Evaluation of impulse oscillation system: comparison with forced oscillation technique and body plethysmography.

The impulse oscillation system (IOS) has been developed recently to measure respiratory system resistance (Rrs) and reactance (Xrs) at different frequencies up to > or = 25 Hz. IOS has, however, not been validated against established techniques. This study compared IOS with the classical pseudorandom noise forced oscillation technique (FOT) and body plethysmographic airway resistance (Raw) in 49 subjects with a variety of lung disorders and a wide range of Raw (0.10-1.28 kPa x L(-1) x s). Rrs,IOS was slightly greater than Rrs,FOT, especially at lower frequencies, with a mean +/- SD difference at 5-6 Hz of 0.14 +/- 0.09 kPa x L(-1) x s. Comparisons with the wave-tube technique applied on two analogues indicated an overestimation by IOS. Xrs,IOS and Xrs,FOT were very similar, with a slightly higher resonant frequency with IOS than with FOT (mean difference +/- SD 1.35 +/- 3.40 Hz). Raw was only moderately correlated with Rrn,FOT and Rrs-IOS; although the mean differences were small (0.04 +/- 0.14 kPa x L(-1)s for Rrs6,FOT and -0.10 +/- 0.14 kPa x L(-1) x s for Rrs5,IOS), IOS and FOT markedly underestimated high resistance values. In conclusion, the impulse oscillation system yields respiratory system resistance and reactance values similar, but not identical to those provided by the forced oscillation technique.

Influence of upper airway shunt on total respiratory impedance in infants.

When input impedance is determined by means of the forced oscillation technique, part of the oscillatory flow measured at the mouth is lost in the motion of the upper airway wall acting as a shunt. This is avoided by applying the oscillations around the subject's head (head generator) rather than at the mouth (conventional technique). In seven wheezing infants, we compared both techniques to estimate the importance of the upper airway wall shunt impedance (Zuaw) for the interpretation of the conventional technique results. Computation of Zuaw required, in addition, estimation of nasal impedance values, which were drawn from previous measurements (K. N. Desager, M. Willemen, H. P. Van Bever, W. De Backer, and P. A. Vermeire. Pediatr. Pulmonol. 11: 1-7, 1991). Upper airway resistance and reactance at 12 Hz ranged from 40 to 120 and from 0 to -150 hPa. l(-1). s, respectively. Varying nasal impedance within the range observed in infants did not result in major changes in the estimates of Zuaw or lung impedance (ZL), the impedance of the respiratory system in parallel with Zuaw. The conventional technique underestimated ZL, depending on the value of Zuaw. The head generator technique slightly overestimated ZL, probably because the pressure gradient across the upper airway was not completely suppressed. Because of the need to enclose the head in a box (which is not required with the conventional technique), the head generator technique is difficult to perform in infants.

Influence of awareness of the recording of breathing on respiratory pattern in healthy humans.

This study was designed to test whether awareness of the measurement of breathing influences the breathing pattern in healthy subjects under routine laboratory conditions. Seventy four subjects (40 females and 34 males), aged 21-63 yrs, were studied under three different conditions whilst their breathing was being recorded for 5 min by means of inductance plethysmography (Respitrace): 1) subjects were misled into believing that their breathing was not being recorded but that they had to wait for 5 min whilst equipment was calibrated; 2) subjects were instructed that their breathing pattern was being recorded for 5 min; 3) the subject's breathing was recorded for 5 min with mouthpiece and pneumotachograph. The first two conditions were randomized. The Respitrace was calibrated by means of multiple linear regression carried out during the 5 min period of quiet breathing through a mouthpiece. Awareness of the recording of breathing caused prolongation of inspiratory (tI) and expiratory time (tE). Breathing through the mouthpiece resulted in an increase of tI, tE and tidal volume (VT). The breathing irregularities (sighs and end-expiratory pauses) decreased when subjects were aware of the recording of breathing and nearly disappeared when subjects breathed through the mouthpiece. The end-tidal carbon dioxide concentration was not significantly different between the three conditions. Mouthpiece breathing often induced some respiratory discomfort and even anxiety, particularly in females. Awareness by the subject that his or her breathing was being recorded altered the spontaneous breathing pattern, mainly the breathing frequency. In addition, use of a mouthpiece markedly increased tidal volume, particularly in females in whom mouthpiece breathing induced more complaints than in males.

Unsteadiness of breathing in patients with hyperventilation syndrome and anxiety disorders.

The breathing pattern of 399 patients with hyperventilation syndrome (HVS) and/or with anxiety disorders and that of 347 normal controls was investigated during a 5 min period of quiet breathing and after a 3 min period of voluntary hyperventilation. The diagnosis of HVS was based on the presence of several suggestive complaints occurring in the context of stress, and reproduced by voluntary hyperventilation. Organic diseases as a cause of the symptoms were excluded. The anxiety disorders were diagnosed by means of an abbreviated version of the Anxiety Disorders Interview Schedule (ADIS). There was a large overlap between the two diagnoses. Simply breathing via a mouthpiece and pneumotachograph made end-tidal CO2 fractional concentration (FET,CO2) decrease progressively both in hyperventilators and in patients with anxiety disorders, but not in normals. At the start of the measurement the FET,CO2 was not different between patients and healthy subjects. In patients < or = 28 yrs, the decrease of FET,CO2 resulted from a higher tidal volume, and in patients > or = 29 years from an increase in frequency. After voluntary hyperventilation, the recovery of FET,CO2, was delayed in patients, due to a slower normalization of respiratory frequency in females and in older males, and of tidal volume in younger males, and also due to less frequent end-expiratory pauses. When breathing was recorded first by means of inductive plethysmography (Respitrace), the progressive decline of FET,CO2 seen in patients was not observed: from the onset of the recording, FET,CO2 was reduced in patients. It did not change further when, immediately afterwards, the subject switched to mouthpiece breathing. The finding that breathing through a mouthpiece induces hyperventilation in patients and that recovery of FET,CO2 is delayed after voluntary hyperventilation, suggests that the respiratory control system is less resistant to challenges (mouthpiece or voluntary hyperventilation) in those patients. On the other hand, the lower values of FET,CO2 measured during recording by means of a Respitrace probably result from a challenge, prior to the recordings, induced by the fitting of the measuring device to the patient. This unsteadiness of breathing characterizes patients with hyperventilation syndrome and those with anxiety disorders, but is not sufficiently sensitive to be used for individual diagnosis.

Two-point calibration procedure of the forced oscillation technique.

The forced oscillation technique is usually calibrated by loading the measuring device with a known impedance. A correction function is calculated, relating the measured and reference impedances at each frequency. However, this one point calibration procedure does not account for transducer asymmetry. A procedure has previously been presented to circumvent this problem: in addition to one known reference impedance, the calibration was repeated with the system occluded (infinite impedance). The aim of the present study was to evaluate a variant of this procedure, in which instead of resorting to an extreme condition imposing high requirements on the flow measuring system, two reference loads of 4 and 50 hPal-1 s were measured, thus covering the range of impedances observed in children and infants (a two-point procedure). The calibration procedure was performed with these two impedances and evaluated with a third impedance of approximately 17 hPal-1 s. The results of three calibration procedures were compared: one-point, two-point and a previously reported calibration procedure. Impedances consisted of sintered glass and mesh wire screens mounted in glass or polyvinyl tubes. For low impedance values, in the range of 4 to 17 hPal-1 s, measured and predicted values were similar for the three calibration procedures at frequencies from 4-52 Hz, although with the one point calibration procedure there was some underestimation above 44 Hz. With the highest load, especially above 32 Hz, marked discrepancies between measured and predicted values were observed with the one-point calibration procedure and the previously reported calibration procedure. Under these circumstances the two-point procedure is preferred.

Membranous bronchioles and connective tissue network of normal and emphysematous lungs.

Three-dimensional reconstructions of the septal system of normal human lungs revealed that airways course within the interlobular septa, i.e., between the two blades formed by the peripheral boundaries of adjacent lobuli of whatever order, and enter the supplied pulmonary unit at its side. This is not in keeping with the classic view of a peripheral airway in the center of a lung unit and submitted to radial traction by attached alveolar septa. The basic design of the lung fibrous scaffold appears to be in conformity with the laws of fractal geometry. Similar reconstructions in centrilobular emphysema disclosed tortuosities of both intra-acinar and interlobular septa, with consequent distortions of the corresponding intraseptal bronchioles and collapse of lung units of different sizes. It is suggested that in centrilobular emphysema competition for space, besides intrinsic airways narrowing because of inflammation and loss of elastic recoil, is a cause of flow limitation.

Anatomy of membranous bronchioles in normal, senile and emphysematous human lungs.

Serial reconstructions of the membranous bronchioles (MB) were performed in randomly selected tissue blocks cut parallel to the pleural surface in fixated human lungs. Two to four normal, senile, and emphysematous lungs were examined. Three (2 in senile lungs) orders of MB were observed with a dichotomous branching pattern. Emphysematous lungs are characterized by an overall decrease in airway diameter with localized stenoses. Comparison with mean airway diameter (d) and density [n (no. of MBs per cm2 of lung tissue)] of MBs obtained using standard morphometric techniques (random sections approximately 1 cm from the pleura) showed that the values of d and n are biased because of the inclusion in the measurements of a number of respiratory bronchioles and bronchi. When these misclassifications are corrected for, it appears that d corresponds quite well to the mean diameter of the terminal bronchioles (TB) and n to approximately twice the density of TBs. After correction, n is not significantly reduced in emphysematous lungs (the grossly destroyed areas being excluded) compared with normal lungs. The estimate of the number of TBs obtained from the present data is markedly less than that calculated by Weibel (Morphometry of the Human Lung. Berlin: Springer-Verlag, 1963), which suggests that the number of bronchi was overestimated by Weibel by at least one generation. Finally, values of peripheral airway resistance computed from the present anatomic data correspond quite well to direct measurement performed on the same lungs before fixation (Verbeken et al., J. Appl. Physiol. 72:2343-2353, 1992).

Shunt properties of large intrathoracic airways.

The impedance of the wall of human intrathoracic trachea and central airways was measured by submitting preparations of excised airways to forced oscillations at various frequencies from 2 to 32 Hz. Both real (resistance) and imaginary (reactance) parts of wall impedance demonstrate a marked frequency dependence, varying with transmural pressure. These variations of resistance and reactance are related and are linked to the static elastic properties of the airways. The data allow us to calculate the total shunt impedance of the central intrathoracic airways. When the latter shunt values are used to correct measurements of impedance values of excised emphysematous lungs, it turns out that the shunt does not modify markedly the observed frequency dependence of resistance and compliance of those lungs, at least at transpulmonary pressures > 0.2 kPa. A model study suggests, in addition, that the latter frequency characteristics cannot be explained satisfactorily by parallel mechanical inhomogeneities. We submit that the frequency dependence of resistance and compliance of excised emphysematous lungs is determined mainly by the visco- and/or plastoelastic properties of lung tissue itself.

Structure and function in fibrosing alveolitis.

Lung volumes, maximal expiratory volume and flows, elastic recoil pressure, and impedances at various levels of the bronchial tree, as well as tissue impedance, were measured in 13 human lungs that demonstrated generalized fibrosis at autopsy. After fixation, mean internal chord of air spaces (Lma), transsection length of the alveolar walls (Lmw), and internal diameter (d) and density of membraneous bronchioles (n/cm2) were determined in the same lungs by use of morphometric techniques. The results of functional and structural measurements were correlated and compared with measurements obtained similarly in 10 normal lungs. This study shows that the functional alterations typical for fibrosing alveolitis can be attributed to the replacement of part of the parenchyma by fibrous tissue and to modifications of the mechanical properties of still-functional units. The lungs were characterized structurally by an increase of Lmw and d. In addition, in three lungs, an increase of Lma and a decrease of n/cm2 were observed. Functionally, these lungs demonstrated a pattern compatible with a mixture of fibrosis and emphysema.

Functional alterations accompanying a rapid decline in ventilatory function.

In a study of two groups of healthy males matched for age, smoking habits, and duration of follow-up, but differing in the rapidity of decline of FEV1 and/or vital capacity (VC), we measured lung volumes before and after bronchodilator inhalation, forced expiratory flows, diffusion capacity for CO (DLCO), and total respiratory impedance. A discriminant analysis showed that the separation between the two groups was achieved best by DLCO, weight, and FEV1/VC among the smokers and by body height and DLCO among the nonsmokers. The fact that DLCO turns out to discriminate between people with a rapid and a normal spirographic decline in the present group points to the possibility of using this measurement, in combination with FEV1/VC and weight, as a predictor of rapid decline of lung function in middle-aged healthy male smokers.

Changes of respiratory input impedance during breathing in humans.

Changes of total respiratory resistance (Rrs) and reactance (Xrs) were studied between 8 and 32 Hz at five moments during the respiratory cycle in healthy adults (group A) and children (group B) and in patients with chronic obstructive lung disease (group C) and with upper airway obstruction (group D). Two forced oscillation techniques were used: the conventional one and the head generator, with the oscillations applied at the mouth and around the head of the subject, respectively. Both techniques yielded similar results. Rrs is lowest during the transition from inspiration to expiration and highest in the course of expiration, except in group D. Mean Xrs is highest at the transitions from inspiration to expiration or vice versa and lowest during expiration, except in group D. In groups C and D, the increases of Rrs are accompanied by a more pronounced negative frequency dependence of Rrs. The variations of Rrs and Xrs appear to be markedly flow dependent and may be a consequence of the interaction of breathing with oscillatory flows.

Tissue and airway impedance of excised normal, senile, and emphysematous lungs.

We partitioned pulmonary resistance (RL) in excised normal, senile, and emphysematous human lungs at various distending pressures; peripheral resistance (Rp) was measured by means of retrograde catheters and lung tissue resistance (Rti) by means of pleural capsules. By subtracting Rp from RL and Rti from Rp, we obtained, respectively, central (Rcaw) and peripheral (Rpaw) airway resistance. We determined also lung volumes, the elastic recoil pressure-volume curve, and the forced expiratory volume in 1 s-to-vital capacity ratio (FEV1/VC). The functional data were related to morphometry: mean linear intercept (Lm), diameter (d), and density (n/cm2) of membranous bronchioles. In the three groups of lungs, Rti demonstrates a marked negative frequency dependence and increases with transplumonary pressure. In emphysematous lungs, the increase of RL is mainly due to an increase of Rpaw; in addition, Rcaw and Rti are higher than normal. In the group of senile lungs, airway resistances are within normal range, but Rti is slightly increased. FEV1/VC is related to Rpaw and elastic recoil pressure; Rpaw is related to d and n/cm2, and Rti is related to dynamic elastance and to Lm.

The senile lung. Comparison with normal and emphysematous lungs. 1. Structural aspects.

As part of a study of the structural-functional correlations of excised human lungs obtained at autopsy, the parenchyma and peripheral airways were examined by means of morphometric techniques. Among the 30 lungs characterized by the absence of fibrosis, ten differed from the normal and emphysematous lungs by a homogeneous dilatation of the airspaces, in excess of the dimensions predicted on the basis of age. Study of the standard deviations of the mean linear intercepts showed that the airspace dilatation was more regular than in emphysematous lungs; in addition, there was no clear-cut destruction, as estimated from the number of alveolar attachments. These lungs were characterized in addition by an increased thickening of alveolar septa, without inflammation or fibrosis, normal size of the diameter, and reduced density of the membranous bronchioles. Since these lungs were from people older than 60 years, it is assumed that they represent cases of exaggerated airspace enlargement of the aging lung, differing from emphysema by the absence of destruction of alveolar walls. The term "senile lung" is proposed or this condition.

The senile lung. Comparison with normal and emphysematous lungs. 2. Functional aspects.

Senile lungs are characterized by a homogeneous enlargement of the alveolar airspaces, without fibrosis or destruction of their walls. Study of the functional characteristics of excisea senile lungs showed an increase in minimal air and a shift to the left of the elastic recoil pressure-volume curves, less pronounced than in emphysematous lungs. Maximal expiratory volumes and flows were normal. Total lung capacity was not significantly increased, but this may be a consequence of preagonal edema. Comparison of normal, senile, and emphysematous lungs showed a close relationship between recoil pressures and mean linear intercept, Lm, and between forced expiratory volume in 1 s and diameter and density of the membranous bronchioles. It is concluded that airspace enlargement may precede emphysema and may be responsible for changes in lung elasticity. In this respect, senile lungs are an example of the functional changes caused by an isolated airspace enlargement.

Total respiratory resistance and reactance in ankylosing spondylitis and kyphoscoliosis.

Ankylosing spondylitis and kyphoscoliosis both alter the function of the lung by modifying the mechanical properties of the thoracic cage. The purpose of the present study was to assess the changes in total respiratory resistance (Rrs) and reactance (Xrs) in these patients and to compare these data with conventional pulmonary function tests. In 16 patients with ankylosing spondylitis and seven with kyphoscoliosis we measured lung volumes, maximal flows, diffusing capacity, airway resistance, lung compliance and Rrs and Xrs between 2-26 Hz by means of the forced oscillation technique (FOT). In the patients with ankylosing spondylitis mean total lung capacity was 83% predicted (range 60-105%). Mean values of Rrs were normal; there was a small decrease in Xrs at the lowest frequency. In the patients with kyphoscoliosis mean total lung capacity (TLC) was 41% predicted for arm span (range 26-75%). Mean Rrs was elevated with a negative frequency dependence, and mean Xrs was decreased. The observed differences in Rrs and Xrs between the two groups of patients are related to differences in severity of the restriction. There is evidence that the changes in Rrs and Xrs in both groups are mainly attributable to an increase in chest wall resistance and a decrease in chest wall compliance, while in the patients with kyphoscoliosis an increase in airway resistance and a decrease in lung compliance also intervenes.

Total respiratory resistance and reactance in patients with diffuse interstitial lung disease.

In 54 patients with interstitial lung diseases and no signs of airway obstruction we measured lung volumes, maximal expiratory flows, diffusing capacity (DLCO), total respiratory resistance (Rrs) and reactance (Xrs) between 4 and 26 Hz by means of the forced oscillation technique. In all patients DLCO was less than 75% of the expected value. Patients were classified into two groups depending on total lung capacity (TLC): group A with TLC less than 80% of expected, and group B with TLC of 80% or more. Group A demonstrated a decrease of Xrs especially at low frequencies, with small, not significant changes in Rrs. In the patients in this group with the lowest values of TLC (less than 50%), we observed an increase of Rrs at low frequencies causing a negative frequency dependence of Rrs. In group B no distinct changes of Rrs and Xrs occurred. Canonical correlation analysis between routine lung function data and forced oscillation parameters, showed tight correlations between TLC in absolute value or VC in percent of the predicted value on the one hand and average level of Xrs and average slope of Xrs (and Rrs) vs frequency curves on the other hand. Measurements of lung mechanics in five additional patients and comparison with a model of the respiratory system suggest that the changes of Rrs and Xrs are not explained totally by the observed increase in lung tissue resistance and decrease in lung compliance. The observed changes in Rrs and Xrs are not specific for restrictive lung disorders; similar changes are met also in moderately advanced obstructive diseases.

Effect of upper airway shunt and series properties on respiratory impedance measurements.

Because of the contradictory statements published about the influence of the shunt properties of the upper airway on the measurements of the respiratory impedence by means of the forced oscillation technique, this influence has been reevaluated. In healthy adults and children and in patients with obstructive lung disease, the total respiratory impedance was measured by applying oscillations at the mouth (conventional technique) or around the head (head generator technique), with the cheeks either supported by the hands or not. In healthy adults the two techniques (conventional cheeks supported and head generator) yield similar results for respiratory resistance (Rrs) and a more pronounced increase of respiratory reactance (Xrs) with frequency with the head generator. In children and in patients with moderate airway obstruction, the negative frequency dependence of Rrs observed with the conventional technique tends to disappear with the head generator. This is not observed in patients with severe airway obstruction. The differences between the two techniques can be explained by the influence of the shunt impedance of the upper airway on Rrs and Xrs. Correction for this influence by subtracting the impedance measured during a Valsalva maneuver is not satisfactory, since the Valsalva maneuver itself modifies the upper airway shunt. The head generator technique reduces the influence of the upper airway shunt but does not suppress it altogether; the residual error is small, however.

Resistance and reactance of the excised human larynx, trachea, and main bronchi.

We investigated the impedance of excised preparations of the human larynx before and after resection of the vocal cords and of the trachea whether or not in connection with the main bronchi for steady (75-700 ml.s-1) and oscillatory flows (4-64 Hz). To simulate the influence of respiratory flow on oscillatory resistance (Rosc), oscillatory and steady flow were superimposed. This resulted in a marked increase of Rosc, dependent on the value of steady flow, a change of the frequency dependence of Rosc, and a decrease of the reactance. The latter effects were particularly pronounced in the preparations of the larynx, especially with a narrow glottis opening. The influence of steady flow on oscillatory resistances is probably the expression of interactions of steady and oscillatory flow regimes in the larynx. Similar but less pronounced interactions are also met in the trachea. These effects lead to a systematic overestimation of upper airway resistance when measured during spontaneous breathing by means of a forced oscillation technique.

Total respiratory resistance and reactance in patients with upper airway obstruction.

In 18 patients with upper airway obstruction, we measured dynamic lung volumes, maximal flows, airway resistance (Raw), and total respiratory resistance (Rrs) and reactance (Xrs) at various frequencies by means of a forced oscillation method. Patients were classified according to the site and the type of the obstruction. The values of Raw, Rrs and Xrs were tightly correlated and reflected the overall importance of the obstruction. In comparison with patients with chronic obstructive pulmonary disease the values of Rrs tend to be higher and to be influenced more by support of the cheeks during the measurement. These differences are not diagnostic, however.

Effect of rib cage and abdominal restriction on total respiratory resistance and reactance.

In 14 healthy male subjects we studied the effects of rib cage and abdominal strapping on lung volumes, airway resistance (Raw), and total respiratory resistance (Rrs) and reactance (Xrs). Rib cage, as well as abdominal, strapping caused a significant decrease in vital capacity (respectively, -36 and -34%), total lung capacity (TLC) (-31 and -27%), functional residual capacity (FRC) (-28 and -28%), and expiratory reserve volume (-40 and -48%) and an increase in specific airway conductance (+24 and +30%) and in maximal expiratory flow at 50% of control TLC (+47 and +42%). The decrease of residual volume (RV) was significant (-12%) with rib cage strapping only. Abdominal strapping resulted in a minor overall increase in Rrs, whereas rib cage strapping produced a more marked increase at low frequencies; thus a frequency dependence of Rrs was induced. A similar pattern, but with lower absolute values, of Rrs was obtained by thoracic strapping when the subject was breathing at control FRC. Xrs was decreased, especially at low frequencies, with abdominal strapping and even more with thoracic strapping; thus the resonant frequency of the respiratory system was shifted toward higher frequencies. Partitioning Rrs and Xrs into resistance and reactance of lungs and chest wall demonstrated that the different effects of chest wall and abdominal strapping on Rrs and Xrs reflect changes mainly of chest wall mechanics.