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Respiratory mechanical impedance measured at a single frequency is of great interest to describe change in airways dimensions with time in young children with asthma. Adequate filtering is mandatory in order to eliminate spurious values at rapid flow transient or during glottis closure. The aim of the study was to test a new filtering procedure. Respiratory impedance was measured at 12 Hz using the head generator technique in 33 asthmatic children aged 3.5-7.5 years. Two separate measurements were obtained at baseline and one 10 min after salbutamol inhalation. Assuming corrupted data would correspond to major distortion in flow oscillation, the tested procedure calculated an index expressing departure of each flow oscillation from an ideal sinusoid (flow shape index filter (FSIF)). Cut-offs ranging from 5 to 20% were compared to the visual identification and 'by hand' elimination of corrupted data (visual filtering). Sensitivity and specificity of FSIF versus visual filtering indicated an optimal range of cut-off values between 10 and 15% (FSIF10 and FSIF15). Compared with visual filtering, respiratory conductance in inspiration (Grs) was marginally but significantly lower with FSIF10 (p < 0.01) but not FSIF15 and had slightly larger (within measurement) coefficient of variation with either FSIF10 or FSIF15 (p < 0.01). Between-measurement repeatability of Grs and Grs change induced by salbutamol were similarly estimated by FSIF10, FSIF15 or visual filtering. It is concluded that FSIF appears as a valid alternative to visual filtering. The 10% cut-off is a good compromise considering sensitivity (72%), amount of rejected data (<20%) and effect on Grs and variability.

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<0.01). In the COPD patients, the variability of Delta-inst Rrs (30%) was greater than that of FOT Rrs (21%). The agreement between Ers obtained by Delta-inst and by FOT was less than that found for Rrs. Delta-inst is a noninvasive and simple method for reliably assessing resistance. Therefore, it is useful for monitoring airway obstruction and is potentially helpful in adapting the settings for pressure support ventilation in accordance with patient mechanics.

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 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¿V'¿+K3V). Rrs,12 and Rrs,20 yielded similar results. Negative volume dependence was present at baseline and significantly enhanced by methacholine (p<0.01). For instance, the mean+/-SD inspiratory K3 at 20 Hz was 4.1+/-1.3 hPa x s x L(-2) at baseline and -15.0+/-4.3 hPa x s x L(-2) after methacholine, in which case it was also larger on expiration than on inspiration (p<0.05), possibly as a result of upper airway responses. A significant increase in the negative volume dependence of respiratory resistance may thus be shown in preschool children in response to methacholine. The volume dependence (K3) during inspiration may be particularly useful in detecting bronchoconstriction, because it is less likely to be affected by upper airway mechanisms than during expiration.

We have recently demonstrated the feasibility of partitioning total respiratory impedance (Zrs) into its airway (Zaw) and tissular (Zti) components by measuring alveolar gas compression (Vpl) 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 Zrs 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. Zrs and Vpl (method 1) and Zrs 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. Zaw and Zti 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. We conclude that absolute body plethysmography is as reliable as differential body plethysmography to partition Zrs.

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.

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.

The forced oscillation technique (FOT) allows easy assessment of bronchial reactivity. The use of a standard FOT generator (SG) results in changes in respiratory system resistance (delta Rrs,SG) which are affected by an artefact caused by the extrathoracic upper airway (EUA). The aim was to improve the FOT assessment of bronchial reactivity with the SG by computing the change in FOT admittance (delta Ars,SG), which is theoretically unaffected by this artefact. Delta Rrs,SG and delta Ars,SG after bronchial challenge in 17 children were compared with the values measured with a head generator (HG) FOT setup (delta Rrs,HG and delta Ars,HG, respectively), which were taken as a reference, since HG provides data virtually freed from the EUA artefact. At 10 Hz, the SG significantly underestimated the resistance change: delta Rrs,SG=1.77+/-0.62 versus delta Rrs,HG=6.09+/-1.23 hPa x L(-1) x s. Delta Rrs,SG and delta Rrs,HG did not show a significant correlation. By contrast, the amplitude of the change in admittance measured by SG was close to the one obtained with the reference HG: /delta Ars,SG/=29.5+/-4.6 versus /delta Ars,HG/=32.7+/-3.9 mL x hPa(-1) x s(-1). /Delta Ars,SG/ and /delta Ars,HG/ showed a significant correlation (r=0.65, p>0.01). Similar results were found up to 20 Hz. The extrathoracic upper airway artefact was minimized when computing the change in admittance with the standard generator. This forced oscillation technique index may improve the sensitivity in assessing bronchial reactivity with the standard generator setup, which is the most common and easiest to use method for routine lung function testing.

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.

Background: Thoracic gas volume (TGV) may be estimated during spontaneous breathing by measuring simultaneously respiratory impedance (Zrs) and alveolar gas compression (Vpl) at several oscillation frequencies [Peslin and Duvivier: J Appl Physiol 1998;84:862-867]., Objective: The aim of the study was to test the validity of that approach at different levels of the vital capacity (VC)., Methods: We measured Zrs and Vpl at frequencies ranging from 6 to 29 Hz in 10 healthy subjects rebreathing BTPS gas in a constant volume body plethysmograph. In a first series, the subjects were asked to breathe voluntarily at different levels of the VC and oscillation TGV (TGVos) was compared to standard plethysmographic TGV (TGVst) assessed immediately after TGVos measurements. In a second series, the subjects were asked to change stepwise their lung volume in the middle of the forced oscillation recording, and the changes in TGVos (DeltaTGVos) were compared to the changes in lung volume (DeltaV) computed from the integrated flow signal., Results: In most subjects TGVos and TGVst were highly correlated and the slopes of the relationships did not differ significantly from unity. DeltaTGVos and DeltaV were also highly correlated both in individuals and in the group (r = 0.97), and their signless differences averaged 0.23 +/- 0.20 liter., Conclusion: We conclude that forced oscillation estimates of TGV are reliable in healthy subjects over a large part of the VC.

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.

Airway obstruction in patients with sleep apnea-hypopnea syndrome (SAHS) is due to increased critical pressure (Pcrit) of the upper airway. The ideal nasal pressure (Pn) to maintain airway patency should consist of the constant term to account for Pcrit and a term (Rn . V) proportional to flow (V) to account for the dynamic pressure drop through nasal resistance (R n). Continuous positive airway pressure (CPAP) applied to avoid flow limitation results in a Pn greater than required over most of the breathing cycle. The aim was to assess a flow-dependent positive airway pressure (FDPAP) based on adapting Pn to the instantaneous flow: Pn = P0 + k . V. FDPAP was tested on collapsible airway models and its applicability was assessed in nine patients with SAHS during sleep. In models, FDPAP prevented flow limitation with lower mean P n and work of breathing than CPAP. In patients FDPAP allowed the patients to breathe normally with a mean Pn (6.6 +/- 1.2 cm H2O) systematically and significantly (p < 0.05, paired t test) lower than when applying CPAP (9.1 +/- 1.2 cm H2O). The results found in models and in patients suggest that adapting the applied nasal pressure to the instantaneous breathing flow may be of potential practical interest in SAHS.

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 nearly BTPS 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.

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.

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 set up was placed inside a body plethysmograph, and the subjects rebreathed BTPS 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: airways 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-1 and tissue reactance with an elastance of 36 +/- 8 hPa/I. 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.

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.

We evaluated the effect of different vasodilators on ventricular end-systolic stress by investigating the impact of sodium nitroprusside, nifedipine, and hydralazine on blood pressure, aortic stiffness, and wave reflection during drug-induced hypotension (to 80 mm Hg mean blood pressure) in normotensive (central aortic mean blood pressure, 116 to 119 mm Hg; systolic pressure, 133 to 137 mm Hg), nonanesthetized, unrestrained rats. Aortic stiffness was evaluated from the slope of the linear regression relating pulse wave velocity (PWV) to central aortic mean or pulse pressure. The fall in central aortic systolic blood pressure was less than the fall in mean pressure, especially after hydralazine (122+/-4 mm Hg; sodium nitroprusside, 107+/-2; and nifedipine, 112+/-3 mm Hg; P<.05). The PWV/mean pressure slope was linear, positive, and similar in all three groups (hydralazine, 3.3+/-0.2; sodium nitroprusside, 3.8+/-0.3; and nifedipine, 3.9+/-0.3 cm x s[-1]x mm Hg[-1]; P>.05). The PWV/pulse pressure slope was linear, negative, and less steep in the case of hydralazine (-4.9+/-0.6; sodium nitroprusside, -15.5+/-3.7; and nifedipine, -13.5+/-2.9 cm x s[-1] x mm Hg[-1]; P<.05). The travel time and augmentation index of the reflected wave were similar in all groups. In conclusion, sodium nitroprusside and nifedipine had a more beneficial effect on end-systolic stress than did hydralazine. This does not appear to be related to any specific effect on wave reflection or the "static" relationship between PWV and aortic mean blood pressure; it may be related to the effects of these drugs on the "dynamic" relationship between PWV and pulse pressure.

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 (Eteff) and tissue resistance (Rt) 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 Rt varies little during breathing while Eteff presents much larger phasic variations than can be explained by the curvature of the static pressure-volume curve (Tomalak et a1., 1997). The aim of this study was to test the hypothesis that the large variations of Eteff were related to the activity of respiratory muscles. For this, we studied in six healthy subjects the changes in Eteff and Rt 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 Eteff during the inspiratory and expiratory phases, respectively; in contrast, ASV decreased Eteff during inspiration and almost completely abolished its positive volume dependence. The changes of Rt usually paralleled those of Eteff. We conclude that respiratory muscle activity is responsible for most of the variations of Eteff during spontaneous breathing.

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.

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 (f(os)) 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 f(os) and Eti,eff to vary curvilinearly with f(os)2, which is suggestive of mechanical inhomogeneity. Rti presented a weak volume dependence during breathing, variable in sign according to f(os) and 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.

Large phasic variations of respiratory mechanical impedance (Zrs) have been observed during induced expiratory flow limitation (EFL) (M. Vassiliou, R. Peslin, C. Saunier, and C. Duvivier. Eur. Respir. J. 9: 779-786, 1996). To clarify the meaning of Zrs during EFL, we have measured from 5 to 30 Hz the input impedance (Zin) of mechanical analogues of the respiratory system, including flow-limiting elements (FLE) made of easily collapsible rubber tubing. The pressures upstream (Pus) and downstream (Pds) from the FLE were controlled and systematically varied. Maximal flow (Vmax) increased linearly with Pus, was close to the value predicted from wave-speed theory, and was obtained for Pus-Pds of 4-6 hPa. The real part of Zin started increasing abruptly with flow (V) > 85% Vmax and either further increased or suddenly decreased in the vicinity of Vmax. The imaginary part of Zin decreased markedly and suddenly above 95% Vmax. Similar variations of Zin during EFL were seen with an analogue that mimicked the changes of airway transmural pressure during breathing. After pressure and V measurements upstream and downstream from the FLE were combined, the latter was analyzed in terms of a serial (Zs) and a shunt (Zp) compartment. Zs was consistent with a large resistance and inertance, and Zp with a mainly elastic element having an elastance close to that of the tube walls. We conclude that Zrs data during EFL mainly reflect the properties of the FLE.

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<0.001), and sRaw from 2.34 +/- 1.90 to 7.55 +/- 3.08 hPa x s (p<0.001). The data are consistent with a simple model, in which gas conditioning in the airways and external dead space occurred with a time constant of 0.39 s. We conclude that the electronic BTPS correction of the instrument was inadequate, probably because it is assumed that gas conditioning in the airways is instantaneous. We recommend that, with similar instruments, airway resistance be measured using as high a panting frequency as feasible.

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 < 0.005). A decrease in FEV1 > 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).

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.

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*.

Measurements of airway resistance (Raw) by body plethysmography during unconditioned air breathing are implicitly based on the assumption that the warming and humidification of air in the airways are instantaneous. Simulation with a simple model suggests that Raw may be frequency dependent and substantially underestimated at most breathing frequencies if the time constant of gas conditioning (theta) is between 0.01 and 0.3 s. We measured the frequency dependence of the real (Re) and imaginary parts of the relationship between the plethysmographic signal and airway flow from 0.5 to 3 Hz in six healthy subjects in several situations. During breathing of unconditioned air through a heated pneumotachograph, Re increased by 47 +/- 70% between 2 and 3 Hz; the data were consistent with a theta of 0.087 +/- 0.023 s. Additional dead spaces moderately increased theta: 0.105 +/- 0.031 and 0.120 +/- 0.027 s with 50-cm-long polyvinyl chloride and copper tubes, respectively. During breathing of saturated air conditioned at 34, 36, 38, and 40 degrees C, Re exhibited a much smaller positive frequency dependence, most of which was probably due to a flow dependence of Raw. We conclude that unless the inspired gas is conditioned, plethysmographic Raw is likely to be substantially underestimated, particularly when measured during spontaneous breathing.

Lung mechanics was studied in six paralyzed tracheotomized rabbits ventilated with a specially devised computer-controlled ventilator. The target flow waveform contained noninteger multiple frequencies ranging from 0.83 to 6-10 Hz and met a neither-sum-nor-difference criterion to minimize the effects of nonlinearity (B. Suki and K. Lutchen. IEEE Trans. Biomed. Eng. 39: 1142-1151, 1992). The actual flow, however, contained harmonics of the two lowest frequencies. Measurements were performed at mean airway pressure (Paw) levels of 8 and 12 hPa and during histamine-induced bronchoconstriction. Smooth impedance curves were observed in unchallenged rabbits at low mean Paw levels. In contrast, unrealistic impedance fluctuations, suggestive of cross talk from the unwanted frequency components in the flow input, were seen at high mean Paw levels and during acute bronchoconstriction. Model analysis was performed by using the actual flow signal as an input to various nonlinear models. The impedance fluctuations observed at high mean Paw levels were well simulated by a model featuring a volume-dependent elastance, and those observed after histamine were almost perfectly reproduced by a model where resistance increased with the reciprocal of lung volume. We conclude that impedance data biased by cross talk may provide useful information on the presence and nature of respiratory system nonlinearities.

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.

We have tested in eight rabbits the feasibility of measuring respiratory (Zrs) and lung (ZL) impedances in the low-frequency domain, including below the breathing frequency (fb), during conventional mechanical ventilation (CMV). The animals were tracheotomized and ventilated with a tidal volume (VT) of 20 ml at a fb of 1 Hz. The excitation signal was provided by a flow generator connected in parallel with the ventilator; it included six components ranging from 0.45 to 14.8 Hz, which met the neither-sum-nor-difference criterion of B. Suki and K. Lutchen (IEEE Trans. Biomed. Eng. 39: 1142-1151, 1992) to minimize the influence of nonlinearities. Zrs and ZL were also measured at the same mean lung volume and with the same excitation signal both during apnea and when the ventilator signal was replaced by a sine wave with the same VT and fb (SMV). The real parts (Re) of both Zrs and ZL, as well as the effective elastances, were significantly larger during apnea than during CMV and SMV over the whole frequency range. Re(Zrs) and Re(ZL) were similar during CMV and SMV above fb but they were lower during CMV at 0.45 Hz. The latter difference seems to be related to the presence of harmonics of fb and of additional frequency components due to pulse amplitude modulation. We conclude that, because of nonlinearities, it is feasible to measure Zrs and ZL during CMV only at and above fb.

The aim of this work was to demonstrate that the three compartments of the lung T network and the chest wall impedance (Zcw) can be identified from input and transfer impedances of the respiratory system if the pleural pressure is recorded during the measurements. The method was tested in six healthy volunteers in the range of 8-32 Hz. The impedances resulting from the decomposition confirm the adequacy of the monoalveolar structure commonly used in healthy subjects. Indeed, the T shunt impedance is well modeled by a purely compliant element, the mean compliance [0.038 +/- 0.081 (SD) l/kPa], which coincides within 9.5 +/- 6.3% of the alveolar gas compressibility derived from thoracic gas volume (0.036 +/- 0.011 l/kPa). The results obtained provide experimental evidence that the alveolar gas compression is predominantly isothermal and that lung tissue impedance is negligible throughout the whole frequency range. The shape of Zcw is consistent with a low compliance-low inertance pathway in parallel with a high compliance-high inertance pathway. We conclude that the proposed method is able to reliably identify the T network featuring the lung and Zcw.

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.

Salbutamol is a potent beta 2-adrenoceptor agonist given to patients with bronchial asthma who are frequently hypoxemic. The aims of this study were to document the influence of chronic hypoxia on salbutamol tissue concentrations and on salbutamol effect on total respiratory resistance. To this purpose, salbutamol (60 micrograms/kg) was administered intravenously to four groups of six rabbits exposed to four experimental conditions: (1) control rabbits breathing air, (2) histamine-induced bronchoconstriction in rabbits breathing air, (3) animals with chronic hypoxia, (4) histamine-induced bronchoconstriction in animals with chronic hypoxia. The area under salbutamol plasma concentration time curve (0 to 45 min) was not affected by these experimental conditions. Compared with control rabbits breathing air, following histamine-induced bronchoconstriction, salbutamol concentrations rose by 40 to 50% in lung and heart (p < 0.05). Hypoxia did not affect salbutamol distribution in these organs; however, in hypoxic animals, histamine-induced bronchoconstriction increased salbutamol concentrations only in the heart (p < 0.05), without affecting those in the lung. Compared with rabbits breathing air and with histamine-induced bronchoconstriction, the effect of salbutamol was reduced in rabbits under chronic hypoxia and histamine-induced bronchoconstriction (p < 0.05). We conclude that chronic hypoxia reduces salbutamol effect on pulmonary resistance, possibly by decreasing salbutamol lung concentrations.

We compared the effects of the laryngeal mask and tracheal tube on total respiratory resistance in 10 anaesthetised, mechanically ventilated patients undergoing otological microsurgery. The subjects were randomly divided into two groups. In the first group, the tracheal tube (Rüsch) was inserted for the first series of measurements. This was then replaced by a laryngeal mask (Intavent) and a second series of measurements was made during the first hour of operation. In the second group, the same protocol was applied with inverse order in the use of the devices. From the measurement of respiratory flow and pressure at the airway opening, total respiratory resistance was calculated by multiple linear regression. The data were corrected to eliminate the previously determined nonlinear resistance of the two devices. Arterial blood pressure, electrocardiogram, oxygen saturation and end-tidal carbon dioxide concentration were continuously monitored. With the laryngeal mask and the tracheal tube, mean (SE) minute ventilation was 9.4(0.9)l.min-1 and 8.1(0.9)l.min-1, respectively for end-tidal carbon dioxide concentrations between 3.6 and 4.1%. Although the glottic resistance was included in the measurement performed with the laryngeal mask but not with the tracheal tube, mean (SE) total respiratory resistance was not significantly different with the two devices (0.61(0.32) and 0.69(0.35) kPa.l-1.s, respectively). Leakage was avoided with the laryngeal mask because the insufflation pressure never exceeded 1.7 kPa except in one patient suffering from severe chronic obstructive pulmonary disease who had a total respiratory resistance of 1.45 kPa.l-1.s. During the first hour of the operation all respiratory variables remained stable irrespective of the device used.

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.

The frequency dependence of respiratory mechanical properties was studied in 10 paralyzed, artificially ventilated rabbits, by superimposing a single sinusoidal signal with a frequency of 10, 20 or 30 Hz upon the ventilator waveform. The tracheal pressure and flow signals were analyzed both with the usual first order model, which provided total respiratory elastance (Ers) and resistance (Rrs), and by Fourier analysis, which provided respiratory impedance (Zrs) at the breathing frequency (0.85 Hz) and at the superimposed oscillation frequency. The real part of Zrs (Re(Zrs)) decreased by 30% from 0.85 to 10 Hz (P < 0.001), but did not vary significantly from 10 to 30 Hz. This finding is satisfactorily explained by tissue viscoelasticity. Following a histamine aerosol, the frequency dependence of Re(Zrs) changed very little in three out of four rabbits, but increased substantially in the fourth. In that instance, assuming that lung hysteresivity was not markedly modified by histamine, the results suggest inhomogeneous airway obstruction and/or airway wall shunting.

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.

We previously found that a significant underestimation of respiratory mechanical impedance (Zrs) at high frequency may result from the upper airway artefact in children, when pressure is directly varied at the mouth. To determine the importance of this artefact in estimating lung response to bronchomotor agents with the forced oscillation technique, input respiratory mechanical impedance was measured using 6-32 Hz pseudorandom pressure oscillations applied directly to the mouth (standard generator (SG)) and around the subject's head (head generator (HG)) in 35 children aged 2.5-13 yrs. Changes in resistance were generally larger with HG than SG. The mean +/- SEM changes in resistance of the respiratory system (Rrs) at 20 Hz induced by acetylcholine or allergen challenge were 15 +/- 4% for SG and 67 +/- 12% for HG, and changes induced by bronchodilators were -25 +/- 2% for SG, and -46 +/- 4% for HG (p < 0.01). Challenge induced negative frequency dependence of Rrs with SG and positive frequency dependence with HG. There was significant increase in inertance after salbutamol with SG, but no significant change occurred with HG. With both methods, respiratory compliance decreased significantly after challenge. Computer simulations showed that the difference in change in Rrs induced by airway challenge with HG and SG could be explained by the effect of the upper airway wall impedance (Zuaw). Zuaw could also account for the change in inertance and compliance observed with SG, but not for the change in compliance with HG. The latter could be reproduced by simulating unequal distribution of mechanical time constants within the lung, increased peripheral lung resistance with compliant central airways.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Changes in respiratory mechanics have occasionally been observed during high-frequency ventilation. In this study we investigated whether small pressure oscillations such as those used for respiratory impedance measurements modified total respiratory resistance (Rrs) and total respiratory elastance (Ers). The latter were measured in six paralyzed artificially ventilated rabbits with and without superimposed pressure oscillations at the airway opening. Rrs and Ers were obtained by least square fitting of low-pass filtered tracheal pressure and flow to the usual first-order model. Pressure oscillations of 2-4 hPa peak-to-peak at 10, 20, and 30 Hz applied for periods of 10 min had virtually no effect on Ers (changes ranging from -2.5 to 2.6%) and Rrs (0-8.2%). Analysis of variance did not show a significant difference on the pooled data. Pressure oscillations were also applied every other minute after a histamine aerosol. Ers and Rrs were similarly unchanged. We conclude that the small pressure oscillations used in respiratory impedance measurements do not modify lung mechanical properties and lung response to bronchomotor agents.

The shape of the capnogram is modified by airway obstruction, and the evaluation of this deformation, using measurable indices, could allow an indirect measurement of bronchial patency. A previous study undertaken in asthmatic subjects showed a good correlation between a capnographic index (end-tidal slope) and a spirometric parameter (forced expiratory volume in one second as a percentage of predicted (FEV1 %pred)) and suggested the study of other indices. The correlations between capnographic and spirometric indices were measured in 10 healthy subjects and 30 asthmatic patients. The usefulness of eight descriptive indices, analysing the successive phases of the capnogram, was assessed by measuring their reproducibility and their sensitivity to airway obstruction. The intraindividual and interindividual variabilities (Vi and VI) and the noise/signal ratio (Vi/VI) were measured by comparing the results of two successive capnographic measurements in 14 asthmatic subjects. The results show an increasing noise/signal ratio along the expiration (between 23 and 62%). Significant correlations between spirometry and capnography were found with all indices, but the strongest were observed with indices analysing the intermediate phase of the capnogram, that is the angle between the ascending phase (E2) and the alveolar plateau (E3). The correlations show that the analysis of the capnogram's shape is a quantitative method for evaluating the severity of bronchospasm. This ability, added to specific advantages (noninvasiveness, effort-independency, measurements during tidal breathing) opens new fields of application to capnography, such as measurement of bronchospasm in children and computerized monitoring of asthma.

The aim of this investigation was to assess the optimal frequency range for analyzing respiratory transfer impedance (Ztr) in terms of tissue and airway mechanical properties using the six-element model of DuBois et al. (J. Appl. Physiol. 8:587-594, 1956). Ztr was measured in nine healthy subjects from 2 to 64 Hz by studying the relationship between airway flow and pseudorandom pressure oscillations applied around the chest. The measurements were performed with and without two mechanical loads placed at the mouth: an added inertance of 1.4 Pa.s2.l-1 and an added resistance of 1.65 hPa.s.l-1. The data were corrected for the shunt effect of upper airway walls. The changes in Ztr induced by the loads were very consistent up to 56 Hz with the T-network topology assumed in DuBois's model; the agreement deteriorated at higher frequencies, presumably due to the difficulty of obtaining a homogeneous pressure field around the chest. The fit of the model to the data also worsened sharply at above 56 Hz. In the 2- to 56-Hz frequency range, similar values of the tissue and airway coefficients were obtained with and without the loads. In that frequency range the confidence intervals of the coefficients were better than 10%. We conclude that DuBois's model is valid from 2 to 56 Hz in healthy subjects and allows accurate partitioning of airways and tissue properties. In addition, we present evidence that the upper airway shunt negligibly influences Ztr data and the derived coefficients provided airway flow is measured with a low-impedance pneumotachograph.