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Biomedical subjects

D L Sherrill

Publications and source records attributed to D L Sherrill.

At least 55 records · Page 3Linked to original sources

Using smoothing splines for detecting ventilatory thresholds.

A recently developed nonparametric regression technique, called a polynomial smoothing spline, is presented for detecting the ventilatory threshold (VT) and respiratory compensation (RC) points from gas exchange response data taken during an incremental exercise test. This type of curve fitting has the advantage of not requiring investigators to specify, a priori, the form of the underlying model, as is required with all linear regression techniques. This procedure yields a mathematically optimal fitted curve through the O2 uptake (VO2) vs CO2 output (VCO2) data and estimates of the process' first and second derivatives. A breakpoint or threshold is indicated by an increase in the value of the derivative and a peak in the second derivative. To evaluate this approach we analyzed gas exchange data collected on nine healthy subjects during a ramp exercise test (15 W.min-1) to the limits of tolerance. Utilizing this procedure we detected VT and RC breakpoints in four subjects and only VT breakpoints in the remaining five subjects. Our results and those obtained using the more conventional linear regression method were similar for those subjects whose RC points were detected using the smoothing spline procedure. However, using regression techniques for subjects with low or otherwise undetectable RC breakpoints, the linear regression method yielded less reliable results in our hands.

Anaerobic Threshold↗

Epidemiology of chronic obstructive pulmonary disease.

Morbidity and mortality rates for chronic obstructive pulmonary disease (COPD) have been increasing over time. Epidemiologic investigators of COPD have been exploring the reasons for these increases through prevalence surveys and longitudinal studies. This article examines some of the recent findings.

Air Pollution↗

Application of the general linear model for smoothing gas exchange data.

The precision of an interpretation of gas exchange records in progressive exercise is limited by the typical breath-to-breath variation in the data. Recently, two procedures have been proposed for minimizing the "noise" in the estimates of alveolar gas exchange time series data. One approach utilizes an estimate of pulmonary blood flow (Q) for smoothing purposes. The other approach utilizes an estimate of effective lung volume (V'L) for smoothing purposes. In this paper, we formulate the smoothing problem as a general linear model and demonstrate the concurrent estimates of both V'L and Q. Furthermore, we investigate the interaction between V'L and Q. Specifically, when a high value of lung volume is used (such as the subject's resting functional residual capacity) in the alveolar gas exchange algorithm, the estimate of Q is biased low and the result is a less effective smoothing of the data. In addition, we demonstrate how the Q estimate can be improved by utilizing more appropriate estimates of arterial carbon dioxide tension.

Algorithms↗

On the temporal relationships between lung function and somatic growth.

A sample population of healthy nonsmoking male (n = 416) and female (n = 608) subjects derived from all non-Hispanic white subjects 5 to 60 yr of age enrolled in the Tucson Epidemiological Study of Airway Obstructive Disease was studied to evaluate the temporal relationships between various pulmonary function measures and somatic growth. Pulmonary function measures derived from the maximal expiratory flow volume (MEFV) curve included FVC, FEV1, maximal expiratory flow after 50% of vital capacity had been expired (Vmax50), and maximal midexpiratory flow (FEF25-75). The lung function and somatic growth longitudinal data were characterized by a nonparametric polynomial smoothing spline model. This procedure yields an optimal fitted curve through the data, an estimate of the growth velocity curve, and 95% confidence bands. Temporal relationships between the fitted growth curves were determined examining the ages at which the growth velocity peaks (GVP) occur. In addition, the age of growth cessation was estimated using lower limits of the 95% confidence bands of each growth velocity curve. The results indicate that the point estimates of the somatic GVPs precede all peak lung function measurements derived from the MEFV curve in both males and females. The only statistically significant difference between when the GVPs for somatic growth and functional lung growth occurred was for FEV1 and FEF25-75 in males, though similar trends were apparent in all other variables, suggesting that the timing of maximal body growth velocity precedes that of maximal lung functional growth and that the early growth spurt in females includes the lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A mathematical procedure for estimating the spatial relationships between lung function, somatic growth, and maturation.

A mathematical procedure is described for examining growth velocity rates of lung function (FEV1) in relationship to somatic growth and maturation. This procedure uses a polynomial smoothing spline model to yield a fitted curve through the data and to estimate the process first derivatives (i.e. growth velocity curves). We demonstrate this technique using data from children and adolescents enrolled in the Tucson Epidemiological Study of Airway Obstructive Diseases. The study group consisted of 772 healthy normal subjects, aged 3 to 25 y. The results for the normal subjects (male and female) indicate that the growth velocity peak (GVP) of somatic growth leads the GVP of functional growth (FEV1) by approximately 7 and 11 mo for females and male subjects, respectively, and that the GVP of maturation lags behind that of functional growth (FEV1) by approximately 1 y (male and female subjects). In addition, the normal subjects' growth velocity curves for FVC and FEV1/FVC were examined. The FEV1/FVC ratio was consistently high, and its growth velocity was not significantly different than 0 over the age range studied. This suggests that in normal children, the GVP seen in FEV1 is primarily due to a GVP in vital capacity or lung vol, rather than to a direct effect on expiratory flow rates alone. From this study we concluded that the polynomial smoothing spline procedure can adequately model the inherently noisy pulmonary function data and additionally yield an accurate estimate of the process first derivative.

Adolescent↗

On the estimation of pulmonary blood flow from CO2 production time series.

It may be possible to estimate a nominal pulmonary blood flow (Q) during an exercise stress test via the algorithm used to estimate breath-by-breath alveolar CO2 production. Recently it has been demonstrated that by relating breath-to-breath fluctuations in alveolar CO2 production to breath-to-breath fluctuations in end-tidal CO2, an optimizing parameter related to Q can be determined that can be used to process the CO2 production fluctuations and minimize their variation. However, the reported values of Q using this procedure appear to be biased low. Using a computer simulation of gas exchange, we demonstrate that the estimate of Q is biased low when the nominal lung volume used in the alveolar gas exchange algorithm is too large. Furthermore, alveolar CO2 transport is determined by an integral of alveolar CO2 over the breath time and, thus, is a path-dependent quantity. The use of end-tidal CO2 fluctuations to approximate fluctuations in this integral contributes to an error in the estimation of Q which yields estimates that are biased low. Alternatively, the use of mean alveolar CO2 fluctuations yield more appropriate Q estimates. These results suggest practical implications for estimating effective pulmonary blood flow during an exercise stress test by using breath-to-breath estimates of mean alveolar CO2.

Blood Flow Velocity↗

Kinetics of VO2 with impulse and step exercise in humans.

The constancy of the time course (i.e., dynamic linearity) of the O2 uptake (VO2) response to exercise was examined by testing the law of superposition on data from impulse and step work rate forcings. Two impulses (10 s at a 235-W increase above a 25-W base line, I-235; and 5 s at a 475-W increase above a 25-W base line, I-475), four steps (ST) (25-65 W, ST1; 65-105 W, ST2; 25-105 W, ST3; and 25-145 W, ST4), and the corresponding off-transient responses were performed six to eight times by each of five subjects. The integrated area (G) of the VO2 response for I-235 was similar to that of ST1 and ST2 (P greater than 0.05); the I-475 G was significantly greater (P less than 0.05). The time constant of VO2 during the step function on-transient response for the second exponential component was significantly faster for ST1 and significantly slower for I-235 and I-475 than for ST2, ST3, and ST4 (P less than 0.05). However, I-235 and I-475 time constants for VO2 were not different from the ST off-transient values. Attempts to superimpose the integral of the impulse on the ST data showed that the early rapid increase in VO2 in the ST was underpredicted by the impulse and that the impulse response lagged behind the ST at all points before steady state. It can be concluded that VO2 kinetics failed the test of superposition and are therefore described by a nonlinear dynamic system.

Adolescent↗

Analgesic and respiratory effects of extradural sufentanil in volunteers and the influence of adrenaline as an adjuvant.

The effects of extradural sufentanil 50 micrograms were investigated in 10 normal volunteers. Eight of these were studied at a second session when adrenaline 1:200,000 was added to the sufentanil. Well-defined segmental analgesia developed rapidly after plain sufentanil and lasted approximately 3 h. Respiration was depressed for about the same period and was greatest in the first 2 h, as shown by a 15% increase in PECO2, while the slope and VE50 of the carbon dioxide response curve were depressed by 45% and 55%, respectively. Moderate drowsiness occurred in most subjects, while other side effects of itching, nausea and urinary retention occurred less frequently and were not severe. Addition of adrenaline 1:200,000 intensified segmental analgesia and prolonged duration to 5 h, while side effects were lessened. It is concluded that extradural sufentanil shows considerable promise for clinical use, and that the risk: benefit ratio is improved by adding adrenaline 1:200,000.

Adult↗

On-line computer estimation of carbon dioxide response curves.

Anesthesiologists are concerned with the effect of various anesthetics on a patient's central nervous ventilatory control. The most widely accepted method of determining the effect of a drug is to compare carbon dioxide response curves (delta VE/delta PETCO2, where VE = minute ventilation [in L/min] and PETCO2 = end-tidal carbon dioxide [in mm Hg]) measured before and after administration of the drug. Additional information concerning neuromechanical control can be obtained by also including a measure of the airway occlusion pressure (generally measured 100 ms after occlusion, i.e., P100). To facilitate these measurements we have developed a portable, computer-controlled data acquisition system. It includes an Apple II+ computer and measures VE, PETCO2, and P100. Each subject rebreathes exhaled carbon dioxide through a two-way breathing valve attached to a 9-liter reservoir, which is initially filled with 5% carbon dioxide and balance oxygen. Exhaled carbon dioxide concentrations are measured with an infrared medical gas analyzer on samples taken through a catheter connected at the mouthpiece. The exhaled flow is measured with a pneumotachograph in conjunction with a differential pressure transducer, and P100 is determined with a Validyne MP45 pressure transducer.

Airway Resistance↗

On the estimation of hypoxic ventilatory response.

The shape parameter, A, has been used to assess hypoxic sensitivity (ventilatory response, VE, to lowered alveolar oxygen tension, PAO2) in the model of the form VE = VEO + A/(PAO2 - C) where C is held constant at 32. In this paper we examine the consequence of holding C constant versus estimating both A and C from the data. Using computer-simulated data from 59 subjects whose A and C values had been previously determined, we indicate that when the actual C value is substantially different from 32, the model with C = 32 does not fit the data. In this case, the estimated A value with C = 32 is highly dependent upon the lowest value of PAO2 obtained in the experimental protocol and can be markedly different from the actual A value. In contrast, when C is also estimated from the subject's data the model fits the data and the estimate of A is unbiased but the precision may be diminished when the actual value of C is low. To improve this precision, we propose a Bayesian estimation scheme that adds a "soft" constraint on C.

Computers↗

On the maximum likelihood estimation of respiratory response slopes.

Several approaches have been suggested for estimating a respiratory response slope when both x and y variables are observed with error. Recently, a maximum likelihood estimate under the assumption of a bivariate normal distribution has been proposed. A method of moments solution yields a slope estimate of y/x as long as the underlying process mean is nonzero. This paper extends the maximum likelihood approach to the case where the process mean is zero. In this case, certain additional error assumptions must be made to yield a unique estimate. These concepts are applied to the problem of estimating an effective lung volume for steady-state breath-to-breath gas exchange data during exercise.

Lung Volume Measurements↗

Estimation of response slopes in respiratory control.

The ventilatory response to changes in alveolar (arterial) CO2 is widely used as an index of respiratory control behavior. Methods for estimating these response slopes should incorporate the possibility that there may be errors in both the independent (partial pressure of CO2) and dependent (ventilation) variables. In a recent paper Daubenspeck and Ogden (J. Appl. Physiol. Respirat. Environ. Exercise Physiol. 45:823-829, 1978) have suggested problems inherent in the traditional technique of reduced major axis and have suggested a more contemporary technique of directional statistics. We have previously analyzed both techniques and developed a method to overcome the problems of reduced major axis and problems inherent in the use of directional statistics. Under the assumption of a bivariate normal distribution, we demonstrate that our slope estimate is similar to the maximum likelihood estimate proposed by Mardia et al. (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 54: 309-313, 1983) for this problem. In addition, we demonstrate a bootstrap statistical approach when the distributions are not normally distributed. These concepts are illustrated using O2-CO2 interaction data.

Carbon Dioxide↗

Quantitative recovery of expired nitrogen and nitrous oxide from venous gas emboli.

It has not been previously established whether venous gas emboli dissolve from pulmonary blood vessels into adjacent airways, or pass as microbubbles directly into the systemic circulation. We reported here the quantitative recovery of embolized gases from the airways, in amounts which substantiate the complete elimination of such gases by dissolution. A computer controlled quadrupole mass spectrometer was used to measure the net expired volumes of N2 or N2O following the injection of 40 ml boluses of these gases into the airways (AW) or right ventricles (RV) of 5 mongrel dogs. Every 20 ms, linearized flow signals were multiplied by gas concentrations, and the products summed for inspired and expired volumes of each breath. Intubated dogs were ventilated with 100% oxygen under Na-pentobarbital and either succinylcholine chloride or pancuronium bromide anesthesia; Swan-Ganz catheters were used for RV injections and for monotoring cardiovascular parameters. The overall mean % volume recoveries were 70.4 for AW-N2O, 68.2 for RV-N2O, 83.7 for AW-N2, and 46.7 for RV-N2. As expected, the AW percent volume recoveries increased with decreasing aqueous solubilities, and represented maximal values obtainable for RV emboli, due to alveolar reabsorption of gases excreted from the pulmonary circulation. Although all RV-N2O could thus be accounted for, RV-N2 recoveries were significantly less than AW-N2. The remaining RV-N2 did not pass as bubbles into the pulmonary veins, but continued to obstruct the pulmonary arterioles, as demonstrated with the use of nitrous oxide challenges in the inspired gas mixture.

Animals↗

Model utility in the study of cardiorespiratory control.

This study investigates the utility of differing modeling approaches to the study of cardiorespiratory control. Models are classified in terms of intended purpose. A structural model predicts behavior based on a hypothetical physiological structure. An empirical model summarizes observed behavior. A functional model attempts to relate physiological structure to observed behavior. Models from the literature for exercising man illustrate these concepts and motivate the importance of experimental design in terms of the dynamic variation of a work-rate input.

Biomedical Engineering↗

A model evaluation of estimates of breath-to-breath alveolar gas exchange.

A mathematical model has been implemented for evaluation of methods for estimating breath-to-breath alveolar gas exchange during exercise in humans. This model includes a homogeneous alveolar gas exchange compartment, a dead space compartment, and tissue spaces for CO2 (alveolar and dead space). The dead space compartment includes a mixing portion surrounded by tissue and an unmixed (slug flow) portion which is partitioned between anatomical and apparatus contributions. A random sinusoidal flow pattern generates a breath-to-breath variation in pulmonary stores. The Auchincloss algorithm for estimating alveolar gas exchange (Auchincloss et al., J. Appl. Physiol. 21: 810-818, 1966) was applied to the model, and the results were compared with the simulated gas exchange. This comparison indicates that a compensation for changes in pulmonary stores must include factors for alveolar gas concentration change as well as alveolar volume change and thus implies the use of end-tidal measurements. Although this algorithm yields reasonable estimates of breath-to-breath alveolar gas exchange, it does not yield a "true" indirect measurement because of inherent error in the estimation of a homogeneous alveolar gas concentration at the end of expiration.

Evaluation Studies as Topic↗