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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.

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.

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.

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).

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.

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.

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 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.

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 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.

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.

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.

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.

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.

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.

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.

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.

A potentially useful method to monitor respiratory mechanics in artificially ventilated patients consists of analyzing the relationship between tracheal pressure (P), lung volume (V), and gas flow () by multiple linear regression (MLR) using a suitable model. Contrary to other methods, it does not require any particular flow waveform and, therefore, may be used with any ventilator. This approach was evaluated in three neonates and seven young children admitted into an intensive care unit for respiratory disorders of various etiologies. P and V were measured and digitized at a sampling rate of 40 Hz for periods of 20–48 s. After correction of P for the non-linear resistance of the endotracheal tube, the data were first analyzed with the usual linear monoalveolar model: P = PO + E.V + R. where E and R are total respiratory elastance and resistance, and PO is the static recoil pressure at end-expiration. A good fit of the model to the data was seen in five of ten children. PO, E, and R were reproducible within cycles, and consistent with the patient's age and condition; the data obtained with two ventilatory modes were highly correlated. In the five instances in which the simple model did not fit the data well, they were reanalyzed with more sophisticated models allowing for mechanical non-homogeneity or for non-linearity of R or E. While several models substantially improved the fit, physiologically meaningful results were only obtained when R was allowed to change with lung volume. We conclude that the MLR method is adequate to monitor respiratory mechanics, even when the usual model is inadequate. © 1992 Wiley-Liss, Inc.

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.

The upper airway wall impedance (Zuaw) may be responsible for a large artifact in the measurement of respiratory system impedance (Zrs) in children. In 17 normal children aged 3.5-13 years Zuaw and Zrs were estimated by varying transrespiratory pressure directly at the mouth (conventional method: Z1) and around the subject's head (head generator method: Z2) from 4 to 32 Hz. Zrs and Zuaw were calculated from Z1 = Zrs.Zuaw/(Zrs+Zuaw) and Z2 = Zrs (1 + Zp/Zuaw), where Zp is the impedance of the pneumotachograph. From the real and imaginary part of Z1, Z2, Zrs, and Zuaw, the corresponding resistance, inertance, compliance and resonant frequency were calculated assuming simple RIC models. No significant difference was found between the mean +/- SE of parameters derived from Zrs (respectively, 6.8 +/- 0.4 cmH2O.L-1.s, 0.034 +/- 0.001 cmH2O.L-1.s2, 10.4 +/- 0.8 m.cmH2O-1, 9.1 +/- 0.3 Hz) and Z2 (6.8 +/- 0.4 cmH2O.L-1.s, 0.038 +/- 0.002 cmH2O.L-1.s2, 10.7 +/- 0.7 ml.cmH2O-1, 8.7 +/- 0.4 Hz). All but the compliance, derived from Z1 were significantly different (P less than 0.01) from those derived from Zrs (5.3 +/- 0.3 cmH2O.L-1.s, 0.008 +/- 0.001 cmH2O.L-1.s2, 11.9 +/- 1.2 ml.cmH2O-1, and 20.3 +/- 1.6 Hz). Respiratory resistance and compliance correlated significantly with height (r = -0.56 and 0.86, respectively), in contrast to upper airway wall resistance (Ruaw) and compliance (Cuaw). Ruaw (8.6 +/- 0.8 cmH2O.L-1.s), Cuaw (1.2 +/- 0.2 m.cmH2O-1), and upper airway wall inertance (0.030 +/- 0.004 cmH2O.L-1.s2) were close to those obtained by direct measurements in adults. The mechanical properties of the upper airway wall are responsible for a significant error in the measurement of Zrs by the conventional method in normal children. Most of the artifact may be corrected for by applying pressure around the child's head.

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.

Short-term intraindividual variability of the parameters derived from respiratory transfer impedance (Ztr) measured from 4 to 32 Hz was studied in 10 healthy subjects. The corresponding 95% confidence intervals (CIo) were compared with those computed from a single set of data (CIL) according to Lutchen and Jackson (J. Appl. Physiol. 62: 403-413, 1987). Ztr was analyzed with the six-coefficient model of DuBois et al. (J. Appl. Physiol. 8: 587-594, 1956), which includes airway resistance (Raw) and inertance (Iaw), tissue resistance (Rti), inertance (Iti), and compliance (Cti), and alveolar gas compressibility (Cg). The lowest variability was seen for Iaw (CIo = 11.1%), closely followed by Raw (14.3%) and Cti (14.8%), and the largest for Rti and Iti (24.6 and 93.6%, respectively). Using a simpler model, where Iti was excluded, significantly decreased the variability of Iaw (P less than 0.01) and Rti (P less than 0.05) but was responsible for a systematic decrease of Raw and Iaw and increase of Rti. Except for Raw with both models and Iaw with the simpler model, CIL was greater than CIo. Whatever the model, a high correlation between both sets of confidence intervals was found for Rti and Iaw, whereas no correlation was seen for Raw. This suggests that the variability of the former coefficients mainly reflects experimental noise, whereas that of the latter is largely due to biological variability.

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.

The bronchial resistances in 17 patients scheduled for ENT surgery were studied during general anaesthesia carried out with propofol and alfentanil. There were nine controls, all free from any allergic pathology. The other eight had bronchial hyperreactivity, with clinical asthma (one or two crises a month) treated with bronchodilators. Two had a complete Fernand-Widal syndrome, and the remaining six documented allergic asthma. All the patients were premedicated with hydroxyzine 2 mg.kg-1 orally on the eve of surgery, and two hours beforehand. Those patients who were on bronchodilators were given their drugs as usual with the premedication. Because bronchial resistances were measured with the patient breathing spontaneously (forced oscillation technique), induction was carried out in two steps, first with propofol 1.5 mg.kg-1, followed, two minutes later, by alfentanil 7 micrograms.kg-1. Once the bronchial resistances had been assessed the patient was given a further 2 mg.kg-1 dose of propofol, and alfentanil 40 micrograms.kg-1. The patient was then intubated, and anaesthesia maintained with propofol 9 mg.kg-1.h-1, and alfentanil 15 micrograms.kg-1 every fifteen minutes. In all, bronchial resistances were measured on the day before surgery, after premedication but before the patient had been given any anaesthetic drug, two minutes after the first injection of propofol, two minutes after the first injection of alfentanil, and after extubation. There were no significant differences between the two groups. Despite the small number of patients included in this study, it would seem that hydroxyzine, propofol and alfentanil may be used safely in patients with hyperreactive bronchi.

Respiratory impedance may be studied by measuring airway flow (Vaw) when pressure is varied at the mouth (input impedance) or around the chest (transfer impedance). A third possibility, which had not been investigated so far, is to apply pressure variations simultaneously at the two places, that is to vary ambient pressure (Pam). This provides respiratory impedance to ambient pressure changes (Zapc = Vaw/Pam). In that situation airway impedance (Zaw) and tissue impedance (Zt) are mechanically in parallel, and both are in series with alveolar gas impedance (Zg): Zapc = Zaw + Zg + Zaw.Zg/Zt. We assessed the frequency dependence of Zapc from 0.05 to 2 Hz in nine normal subjects submitted to sinusoidal Pam changes of 2-4 kPa peak to peak. The real part of Zapc (Rapc) was of 6.2 kPa.1(-1).s at 0.05 Hz and decreased to 1.9 kPa.1(-1).s at 2 Hz. Similarly the effective compliance (Capc), computed from the imaginary part of Zapc, decreased from 0.045 1.kPa-1 at 0.05 Hz to 0.027 1.kPa-1 at 2 Hz. Breathing against an added resistance of 0.46 kPa.1(-1).s exaggerated the negative frequency dependence of both Rapc and Capc. When values of airway resistance and inertance derived from transfer impedance data were introduced, Zapc was used to compute effective tissue resistance (Rt) and compliance (Ct). Rt was found to decrease from 0.32 to 0.15 kPa.1(-1).s and Ct from 1.11 to 0.64 1.kPa-1 between 0.25 and 2 Hz. Ct was slightly lower with the added resistance. These results are in good agreement with the data obtained by other approaches.

Mechanical properties of the lung were studied in nine healthy lowlanders during a 6-day sojourn at an altitude of 3,457 m. In comparison to sea-level values, it was found at altitude that 1) lung volumes measured by plethysmography including total lung capacity, vital capacity, and functional residual capacity (FRC) presented small changes not exceeding 300 ml; 2) static and dynamic lung compliances were not modified but static pressure-volume curves of lungs were shifted progressively to the left (the decrease in lung elastic recoil averaged about 2 cmH2O on days 4–6); and 3) maximal midexpiratory flow, forced expiratory volume in 1 s, and maximal expiratory and inspiratory flows were increased and, conversely, airways and pulmonary flow resistances were decreased on most days at altitude. The unchanged FRC in the face of a decreased lung recoil may be explained by an increase in thoracic blood volume at altitude, but other possible mechanisms are discussed. The decrease in resistances and increase in maximal flows may be partly explained by the decreased air density at altitude, but another contributing factor such as a bronchodilatation is also suggested. It is proposed that changes in lung mechanics at altitude may account for some of the changes in the pattern of breathing and mouth occlusion pressure (P0.1) observed during acclimatization of lowlanders to altitude.

In a group of 34 inpatients showing varying degrees of airflow obstruction we studied the relationship between breath sound intensity (BSI) and abnormalities of lung function. The BSI was evaluated by chest auscultation to provide a score, in a manner similar to that described by Pardee et al. (1976), and was found to correlate closely with indices of airflow obstruction of their logarithms such as specific conductance (r = 0.759), maximal expiratory flow at 50% of vital capacity (r = 0.790), forced expiratory volume in one second (r = 0.768), and forced expiratory volume to vital capacity ratio (r = 0.860). Correlations with lung volumes, although statistically significant, were weaker. Multiple correlation studies showed that BSI score correlated independently with indices of both airflow obstruction and lung distension. In our experience, BSI score can be useful not only in the detection but also the quantification of airflow obstruction, although its predictive power is impaired in subjects with associated restrictive disorders. It can also fail to detect mild, pure airflow obstruction.

The validity of a new method for measuring thoracic gas volume (Vtg) was studied in 18 bronchitic patients with mild to severe airway obstruction. The method entailed submitting the subject to very slow sinusoidal variations of ambient pressure (delta Pam) and studying the relationship between delta Pam and the resulting gas displacement at the mouth (delta Vaw): Vtgapc = PB.delta Vaw/delta Pam.cos phi, where PB is barometric minus alveolar water vapor pressure, and phi is the phase angle between Pam and Vaw. delta Pam of 40 cm H2O at 0.05 Hz were achieved by placing the subject in a 410-I body chamber connected to a large stroke volume reciprocating pump. Pam and Vaw were processed digitally by Fourier transform to obtain their amplitude ratio and phase angle at the frequency of interest. Vtg was also measured by body plethysmography (Vtgplet) during slow panting maneuvers (0.79 +/- 0.19 Hz) and also in order to detect any artifactual frequency dependence at a higher panting frequency (1.71 +/- 0.27 Hz); the agreement between the 2 estimates in all subjects (r = 0.975) suggested that Vtgplet could be taken as a valid reference. Functional residual capacities derived from Vtgapc and Vtgplet were not significantly different (5.113 +/- 1.198 versus 5.260 +/- 1.328 L) and were highly correlated (r = 0.915). Intermethod differences averaged 1.7 +/- 10.5% and were not significantly correlated to functional indices. We conclude that the new method provides accurate Vtg values in patients with chronic airway obstruction.

The influence of inspiratory and expiratory flow magnitude, lung volume, and lung volume history on respiratory system properties was studied by measuring transfer impedances (4-30 Hz) in seven normal subjects during various constant flow maneuvers. The measured impedances were analyzed with a six-coefficient model including airway resistance (Raw) and inertance (Iaw), tissue resistance (Rti), inertance (Iti), and compliance (Cti), and alveolar gas compressibility. Increasing respiratory flow from 0.1 to 0.4 1/s was found to increase inspiratory and expiratory Raw by 63% and 32%, respectively, and to decrease Iaw, but did not change tissue properties. Raw, Iti, and Cti were larger and Rti was lower during expiration than during inspiration. Decreasing lung volume from 70 to 30% of vital capacity increased Raw by 80%. Cti was larger at functional residual capacity than at the volume extremes. Preceding the measurement by a full expiration rather than by a full inspiration increased Iaw by 15%. The data suggest that the determinants of Raw and Iaw are not identical, that airway hysteresis is larger than lung hysteresis, and that respiratory muscle activity influences tissue properties.

The effects of hypotension induced by trimetaphan on ventilatory control were assessed in sixteen normal subjects under halothane anaesthesia. The breathing pattern, mouth occlusion pressures, lung mechanics, acid-base balance, and arterial blood gases were analysed before and during trimetaphan infusion. During induced hypotension, the only significant change in the ventilatory variables was an increase in the ratio of inspiratory duration to total cycle duration from 0.39 +/- 0.05 (SD) to 0.42 +/- 0.03; P less than 0.01. The average minute ventilation remained unchanged. No modification in lung mechanics was observed, but all subjects developed a slight but significant hypocapnic alkalosis: PaCO2 was reduced from 5.5 +/- 0.4 to 5.2 +/- 0.4 kPa (P less than 0.001) and pH increased from 7.34 to 7.36 (P less than 0.05), without change in standard bicarbonate concentration. Our data indicate that the reduction in sympathetic nervous system activity induced by trimetaphan infusion in spontaneously breathing man causes only a minor alveolar hyperventilation. The weak respiratory response to hypotension suggests that changing peripheral afferent activity has little influence on the typically rapid breathing pattern induced by halothane.

Total respiratory input (Zin) and transfer (Ztr) impedances were obtained from 4 to 30 Hz in 10 healthy subjects breathing air and He-O2. Zin was measured by applying pressure oscillations around the head to minimize the upper airway shunt and Ztr by applying pressure oscillations around the chest. Ztr was analyzed with a six-coefficient model featuring airways resistance (Raw) and inertance (Iaw), alveolar gas compressibility, and tissue resistance, inertance, and compliance. Breathing He-O2 significantly decreased Raw (1.35 +/- 0.32 vs. 1.74 +/- 0.49 cmH2O.l-1.s in air, P less than 0.01) and Iaw (0.59 +/- 0.33 vs. 1.90 +/- 0.44 x 10(-2) cmH2O.l-1.s2), but, as expected, it did not change the tissue coefficients significantly. Airways impedance was also separately computed by combining Zin and Ztr data. This approach demonstrated similar variations in Raw and Iaw with the lighter gas mixture. With both analyses, however, the changes in Iaw were more than what was expected from the change in density. This indicates that factors other than gas inertance are included in Iaw and reveals the short-comings of the six-coefficient model to interpret impedance data.

We studied the correlation between density-dependence parameters (delta He, volume of isoflow) and age, body build, spirography and forced expiratory fows in 69 healthy non-smokers (16 females) aged 18 to 51 years. Density dependence variables showed no significant differences between young (less than 35 years) males and females. Volume of isoflow per cent of forced vital capacity (Viso V % FVC) was poorly significantly related to age (r = +0.25 P less than 0.05) and weight (r = +0.27 P less than 0.05). Significant correlations were found between density dependence at low lung volume and the FEV1/VC ratio (r = 0.31, P = 0.01 for delta He 25%; r = -0.40, P less than 0.001 for Viso V% FVC) or the forced expiratory flows with air (Viso V% FVC vs. FEF 25% r = -0.42, P less than 0.001). These correlations were closer in females as compared to males. Volume of isoflow was well related to delta He 25% (r = -0.64, P less than 0.001), but the relationship with delta He 50% was weaker (r = -0.38; P less than 0.01).

The real--Re(Z)--and imaginary--Im(Z)--parts of the ventilatory system impedance were measured between 6 and 30 Hz in 18 normal infants and in 19 with airway obstruction. The intercept (R0) and slope (S) of the Re(Z)-frequency function, as well as inertance (I) and compliance (C) estimated from Im(Z), were compared with ventilatory system resistance (Rrs) and compliance (Crs) (single-breath method). R0 correlated significantly with Rrs (r = 0.86), although the slope of the regression equation was significantly lower than 1 (P less than 0.01). Negative frequency dependence of Re(Z) was observed in all subjects and a significant correlation was found between S and Rrs (r = -0.80). "Inertance" was negative in 20 subjects and correlated negatively with Rrs (r = -0.61). C correlated with Crs (r = 0.64) and with 1/Rrs (r = 0.85). The ratio of C to Crs (mean +/- SD = 0.168 +/- 0.082) also correlated with 1/Rrs (r = 0.51). The main characteristics of the total impedance/frequency function could be simulated with a model featuring the upper airway wall (Zuaw) in parallel with the ventilatory system (Zrs). It is suggested that the differential change in Zuaw and Zrs with growth accounts for the marked frequency dependence of Re(Z) as well as the inaccurate estimation of both I and C in this population.

The helium to air difference in maximal expiratory flow at mid-vital capacity (ΔHe 50%) and the volume at which air and helium expired flow rates become identical (Viso\(\mathop V\limits^ \bullet \)) are currently measured from maximal expiratory flow-volume (MEFV) curves with the largest forced vital capacities (FVC) superimposed at residual volume (RV). True FVC and maximal flows may be obtained by superimposing several MEFV tracings to construct a “composite” (envelope) curve. From both theoretical and practical points of view, total lung capacity (TLC) is a more logical and more reproducible reference for matching air and helium-oxygen MEFV curves. The use of composite MEFV matched at TLC was compared to the conventional procedure in 41 healthy subjects aged 18 to 54 years. No significant difference for δHe 50% and Viso\(\mathop V\limits^ \bullet \) resulted from the application of the modifications proposed but the number of subjects with absent Viso\(\mathop V\limits^ \bullet \) increased with superimposition at TLC. The intersubject variability of the ΔHe 50% was decreased and that of Viso\(\mathop V\limits^ \bullet \) was increased. The sensitivity of both variables to the relationship between air and He + O2 FVC is stressed.

Thoracic gas volume (TGV) and specific airway resistance (sRaw) are commonly measured using pressure type and flow type body plethysmographs. Within-subject variability of the data, defined as the coefficient of variation of eight to ten measurements during the same session, was assessed with the two kinds of instruments and compared in fifteen normal subjects. The reproducibility of data obtained several days apart was also compared. All measurements were made in a 480-l body chamber, which could be used in both the pressure and the flow mode. The signals were processed digitally using three different algorithms: 1) simple linear regression (LR); 2) linear regression with drift correction achieved by adding to, or subtracting from the plethysmographic signal a term proportional to time (LRC); 3) Fourier analysis (FFT). Within-subject variability of TGV was much larger with flow than with pressure plethysmography when the signals were processed by LR (14.5 +/- 7.5 vs 6.3 +/- 3.0%; p less than 0.001), but almost the same using LRC (6.7 +/- 3.2 vs 5.4 +/- 2.7%) and FFT (6.1 +/- 2.4 vs 5.0 +/- 2.4%). For sRaw, variabilities were larger and less influenced by methodological factors. Adequate digital processing may therefore largely remedy the inherently greater variability of TGV measurements with flow plethysmographs.

Frequency dependence of thoracic gas volume (Vtg) and phase angles between volume and mouth pressure signals were evaluated in 10 normal subjects and in 31 patients with bronchitis, who panted sequentially at 0.8 Hz and 2.5 Hz during the same occlusion. A slight negative frequency dependence of Vtg (-1.2 +/- 0.9%/Hz, -m +/- SD), accompanied by a very small phase lag of volume with respect to pressure variations (-1.5 +/- 0.9 degrees at 2.5 Hz) was found in normal subjects. In contrast, patients with bronchitis exhibited a mild positive frequency dependence of Vtg (+ 0.5 +/- 1.7%/Hz and + 0.8 +/- 2.3%/Hz in subjects with normal and increased airway resistance, respectively), whereas the volume signal slightly led the pressure signal at 2.5 Hz. Both the frequency dependence and the phase difference increased when the subjects with the largest airway resistance did not support their cheeks during the panting maneuvers. The data confirm previous indirect evidence that Vtg is, in most instances, accurately measured by Boyle's law in mild and moderate chronic airway obstruction.

Summary. The variability (coefficient of variation of five consecutive measurements), reproducibility (difference of results at 1 h and 24 h), and interobserver difference (independent reading of the tracings by two observers) of airways resistance (Raw) and static lung volumes (residual volume, functional residual capacity, total lung capacity) using a body plethysmograph were assessed in 14 healthy subjects and in 25 patients with various respiratory disorders. The variability was low for TLC (4–5%), moderate for FRC (74%) and high for Raw (28%). No significant changes of Raw or lung volumes were found for the groups at 1 h and 24 h. Between observers, a slight difference existed for FRC and Raw in normal subjects; the difference was higher (4·5% for FRC and 11 % for Raw) and became significant in patients. The overestimation of Raw by observer 2 as compared to observer 1 was more important at larger values. The present findings call for caution when pooling results obtained by several observers in large-scale studies, or when comparing figures obtained by different technicians in the pulmonary function laboratory.

Respiratory input impedance (Zrs) was measured from 8 to 256 Hz in 10 healthy subjects by a method that eliminated the shunt impedance of extrathoracic airway walls. It consisted of combining the data obtained with a pressure input at the mouth (standard method, Zst) and with a pressure input around the head (Zhg) Zrs = Zst.(Zp + Zhg)/(Zp + Zst) where Zp is the impedance of the mouthpiece and pneumotachograph. Large quantitative differences were observed between Zrs and Zst, demonstrating that the standard method is unreliable at such frequencies. The real part of Zrs increased from 2.6 +/- 0.8 cmH2O.l-1.s at 8 Hz to a maximum of 38 +/- 19 cmH2O.l-1.s at 158 +/- 49 Hz. The imaginary part exhibited a maximum of 19 +/- 8 cmH2O.l-1.s at 126 +/- 38 Hz, a resonance at 157 +/- 43 Hz, and a minimum of lambda 19 +/- 16 cmH2O.l-1.s at 185 +/- 45 Hz. The data were analyzed with five models featuring alveolar gas compressibility; tissue resistance, inertance, and compliance; and different representations of the airways with lumped and distributed parameters. All except the simplest (lumped frequency-dependent resistance) fitted the data equally well, but none provided reliable estimates of gas compliance. Three models gave a consistent description of the airway in terms of equivalent rigid tubes (cross-sectional area 3.5-3.7 cm2, length 47-51 cm). We conclude that high-frequency input impedance could prove useful in exploring the airways but not the peripheral lung.

Mechanical impedance of the respiratory system was measured at 5, 10, 15 and 20 Hz in 47 healthy non-smokers, 20 ex-smokers and 51 current smokers. Besides the resistance and its frequency dependence, the compliance, the inertance and the resonant frequency of the respiratory system were computed using the assumption of a second order linear system. The data were normalized for sex, age and body height on the basis of correlations observed in non-smokers. No significant difference was found in ex-smokers. In smokers the resistance was significantly increased at all frequencies. However, it was normal in a number of subjects with abnormally low maximal expiratory flows. unlike maximal flows, forced oscillations indices were not correlated to tobacco consumption expressed in pack-years. The results do not indicate that impedance measurements breathing air may be specially useful for early detection of airway abnormalities.

To assess their value for early recognition of airway abnormalities, forced expiration slope ratios as recently defined by Mead, were measured at 5 lung volumes in 114 healthy nonsmokers and in 76 cigarette smokers. In healthy nonsmokers, slope ratios were independent of sex and body height, but were significantly correlated with age. They tended to be higher at low lung volume, particularly in older subjects. In male smokers with a tobacco consumption of less than 5 pack-years, slope ratios were increased at both ends of the volume range, suggesting nonhomogeneous lung emptying and peripheral airway obstruction. With increasing tobacco consumption, slope ratios tended to return to normal values at low lung volume, perhaps because of airway closure. In female smokers, slope ratios were decreased at high lung volume and increased at low lung volume, suggesting that both central and peripheral airways were abnormal. Mead's analysis appeared to be a useful tool for discussing the data in terms of functional abnormalities. However, because of their large variability, slope ratios were not as successful as transit time indices for recognizing abnormal subjects.