Riboflavin-responsive complex I deficiency.

Three patients from a large consanguineous family, and one unrelated patient had exercise intolerance since early childhood and improved by supplementation with a high dosage of riboflavin. This was confirmed by higher endurance power in exercise testing. Riboflavin had been given because complex I, which contains riboflavin in FMN, one of its prosthetic groups, had a very low activity in muscle. Histochemistry showed an increase of subsarcolemmal mitochondria. The low complex I activity contrasted with an increase of the activities of succinate dehydrogenase, succinate-cytochrome c oxidoreductase and cytochrome c oxidase. Isolated mitochondria from these muscle specimens proved deficient in oxidizing pyruvate plus malate and other NAD(+)-linked substrates, but oxidized succinate and ascorbate at equal or higher levels than controls. Two years later a second biopsy was taken in one of the patients, and the activity of complex I had increased from 16% to 47% of the average activity in controls. In the four biopsies, cytochrome c oxidase activity correlated negatively with age. We suspect that this is due to reactive oxygen species generated by the proliferating mitochondria and peroxidizing unsaturated fatty acids of cardiolipin. Three of the four patients had low blood carnitine, and all were found to have hypocarnitinemic family members.

Random walk type models for indicator-dilution studies: comparison of a local density random walk and a first passage times distribution.

The relative merits of the local density random walk and the first passage times distributions were compared with respect to their practical applicability in cardiovascular research and clinical practice. Open indicator-dilution curves of varying shape were used, and reference values for area and mean transit times were calculated numerically. Curves not perturbed by recirculation were obtained in two different ways. Thermodilution curves were obtained in an animal model at the left and the right side of the heart respectively and conductivity curves with 0.5% NaCl solution as indicator were obtained in a hydrodynamic circulation model. The fits of the two types of distribution were equally accurate for the more symmetrical curves; for very skewed curves the local density random walk fit proved to be more accurate. This result could be related to the greater difference in shape between the first passage times and local density random walk distribution for a large degree of asymmetry. For this reason the local density random walk distribution for fitting indicator-dilution curves was used in a variety of other experimental conditions.

Is delayed introduction of inhaled corticosteroids harmful in patients with obstructive airways disease (asthma and COPD)? The Dutch CNSLD Study Group. The Dutch Chronic Nonspecific Lung Disease Study Groups.

BACKGROUND: The institution of inhaled corticosteroids is generally advocated for effective treatment of patients with asthma. It is yet unknown what is the best time to start inhaled corticosteroid therapy and especially whether delayed introduction is harmful. PHASE 1: In a previous study in patients with asthma and COPD, we found that 2.5 years of treatment with a beta 2-agonist plus inhaled corticosteroid (BA + CS) was more effective in improving the FEV1 and the provocative concentration of histamine causing a 20% reduction in FEV1 (PC20) than treatment with a beta 2-agonist plus anticholinergic (BA + AC) or placebo (BA + PL). PHASE 2: We extended this study with 6 months to investigate whether delayed introduction of inhaled CS therapy (800 micrograms beclomethasone dipropionate) in the groups previously not treated with inhaled CS (BA +/- AC) could also improve FEV1 and PC20 to the same degree. A distinction was made between patients with predominantly asthma (high baseline reversibility, delta FEV1 > or = 9% of predicted), and predominantly COPD (low baseline reversibility, delta FEV1 < 9% of predicted). RESULTS: Improvement of FEV1 percent predicted by inhaled CS was comparable both in the asthmatics between phase 1 (13.8% predicted) and phase 2 (8.5% predicted; p = 0.31) as well as in the patients with COPD (2.5% and 1.5% predicted, respectively). PC20, however, increased significantly more in the asthmatics in phase 1 (1.77 doubling concentration [DC]) than in phase 2 (0.79 DC; p = 0.03). Improvement of PC20 in the patients with COPD was not significantly higher in phase 1 (0.74 DC) than in phase 2 (0.00 DC; p = 0.19). CONCLUSIONS: Our study indicates that although delayed introduction of inhaled CS in asthmatics leads to similar improvements in FEV1, improvements in PC20 are significantly less. These findings in patients with longer-existing asthma concur with other findings in newly detected asthma. We suggest that institution of inhaled CS therapy should not be postponed in asthmatics with documented airways obstruction and reversibility.

Diffusion capacity in heart transplant recipients.

Preoperative diffusion capacity per liter alveolar volume (Kco) in cardiac transplant recipients with an intrinsic normal lung is within the normal range. In the first postoperative year, Kco showed a significant mean decrease of 12 percent (p less than 0.004). Lung function (TLC, VC, FEV1) tended to normalize after heart transplantation. Ventilation distribution remained stable before and after heart transplantation. Preoperatively, weak correlations were found between Kco and diastolic pulmonary arterial pressure (dPAP) and mean pulmonary capillary wedge pressure (PCWP). Postoperatively, correlation between Kco and PCWP was weak, and between Kco and dPAP it was not significant at all. These pressures determine the capillary blood volume before and after transplantation. Probably these weak correlations indicate that intrapulmonary factors, not cardiac factors, are of primary importance in the regulation of blood distribution. The percentage of decrease in Kco in the first postoperative year correlated with the change in dPAP and PCWP, but also with the cyclosporine level in the first posttransplant year. No correlation was found between cyclosporine level and pulmonary vascular resistance. It is suggested that higher levels of cyclosporine influence the alveolar capillary membrane, so that Kco decreases. The percentage of decrease in Kco was significantly more outspoken in patients who had rales on auscultation preoperatively. Using multiple regression analysis, we found that the factors most strongly related to the percentage of change in Kco in the first posttransplant year were the preoperative Kco, the cyclosporine level in the first postoperative year, and the change in dPAP in that year.

Influence of lung parenchymal destruction on the different indexes of the methacholine dose-response curve in COPD patients.

STUDY OBJECTIVES: The interpretation of nonspecific bronchial provocation dose-response curves in COPD is still a matter of debate. Bronchial hyperresponsiveness (BHR) in patients with COPD could be influenced by the destruction of the parenchyma and the augmented mechanical behavior of the lung. Therefore, we studied the interrelationships between indexes of BHR, on the one hand, and markers of lung parenchymal destruction, on the other. PATIENTS AND METHODS: COPD patients were selected by clinical symptoms, evidence of chronic, nonreversible airways obstruction, and BHR, which was defined as a provocative dose of a substance (histamine) causing a 20% fall in FEV(1) (PC(20)) of

High fat, low carbohydrate, enteral feeding in patients weaning from the ventilator.

OBJECTIVE: To study whether high fat, low carbohydrate enteral nutrition could reduce VCO2 in patients during ventilator support and weaning from the ventilator in order to facilitate the weaning process. DESIGN: prospective, randomized controlled study. SETTING: Medical ICU of a university hospital. PATIENTS: 32 ventilator-dependent patients with a prospect of weaning from mechanical ventilation. INTERVENTIONS: high fat feeding administered to 15 patients and standard isocaloric feeding administered to 17 patients, both in a dosage of 1.5 times basal metabolic rate. MEASUREMENTS AND RESULTS: Respiratory and metabolic measurements were obtained both during mechanical ventilation and weaning procedures. High fat feeding was associated with significantly lower RQ values compared with standard feeding; the mean (+/- SEM) RQ values during mechanical ventilation amounted to 0.91 +/- 0.01 and 1.00 +/- 0.02 and during weaning to 0.72 +/- 0.02 and 0.86 +/- 0.02 for high fat and standard nutrition respectively (both p-values < 0.001). High fat feeding reduced the CO2-excretion both during mechanical ventilation and weaning, but only the decrease during weaning proved to be significant; the mean (+/- SEM) CO2-excretion amounted to 0.177 +/- 0.010 and 0.231 +/- 0.011 1/min STPD for the high fat and standard feeding respectively (p < 0.01). No significant differences were found in the PaCO2 during weaning between the two feeding groups. CONCLUSION: High fat, low carbohydrate enteral feeding significantly reduced the RQ values in ventilated patients with decreases in VCO2, but in this study failed to reduce PaCO2 during weaning from the ventilator.

Clinical evaluation of diminished early expiratory flow (DEEF) ventilation in mechanically ventilated COPD patients.

OBJECTIVE: To evaluate the cardiopulmonary effects, especially the end-expiratory lung volume (EEV) and ventilation inhomogeneity during diminished early expiratory flow ventilation (DEEF), which resembles pursed-lips breathing, with the conventional intermittent positive pressure ventilation (IPPV) in postoperative mechanically ventilated patients with chronic obstructive pulmonary disease (COPD). DESIGN: A prospective study measuring cardiopulmonary parameters during IPPV, DEEF, and positive end-expiratory pressure (PEEP) as a control mode. In the PEEP mode, PEEP values were chosen such that the mean airway pressure during a breath cycle was equal to that during the DEEF mode, which was higher than the conventional IPPV mode. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: 20 postoperative mechanically ventilated COPD patients who were optimally pretreated and had normal blood oxygenation. INTERVENTIONS: Measurements were started in the IPPV (IPPV1) mode, continued in a randomized order with DEEF or PEEP, and completed with a second IPPV (IPPV2) mode, with 1 h equilibration time in each mode before each measurement. MEASUREMENTS AND RESULTS: A multi-breath indicator gas wash-out test was used to calculate the EEV and ventilation inhomogeneity. There was a 9% increase (p < 0.05) in the mean EEV during both the DEEF and PEEP mode compared to IPPV. No significant changes in the ventilation inhomogeneity and deadspace fractions or the hemodynamic parameters were found during the different ventilatory modes. CONCLUSIONS: There was no improvement in pulmonary and hemodynamic parameters during the DEEF mode in comparison to the IPPV mode. The small increase in EEV during DEEF was probably caused by the slightly higher mean expiratory pressures as in the PEEP mode. However, this had no effect on the hemodynamic parameters. As we could not observe any improvement with the DEEF ventilation in our optimally pretreated postoperative COPD patients, we do not advise applying this therapy in this group of patients, since this mode of ventilation may cause barotrauma if not monitored adequately.

Flow-volume curves as measurement of respiratory mechanics during ventilatory support: the effect of the exhalation valve.

OBJECTIVE: To assess the feasibility of expiratory flow-volume curves as a measurement of respiratory mechanics during ventilatory support: to what extent is the shape of the curve affected by the exhalation valve of the ventilator? DESIGN: Prospective, comparative study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: 28 consecutive patients with various conditions, mechanically ventilated with both the Siemens Servo 900C and 300 ventilators, were studied under sedation and paralysis. INTERVENTIONS: The ventilator circuit was intermittently disconnected from the ventilator at end-inspiration in order to obtain flow-volume curves with and without the exhalation valve in place. MEASUREMENTS AND RESULTS: Peak flow (PEF) and the slope of the flow-volume curve during the last 50 % of expired volume (SF50) were obtained both with and without the exhalation valve in place. The exhalation valve caused a significant reduction in peak flow of 0.3 l/s (from 1.27 to 0.97 l/s) with the Siemens Servo 900 C ventilator and of 0.42 l/s (from 1.36 to 0.94 l/s) with the Siemens Servo 300 ventilator (p < 0.001). The SF50 was not affected. CONCLUSION: In mechanically ventilated patients, the exhalation valve causes a significant reduction in peak flow, but does not affect the SF50. This study further suggests that the second part of the expiratory flow-volume curve can be used to estimate patients' respiratory mechanics during ventilatory support.

Detection of flow limitation in mechanically ventilated patients.

OBJECTIVE: In mechanically ventilated patients flow limitation often goes unrecognised. We compared three methods for detection of flow limitation in mechanically ventilated patients: the resistance method, the negative expiratory pressure (NEP) method, and the interrupter method. DESIGN: Prospective study. SETTING: A medical intensive care unit in a university hospital. PATIENTS: Twenty-six patients (20 COPD, six other pathology), mechanically ventilated under sedation. MEASUREMENTS AND RESULTS: Respiratory mechanics were obtained during application of the three methods. For the resistance method, flow limitation was expressed as percentage of expiratory tidal volume, in which flow did not decrease (FLP-R). For the NEP method, flow limitation was expressed as percentage of expiratory tidal volume in which flow did not increase (FLP-NEP). For the interrupter method, flow limitation was expressed as area of spike-overshoot in flow after interruption. In 18 COPD patients, flow limitation was detected by all methods; mean FLP-R 76% (SD 12%), mean FLP-NEP 90% (SD 11%), mean spike area 21 ml (SD 7 ml). In three patients with other pathology, these values were, respectively, 20% (SD 19%), 48% (SD 21%), and 5 ml (SD 4 ml). The three methods were in close agreement. In nine patients the resistance method increased flow and in six patients the NEP method decreased flow compared to the unimpeded breath. CONCLUSIONS: In mechanically ventilated patients, flow limitation can well be detected by the resistance-, NEP-, and interrupter methods. However, the NEP method can overestimate the flow limited portion, while the resistance method can underestimate the flow limited portion. The interrupter method is found to be less practical.

Expiratory time constants in mechanically ventilated patients with and without COPD.

OBJECTIVE: In mechanically ventilated patients, the expiratory time constant provides information about the respiratory mechanics and the actual time needed for complete expiration. As an easy method to determine the time constant, the ratio of exhaled tidal volume to peak expiratory flow has been proposed. This assumes a single compartment model for the whole expiration. Since the latter has to be questioned in patients with chronic obstructive pulmonary disease (COPD), we compared time constants calculated from various parts of expiration and related these to time constants assessed with the interrupter method. DESIGN: Prospective study. SETTING: A medical intensive care unit in a university hospital. PATIENTS: Thirty-eight patients (18 severe COPD, eight mild COPD, 12 other pathologies) were studied during mechanical ventilation under sedation and paralysis. MEASUREMENTS AND RESULTS: Time constants determined from flow-volume curves at 100%, the last 75, 50, and 25% of expired tidal volume, were compared to time constants obtained from interrupter measurements. Furthermore, the time constants were related to the actual time needed for complete expiration and to the patient's pulmonary condition. The time constant determined from the last 75% of the expiratory flow-volume curve (RCfv75) was in closest agreement with the time constant obtained from the interrupter measurement, gave an accurate estimation of the actual time needed for complete expiration, and was discriminative for the severity of COPD. CONCLUSIONS: In mechanically ventilated patients with and without COPD, a time constant can well be calculated from the expiratory flow-volume curve for the last 75% of tidal volume, gives a good estimation of respiratory mechanics, and is easy to obtain at the bedside.

Extrapolation of thermodilution curves obtained during a pause in artificial ventilation.

The feasibility of three mathematical models to extrapolate the tail of thermodilution curves, when flectures are present in the descending limb, was tested in anesthetized pigs. The models were a local random walk model (LDRW), a log-normal distribution, and a two-compartment model. First, the accuracy of the extrapolation of the tail by each model was tested on two undisturbed curves by taking the truncation at five different points on the descending limb. The extrapolated curve area obtained from each model was compared with total area of the undisturbed curve. Next, dilution curves obtained during inspiratory hold maneuvers and characterized by deflection points were analyzed, taking the truncation just before deflection. The estimates of cardiac output by the models were compared with electromagnetically measured flow in the pulmonary artery. The area of the dilution curve was estimated more accurately when more information on the descending limb was available. The LDRW model and the log-normal distribution were superior to the two-compartment model regarding accuracy of cardiac output estimation and root-mean-square errors of the fit. Both models estimated curve area with an error less than 5% when truncation of the descending limb occurred below 60% of the peak value. In circumstances of mechanical ventilation, where only short periods of constant flow will be present, analyses of dilution curves based on the LDRW model or the log-normal distribution are recommended.

Wave-speed-determined flow limitation at peak flow in normal and asthmatic subjects.

The purpose of this study was to examine whether peak expiratory flow is determined by the wave-speed flow-limiting mechanism. We examined 17 healthy subjects and 11 subjects with stable asthma, the latter treated with inhaled bronchodilators and corticosteroids. We used an esophageal balloon and a Pitot-static probe positioned at five locations between the right lower lobe and midtrachea to obtain dynamic area-transmural pressure (A-Ptm) curves as described (O. F. Pedersen, B. Thiessen, and S. Lyager. J. Appl. Physiol. 52: 357-369, 1982). From these curves we obtained cross-sectional area (A) and airway compliance (Caw = dA/dPtm) at PEF, calculated flow at wave speed (Vws = A[A/(Caw*rho)0.5], where rho is density) and speed index is (SI = V/Vws). In 13 of 15 healthy and in 4 of 10 asthmatic subjects, who could produce satisfactory curves, SI at PEF was > 0.9 at one or more measured positions. Alveolar pressure continued to increase after PEF was achieved, suggesting flow limitation somewhere in the airway in all of these subjects. We conclude that wave speed is reached in central airways at PEF in most subjects, but it cannot be excluded that wave speed is also reached in more peripheral airways.

Eosinophils in the bronchial mucosa in relation to methacholine dose-response curves in atopic asthma.

Asthma is characterized by both local infiltration of eosinophils in the bronchial mucosa and bronchial hyperreactivity (BHR). A detailed characterization of BHR implies analysis of a histamine or methacholine dose-response curve yielding not only the dose at 20% fall of baseline forced expiratory volume in 1 s (FEV1), but also a plateau (P) representing the maximal narrowing response in terms of percent change in FEV1 and reactivity as the steepest slope at 50% of P (%FEV1/doubling dose). In the baseline condition, the specific airway conductance (sGaw) may be considered closely related to airway lumen diameter. In 20 nonsmoking asthmatic patients, methacholine dose-response curves were obtained, and a sigmoid model fit yielded the BHR indexes. Immunohistochemistry with the monoclonal antibodies (EG1 and EG2) was used to recognize the total number of eosinophils and activated eosinophils, respectively. The number of activated eosinophils was significantly correlated to both P (r = 0.62; P < 0.05) and sGaw (r = -0.52; P < 0.05), whereas weaker and nonsignificant correlations were found for dose at 20% fall of baseline FEV1 and the total number of eosinophils. We conclude that the number of activated eosinophils can be considered a marker of the inflammation-induced decrease of airway lumen diameter as represented by the plateau index and sGaw.

What limits endurance in normal children?

We have compared the results of a standard progressive maximal exercise test to those of an endurance exercise test in 22 healthy school children (13 girls, 9 boys, mean age 14.8 years) in order to examine whether it is possible to extrapolate results from a maximal test to predict their endurance capacity. All children performed a standard progressive maximal exercise test (15 W increments every minute until exhaustion) and an endurance test (individually calculated loads to mimic cycling at 20 km/h against a windforce 5 of Beaufort for 30 minutes) on 2 separate days. In both tests metabolic [oxygen uptake (VO2), CO2 production, blood lactate accumulation], ventilatory [minute ventilation (VE)], and circulatory variables were measured. From the maximal test the threshold of lactate accumulation (LT) was determined. Thirteen children were capable of enduring the 30 minute exercise (Group 1), and 9 could not complete the endurance test (Group 2). These two groups were comparable with respect to age, height, and baseline lung function. Children in Group 2 had a higher mean weight (P < 0.005) than those in Group 1. Eight of the 9 children in Group 2 were girls, whereas Group 1 consisted of 5 girls and 8 boys. There was no significant difference between Group 1 and 2 in the mean values of VO2 max, maximal respiratory exchange ratio (R max), VEmax, LT, oxygen pulse, and other variables obtained during the maximal exercise tests. Lactate accumulation during the endurance test in Group 2 was larger than in Group 1 (P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of accuracy and applicability of a portable electronic diary card spirometer for asthma treatment.

A pocked-sized turbine flowmeter and spirometer device, integrated with an electronic diary card (EDC-spirometer, Micro Medical, U.K.), was tested with a mechanical calibrator, in an outpatient clinic and in the home situation. A screen pneumotachometer was used as flow and volume reference. Ten devices were tested; interdevice variability was small with a mean variation coefficient of 1.1% for both forced expiratory volume in 1 s (FEV1) and peak expiratory flow (PEF) (SD 0.5 and 0.4, respectively) for eight settings of the calibrator. Mean difference from reference was -0.13 l (SD 0.04) for FEV1 (range 0.38-3.16) and 0.09 l s-1 (SD 0.09) for PEF (range 4.2-11.7). No significant deviation from linearity was present. Results obtained in the outpatient clinic confirmed the accuracy of FEV1 and PEF data obtained with the calibrator. However, linear regression analysis showed a mean underestimation of 0.45 l (SD of estimate 0.29) for forced vital capacity over the whole measurement range, probably due to a restricted integration time. In 10 optimally-treated chronic obstructive pulmonary disease patients in a family practice, PEF measurements were done in the home situation, both with the EDC spirometer and a mini-Wright peak flow meter. No significant differences in the diurnal variation of PEF were found. The PEF data from the mini-Wright meter were corrected for earlier reported flow-dependent systematic deviations. In the home situation, patients preferred the EDC spirometer. It is concluded that this device is applicable in the follow-up and treatment of asthma at home.

Modeling of the expiratory flow pattern of spontaneously breathing cats.

A mathematical model was developed describing the entire expiratory flow pattern during spontaneous, tidal breathing in the absence of expiratory muscle activity. It provides estimates for the time constants of the respiratory system (tau RS(model)) and of the decay of continuing inspiratory muscle activity in early expiration (tau mus(model)). In ten anesthetized, tracheostomized cats flow, tracheal pressure and diaphragmatic EMG were measured during normal expirations and expirations with four different added resistances. No significant differences were found between tau RS(model) (0.21-0.49 sec) obtained by fitting the model to the flow data and tau RS obtained from the straight part of the expiratory flow-volume curve. tau mus(model) (0.050-0.052 sec) was comparable to similar time constants obtained from the integrated diaphragmatic EMG or from end-inspiratory, tracheal occlusion pressure. Fitted peak flow and time to peak tidal expiratory flow were not significantly different from those measured. In conclusion, for spontaneously breathing, anesthetized cats our model provides a close fit of the expiratory flow and parameter estimates were comparable with independently measured values.

Long-term results of uvulopalatopharyngoplasty for obstructive sleep apnea syndrome.

OBJECTIVES: Assessment of the long-term effect of uvulopalatopharyngoplasty (UPPP) on snoring, excessive daytime sleepiness, and nocturnal oxygen desaturation index (ODI) in patients with obstructive sleep apnea syndrome. STUDY DESIGN: Evaluation of snoring, excessive daytime sleepiness, and ODI in patients treated by UPPP earlier. MATERIALS AND METHODS: Patients (n = 58) with a follow-up period of 11 to 74 months (median, 34 mo) were included in this study. Snoring and excessive daytime sleepiness were scored on specially designed semiquantitative scales. In all patients ODI was calculated from pulse-oximetry combined with polysomnography at base line and by polygraphy (MESAM 4) during follow-up in 38 patients. Long-term response was compared with 6-month response in the same cohort. RESULTS: There was a long-term improvement of snoring in 63% of patients, no change in 23%, and a deterioration in 14% (P < .00001). Overall snoring increased slightly between 6 months and long-term follow-up. There was an improvement of excessive daytime sleepiness in 38%, no change in 27%, and a deterioration in 35% (P = .80). Excessive daytime sleepiness showed a relapse to preoperative levels between 6 months and long-term follow-up. The median improvement of ODI was -1 (95% interpercentile range, 73-51) and was not significant (P = .35). In 5 of 13 patients in whom ODI at baseline exceeded 20, ODI was reduced to less than 20. In 4 of the 38 patients ODI was reduced to less than 5. The improvement of ODI decreased significantly between 6 months and long-term follow-up (P = .03). No relation was found between body mass index, Mueller maneuver, X-cephalometry, and long-term outcome. An additional finding was that the ODI decreased after UPPP in combination with tonsillectomy, compared with a slight increase after UPPP alone; the difference was significant (P = .008). CONCLUSION: The response to UPPP for obstructive sleep apnea syndrome decreases progressively over the years after surgery. UPPP in combination with tonsillectomy was more effective than UPPP alone.

Computer-controlled mechanical lung model for application in pulmonary function studies.

A computer controlled mechanical lung model has been developed for testing lung function equipment, validation of computer programs and simulation of impaired pulmonary mechanics. The construction, function and some applications are described. The physical model is constructed from two bellows and a pipe system representing the alveolar lung compartments of both lungs and airways, respectively. The bellows are surrounded by water simulating pleural and interstitial space. Volume changes of the bellows are accomplished via the fluid by a piston. The piston is driven by a servo-controlled electrical motor whose input is generated by a microcomputer. A wide range of breathing patterns can be simulated. The pipe system representing the trachea connects both bellows to the ambient air and is provided with exchangeable parts with known resistance. A compressible element (CE) can be inserted into the pipe system. The fluid-filled space around the CE is connected with the water compartment around the bellows; The CE is made from a stretched Penrose drain. The outlet of the pipe system can be interrupted at the command of an external microcomputer system. An automatic sequence of measurements can be programmed and is executed without the interaction of a technician.

Serial lung model for simulation and parameter estimation in body plethysmography.

A serial lung model with a compressible segment has been implemented to simulate different types of lung and airway disorders such as asthma, emphysema, fibrosis and upper airway obstruction. The model described can be used during normal breathing, and moreover the compliant segment is structured according to more recent physiological data. A parameter estimation technique was applied and its reliability and uniqueness were tested by means of sine wave input signals. The characteristics of the alveolar pressure/flow patterns simulated with the model agree to a great extent with those found in the literature. In the case of absence of noise the parameter estimation routine produced unique solutions for different simulated pathologic classes. The sensitivity of the different parameters depended on the values belonging to each class of pathology. Some more simplified models are presented and their advantages over the complex model in special types of pathology are demonstrated. Noise added to the simulated flow appeared to have no influence on the estimated parameters, in contradiction to the effects with noise added to the pressure signal. In that case effective resistance was accurately estimated. Where parameters had no influence, as for instance upper airway resistance in emphysema or peripheral airway resistance in upper airway obstruction, the measurement accuracy was less. In all other cases, a satisfactory accuracy could be obtained.

Computer-controlled flow resistance.

A computer-controlled flow resistance (CCR), to be used in a computer-controlled lung model, is presented. Flow is forced through a slit between a cylinder and a sleeve around the cylinder. The resulting flow resistance depends on the width, circumferences and the variable length of the slit. The variation in the length is computer-controlled by the position of the sleeve with respect to the cylinder. The total flow resistance also depends on inlet and outlet resistance at both sides of the slit and on flow. The dependence on flow is primarily due to the shape of the inlet of the slit. The resistance of the slit itself is almost independent of flow. The resistance is calculated during a calibration phase at different positions of the sleeve, for flow values from 0.05 to 1.0 litre.s-1 (inflow) and from -0.05 to -1.0 litre.s-1 (outflow). To simulate a required resistance pattern, as, for instance, will occur during breathing, at each moment the set position of the sleeve is calculated by means of an interpolation from the relationship between flow resistance and position of the sleeve. The internal diameter of the sleeve is fixed. To tune the resistance range for a specific simulation, the cylinder is changed for one with different diameter, changing the width of the slit.