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

Controlled expiration in mechanically-ventilated patients with chronic obstructive pulmonary disease (COPD)

In patients with severe chronic obstructive pulmonary disease (COPD), lung emptying may be affected by flow limitation. We tested the hypothesis that the airway compression leading to flow limitation can be counteracted by controlling the expiratory flow. The effects of an external resistor on lung emptying were studied in six patients with COPD, who were mechanically ventilated whilst sedated and paralysed. Respiratory mechanics were obtained during ventilatory support with and without the resistor. Airway compression was assessed using the interruptor method. For the study, a turbulent resistor was applied with the highest resistance level that did not increase the end-expiratory lung volume. At this resistance level, external positive end-expiratory pressure (PEEP) was generated in all patients. As total PEEP levels remained unchanged at both settings during the controlled expiration, the levels of intrinsic PEEP were significantly decreased from 0.96+/-0.30 to 0.53+/-0.19 kPa (mean+/-SD). Comparison of the expiratory flow-volume curves at both settings revealed that, during the controlled expiration, the flows were significantly decreased during the first 40% of the expired volume and significantly increased during the last 60%. As the end-expiratory lung volumes remained unchanged during both settings, these increments in flow indicated a decrease in effective resistance. Airway compression was observed during unimpeded expirations in all patients using the interruptor method. During the application of the resistor, airway compression was no longer detectable. In patients with chronic obstructive pulmonary disease receiving ventilatory support, the application of an external resistor could decrease effective expiratory resistance by counteracting airway compression, without increments in end-expiratory lung volume

Does phase 2 of the expiratory PCO2 versus volume curve have diagnostic value in emphysema patients?

It has been postulated that serial inhomogeneity of ventilation in the peripheral airways in emphysema is represented by the shape of expiratory carbon dioxide tension versus volume curve. We examined the diagnostic value of this test in patients with various degrees of emphysema. The volumes between 25-50% (V25-50) and 25-75% (V25-75) of the expiratory carbon dioxide tension versus volume curve were determined in 29 emphysematous patients (20 severely obstructed and 9 moderately obstructed), 12 asthma patients in exacerbation of symptoms, and 28 healthy controls. Discriminant analysis was used to examine whether these diagnostic groups could be separated. With regard to phase 2 of the expiratory CO2 versus volume curve (mixture of anatomic deadspace and alveolar air), a plot of intercept versus slope of the relationships of (V25-50) and (V25-75) versus inspiratory volume (VI) from functional residual capacity (FRC), obtained during natural breathing frequency, proved to be most discriminating in the separation between healthy controls and severely obstructed emphysema patients. Separating healthy controls and severely obstructed emphysema patients on the basis of the discriminant line for V25-50, 9 of the 12 asthma patients in exacerbation were classified as normal, and only 5 of the 9 moderately obstructed emphysema patients as emphysematous. For V25-75 involvement of phase 3 of the curve (alveolar plateau) in asthma patients in exacerbation caused a marked overlap with the severely obstructed emphysema patients. In the healthy controls, a fixed breathing frequency of 20 breaths.min-1 led to an increase of both volumes.(ABSTRACT TRUNCATED AT 250 WORDS

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 </= 8 mg/mL. BHR was subsequently studied by methacholine dose-response curves to which a sigmoid model was fitted for the estimation of plateau values and reactivity. Model fits of quasi-static lung pressure-volume (PV) curves yielded static lung compliance (Cstat), the exponential factor (KE) and elastic recoil at 90% of total lung capacity (P90TLC). Carbon monoxide (CO) transfer was measured with the standard single-breath method. RESULTS: Twenty-four patients were included in the study, and reliable PV data could be obtained from 19. The following mean values ( +/- SD) were taken: FEV(1), 65 +/- 12% of predicted; reversibility, 5.6 +/- 3.1% of predicted; the PC(20) for methacholine, 4.3 +/- 5.2 mg/mL; reactivity, 11.0 +/- 5.6% FEV(1)/doubling dose; plateau, 48.8 +/- 17.4% FEV(1); transfer factor, 76.7 +/- 17.9% of predicted; transfer coefficient for carbon monoxide (KCO), 85.9 +/- 22.6% of predicted; Cstat, 4.28 +/- 2.8 kPa; shape factor (KE), 1.9 +/- 1.5 kPa; and P90TLC, 1.1 +/- 0.8 kPa. We confirmed earlier reported relationships between Cstat, on the one hand, and KE (p < 0.0001), P90TLC (p = 0.0012), and KCO percent predicted (p = 0.006), on the other hand. The indexes of the methacholine provocation test were not related to any parameter of lung elasticity and CO transfer. CONCLUSION: BHR in COPD patients who smoke most probably is determined by airways pathology rather than by the augmented mechanical behavior caused by lung parenchymal destruction

Effects of fluticasone propionate on methacholine dose-response curves in nonsmoking atopic asthmatics

Methacholine is frequently used to determine bronchial hyperresponsiveness (BHR) and to generate dose-response curves. These curves are characterized by a threshold (provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20) = sensitivity), slope (reactivity) and maximal response (plateau). We investigated the efficacy of 12 weeks of treatment with 1,000 microg fluticasone propionate in a double-blind, placebo-controlled study in 33 atopic asthmatics. The outcome measures used were the influence on BHR and the different indices of the methacholine dose-response (MDR) curve. After 2 weeks run-in, baseline lung function data were obtained and a MDR curve was measured with doubling concentrations of the methacholine from 0.03 to 256 mg x mL(-1). MDR curves were repeated after 6 and 12 weeks. A recently developed, sigmoid cumulative Gaussian distribution function was fitted to the data. Although sensitivity was obtained by linear interpolation of two successive log2 concentrations, reactivity, plateau and the effective concentration at 50% of the plateau value (EC50) were obtained as best fit parameters. In the fluticasone group, significant changes occurred after 6 weeks with respect to means of PC20 (an increase of 3.4 doubling doses), plateau value fall in forced expiratory volume in one second (FEV1) (from 58% at randomization to 41% at 6 weeks) and baseline FEV1 (from 3.46 to 3.75 L) in contrast to the placebo group. Stabilization occurred after 12 weeks. Changes for reactivity were less marked, whereas changes in log, EC50 were not significantly different between the groups. We conclude that fluticasone is very effective in decreasing the maximal airway narrowing response and in increasing PC20. However, it is likely that part of this increase is related to the decrease of the plateau of maximal response

Dead space and slope indices from the expiratory carbon dioxide tension-volume curve

The slope of phase 3 and three noninvasively determined dead space estimates derived from the expiratory carbon dioxide tension (PCO2) versus volume curve, including the Bohr dead space (VD,Bohr), the Fowler dead space (VD,Fowler) and pre-interface expirate (PIE), were investigated in 28 healthy control subjects, 12 asthma and 29 emphysema patients (20 severely obstructed and nine moderately obstructed) with the aim to establish diagnostic value. Because breath volume and frequency are closely related to CO2 elimination, the recording procedures included varying breath volumes in all subjects during self-chosen/natural breathing frequency, and fixed frequencies of 10, 15 and 20 breaths x min(-1) with varying breath volumes only in the healthy controls. From the relationships of the variables with tidal volume (VT), the values at 1 L were estimated to compare the groups. The slopes of phase 3 and VD,Bohr at 1 L VT showed the most significant difference between controls and patients with asthma or emphysema, compared to the other two dead space estimates, and were related to the degree of airways obstruction. Discrimination between no-emphysema (asthma and controls) and emphysema patients was possible on the basis of a plot of intercept and slope of the relationship between VD,Bohr and VT. A combination of both the slope of phase 3 and VD,Bohr of a breath of 1 L was equally discriminating. The influence of fixed frequencies in the controls did not change the results. The conclusion is that Bohr dead space in relation to tidal volume seems to have diagnostic properties separating patients with asthma from patients with emphysema with the same degree of airways obstruction. Equally discriminating was a combination of both phase 3 and Bohr dead space of a breath of 1 L. The different pathophysiological mechanisms in asthma and emphysema leading to airways obstruction are probably responsible for these results

Physiological and morphological determinants of maximal expiratory flow in chronic obstructive lung disease

Maximal expiratory flow in chronic obstructive pulmonary disease (COPD) could be reduced by three different mechanisms; loss of lung elastic recoil, decreased airway conductance upstream of flow-limiting segments; and increased collapsibility of airways. We hypothesized that decreased upstream conductance would be related to inflammation and thickening of the airway walls, increased collapsibility would be related to decreased airway cartilage volume, and decreased collapsibility to inflammation and thickening of the airway walls. Lung tissue was obtained from 72 patients with different degrees of COPD, who were operated upon for a solitary peripheral lung lesion. Maximal flow-static recoil (MFSR) plots to estimate upstream resistance and airway collapsibility were derived in 59 patients from preoperatively measured maximal expiratory flow-volume and pressure-volume curves. In 341 transversely cut airway sections, airway size, airway wall dimensions and inflammatory changes were measured. Airflow obstruction correlated with lung elastic recoil and the MFSR estimate of airway conductance but not to airway collapsibility or to the amount of airway cartilage. The upstream conductance decreased as the inner wall became thicker. Airway collapsibility did not correlate with the amount of airway cartilage, inflammation, or airway wall thickness. We conclude that the maximal flow-static recoil model does not adequately reflect the collapsibility of the flow-limiting segment