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Ventilatory and mouth occlusion pressure (P0.1) responses to progressive isocapnic-hypoxia and hyperoxic-hypercapnia were compared in eleven healthy sleeping men during the same night. Hypoxic and hypercapnic responses were determined during wakefulness, non-rapid and rapid-eye-movement sleep. The following parameters were measured: minute ventilation (VE), tidal volume (VT), 'duty cycle' (TI/TT), mean inspiratory flow rate (VT/TI) and P0.1, an index of the neuromuscular inspiratory drive. To allow a direct comparison between the two types of chemostimuli, responses were characterized by the value of the different parameters at 'equivalent' levels of hypoxia and hypercapnia, i.e., at levels which produced the same P0.1 during wakefulness: an oxyhaemoglobin saturation (Sao2) of 94% during the isocapnic-hypoxic tests (PETCO2 = 42.5 +/- 1.2 mmHg) was found to be equivalent to a PETCO2 of 47.4 +/- 3.7 mmHg during hypoxic-hypercapnic tests. For both tests, the arousal levels of the stimulus and of P0.1 were similar in all sleep stages. Sleep did not significantly modify P0.1 or breathing pattern responses to hypoxia (Sao2 = 94%). In contrast, at the 'equivalent' level of hypercapnic stimulation, P0.1 (P less than 0.05) and VE (P less than 0.01) responses were significantly impaired, particularly in REM sleep, with a decrease in VT (P less than 0.01) and VT/TI (P less than 0.05) responses. The results suggest that CO2 intracranial receptor mechanisms are more affected by sleep than the O2 peripheral receptor activity.

Lung volumes are subdivided into static and dynamic lung volumes. Static lung volumes are measured by methods which are based on the completeness of respiratory manoeuvres, so that the velocity of the manoeuvres should be adjusted accordingly. The measurements taken during fast breathing movements are described as dynamic lung volumes and as forced inspiratory and expiratory flows. ### 1.1 Static lung volumes and capacities The volume of gas in the lung and intrathoracic airways is determined by the properties of lung parenchyma and surrounding organs and tissues, surface tension, the force exerted by respiratory muscles, by lung reflexes and by the properties of airways. The gas volumes of thorax and lung are the same except in the case of a pneumothorax. If two or more subdivisions of the total lung capacity are taken together, the sum of the constituent volumes is described as a lung capacity. Lung volumes and capacities are described in more detail in § 2. #### 1.1.1 Determinants Factors which determine the size of the normal lung include stature, age, sex, body mass, posture, habitus, ethnic group, reflex factors and daily activity pattern. The level of maximal inspiration (total lung capacity, TLC) is influenced by the force developed by the inspiratory muscles (disorders include e.g. muscular dystrophy), the elastic recoil of the lung (disorders include e.g. pulmonary fibrosis and emphysema) and the elastic properties of the thorax and adjacent structures (disorders include e.g. ankylosis of joints). The level of maximal expiration (residual volume, RV) is determined by the force exerted by respiratory muscles (disorders include e.g. muscle paralysis), obstruction, occlusion and compression of small airways (disorders include e.g. emphysema) and by the mechanical properties of lung and thorax (disorders include diffuse fibrosis, kyphoscoliosis). Assessing the total lung capacity is indispensable in establishing a restrictive ventilatory defect or in diagnosing abnormal lung distensibility, as may occur in patients …

The forced oscillation technique is useful in detecting changes in upper airway obstruction in patients with sleep apnoea undergoing continuous positive airway pressure (CPAP) ventilation. The aim of this study was to implement and evaluate a method for estimating respiratory impedance (Zrs) from the pressure and flow recorded at the inlet of the CPAP tubing. The method is based on correcting impedance measured at the inlet of the CPAP tubing (Zi) for the effect of the tubing and the exhalation port. The method was evaluated in mechanical analogues and in a healthy subject. Sinusoidal oscillation of 5, 10 and 20 Hz were superimposed on CPAP (5-15 cmH2O). At 5 Hz, the changes in airflow obstruction were substantially underestimated by Zi. Furthermore, Zi exhibited a negative dependence on Zrs at 20 Hz. The assessment of Zrs was greatly improved after correcting Zi for the effects of the CPAP tubing and the exhalation port. Zrs was well estimated at low frequencies, reaching very high values during total occlusion (>60 cmH2O x s x L(-1) at 5-10 Hz). These results indicate that changes in airflow obstruction can be detected using the forced oscillation technique from pressure and flow recorded on the continuous positive airway pressure device. This facilitates the clinical application of the forced oscillation technique for monitoring upper airway patency during sleep.

Enhanced negative volume dependence of airway resistance is associated with bronchoconstriction in tracheostomized paralysed open-chest animals. Significant upper airways responses may be associated with bronchoconstriction and could thereby alter the pattern of volume dependence in spontaneously breathing subjects. The aim of the study was to test whether volume dependence of respiratory resistance (Rrs) could be demonstrated in preschool children undergoing routine methacholine challenge. The volume dependence of respiratory oscillation resistance at 12 and 20 Hz (Rrs,12 and Rrs,20) was examined in eight 4-5.5-yr-old children showing a positive response to methacholine. Multiple linear regression analysis was also used to account for flow dependence during tidal breathing (Rrs,12 or Rrs,20=K1+K2 inverted question markV' inverted question mark+K3V). Rrs,12 and Rrs,20 yielded similar results. Negative volume dependence was present at baseline and significantly enhanced by methacholine (p

Thoracic gas volume (TGV) may be measured and total respiratory impedance (Zrs) may be partitioned into its airway and tissue (Zti) components by combining forced oscillations and plethysmographic measurements of alveolar gas compression (Vpl) (Peslin, Duvivier, 1998, J. Appl. Physiol. 84, 553-561 and 862-867). The method requires that the thermal component of Vpl (Vpl,th) be eliminated by conditioning inspired gas to BTPS. We have evaluated a technically simpler method where Vpl,th is corrected using a thermal gain (G) and a thermal time constant (theta). Zrs and the relationship between Vpl and flow (Hpl) were measured in 15 healthy subjects at frequencies from 4 to 29 Hz. G was obtained from the breathing component of Vpl in phase with volume. Zti and TGV (TGVos) were computed from Zrs and from Hpl after the latter was corrected using G and different values of theta. With theta = 27.5 ms both the difference between TGVos and standard plethysmographic TGV, and the difference between Zti spectra obtained with and without gas conditioning were minimal. We conclude that the simpler method is adequate for both purposes.

In population studies, the provocative dose (PD) of bronchoconstrictor causing a significant decrement in lung function cannot be calculated for most subjects. Dose-response curves for carbachol were examined to determine whether this relationship can be summarized by means of a continuous index likely to be calculable for all subjects, namely the two-point dose response slope (DRS) of mean resistance (Rm) and resistance at 10 Hz (R10) measured by the forced oscillation technique (FOT). Five doses of carbachol (320 microg each) were inhaled by 71 patients referred for investigation of asthma (n=16), chronic cough (n=15), nasal polyposis (n=8), chronic rhinitis (n=8), dyspnoea (n=8), urticaria (n=5), post-anaphylactic shock (n=4) and miscellaneous conditions (n=7). FOT resistance and forced expiratory volume in one second (FEV1) were measured in close succession. The PD of carbachol leading to a fall in FEV1 > or = 20% (PD20) or a rise in Rm or R10 > or = 47% (PD47,Rm and PD47,R10) were calculated by interpolation. DRS for FEV1 (DRSFEV1), Rm (DRSRm) and R10 (DRSR10) were obtained as the percentage change at last dose divided by the total dose of carbachol. The sensitivity (Se) and specificity (Sp) of DRSRm, DRS10 delta%Rm and delta%R10 in detecting spirometric bronchial hyperresponsiveness (BHR, fall in FEV1 > or = 20%) were assessed by receiver operating characteristic (ROC) curves. There were 23 (32%) "spirometric" reactors. PD20 correlated strongly with DRSFEV1 (r=-0.962; p=0.0001); PD47,Rm correlated significantly with DRSRm (r=-0.648; p=0.0001) and PD47,R10 with DRSR10 (r=-0.552; p=0.0001). DRSFEV1 correlated significantly with both DRSRm (r=0.700; p=0.0001) and DRSR10 (r=0.784; p=0.0001). The Se and Sp of the various FOT indices to correctly detect spirometric BHR were as follows: DRSRm: Se=91.3%, Sp=81.2%; DRSR10: Se=91.3%, Sp=95.8%; delta%Rm: Se=86.9%, Sp=52.1%; and delta%R10: Se=91.3%, Sp=58.3%. Dose-response slopes of indices of forced oscillation technique resistance, especially the dose-response slope of resistance at 10Hz are proposed as simple quantitative indices of bronchial responsiveness which can be calculated for all subjects and that may be useful in occupational epidemiology.

Simultaneous measurement of input (Zin) and transfer impedances (Ztr) allows separation of airway and tissue properties at a single frequency, without making assumptions concerning the structure of the two compartments. This approach offers the possibility of studying the variation in airway impedance (Zaw) during the respiratory cycle. Zin and Ztr were measured at frequencies of 10, 20, 30 and 40 Hz in eight healthy subjects to study the variations in Zaw according to a modification of the Rohrer's equation: X=K1+K2(V'ao)-K3V, where V is volume and V'ao the flow at the airway opening. The results showed that Zaw could be modelled as a simple resistance-inertance pathway. Variations in airway resistance (Raw) with flow were greater during expiration than during inspiration with K2 values varying from 0.76-0.90 hPa x s2 x L(-2) during inspiration and 0.84-1.47 hPa x s2 x L(-2) during expiration, independently of frequency. Raw was negative volume dependent; it decreased more with increasing volume during inspiration than during expiration. Airways inertance calculated from the imaginary part of Zaw also underwent systematic variations during the respiratory cycle, but, in contrast to Raw, flow dependence was negative during both phases. In conclusion, the approach used in this study allows flow and volume dependencies of airways mechanical properties to be studied and can also provide indices of airway patency independently of flow, which is of great potential interest for studying variations in airway resistance during bronchomotor tests.

Test reproducibility is an important consideration when interpreting results and should be set as a goal during data collection. Reproducibility criteria may need to be different for different subject groups and are instrument and procedure-dependent. Ideally, the within-subject variability for each lung volume and measurement technique used should be established for each laboratory. These values also need to be established for each different subject group (age and disease). At a minimum, test reproducibility should be monitored and controlled and each laboratory should define their between-day reproducibility of measurements on at least one "reference" subject from ongoing periodic (e.g., weekly or monthly) measurements as part of their laboratory's quality control programme. For plethysmographic measurements functional residual capacity (FRC)pleth multiple determinations and a corresponding test reproducibility criteria is probably justified.

The purpose of this study was to test a plethysmographic method of measuring thoracic gas volume (TGV) that, contrary to the usual panting method, would not require any active cooperation from the subject. It is based on the assumption that the out-of-phase component of airway impedance varies linearly with frequency. By using that assumption, TGV may be computed by combining measurements of total respiratory impedance (Zrs) and of the relationship between the plethysmographic signal (Vpl) and airway flow (V˙) during forced oscillations at several frequencies. Zrs and Vpl/V˙were measured at 10 noninteger multiple frequencies ranging from 4 to 29 Hz in 15 subjects breathing gas in nearlybtps conditions. Forced oscillation measurements were immediately followed by determination of TGV by the standard method. The data were analyzed on different frequency ranges, and the best agreement was seen in the 6- to 29-Hz range. Within that range, forced oscillation TGV and standard TGV differed little (3.92 ± 0.66 vs. 3.83 ± 0.73 liters, n = 77, P < 0.05) and were strongly correlated ( r = 0.875); the differences were not correlated to the mean of the two estimates, and their SD was 0.35 liter. In seven subjects the differences were significantly different from zero, which may, in part, be due to imperfect gas conditioning. We conclude that the method is not highly accurate but could prove useful when, for lack of sufficient cooperation, the panting method cannot be used. The results of computer simulation, however, suggest that the method would be unreliable in the presence of severe airway inhomogeneity or peripheral airway obstruction.

The aim of the study was to describe the pattern of respiratory oscillation mechanics and responses to positive end-expiratory pressure (PEEP) in bronchiolitis. Six infants were studied during the course of mechanical ventilation. A 20 Hz sinusoidal pressure variation was applied at the endotracheal tube where flow was measured with a pneumotachograph. Resistance and reactance obtained from the complex pressure-flow ratio were separated during inspiration (R(rs,i); X(rs,i)) and expiration (R(rs,e); X(rs,e)), and the differences between R(rs,i) and R(rs,e) (deltaR(rs)) and X(rs,i) and X(rs,e) (deltaX(rs)) were calculated. The data were corrected for the mechanical characteristics of the endotracheal tube. The measurements were repeated while PEEP was varied between 0 and 8 hPa. Two infants were found to have normal R(rs) and near-zero X(rs) and both parameters exhibited little change within the respiratory cycle or with varying PEEP. Four infants had high R(rs) at zero PEEP. In two, R(rs,i) was markedly elevated (108.5 and 85.2 hPa.s/L, respectively), and X(rs,i) was markedly negative (-25.0 and -22.5 hPa.s/L, respectively) at zero PEEP, while deltaR(rs) and deltaX(rs) were small. R(rs,i) and the absolute value of X(rs,i) decreased with increasing PEEP. This pattern of oscillation mechanics was consistent with low lung volumes and atelectasis, being reversed by increasing PEEP. In the remaining two subjects, R(rs,i) was moderately elevated (57.8 and 53.6 hPa.s/L, respectively) and X(rs,i) moderately negative (-12.5 and -7.7 hPa.s/L, respectively) at zero PEEP. DeltaR(rs) (-59.8 and -56.5 hPa.s/L, respectively) and delta(rs) (28.1 and 48.7 hPa.s/L, respectively) were large, but were dramatically reduced by increasing PEEP. These patterns were consistent with expiratory airflow limitation. Measurements of respiratory impedance are, therefore, informative in regard to the pathophysiological mechanisms occurring in bronchiolitis during mechanical ventilation, and they may be helpful in setting the level and assessing the effect of PEEP.

New Zealand male rabbits were anaesthetized with thiopental, tracheotomized, curarized by vecuronium bromide and mechanically ventilated. Six rabbits received L-NAME 10 mg kg -1 i.v., six rabbits L-NAME 15 mg kg -1 iv, and six rabbits received saline i.v. (controls), 5 min before a histamine aerosol (2% solution during 5 min). Six others rabbits received an injection of L-NAME 15 mg kg -1 iv, 5 min before the histamine aerosol, followed by an infusion of L-arginine over a 60- min period. Total respiratory resistance (Rrs) and elastance (Ers) were derived by least square analysis of the relationship between tracheal pressure and flow, and computed every minute before and over a 1-h period after the histamine aerosol. Oxygen free radicals (OFR) were measured with a luminometer, in microsomes from lung homogenates at the end of the experiment. Compared with the histamine response of the control group, the Rrs response in the L-NAME 10 group was slightly less, while Ers changes were the same in the two groups. In contrast, L-NAME 15 was responsible for an increased Rrs response, the difference being significant (P < 0.05) only between 15 and 40 min after the aerosol (+114% vs. + 85% in controls at the 20th min). The increase in Ers with L-NAME 15 was stronger and significantly larger (+71% vs. +42% in controls at the 20th min after the histamine aerosol, P < 0.001). The relatively greater effect of L-NAME on Ers than on Rrs suggests that NO predominantly modulates the response to histamine of the peripheral lung rather than that of the large airways. Furthermore, the effect of L-NAME on Rrs was completely abolished by L-arginine, while its effect on Ers was only partially reversed. This suggests that the changes in Ers are partly related to a hardly reversible phenomenon. Possibly, the mechanical changes are linked with the rise of OFR in the lung parenchyma, which were significantly higher in the L-NAME 15 group compared to the control group (P < 0.05).

Instantaneous respiratory effective elastance (E t eff ) and tissue resistance (R t ) may be measured by studying the relationship between flow at the airway opening and at the chest during forced oscillations; using that method it has been shown that R t varies little during breathing while E t eff presents much larger phasic variations than can be explained by the curvature of the static pressure-volume curve ( Tomalak et al., 1997 ). The aim of this study was to test the hypothesis that the large variations of E t eff were related to the activity of respiratory muscles. For this, we studied in six healthy subjects the changes in E t eff and R t induced by inspiratory and expiratory elastic loading (IEL and EEL, respectively), resistive loading (REL) and assisted ventilation (ASV) while keeping lung volume, ventilation and breathing pattern as constant as possible. IEL and EEL predominantly increased E t eff during the inspiratory and expiratory phases, respectively; in contrast, ASV decreased E t eff during inspiration and almost completely abolished its positive volume dependence. The changes of R t usually paralleled those of E t eff . We conclude that respiratory muscle activity is responsible for most of the variations of E t eff during spontaneous breathing.

Abstract We tested the hypothesis that a simple change in wall composition (medial calcium overload of elastic fibers) can decrease aortic elasticity. Calcium overload was produced by hypervitaminosis D plus nicotine (VDN) in the young rat. Two months later, measurement of central aortic mean blood pressure in the unanesthetized, unrestrained rat showed that the VDN rat suffered from isolated systolic hypertension but that mean blood pressure was normal. Wall thickness and internal diameter determined after in situ pressurized fixation were unchanged, as was calculated wall stress. Wall stiffness was estimated from (1) elastic modulus (determined with the Moens-Korteweg equation and values for aortic pulse wave velocity in the unanesthetized, unrestrained rat and arterial dimensions) and (2) isobaric elasticity (=slope relating pulse wave velocity to mean intraluminal pressure in the phenylephrine-infused, pithed rat preparation). Both increased after VDN, and both were significantly correlated to the wall content of calcium and the elastin-specific amino acids desmosine and isodesmosine. Left ventricular hypertrophy occurred in the VDN model, and left ventricular mass was related to isobaric elasticity. In conclusion, elastocalcinosis induces destruction of elastic fibers, which leads to arterial stiffness, and the latter may be involved in the development of left ventricular hypertrophy in a normotensive model.

Tomalak, W., R. Peslin, and C. Duvivier. Respiratory tissue properties derived from flow transfer function in healthy humans. J. Appl. Physiol. 82(4): 1098–1106, 1997.—Assuming homogeneity of alveolar pressure, the relationship between airway flow and flow at the chest during forced oscillation at the airway opening [flow transfer function (FTF)] is related to lung and chest wall tissue impedance (Zti): FTF = 1 + Zti/Zg, where Zg is alveolar gas impedance, which is inversely proportional to thoracic gas volume. By using a flow-type body plethysmograph to obtain flow rate at body surface, FTF has been measured at oscillation frequencies ( fos) of 10, 20, 30 and 40 Hz in eight healthy subjects during both quiet and deep breathing. The data were corrected for the flow shunted through upper airway walls and analyzed in terms of tissue resistance (Rti) and effective elastance (Eti,eff) by using plethysmographically measured thoracic gas volume values. In most subjects, Rti was seen to decrease with increasing fosand Eti,eff to vary curvilinearly with fos2, which is suggestive of mechanical inhomogeneity. Rti presented a weak volume dependence during breathing, variable in sign according to fosand among subjects. In contrast, Eti,eff usually exhibited a U-shaped pattern with a minimum located a little above or below functional residual capacity and a steep increase with decreasing or increasing volume (30–80 hPa/l2) on either side. These variations are in excess of those expected from the sigmoid shape of the static pressure-volume curve and may reflect the effect of respiratory muscle activity. We conclude that FTF measurement is an interesting tool to study Rti and Eti,eff and that these parameters have probably different physiological determinants.

Assessment of upper airway mechanics in patients with obstructive sleep apnea/hypopnea (OSA) can be carried out qualitatively from indirect signals (flow pattern, snoring, strain gauges, inductance plethysmography) or quantitatively by means of invasive estimation of esophageal pressure. The forced oscillation technique (FOT) is a noninvasive method of potential interest for quantitatively assessing airway obstruction in the sleeping patient. The aim of this work was to ascertain in a model study whether FOT could provide an index of airway obstruction when applied at the conditions of total and partial occlusions similar to the ones found in patients with OSA. An airway analog closely mimicking upper airway collapsibility was constructed and mechanically characterized by the relationship between its flow, upstream and downstream pressures as well as by means of FOT. We simulated total collapse (apnea), different levels of partial collapse with flow limitation (hypopnea), and release of airway obstruction when the collapsible analog was used as an artificial upper airway in a spontaneously breathing subject submitted to continuous positive airway pressure (CPAP) up to 14 cm H2O.s/L. The results showed that the amplitude of airway impedance measured by FOT was a suitable index to detect obstruction in collapsible segments. We concluded from this realistic model study that FOT could be a valuable tool for quantitatively assessing airway obstruction in patients with OSA treated with CPAP. This noninvasive technique is potentially useful both in studying upper airway mechanics in detail and in automatically monitoring airway obstruction in routine studies.

The upper airways may contribute to increases in airway resistance in response to a bronchial challenge, and thus decrease the specificity of such challenge tests to diagnose airway hyperresponsiveness when forced oscillation techniques are used to evaluate changes in respiratory system resistance (Rrs). A concomitent decrease in respiratory system reactance (Xrs) may indicate a change in the intrathoracic airways and/or lung parenchyma, provided that extrathoracic airway wall motion is prevented. To test the value of Xrs in the evaluation of bronchial hyperresponsiveness, we studied the respiratory impedance response to methacholine in 38 children with a history of asthma (aged 6-14.5 years), and compared the results to changes in the forced expiratory volume in one second (FEV1). Rrs and Xrs were measured by the forced oscillation technique with pseudorandom (11 subjects) or sinusoidal (27 subjects) pressure variations applied around the child's head to minimize upper airway wall motion. Changes in Rrs and in Xrs at 12 Hz (Rrs12, Xrs 12) correlated significantly with changes in FEV1 (P or = 20% was observed in 23 subjects. When these 23 subjects were compared with the 15 children who did not show significant changes in FEV1, the responding group had larger mean +/- SEM changes in Rrs (116.0 +/- 13.2% vs 60.4 +/- 11.4%, P < 0.006) and in Xrs (-2.1 +/- 0.4 hPa.s/L vs -0.9 +/- 0.3 hPa.s/L, P < 0.03) than the nonresponders. The receiver operating characteristics (ROC) curve analysis was used to assess the diagnostic value, i.e., specificity and sensitivity, of different levels of change in Rrs and Xrs, with reference to FEV1. The overall incidence of false results was similar for Rrs and Xrs. The optimum diagnostic value for Rrs was a 70% increase, which corresponded to a sensitivity of 87% and a specificity of 67%. For Xrs the optimum decision level was -1 hPa.s/L, corresponding to a sensitivity of 70% and a specificity of 80%. It is concluded that Xrs may improve the specificity of the forced oscillation technique in interpreting the airway response to methacholine. This may be of particular interest in young children unable to perform forced expirations.

Specific airway resistance (sRaw) measured by body plethysmography without conditioning of the inspired air to BTPS exhibits a strong frequency dependence related to the fact that the warming and wetting of the gas in the airways is not instantaneous (R. Peslin, C. Duvivier, M. Vassiliou, and C. Gallina. J. Appl. Physiol. 79: 1958-1965, 1995). We have tested three methods in 21 healthy subjects to correct for that artifact by using a simple model, assuming a first-order thermal process characterized by a single time constant. The corrections required entering an assumed constant value for (methods 1 and 2) and/or for airway inertance (methods 1 and 3) and/or measuring the inspired gas temperature and water vapor saturation (methods 2 and 3). The frequency dependence of sRaw was measured from 0.5 to 3 Hz both with (sRawETPS) and without (sRawam) gas conditioning. With optimal values for and/or airway inertance, the mean difference between sRawam and sRawETPS was close to zero with all three methods, but the root mean square difference was significantly lower with method 2 (0.83 +/- 0.35 hPa.s compared with 1.21 +/- 0.54 and 1.20 +/- 0.49 hPa.s with methods 1 and 2, respectively). We conclude that the thermal artifact of sRaw measurements may be best corrected by using temperature measurements and an assumed time constant (0.152 s with our equipment).

We have previously observed large phasic variations of respiratory mechanical impedance in chronic obstructive pulmonary disease (COPD) patients mechanically-ventilated for acute respiratory failure, and postulated that they were due to expiratory flow limitation (EFL). The aim of this study was to test that assumption experimentally and to assess the value of impedance for automatic and noninvasive detection of EFL during mechanical ventilation. The study was performed: 1) in a mechanical analogue, including a flow-limiting element; and 2) in eight anaesthetized and paralysed rabbits, before and during histamine infusion. In both instances, EFL was obtained by lowering the expiratory pressure, using a computer-controlled ventilator; the absence of flow increase when expiratory pressure was further lowered was taken as evidence of EFL. Impedance was measured by applying 15 Hz oscillations at the airway opening. Its real (Re) and imaginary (Im) parts were measured separately during the inspiratory and the expiratory phases, and their differences were related to the mean inspiratory modulus. With the analogue, EFL was accompanied by large decreases both of Re and Im during the expiratory phase. In the rabbits, phasic variations of Re were variable in sign and were not significantly different with and without EFL. In contrast, EFL systematically and specifically decreased Im during the expiratory phase. A threshold of -50% provided a sensitivity of 96% and a specificity of 100% for detecting EFL. The observed phasic variations may be explained by airway wall shunt properties. The study suggests that a large decrease of the imaginary part of impedance during the expiratory phase is a sensitive and specific index of expiratory flow limitation during artificial ventilation.

The aim of this study was to establish the ability to estimate separate airway and tissue properties from transfer respiratory impedance (Zrs,tr) data in the presence of airway obstruction. Zrs,tr, thoracic gas volume (TGV) and airway resistance (Raw,pleth) were measured in the presence of obstruction and after use of a bronchodilator (BD) in 13 normal or asymptomatic asthmatic adults and 28 children with symptomatic asthma. An analytical approach was used to solve the equations of a simplified variant of DuBois' model, including airway resistance (Raw*) and inertance (Iaw), tissue compliance (Ct) and resistance (Rt) and pulmonary gas compliance (Cg). The equations of the model could not be reliably solved in four children before BD. Mean Raw,pleth was not different from mean Raw* in adults before (mean +/- SEM) (3.4 +/- 0.5 vs 3.1 +/- 0.3 hPa.s.L-1) or after BD (1.4 +/- 0.2 vs 1.8 +/- 0.2 hPa.s.L-1), or in children after BD (2.9 +/- 0.3 vs 3.2 +/- 0.2 hPa.s.L-1, respectively). In children before BD, Raw* was significantly underestimated compared with Raw,pleth (3.8 +/- 0.4 vs 5.4 +/- 0.6 hPa.s.L-1). Overall, a significant positive correlation was found between the difference [Raw,pleth - Raw*] and Raw,pleth (r = 0.82). In adults, BD induced a decrease in Raw* and Rt, an increase in Ct, and no change in Iaw. In children after BD, there was no significant change in Raw* or Ct, whilst Rt decreased and Iaw increased. Taking Raw,pleth as the gold standard, it is concluded that coherent estimation of parameters of DuBois' model may be obtained from combined Zrs,tr and TGV measurements in normal subjects and moderately obstructed adults, but not in children with significant airway obstruction. This seems to be due to the systematic under-estimation of Raw*.

BACKGROUND--The use of lung sound monitoring during bronchial provocation testing has not been clearly demonstrated. The appearance of wheeze and changes in inspiratory breath sound intensity have been analysed and related to changes in spirometric parameters and to airways hyperresponsiveness. METHODS--Lung sounds were recorded in 38 patients undergoing a routine carbachol airway challenge (CAC) test. Spirometric testing was performed before and after the inhalation of each of five cumulative doses of 320 micrograms carbachol; a fall in forced expiratory volume in one second (FEV1) by 20% or more was considered as significant. Lung sound analysis was carried out using a computerised system. RESULTS--The CAC test was positive (CAC+) in 21 patients and negative (CAC-) in 17. At the final stage of the challenge, wheeze was identified in 10 positive patients (48%) and in one negative patient (6%); in non-wheezers the inspiratory breath sound intensity decreased significantly from baseline in 11 CAC+ patients (mean (SD) change -35 (24%)) but not in 16 CAC- patients (mean (SD) change 5 (24%)). In all non-wheezers a linear relationship was found between breath sound intensity and the squared inspiratory airflow (r = 0.53-0.92) which became looser after the inhalation of carbachol. CONCLUSION--When unertaking bronchial provocation testing the accurate identification of wheeze may prove useful in avoiding or shortening the test because of the presumed relationship between wheeze and airways hyperresponsiveness. Changes in breath sound intensity may also be useful, but further studies are required to define the threshold for significant changes in this index.

Respiratory resistance (Rrs) and elastance (Ers) are commonly measured in artificially-ventilated patients or animals by multiple linear regression of airway opening pressure (Pao) versus flow (V') and volume (V), according to the first order model: Pao = P0 + Ers.V + Rrs.V', where P0 is the static recoil pressure at end-expiration. An alternative way to obtain Rrs and Ers is to derive them from the Fourier coefficients of Pao and V' at the breathing frequency. A potential advantage of the second approach over the first is that it should be insensitive to a zero offset on V' and to the corresponding volume drift. The two methods were assessed comparatively in six tracheotomized, paralysed and artificially ventilated rabbits with and without adding to V' an offset equal to 5% of the mean unsigned flow. The 5% flow offset did not modify the results of Fourier analysis, but increased Rrs and Ers from linear regression by 15.8 +/- 4.6% and 4.55 +/- 0.64%, respectively. Without additional offset, differences between the two methods averaged 30.2 +/- 14.0% for Rrs and 9.3 +/- 6.2% for Ers. The differences almost completely disappeared (2.47 and 0.61%, respectively) when the flow signal was zero-corrected using the assumption that inspired and expired volumes were the same. After induced bronchoconstriction, however, Ers was still slightly larger by linear regression than by Fourier analysis, which may result from nonlinearities and/or frequency dependence of the parameters. We conclude that the regression method requires zero flow correction and that Fourier analysis is an attractive alternative.

Methacholine airway challenge (MAC) is a simple and useful means to assess bronchial hyperreactivity in workers exposed to various occupational hazards. Recently, wheeze detection by tracheal auscultation has been proposed as an indicator of bronchial responsiveness during bronchial provocation test in children. Our aim was to examine the relationship between the appearance of wheezes and the concurrent changes in forced expiratory volume in one second (FEV1) observed during MAC test in adults. Three cumulative doses of a methacholine solution (100 micrograms, 500 micrograms and 1500 micrograms) were inhaled by 45 workers with occupational exposure to flour dust. Spirometry was done using an electronic spirometer. Tracheal sounds were recorded with an electronic stethoscope placed over the anterior cervical triangle, 2 cm above the sternal notch. The amplified sounds were stored on magnetic tape, band-pass filtered (50-2000 Hz), and digitized at a sampling rate of 4096 Hz into a GenRad Vibration Control System. Wheezes were detected by fast Fourier transform (FFT) analysis and their presence compared to a 20% fall in FEV1. A positive MAC test by spirometry was found in 12 subjects whereas wheezes were identified in 14 subjects. Among the wheezing subjects, nine had a positive MAC test (range of fall in FEV1 = 20.6 to 42.3%) and five had a negative one (range of fall in FEV1 = 3.6 to 16.9%). Moreover, no wheezes were found in the remaining three subjects with a positive MAC test (range of fall in FEV1 = 20.7 to 27.4%). Taking a 20% fall in FEV1 as reference, wheezes were 75% sensitive and 84.8% specific to detect airflow obstruction. In conclusion, since it carries a significant although small false-negative rate, the acoustic technique based upon wheeze detection cannot, at the present time, fully replace spirometry during airway challenge testing in subjects with suspected asthma.

Physiological and clinical studies have shown that the standard method of measuring respiratory impedance by forced oscillation leads to less efficient control of the upper airway shunt effect than the head generator method. To test the effects of these two techniques in epidemiological studies, we compared, in a sample of 73 French agricultural workers, the values obtained with each method for five forced oscillation parameters: resistance, frequency dependence of resistance, inertance, compliance and resonant frequency. For these comparisons, subjects were classified according to four respiratory status factors: smoking status, cough, expectoration and airway obstruction assessed from the maximum expiratory flow volume curve. Logistic regression models using the set of four forced oscillation parameters (excluding resonant frequency, which is derived from compliance and inertance) were then used to analyse the ability of each method to classify the subjects in each group. Significant differences between the two methods were observed for the mean values obtained for all five parameters. However, when each parameter was considered separately, the correlations between the values for each method were significant. Each method possessed the necessary ability to separate subjects into our group classification, but the significant relationships were not always found for the same parameters. Finally, logistic regression models showed that the two methods led to almost the same classification of the subjects. According to our results, the standard method of applying forced oscillation at the mouth seems an acceptable device for measuring respiratory impedance for epidemiological purposes.

Lung impedance (ZL) was measured from 0.1875 to 32 Hz in spontaneously breathing healthy subjects by spectral analysis of the pressure and flow signals generated simultaneously by the muscular generator of breathing and by a forced oscillation system. This method did not require cooperation from the subject to perform panting or special ventilatory maneuvers and therefore allowed us to analyze the frequency dependence of lung resistance, reactance, and elastance (-2 pi.frequency.reactance) at the physiological conditions of normal breathing. Resistance and elastance parameters were also computed by multiple linear regression of the time-domain pressure and flow data on a simple resistance-elastance model. Resistances and elastances computed at the breathing frequency by spectral analysis and by multiple linear regression were similar (nonsignificant differences < 4 and 10%, respectively). The results obtained when comparing ZL from the breathing component (0.1875–0.75 Hz) of the recorded signals and from the forced oscillation component (2–32 Hz) were fairly consistent. ZL (0.1875–10 Hz) was interpreted in terms of a model consisting of an airway compartment, including a resistance and an inertance, in series with a viscoelastic tissue compartment (J. Hildebrandt. J. Appl. Physiol. 28: 365–372, 1970) characterized by two parameters. The model analysis provided parameter values (resistance 2.49 +/- 0.58 hPa.l-1.s, inertance 1.70 +/- 0.29 Pa.l-1.s2, Hildebrandt parameters 4.87 +/- 2.28 and 0.73 +/- 0.99 hPa/l) consistent with the hypothesis that lung tissue in healthy humans during spontaneous breathing behaves as a viscoelastic structure with a hysteresivity of approximately 0.10.

We investigated the changes in pulmonary mechanics in five anesthetized paralyzed tracheostomized open-chest dogs after step changes in lung volume. We applied small-amplitude (10-ml) volume oscillations at 6 Hz at the tracheal opening for 50-s periods, during which we applied a step volume change of 250, 500, or 750 ml to the lungs. Alveolar capsule measurements of alveolar pressure allowed us to calculate cycle-by-cycle values for airway resistance (Raw) and reactance (Xaw) and lung tissue resistance (Rti) and reactance (Xti). Before the step changes in lung volume, when transpulmonary pressure (Ptp) had a mean value of 0.65 kPa, Raw was markedly greater than Rti. The situation was reversed after the step changes, however, when Raw decreased and Rti increased. Both Raw and Xaw showed negative dependences on Ptp and hence on airway caliber, as expected, and also decreased transiently after the step volume changes, almost certainly due to a vagally mediated bronchodilation reflex. Both Rti and Xti showed clear linear dependences on Ptp and were themselves tightly coupled. Furthermore, our estimate of bulk modulus for lung tissue at 6 Hz is comparable to its previously reported values at much lower oscillation frequencies.

Potential advantages of the forced oscillation technique over other methods for monitoring total respiratory mechanics during artificial ventilation are that it does not require patient relaxation, and that additional information may be derived from the frequency dependence of the real (Re) and imaginary (Im) parts of respiratory impedance. We wanted to assess feasibility and usefulness of the forced oscillation technique in this setting and therefore used the approach in 17 intubated patients, mechanically ventilated for acute respiratory failure. Sinusoidal pressure oscillations at 5, 10 and 20 Hz were applied at the airway opening, using a specially devised loudspeaker-type generator placed in parallel with the ventilator. Real and imaginary parts were corrected for the flow-dependent impedance of the endotracheal tube; they usually exhibited large variations during the respiratory cycle, and were computed separately for the inspiratory and expiratory phases. In many instances the real part was larger during inspiration, probably due to the larger respiratory flow, and decreased with increasing frequency. The imaginary part of respiratory impedance usually increased with increasing frequency during expiration, as expected for a predominately elastic system, but often varied little, or even decreased, with increasing frequency during inspiration. In most patients, the data were inconsistent with the usual resistance-inertance-compliance model. A much better fit was obtained with a model featuring central airways and a peripheral pathway in parallel with bronchial compliance. The results obtained with the latter model suggest that dynamic airway compression occurred during passive expiration in a number of patients. We conclude that the use of forced oscillation is relatively easy to implement during mechanical ventilation, that it allows the study of respiratory mechanics at various points in the respiratory cycle, and may help in detecting expiratory flow limitation.

The reliability of the esophageal balloon technique in measuring high-frequency changes in pleural pressure (Ppl) was investigated in six normal subjects by studying the amplitude ratio (A) and phase angle (phi) of esophageal (Pes) and mouth (Pm) pressures during airway occlusion and while pseudorandom pressure variations (2–32 Hz) were applied to the chest. The measurements were made with a common esophageal balloon-catheter system connected to a high-impedance piezoresistive transducer. When the cheeks were firmly supported, A averaged 1.08 +/- 0.063 at 2 Hz and 1.06 +/- 0.11 at 32 Hz. Pes increasingly led Pm with increasing frequency, and phi averaged 20.8 +/- 4.0 degrees at 32 Hz. Washing the airways with 80% He-20% O2 reduced phi by 50%. When the cheeks were not supported, A exhibited a strong positive frequency dependence, averaging 1.71 +/- 0.34 at 32 Hz, whereas phi increased much faster below 20 Hz and tended to decrease afterward. Because the esophageal transfer function Pes/Ppl = (Pes/Pm)/(Ppl/Pm), we could estimate Pes/Ppl by computing for individual subjects the pressure difference between the pleura and the mouth based on the lung and upper airway wall properties that were measured separately. The results suggest that the ratio of Pes and Ppl remains close to unity from 2 to 32 Hz, but Pes lags slightly behind Ppl (phi equals about -7 degrees at 32 Hz).

The recommendations in this 1993 update do not differ materially from those in the previous report of the European Community for Steel and Coal [1]. However, the list of abbreviations has been extended with respect to the items covered; in addition the European Community has expanded since the previous report, and the report has accordingly been updated to cover the languages spoken in each of the member states. ### 2.1 Symbols for quantities Symbols are used to designate specific quantities, including basic quantities ( e.g. volume, time, pressure, amount of chemical substance) and derived quantities ( e.g. volume by unit time). Letters from the Latin or Greek alphabet are commonly employed as symbols, either roman type as in the USA or italics as recommended by the European Society for Clinical Respiratory Physiology [2] and adopted in the 1983 report of the ECSC. As the number of letters available is limited, inevitably one symbol may be used to designate more than one quantity ( e.g. concentration of chemical substance and compliance). Symbols for …

A setup is described for measuring the respiratory transfer impedance of conscious rats in the frequency range 16–208 Hz. The rats were placed in a restraining tube in which head and body were separated by means of a dough neck collar. The restraining tube was placed in a body chamber, allowing the application of pseudorandom noise pressure variations to the chest and abdomen. The flow at the airway opening was measured in a small chamber connected to the body chamber. The short-term reproducibility of the transfer impedance was tested by repeated measurements in nine Wistar rats. The mean coefficient of variation for the impedance did not exceed 10%. The impedance data were analyzed using different models of the respiratory system of which a three-coefficient resistance-inertance-compliance model provided the most reliable estimates of respiratory resistance (Rrs) and inertance (Irs). The model response, however, departed systematically from the measured impedance. A nine-coefficient model best described the data. Optimization of this model provided estimates of the respiratory tissue coefficients and upper and lower airway coefficients. Rrs with this model was 13.6 +/- 1.0 (SD) kPa.l-1.s, Irs was 14.5 +/- 1.3 Pa.l–1.s2, and tissue compliance (Cti) was 2.5 +/- 0.5 ml/kPa. The intraindividual coefficient of variation for Rrs and Irs was 11 and 18%, respectively. Because most of the resistance and inertance was located in the airways (85 and 81% of Rrs and Irs, respectively), the partitioning in tissue and upper and lower airway components was rather poor. Our values for Rrs and Irs of conscious rats were much lower and our values for Cti were higher than previously reported values for anesthetized rats.

Respiratory mechanics during artificial ventilation are commonly studied with methods which require a specific respiratory pattern. An alternative is to analyse the relationship between tracheal pressure (P) and flow (V') by multiple linear regression (MLR) using a suitable model. The value of this approach was evaluated in 12 unsedated patients, mechanically-ventilated for acute respiratory failure, and most with a history of chronic obstructive or restrictive respiratory disease. After correction for the non-linear resistance of the endotracheal tube, the data were analysed with the linear first order model: P = P0 + E.V + R.V' where E and R are total respiratory elastance and resistance, and P0 is the static recoil pressure at end-expiration. After exclusion of the cycles which clearly exhibited muscular activity, a good fit was observed in 25 out of 36 records (relative root-mean-square error less than 10%); the values of E and R were reproducible within cycles, and consistent with the patient's condition and the ventilatory mode. The intrinsic positive end-expiratory pressure (PEEPi), as derived from P0 and the applied PEEP, averaged 1.1 +/- 1.0 hPa. Using more sophisticated models, allowing for mechanical non-homogeneity or non-linearity of R or E, rarely improved the fit and often provided unrealistic data. In several subjects the discrepancy between the data and the first order model was consistent with expiratory flow limitation, which may severely impair the analysis. We conclude that, except in the case of expiratory flow limitation, the method is useful for routine clinical use and better implemented with the simple linear model.

Respiratory resistance (Rrs) was measured by the forced oscillation technique at 10, 20 and 30 Hz in 54 healthy subjects. The sinusoidal pressure oscillations were applied around the head, rather than at the mouth, so as to minimize transmural pressure across extrathoracic airway walls and the corresponding artefact (Peslin et al., J Appl Physiol, 1985, 59, 1790-1795). The flow (V') and volume (V) dependences of Rrs during the respiratory cycle were analysed by least square regression according to: Rrs = K1 + 2.K2.[V']#- K3.V, where K1 and K2 are Rohrer's constants, and where K3 expresses the (negative) volume dependence of Rrs. The analysis was made separately on the inspiratory and expiratory phases. A good fit was usually found between the data and the model, with a root-mean-square error averaging 15% of the mean Rrs at 10 Hz. At all frequencies K2 and K3 were substantially and significantly larger, and K1 slightly lower during expiration than during inspiration. Rrs, K1 and K3 were minimum at 20 Hz, while K2 exhibited a strong positive frequency dependence. The decrease of Rrs from 10 to 20 Hz was entirely explained by the variations of its linear component, and its increase from 20 to 30 Hz was largely due to its flow dependent component. Both the phasic variations and the frequency dependence of the coefficients suggest that the model is purely descriptive and that coefficients K2 and K3 reflect a number of phenomena, including the variations in glottic aperture during the respiratory cycle.

Lung pressure-volume hysteresis of cat lungs has been found by Hildebrandt (J. Appl. Physiol. 28, 365-372, 1970) to be 20-50% larger than predicted from stress adaptation data on the basis of a viscoelastic model. We have reinvestigated this phenomenon in isolated rat lungs with a different approach, in which the approximation inherent to using a model is avoided : Lung transfer function was derived from the digitally-computed Laplace transform of the pressure decay following a step volume change and used to predict lung pressure-flow relationship in the frequency domain. The latter was expressed in terms of lung effective resistance (Rlc) and effective elastance (Elc), and compared to the observed values (Rl and El) in the frequency range 0.01-0.5 Hz. The measurements were made in 5 lungs at a transpulmonary pressure (Pl) of 0.5 kPa and in 5 others at a Pl of 0.8 kPa. Rl was found to be 23-41% larger than Rlc at Pl = 0.5 and 29-51% larger at Pl = 0.8. El did not differ significantly from Elc at Pl = 0.5 but was 14-28% larger at Pl = 0.8. These results are in good agreement with previous findings. The differences between Rl and Rlc are proportional to the reciprocal of frequency and, thus, correspond to a rate-independent dissipation. They are consistent with a yield stress of 3-6 Pa.

The changes in airways resistance (Raw) and inertance (Iaw) during single inspirations of pure methane, helium, neon, and ethane at a flow of 0.1 l/s were measured in six healthy subjects by use of a forced-oscillation technique. Raw and Iaw were computed from respiratory transfer impedance obtained at a frequency of 20 Hz by applying pressure oscillations at the chest and measuring flow at the mouth with a bag-in-box system. Compared with the air data, the changes of Iaw after inhalation of 500 ml of gas averaged -41.1% with methane, -82.8% with helium, -25.8% with neon, and +4.8% with ethane. These changes were slightly less than the changes in gas density (-45%, -86%, -31%, and +5%, respectively). The inhaled volumes at which 50% of the changes had occurred (V50) did not differ significantly among gases and were approximately 100 ml. For Raw the data were more noisy than for Iaw; they were discarded in two subjects because of a strong and irreproducible volume dependence in air. Consistent differences were seen between the remaining subjects, one of whom exhibited a predominant viscosity dependence of Raw, one a predominant density dependence, and two an intermediate pattern. V50s were larger for Raw than for Iaw, indicating a more peripheral distribution of Raw. For Raw, V50s were lower with helium than with methane, in agreement with the notion that density-dependent resistance is located mainly in the large airways. The results suggest that some information on the serial distribution of Raw and Iaw may be derived from impedance measurements with foreign gases.

Thoracic gas volume (TGV) was measured with an integrated flow plethysmograph in 15 infants aged 2-34 months. End-expiratory (TGVe) and end-inspiratory (TGVi) airway occlusions were compared, after correction of TGV for the occluded volume above functional residual capacity (FRC). The relationship between pressure at the airway opening (Pao) and volume displaced from the box during airway occlusion (Vg) was studied numerically by: 1) an algorithm including a correction for the drift of Vg and linear regression analysis (LR); and 2) Fourier analysis of the signals (FFT). TGVe was significantly higher than TGVi (256 vs 237 ml, 20.4 (square root of residual variance; p less than 0.002). The correlation coefficient of the Pao-Vg relationship was slightly but significantly higher for TGVi than for TGVe: 0.9968 (0.9937-0.9995) vs 0.9947 (0.9840-0.9990) (means and range). No difference was observed between LR and FFT, although the intra-individual coefficient of variation was lower for LR than FFT: 5.2% (1.6-11.3) vs 7.9% (1.9-21.0) (means and range). Model simulations suggested that the difference between TGVe and TGVi could be mainly attributed to gas compression in the instrumental deadspace and upper airway wall motion and/or to uneven distribution of alveolar and pleural pressure associated with chest wall distortion.

Total respiratory input (Zin) and transfer (Ztr) mechanical impedances were measured from 4-30 Hz in 9 patients with severe chronic obstructive pulmonary disease (COPD) and in 12 healthy subjects. Zin was obtained by applying a pressure input around the head to minimize transmural pressure across extrathoracic airway walls, and Ztr was obtained with a pressure input at the chest. In agreement with previous studies total respiratory compliance and inertance were decreased in patients, while effective input resistance was increased and exhibited a negative frequency dependence. Effective transfer resistance (Re(Ztr)) was also increased at all frequencies, and, in some patients, the Re(Ztr)-frequency curve was sigmoid in shape, which was never seen in normals. When Ztr was analysed with a six-coefficient monoalveolar model featuring tissue properties, alveolar gas compliance, and airways properties, the model fitted the data less closely in patients than in normals and, in the former, provided unrealistic coefficients. Such was also the case with a bialveolar model. A better fit with more realistic values for the coefficients was obtained in selected patients with a model where central and peripheral (Rp) airway resistance were separated by a shunt representing airway wall compliance (Cb): Cb was found to range from 0.029-0.062 l.kPa-1 and Rp represented 44-81% of total airway resistance.

At transpulmonary pressures (Ptp) of 7-12 cmH2O, pressure-volume hysteresis of isolated cat lungs has been found to be 20-50% larger than predicted from their amount of stress adaptation (J. Hildebrandt, J. Appl. Physiol. 28: 365-372, 1970). This behavior is inconsistent with linear viscoelasticity and has been interpreted in terms of plastoelasticity. We have reinvestigated this phenomenon in isolated lungs from 12 Wistar rats by measuring 1) the changes in Ptp after 0.5-ml step volume changes (initial Ptp of 5 cmH2O) and 2) their response to sinusoidal pressure forcing from 0.01 to 0.67 Hz (2 cmH2O peak to peak, mean Ptp of 6 cmH2O). Stress adaptation curves were found to fit approximately Hildebrandt's logarithmic model [delta Ptp/delta V = A - B.log(t)] from 0.2 to 100 s, where delta V is the step volume change, A and B are coefficients, and t is time. A and B averaged 1.06 +/- 0.11 and 0.173 +/- 0.019 cmH2O/ml, respectively, with minor differences between stress relaxation and stress recovery curves. The response to sinusoidal forcing was characterized by the effective resistance (Re) and elastance (EL). Re decreased from 2.48 +/- 0.41 cmH2O.ml-1.s at 0.01 Hz to 0.18 +/- 0.03 cmH2O.ml-1.s at 0.5 Hz, and EL increased from 0.99 +/- 0.10 to 1.26 +/- 0.20 cmH2O/ml on the same frequency range. These data were analyzed with the frequency-domain version of the same model, complemented by a Newtonian resistance (R) to account for airway resistance: Re = R + B/ (9.2f) and EL = A + 0.25B + B . log 2 pi f, where f is the frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

The volume dependence of respiratory resistance (Rrs), usually observed during normal breathing, is expected to be accentuated during expiratory flow limitation (EFL). In order to quantify this dependence we studied the pressure, flow, and volume data obtained from eight New Zealand rabbits, artificially ventilated at different levels of applied expiratory pressure (0-10 hPa), before and during histamine i. v. infusion. EFL was provoked by lowering the expiratory pressure and was detected by the application of an additional negative expiratory pressure and by forced oscillations. The analysis of respiratory system mechanics was performed by multiple regression, using the classical linear first-order model and also a nonlinear model, accounting for volume dependence of Rrs. Both models satisfactorily fitted the data in the absence of EFL. The nonlinear model proved to be more appropriate in the presence of EFL. The coefficient expressing the volume dependence of Rrs (Rvd) was significantly more negative during EFL. Rvd values were highly correlated with the fraction of the tidal volume left to be expired at the onset of EFL. A threshold Rvd value of -1,000 (hPa x s x l(-2)) detected EFL with high sensitivity and specificity. We conclude that a strongly negative volume dependence of Rrs is a reliable and noninvasive index of EFL during artificial ventilation.

Noninvasive assessment of respiratory resistance (Rrs) and elastance (Ers), which is not easy with conventional methods, could be useful in the optimization of pressure support ventilation. The aim of this study was to evaluate a simple noninvasive method (Delta-inst) of measuring Rrs during nasal pressure support ventilation. Rrs and Ers (Delta-inst) were computed from inspiratory mask pressure, flow and volume recorded during pressure support ventilation. The Delta-inst method was compared with the forced oscillation technique (FOT) in seven patients with chronic obstructive pulmonary disease (COPD) and in eight healthy subjects without and with added resistance (3.1 cmH2O x s x L(-1)). Rrs measured by Delta-inst (5.2+/-1.7, 7.2+/-0.5 and 6.9+/-1.2 cmH2O x s x L(-1)) and by FOT (5.0+/-0.7, 7.6+/-0.9 and 8.1+/-2.7 cmH2O x s x L(-1)) in healthy subjects without and with added resistance and COPD, respectively, were not significantly different (p>0.05). Rrs measured by both techniques showed a significant coefficient of linear correlation (r=0.70 s) (p

The upper airways may contribute to the increase in respiratory resistance induced by methacholine (Mch). The aim of this study was to simultaneously assess the Mch response of upper airways and lower respiratory resistances (Rua, Rrs,lo) and reactances (Xua, Xrs,lo), and to test whether the change of total respiratory resistance and reactance after Mch were affected by upper airways mechanisms. Seven cats breathing spontaneously were studied under chloralose, urethane anaesthesia. Forced oscillations were generated at 20 Hz by a loud-speaker connected to the pharyngeal cavity. A pneumotachograph was placed between rostral and caudal extremities of the severed cervical trachea. Pressure drops were measured across the upper airways and across the lower respiratory system. Rua, Xua, Rrs,lo and Xrs,lo were obtained after nebulized normal saline and Mch administered directly through the tracheostomy. The analysis focused on Mch tests showing clear positive upper airways response. Volume and flow dependence of Rrs,lo and Rua were assessed during tidal inspiration using multiple linear regression analysis. After Mch, Rrs,lo increased and became negatively volume dependent, while the increase in Rua was associated with no significant change in volume dependence; Xrs,lo became negative while Xua did not change. The upper airways response to methacholine may thus contribute to the increase in total respiratory resistance but may not account for either its negative volume dependence or the decrease in total resistance. It is surmised that these features more specifically reflect alterations in respiratory mechanics occurring at the level of the intrathoracic airways.

The authors have recently demonstrated the feasibility of partitioning total respiratory impedance (Z/sub rs/) into its airway (Z/sub aw/) and tissular (Z/sub ti/) components by measuring alveolar gas compression (V/sub pt/) plethysmographically during pressure oscillations at the airway opening (Peslin et al.). The aim of this study was to comparatively evaluate an alternative approach: the measurement of Z/sub rs/ and of the transfer function (FTF) between airway flow and body surface flow obtained by absolute body plethysmography. The two approaches are theoretically equivalent, provided thermal and other artifacts are properly eliminated. Z/sub rs/ and V/sub pt/ (method 1) and Z/sub rs/ and FTF (method 2) were measured in 11 healthy subjects from 4 to 29 Hz, using a pressure-type and a flow-type plethysmograph, respectively. Inspired gas was conditioned to body temperature and pressure, saturated with water vapor in both instances to minimize thermal factors. Z/sub aw/ and Z/sub ti/ spectra computed from both sets of data were quite similar in shape. Neither airway resistance nor tissue compliance differed significantly; tissue resistance, however, was about 14% lower with method 1, which may be due to imperfect gas conditioning. The reproducibility of the data was similar with the two approaches. It is concluded that absolute body plethysmography is as reliable as differential body plethysmography to partition Z/sub rs/.

Forced-oscillation total respiratory resistance (Rrs) has been shown to underestimate spontaneous breathing lung resistance (RL,sb) in patients with airway obstruction, probably owing to upper airway shunting. The present study reinvestigates that relationship in seven severely obstructed chronic obstructive pulmonary disease patients using a technique that minimizes that artefact. Rrs at 8 and 16 Hz was computed for each successive forced oscillation cycle. Inspiratory and expiratory RL,sb were obtained by analysing transpulmonary pressure (Ptp) with a four-coefficient model, and compared to Rrs over the same periods. "Instantaneous" values of RL,sb were also obtained by computing the dynamic component of Ptp, and compared to simultaneous values of Rrs. In both respiratory phases, good agreement between Rrs and RL,sb was observed up to RL,sb values of approximately 15 hPa x s(-1) x L(-1) at 8 Hz and 10 hPa x s(-1) x L(-1) at 16 Hz. Instantaneous Rrs and RL,sb varied systematically during the respiratory cycle, exhibiting various amounts of flow- or volume-dependence in the seven patients; the amplitudes of their variations were significantly correlated, but Rrs was much more flow-dependent than RL,sb in three patients. Also, Rrs exceeded RL,sb at end-expiration in three instances, which could be related to expiratory flow limitation. In conclusion, total respiratory resistance is reliable up to much higher levels of airway obstruction than previously thought, provided upper airway shunting is avoided.

Whether a subject breathes spontaneously or is artificially ventilated, the pressure which must be applied to the respiratory system to ventilate (Prs) includes two basic components: 1) a static or elastic component (Pel) to sustain the elastic recoil of the lung and chest wall, as described elsewhere in this book; 2) a dynamic or resistive component (Pres) to provide for energy losses by friction occurring in the airways and in the tissues.

Test reproducibility is an important consideration when interpreting results and should be set as a goal during data collection. Reproducibility criteria may need to be different for different subject groups and are instrument and procedure-dependent. Ideally, the within-subject variability for each lung volume and measurement technique used should be established for each laboratory. These values also need to be established for each different subject group (age and disease). At a minimum, test reproducibility should be monitored and controlled and each laboratory should define their between-day reproducibility of measurements on at least one "reference" subject from ongoing periodic (e.g., weekly or monthly) measurements as part of their laboratory's quality control programme. For plethysmographic measurements functional residual capacity (FRC)pleth multiple determinations and a corresponding test reproducibility criteria is probably justified.

Peslin, R., and C. Duvivier. Partitioning of airway and respiratory tissue mechanical impedances by body plethysmography. J. Appl. Physiol. 84(2): 553–561, 1998.—We have tested the feasibility of separating the airway (Zaw) and tissue (Zti) components of total respiratory input impedance (Zrs,in) in healthy subjects by measuring alveolar gas compression by body plethysmography (Vpl) during pressure oscillations at the airway opening. The forced oscillation setup was placed inside a body plethysmograph, and the subjects rebreathedbtps gas. Zrs,in and the relationship between Vpl and airway flow (Hpl) were measured from 4 to 29 Hz. Zaw and Zti were computed from Zrs,in and Hpl by using the monoalveolar T-network model and alveolar gas compliance derived from thoracic gas volume. The data were in good agreement with previous observations: airway and tissue resistance exhibited some positive and negative frequency dependences, respectively; airway reactance was consistent with an inertance of 0.015 ± 0.003 hPa ⋅ s2 ⋅ l−1and tissue reactance with an elastance of 36 ± 8 hPa/l. The changes seen with varying lung volume, during elastic loading of the chest and during bronchoconstriction, were mostly in agreement with the expected effects. The data, as well as computer simulation, suggest that the partitioning is unaffected by mechanical inhomogeneity and only moderately affected by airway wall shunting.

New Zealand male rabbits were anaesthetized with thiopental, tracheotomized, curarized by vecuronium bromide and mechanically ventilated. Six rabbits received L-NAME 10 mg kg-1 i.v., six rabbits L-NAME 15 mg kg-1 iv, and six rabbits received saline i.v. (controls), 5 min before a histamine aerosol (2% solution during 5 min). Six others rabbits received an injection of L-NAME 15 mg kg-1 iv, 5 min before the histamine aerosol, followed by an infusion of L-arginine over a 60- min period. Total respiratory resistance (Rrs) and elastance (Ers) were derived by least square analysis of the relationship between tracheal pressure and flow, and computed every minute before and over a 1-h period after the histamine aerosol. Oxygen free radicals (OFR) were measured with a luminometer, in microsomes from lung homogenates at the end of the experiment. Compared with the histamine response of the control group, the Rrs response in the L-NAME 10 group was slightly less, while Ers changes were the same in the two groups. In contrast, L-NAME 15 was responsible for an increased Rrs response, the difference being significant (P0.05) only between 15 and 40 min after the aerosol (+114% vs. +85% in controls at the 20th min). The increase in Ers with L-NAME 15 was stronger and significantly larger (+71% vs. +42% in controls at the 20th min after the histamine aerosol, P0.001). The relatively greater effect of L-NAME on Ers than on Rrs suggests that NO predominantly modulates the response to histamine of the peripheral lung rather than that of the large airways. Furthermore, the effect of L-NAME on Rrs was completely abolished by L-arginine, while its effect on Ers was only partially reversed. This suggests that the changes in Ers are partly related to a hardly reversible phenomenon. Possibly, the mechanical changes are linked with the rise of OFR in the lung parenchyma, which were significantly higher in the L-NAME 15 group compared to the control group (P0.05).

There are various ways of measuring absolute lung volume. These range from measurements derived from chest radiographs to the more common laboratory measurements employing either gas dilution or plethysmography. The principal difference between the latter two methods is that gas dilution techniques measure gas that is in free communication with the airway opening, whilst plethysmography measures all intrathoracic gas. Once the absolute lung volume is known, the other lung volumes can be measured from the change in volume

Specific airway resistance (sRaw) measured by body plethysmography has been shown to decrease markedly with decreasing breathing frequency when the inspired air is not conditioned to body temperature, atmospheric pressure and saturation with water vapour (BTPS). The phenomenon has been attributed to noninstantaneous gas warming and wetting in the airways. The aim of this investigation was to assess whether the phenomenon was also present in a commercialized plethysmograph featuring an "electronic BTPS correction". Airway resistance (Raw) and sRaw were measured in 15 healthy subjects at six breathing frequencies ranging 0.25-3 Hz, using a constant volume plethysmograph in which a correction for non-BTPS gas conditions was applied by electronically flattening the box pressure-airway flow loop (Jaeger Masterscreen Body, version 4.0). The temperature and water vapour saturations in the box averaged 26.5 +/- 1.3 degrees C and 59 +/- 6%, respectively. Raw and sRaw exhibited a clear positive frequency dependence in all but one subject. From 0.25 to 3 Hz Raw increased from (mean+/-SD) 0.62 +/- 0.55 to 1.71 +/- 0.76 hPa x s x L-1 (p

The upper airways may contribute to increases in airway resistance in response to a bronchial challenge, and thus decrease the specificity of such challenge tests to diagnose airway hyperresponsiveness when forced oscillation techniques are used to evaluate changes in respiratory system resistance (Rrs). A concomitent decrease in respiratory system reactance (Xrs) may indicate a change in the intrathoracic airways and/or lung parenchyma, provided that extrathoracic airway wall motion is prevented. To test the value of Xrs in the evaluation of bronchial hyperresponsiveness, we studied the respiratory impedance response to methacholine in 38 children with a history of asthma (aged 6-14.5 years), and compared the results to changes in the forced expiratory volume in one second (FEV1). Rrs and Xrs were measured by the forced oscillation technique with pseudorandom (11 subjects) or sinusoidal (27 subjects) pressure variations applied around the child's head to minimize upper airway wall motion. Changes in Rrs and in Xrs at 12 Hz (Rrs12, Xrs 12) correlated significantly with changes in FEV1 (P0.005). A decrease in FEV1or = 20% was observed in 23 subjects. When these 23 subjects were compared with the 15 children who did not show significant changes in FEV1, the responding group had larger mean +/- SEM changes in Rrs (116.0 +/- 13.2% vs 60.4 +/- 11.4%, P0.006) and in Xrs (-2.1 +/- 0.4 hPa.s/L vs -0.9 +/- 0.3 hPa.s/L, P0.03) than the nonresponders. The receiver operating characteristics (ROC) curve analysis was used to assess the diagnostic value, i.e., specificity and sensitivity, of different levels of change in Rrs and Xrs, with reference to FEV1. The overall incidence of false results was similar for Rrs and Xrs. The optimum diagnostic value for Rrs was a 70% increase, which corresponded to a sensitivity of 87% and a specificity of 67%. For Xrs the optimum decision level was -1 hPa.s/L, corresponding to a sensitivity of 70% and a specificity of 80%. It is concluded that Xrs may improve the specificity of the forced oscillation technique in interpreting the airway response to methacholine. This may be of particular interest in young children unable to perform forced expirations.

The volume dependence of respiratory elastance makes it difficult to recognize actual changes in lung and chest wall elastic properties in artificially ventilated subjects. We have assessed in six anesthetized, tracheotomized, and paralyzed rabbits whether reliable information on the static pressure-volume (PV) curve could be obtained from recordings performed during step variations of the end-expiratory pressure without interrupting mechanical ventilation. Pressure and flow data recorded during 5- and 10-hPa positive-pressure steps were analyzed in the time domain with a nonlinear model featuring a sigmoid PV curve and with a model that, in addition, accounted for tissue viscoelastic properties. The latter fitted the data substantially better. Both models provided reasonably reproducible coefficients, but the PV curves obtained from the 5- and 10-hPa steps were systematically different. When the PV curves were used to predict respiratory effective elastance, the best predictor was the curve derived from the 10-hPa step with the viscoelastic model: unsigned differences averaged 8.6 +/- 11.1, 26.9 +/- 36.4, and 5.5 +/- 5.8% at end-expiratory pressures of 0, 5, and 10 hPa, respectively. This approach provides potentially useful, although not highly accurate, estimates of respiratory effective elastance-volume dependence.