prevention of a DI from having a residual bronchodilatory effect.

Adolescent↗
PubMed2001

Exact morphometric modeling of rat lungs for predicting mechanical impedance.

We have developed a computational approach that allows for one-to-one mapping of the airway anatomy when predicting the overall lung mechanical properties and their response to explicit constriction patterns imposed on the airway tree. Specifically, we have exploited the database from Raabe et al. (LF-53 Albuquerque, NM: Lovelace foundation for radical Education and Research), to build the first anatomically based computational model of the rat. The model was then used to predict the response to homogeneous and heterogeneous peripheral airway constriction. Unlike in humans, the inherent asymmetry in the airway tree of rats is predicted to be a dominant contributor to the frequency dependence of lung resistance and elastance even if the constriction is imposed homogeneously. A similar approach would, in principal, be applicable for humans, but the Raabe data is not sufficiently complete to permit this.

Algorithms↗
PubMed2001

Inspiratory lung impedance in COPD: effects of PEEP and immediate impact of lung volume reduction surgery.

Frequency-dependent characteristics of lung resistance (RL) and elastance (EL) are sensitive to different patterns of airway obstruction. We used an enhanced ventilator waveform (EVW) to measure inspiratory RL and EL spectra in ventilated patients during thoracic surgery. The EVW delivers an inspiratory flow waveform with enhanced spectral excitation from 0.156 to 8.1 Hz. Estimates of the coefficients in a trigonometric approximation of the EVW flow and transpulmonary pressure inspirations yielded inspiratory RL and EL spectra. We applied the EVW in a group with mild obstruction undergoing various thoracoscopic procedures (n = 6), and another group with severe chronic obstructive pulmonary disease undergoing lung volume reduction surgery (n = 8). Measurements were made at positive end-expiratory pressure (PEEP) of 0, 3, and 6 cmH(2)O. Inspiratory RL was similar in both groups despite marked differences in spirometry. The chronic obstructive pulmonary disease patients demonstrated a pronounced frequency-dependent increase in inspiratory EL consistent with severe heterogeneous peripheral airway obstruction. PEEP appears to have beneficial effects by reducing peripheral airway resistance. Lung volume reduction surgery resulted in increased inspiratory RL and EL at all frequencies and PEEPs, possibly due to loss of diseased lung tissue, pulmonary edema, increased mechanical heterogeneity, and/or an improvement in airway tethering.

Adult↗
PubMed2001

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.

Adult↗
PubMed2001

Hysteresivity of the lung and tissue strip in the normal rat: effects of heterogeneities.

We measured lung impedance in rats in closed chest (CC), open chest (OC), and isolated lungs (IL) at four transpulmonary pressures with a optimal ventilator waveform. Data were analyzed with an homogeneous linear or an inhomogeneous linear model. Both models include tissue damping and elastance and airway inertance. The homogeneous linear model includes airway resistance (Raw), whereas the inhomogeneous linear model has a continuous distribution of Raw characterized by the mean Raw and the standard deviation of Raw (SDR). Lung mechanics were compared with tissue strip mechanics at frequencies and operating stresses comparable to those during lung impedance measurements. The hysteresivity (eta) was calculated as tissue damping/elastance. We found that 1) airway and tissue parameters were different in the IL than in the CC and OC conditions; 2) SDR was lowest in the IL; and 3) eta in IL at low transpulmonary pressure was similar to eta in the tissue strip. We conclude that eta is primarily determined by lung connective tissue, and its elevated estimates from impedance data in the CC and OC conditions are a consequence of compartment-like heterogeneity being greater in CC and OC conditions than in the IL.

Airway Resistance↗
PubMed2000

Fast, robust identification of nonlinear physiological systems using an implicit basis expansion.

Because the number of parameters required by a Volterra series grows rapidly with both the length of its memory and the order of its nonlinearity, methods for identifying these models from measurements of input/output data are limited to low-order systems with relatively short memories. To deal with these computational and storage requirements one can either make extensive use of the structure of the Volterra series estimation problem to eliminate redundant storage and computations (e.g., the fast orthogonal algorithm), or apply a basis expansion, such as a Laguerre expansion, which seeks to reduce the number of model parameters, and hence, the size of the estimation problem. The use of an appropriate expansion basis can also decrease the noise sensitivity of the estimates. In this paper, we show how fast orthogonalization techniques can be combined with an expansion onto an arbitrary basis. We further demonstrate that the orthogonalization and expansion may be performed independently of each other. Thus, the results from a single application of the fast orthogonal algorithm can be used to generate multiple basis expansions. Simulations, using a simple nonlinear model of peripheral auditory processing, show the equivalence between the kernels estimated using a direct basis expansion, and those computed using the fast, implicit basis expansion technique which we propose. Running times for this new algorithm are compared to those for existing techniques.

Algorithms↗
PubMed2000

Effects of collagenase and elastase on the mechanical properties of lung tissue strips.

The dynamic stiffness (H), damping coefficient (G), and harmonic distortion (k(d)) characterizing tissue nonlinearity of lung parenchymal strips from guinea pigs were assessed before and after treatment with elastase or collagenase between 0.1 and 3.74 Hz. After digestion, data were obtained both at the same mean length and at the same mean force of the strip as before digestion. At the same mean length, G and H decreased by approximately 33% after elastase and by approximately 47% after collagenase treatment. At the same mean force, G and H increased by approximately 7% after elastase and by approximately 25% after collagenase treatment. The k(d) increased more after collagenase (40%) than after elastase (20%) treatment. These findings suggest that, after digestion, the fraction of intact fibers decreases, which, at the same mean length, leads to a decrease in moduli. At the same mean force, collagen fibers operate at a higher portion of their stress-strain curve, which results in an increase in moduli. Also, G and H were coupled so that hysteresivity (G/H) did not change after treatments. However, k(d) was decoupled from elasticity and was sensitive to stretching of collagen, which may be of value in detecting structural alterations in the connective tissue of the lung.

Airway Resistance↗
PubMed1999

Airway remodeling in asthma amplifies heterogeneities in smooth muscle shortening causing hyperresponsiveness.

Although airway remodeling and inflammation in asthma can amplify the constriction response of a single airway, their influence on the structural changes in the whole airway network is unknown. We present a morphometric model of the human lung that incorporates cross-sectional wall areas corresponding to the adventitia, airway smooth muscle (ASM), and mucosa for healthy and mildly and severely asthmatic airways and the influence of parenchymal tethering. A heterogeneous ASM percent shortening stimulus is imposed, causing distinct constriction patterns for healthy and asthmatic airways. We calculate lung resistance and elastance from 0.1 to 5 Hz. We show that, for a given ASM stimulus, the distribution of wall area in asthmatic subjects will amplify not only the mean but the heterogeneity of constriction in the lung periphery. Moreover, heterogeneous ASM shortening that would produce only mild changes in the healthy lung can cause hyperresponsive changes in lung resistance and elastance at typical breathing rates in the asthmatic lung, even with relatively small increases in airway resistance. This condition arises when airway closures occur randomly in the lung periphery. We suggest that heterogeneity is a crucial determinant of hyperresponsiveness in asthma and that acute asthma is more a consequence of extensive airway wall inflammation and remodeling, predisposing the lung to produce an acute pattern of heterogeneous constriction.

Airway Resistance↗
PubMed1999

Airway and lung tissue mechanics in asthma. Effects of albuterol.

We examined the partitioning of total lung resistance (RL) into airway resistance (Raw) and tissue resistance (Rti) in patients with mild to moderate asthma (baseline FEV1, 54 to 91% of predicted) before and after albuterol inhalation. An optimal ventilator waveform was used to measure RL and lung elastance (EL) in 21 asthmatics from approximately 0.1 to 8 Hz during tidal excursions. Analysis of the RL and EL provided separate estimates of airway and lung tissue properties. Eleven subjects, classified as Type A asthmatics, displayed slightly elevated RL but normal EL. Their data were well described with a model consisting of homogeneous airways leading to viscoelastic tissues before and after albuterol. The other 10 subjects, classified as Type B asthmatics, demonstrated highly elevated RL and an EL that became highly elevated at frequencies above 2 Hz. These subjects required the inclusion of an airway wall compliance in the model prealbuterol but not postalbuterol. This suggests that the Type B subjects were experiencing pronounced constriction in the periphery of the lung, resulting in shunting of flow into the airway walls. Spirometric data were consistent with higher constriction in Type B subjects. Both groups demonstrated significant (p < 0.05) decreases in Raw and tissue damping after albuterol, but tissue elastance decreased only in the Type B group. The percent contributions of Raw and Rti to RL were similar in both groups and did not change after albuterol. We conclude that in asthma, Raw comprises the majority (> 70%) of RL at breathing frequencies. The relative contributions of Raw and Rti to RL appear to be independent of the degree of smooth muscle constriction.

Administration, Inhalation↗
PubMed1998

Use of transfer impedance measurements for clinical assessment of lung mechanics.

Respiratory transfer impedance (Ztr) measured using the forced oscillation technique requires virtually no patient cooperation and provides a noninvasive approach for acquiring data reflective of lung mechanics. Also, model analysis of Ztr provides reliable estimates of separate airway and tissue properties (1), but only if data out to 64 Hz are acquired. The current study evaluated the clinical utility of Ztr from 1-80 Hz for assessing the degree and type of impaired lung function. Spirometry and Ztr measurements were made on 37 individuals: 11 healthy subjects and 26 patients with lung disease including chronic obstructive pulmonary disease (COPD), asthma, lung cancer, and sarcoidosis. Over the entire patient group, 12 were also smokers. We first established normal ranges for several Ztr features and model estimated mechanical properties. The COPD and smokers groups showed significant differences in portions of their Ztr spectra from that of the healthy group. Key Ztr spectral features included R0, the frequency at which the real part of impedance is zero; and Re4, the real part of impedance at 4 Hz. The key model parameter was airway resistance, Raw. We found Raw, Re4, and R0 to be significantly elevated during disease (p < 0.0005) and to significantly decrease with bronchodilator therapy (p < 0.025). Moreover, we found moderate to strong correlations between R0, Raw, and Re4 versus FVC and R0 versus FEV1. After bronchodilator, changes in R0, Re4, and Raw were correlated with changes in several spirometric indices. The R0 feature has not been previously evaluated since it is typically above 32 Hz (well above 32 Hz in diseased individuals) and not encompassed in previous clinical studies.

Adolescent↗
PubMed1997

Airway and tissue constrictions are greater in closed than in open-chest conditions.

We measured lung impedance (ZL) before and after four doses of methacholine (Mch) infusion in five intact chest (with esophageal balloon) and six open-chest dogs from 0.2 to 8 Hz with an optimal ventilator waveform. From ZL, we estimated airway resistance (R(aw)) and inertance (Iaw) and tissue viscance (GL) and elastance (HL). Two-way analysis of variance revealed that: (1) Mch had a strong influence on all parameters (p < 0.001), but small effect on hysteresivity, nL = GL/HL; (2) closed-chest GL and HL were significantly higher and Iaw lower than their open-chest values (p < 0.002, p < 0.05 and p < 0.0001); and (3) at the highest Mch dose, the relative increase in R(aw) was six times higher in the closed-chest condition. The reduced impact of Mch on open-chest mechanics may be due to constrictions superimposed on grossly different lung configurations and/or some humoral effects initiated by the thoracotomy. We conclude that Mch doses that elicit mild constriction in open-chest condition can cause a severe constriction in intact animals.

Airway Resistance↗
PubMed1997

Partitioning of lung tissue response and inhomogeneous airway constriction at the airway opening.

During a bronchial challenge, much of the observed response of lung tissues is an artifactual consequence of inhomogeneous airway constriction. Inhomogeneities, in the sense of time constant inequalities, are an inherently linear phenomenon. Conversely, if lung tissues respond to a bronchoagonist, they become more nonlinear. On the basis of these distinct responses, we present an approach to separate real tissue changes from airway inhomogeneities. We developed a lung model that includes airway inhomogeneities in the form of a continuous distribution of airway resistances and nonlinear viscoelastic tissues. Because time domain data are dominated by nonlinearities, whereas frequency domain data are most sensitive to inhomogeneities, we apply a combined time-frequency domain identification scheme. This model was tested with simulated data from a morphometrically based airway model mimicking gross peripheral airway inhomogeneities and shown capable of recovering all tissue parameters to within 15% error. Application to our previously measured data suggests that in dogs during histamine infusion 1) the distribution of airway resistances increases widely and 2) lung tissues do respond but less so than previously reported. This approach, then, is unique in its ability to differentiate between airway and tissue responses to an agonist from a single broadband measurement made at the airway opening.

Airway Resistance↗
PubMed1997

Partitioning airway and lung tissue resistances in humans: effects of bronchoconstriction.

The contribution of airway resistance (Raw) and tissue resistance (Rti) to total lung resistance (RL) during breathing in humans is poorly understood. We have recently developed a method for separating Raw and Rti from measurements of RL and lung elastance (EL) alone. In nine healthy, awake subjects, we applied a broad-band optimal ventilator waveform (OVW) with energy between 0.156 and 8.1 Hz that simultaneously provides tidal ventilation. In four of the subjects, data were acquired before and during a methacholine (MCh)-bronchoconstricted challenge. The RL and EL data were first analyzed by using a model with a homogeneous airway compartment leading to a viscoelastic tissue compartment consisting of tissue damping and elastance parameters. Our OVW-based estimates of Raw correlated well with estimates obtained by using standard plethysmography and were responsive to MCh-induced bronchoconstriction. Our data suggest that Rti comprises approximately 40% of total RL at typical breathing frequencies, which corresponds to approximately 60% of intrathoracic RL. During mild MCh-induced bronchoconstriction, Raw accounts for most of the increase in RL. At high doses of MCh, there was a substantial increase in RL at all frequencies and in EL at higher frequencies. Our analysis showed that both Raw and Rti increase, but most of the increase is due to Raw. The data also suggest that widespread peripheral constriction causes airway wall shunting to produce additional frequency dependence in EL.

Adult↗
PubMed1997

Relationship between heterogeneous changes in airway morphometry and lung resistance and elastance.

We present a dog lung model to predict the relation between inhomogeneous changes in airway morphometry and lung resistance (RL) and elastance (EL) for frequencies surrounding typical breathing rates. The RL and EL were sensitive in distinct ways to two forms of peripheral constriction. First, when there is a large and homogeneous constriction, the RL increases uniformly over the frequency range. The EL is rather unaffected below 1 Hz but then increases with frequencies up to 5 Hz. This increase is caused by central airway wall shunting. Second, the RL and EL are extremely sensitive to mild inhomogeneous constriction in which a few highly constricted or nearly closed airways occur randomly throughout the periphery. This results in extreme increases in the levels and frequency dependence of RL and EL but predominantly at typical breathing rates (<1 Hz). Conversely, the RL and EL are insensitive to highly inhomogeneous airway constriction that does not produce any nearly closed airways. Similarly, alterations in the RL and EL due to central airway wall shunting are not likely until the preponderance of the periphery constricts substantially. The RL and EL spectra are far more sensitive to these two forms of peripheral constriction than to constriction conditions known to occur in the central airways. On the basis of these simulations, we derived a set of qualitative criteria to infer airway constriction conditions from RL and EL spectra.

Airway Resistance↗
PubMed1996

Interpretation of respiratory input impedance in healthy infants.

Respiratory input impedance (Zin) is a potentially informative test of pulmonary function in infants who are unable to perform standard tests commonly performed in children and adults Analysis of Zin in dogs using the six-element model of DuBois et al. (J Appl Physiol 8:587, 1956) provides estimates of airways resistance separate from tissue resistance, as well as an estimate of thoracic gas volume. However, reliable estimates of these parameters can only be obtained when Zin displays a distinct antiresonance that is associated with the tissue inertance and alveolar gas compression compliance. To determine whether infants have such an antiresonance. Zin was measured in nine healthy infants (4 < f < 160 Hz). An antiresonance was found at 112.8-10.4 Hz, and the six-element model fit these data well, but the resulting parameters were physiologically unrealistic. We hypothesized that the antiresonance in the measured Zin is the result of shunt compliance proximal to alveolar gas compression compliance. Gas compression in the face mask and nonrigid upper airway walls could provide such a shunt compliance. We investigated another model with four parameters, a single shunt compliance (Cim) representing gas compression in the face mask in parallel with the infant's total respiratory resistance (Rrs) inertance (Irs), and compliance (Crs). This model fits the data well, and the estimated R, (19.3, 4.2 cmH O/L/s) was physiologically reasonable. However, Crs (Crs 1.03-0.58 mL cmH2O) was one order of magnitude smaller than reported Crs. The value for Cim was slightly larger than that based on the estimated volume of gas in the face mask, suggesting an additional influence of upper airway wall shunting. Computer simulations using a model that includes the face mask and upper airway walls confirmed that Cim and the upper airway wall properties significantly influence Zin data over this frequency range. Nevertheless, these simulations suggest that the Rrs estimated from the four-element model is related to airway resistance.

Airway Resistance↗
PubMed1996

How inhomogeneities and airway walls affect frequency dependence and separation of airway and tissue properties.

It has been proposed that during mild-to-moderate bronchoconstriction one can partition airway and tissue properties on the basis of input impedance (Zin) acquired from 0.1 to 5 Hz (K.R. Lutchen, B. Suki, Q. Zhang, F. Peták, B. Daróczy, and Z. Hantos. J. Appl. Physiol. 77: 373-385, 1994). The approach is to apply a homogeneous lung model that contains airway resistance and viscoelastic tissue damping and elastance parameters. The tissue parameters account for the frequency dependence in lung resistance (RL) and elastance (EL). We present an anatomically consistent asymmetrically branching airway model to address two key questions: 1) How will lung inhomogeneities, airway wall shunting, and tissue viscoelasticity contribute to increased frequency dependence and levels of RL and EL during lung constriction? and 2) How much can lung inhomogeneities and airway wall shunting contribute to our assessment of airway, tissue, and overall lung properties derived from Zin? The model incorporates nonrigid airway walls and allows for explicit control over the type and degree of inhomogeneous airway constriction or tissue changes. Our results indicate that, from 0.1 to 5 Hz, airway wall shunting does not become important unless the entire lung periphery experiences significant constriction. Mild-to-moderate inhomogeneous peripheral airway constriction produces a relatively minor additional frequency dependence in RL and EL beyond that due to the tissues alone. With more extreme constriction, however, there is a marked frequency-dependent increase in EL. This phenomenon may render it impossible to distinguish from a single frequency measurement whether an increase in EL during bronchoconstriction is a consequence of a true increase in tissue stiffening or simply a consequence of airway phenomena. Finally, Zin from 0.1 to 5 Hz can be used to provide a reasonable separation of airway and tissue properties for mild-to-moderate homogeneous or inhomogeneous lung constriction. However, during more severe disease, inhomogeneities and/or wall shunting will produce substantial overestimation of tissue damping and hysteretic properties. In fact, the only reliable indicator of a real change in the tissues may be a change in the estimate of tissue elastance that is based on data extending to a sufficiently low frequency.

Airway Resistance↗
PubMed1996

Airway inhomogeneities contribute to apparent lung tissue mechanics during constriction.

Recent studies have suggested that part of the measured increase in lung tissue resistance after bronchoconstriction is an artifact due to increased airway inhomogeneities. To resolve this issue, we measured lung impedance (ZL) in seven open-chest rats with the lungs equilibrated on room air and then on a mixture of neon and oxygen (NeOx). The rats were placed in a body box with the tracheal tube leading through the box wall. A broadband flow signal was delivered to the box. The signal contained seven oscillation frequencies in the 0.234- to 12.07-Hz range, which were combined to produce tidal ventilation. The ZL was measured before and after bronchoconstriction caused by infusion of methacholine (MCh). Partitioning of airway and tissue properties was achieved by fitting ZL with a model including airway resistance (Raw), airway inertance, tissue damping (G), and tissue elastance (H). We hypothesized that if the inhomogeneities were not significant, the apparent tissue properties would be independent of the resident gas, whereas Raw would scale as the ratio of viscosities. Indeed, during control conditions, the NeOx-to-air ratios for G and H were both 1.03 +/- 0.04. Also, there was a small increase in lung elastance (EL) between 0.234 and 4 Hz that was similar on air and NeOx. During MCh infusion, Raw and G increased markedly (45-65%), but the increase in H was relatively small ( < 13%). The NeOx-to-air Raw and H ratios remained the same. However, the NeOx-to-air G ratio increased to 1.19 +/- 0.07 (P < 0.01) and the increase in EL with frequency was now marked and dependent on the resident gas. These results provide direct evidence that for a healthy rat lung airway inhomogeneities do not significantly influence the lung resistance or EL vs. frequency data. However, during MCh-induced constriction, a large portion of the increase in tissue resistance and the altered frequency dependence of EL are virtual and a consequence of the augmented airway inhomogeneities.

Airway Resistance↗