Z. Hantos

The forced oscillation technique in clinical practice: methodology, recommendations and future developments

The forced oscillation technique (FOT) is a noninvasive method with which to measure respiratory mechanics. FOT employs small-amplitude pressure oscillations superimposed on the normal breathing and therefore has the advantage over conventional lung function techniques that it does not require the performance of respiratory manoeuvres. The present European Respiratory Society Task Force Report describes the basic principle of the technique and gives guidelines for the application and interpretation of FOT as a routine lung function test in the clinical setting, for both adult and paediatric populations. FOT data, especially those measured at the lower frequencies, are sensitive to airway obstruction, but do not discriminate between obstructive and restrictive lung disorders. There is no consensus regarding the sensitivity of FOT for bronchodilation testing in adults. Values of respiratory resistance have proved sensitive to bronchodilation in children, although the reported cutoff levels remain to be confirmed in future studies. Forced oscillation technique is a reliable method in the assessment of bronchial hyperresponsiveness in adults and children. Moreover, in contrast with spirometry where a deep inspiration is needed, forced oscillation technique does not modify the airway smooth muscle tone. Forced oscillation technique has been shown to be as sensitive as spirometry in detecting impairments of lung function due to smoking or exposure to occupational hazards. Together with the minimal requirement for the subjects cooperation, this makes forced oscillation technique an ideal lung function test for epidemiological and field studies. Novel applications of forced oscillation technique in the clinical setting include the monitoring of respiratory mechanics during mechanical ventilation and sleep.

Lung volumes and respiratory mechanics in elastase-induced emphysema in mice

Absolute lung volumes such as functional residual capacity, residual volume (RV), and total lung capacity (TLC) are used to characterize emphysema in patients, whereas in animal models of emphysema, the mechanical parameters are invariably obtained as a function of transrespiratory pressure (Prs). The aim of the present study was to establish a link between the mechanical parameters including tissue elastance (H) and airway resistance (Raw), and thoracic gas volume (TGV) in addition to Prs in a mouse model of emphysema. Using low-frequency forced oscillations during slow deep inflation, we tracked H and Raw as functions of TGV and Prs in normal mice and mice treated with porcine pancreatic elastase. The presence of emphysema was confirmed by morphometric analysis of histological slices. The treatment resulted in an increase in TGV by 51 and 44% and a decrease in H by 57 and 27%, respectively, at 0 and 20 cmH(2)O of Prs. The Raw did not differ between the groups at any value of Prs, but it was significantly higher in the treated mice at comparable TGV values. In further groups of mice, tracheal sounds were recorded during inflations from RV to TLC. All lung volumes but RV were significantly elevated in the treated mice, whereas the numbers and size distributions of inspiratory crackles were not different, suggesting that the airways were not affected by the elastase treatment. These findings emphasize the importance of absolute lung volumes and indicate that tissue destruction was not associated with airway dysfunction in this mouse model of emphysema.

Components of respiratory resistance monitored in mechanically ventilated patients

The interrupter technique is commonly adopted to monitor respiratory resistance (Rrs,int) during mechanical ventilation; however, Rrs,int is often interpreted as an index of airway resistance (Raw). This study compared the values of Rrs,int provided by a Siemens 940 Lung Mechanics Monitor with total respiratory impedance (Zrs) parameters in 39 patients with normal spirometric parameters, who were undergoing elective coronary bypass surgery. Zrs was determined at the airway opening with pseudorandom oscillations of 0.2–6 Hz at end inspiration. Raw and tissue resistance (Rti) were derived from the Zrs data by model fitting; Rti and total resistance (Rrs,osc=Raw+Rti) were calculated at the actual respirator frequencies. Lower airway resistance (Rawl) was estimated by measuring tracheal pressure. Although good agreement was obtained between Rrs,osc and Rrs,int, with a ratio of 1.07±0.19 (mean±sd), they correlated poorly (r2=0.36). Rti and the equipment component of Raw accounted for most of Rrs,osc (39.8±11.9 and 43.0±6.9%, respectively), whereas only a small portion belonged to Rawl (17.2±6.3%). It is concluded that respiratory resistance may become very insensitive to changes in lower airway resistance and therefore, inappropriate for following alterations in airway tone during mechanical ventilation, especially in patients with relatively normal respiratory mechanics, where the tissue and equipment resistances represent the vast majority of the total resistance.

Endothelin-1-induced airway and parenchymal mechanical responses in guinea-pigs: the roles of ETA and ETB receptors

Endothelin-1 (ET-1) has been shown to have a constrictor effect on the airways and parenchyma; however, the roles of the ETA and ETB receptors in the ET-1-induced changes in the airway and tissue compartments have not been fully explored. Low-frequency pulmonary impedance (ZL) was measured in anaesthetized, paralysed, open-chest guinea-pigs. ZL spectra were fitted by a model to estimate airway resistance (Raw) and inertance (Iaw), and coefficients of tissue damping (G) and elastance (H), and hysteresivity (eta = G/H). Two successive doses of ET-1 (0.05 and 0.2 nmol x kg(-1)) each evoked significant dose-related increases in Raw, G, H and eta. Pretreatment with 20 nmol x kg(-1) BQ-610 (a highly selective ETA receptor antagonist) resulted in a significantly decreased elevation only in H after the lower dose of ET-1. However, all parameters changed significantly less on the administration of ET-1 after pretreatment with 80 nmol-kg(-1) BQ-610, with 20 nmol x kg(-1) ETR-P1/fl (a novel ETA receptor antagonist) or with 20 nmol x kg(-1) IRL 1038 (an ETB receptor antagonist). The results of the separate assessments of the airway and tissue mechanics demonstrate that endothelin-1 induces airway and parenchymal constriction via stimulation of both receptor types in both compartments.

Lung structure and function in elastase-treated rats: A follow-up study

Structural and functional longitudinal alterations of the lungs were followed in an emphysema model. Rats were treated with porcine pancreatic elastase (PPE, n=21) or saline (controls, C, n=19). Before the treatment and 3, 10, 21 and 105 days thereafter, absolute lung volumes (FRC, TLC and RV) and tissue mechanical parameters (elastance: H; damping: G) were determined. At 3, 21 and 105 days the lungs were fixed in subgroups of rats. From histological samples the equivalent diameter of airspaces (Dalv), elastin (Mec) and collagen densities were assessed. In the PPE group, FRC and RV were higher from 3 days after treatment compared to controls (p<0.001), while TLC exhibited a delayed increase. H and G decreased in the PPE group throughout the study (p<0.001). Higher Mec (p<0.001) and late-phase inflammation were observed at 105 days. We conclude that during the progression of emphysema, septal failures increase Dalv which decreases H; this reveals a strong structure-function relationship.

Computation of the equivalent airway resistance: a comparison with routine evaluations of plethysmographic measurements.

Equivalent (effective) values of airway resistance were determined for total breaths, inspiration and expiration in spontaneously breathing patients by means of an off-line processing system. An improvement in the alveolar pressure determination was achieved by subtracting thermal pressure drifts of the pressure plethysmograph and by taking into account instantaneous values of the intrathoracic gas volume. Equivalent resistance values were compared with the results of several simulated routine evaluations. It was found that the equivalent resistance is best approximated by the graphical procedure using average pressure points at +/- 0.5 liter/sec flow levels.

Computer-aided investigations of respiratory data

In the first part of this paper a computerised evaluation of plethysmographic signals is presented. The off-line processing described eliminates some erroneous simplifications that routine plethysmography is bound to involve. (1) A subtraction of the box pressure baseline permits measurements with perfectly sealed constant volume plethysmographs even in the case of thermal disequilibrium. (2) Alveolar pressure is computed from the box pressure signal, using instantaneous values of the intrathoracic gas volume. (3) This technique enables one to utilise all the measured data for determinations of airway resistance and viscous work, thus yielding more exact values as compared to the graphic evaluations. In Part 2 a three-parameter model of transpulmonary mechanics, applied to fit data of cat experiments, is described. The aim of this study is to demonstrate how transpulmonary parameters (static pleural pressure, compliance and resistance) are modified by the actual state of the pulmonary vascular bed.

Effect of pulmonary edema on changes in lung mechanics in rats

Because of similar pathophysiologic changes, oleic acid (OA)-induced pulmonary edema has been well established as an experimental model of certain types of ARDS. Data in the literature indicate changes mostly in global pulmonary mechanical parameters (lung resistance and compliance) during permeability-type edema. Therefore, we designed this study (1) to separate the OA-induced mechanical responses into airway and parenchymal components, and (2) to examine the relationship between the mechanical parameters and the degree of edema. Anaesthetized, paralyzed, mechanically ventilated rats were given iv. OA in doses of 0 (C n=9), 0.05 (OA0.05 n=8), 0.1 (OA0.1 n=10) and 0.3 (OA0.3 n=5) ml/kg. Respiratory system impedance was measured with a wave-tube low-frequency forced oscillation technique, and a model fitting was used to estimate airway (Raw) and lung tissue parameters (G, parenchymal damping; H, elastance). Pulmonary edema was quantified by gravimetric analysis (WW/DW, wet-to-dry weight ratio). In the OAL0.05 group, transient, but significant increase in Raw, only slight increase in H, and no response in G was observed. Different responses were obtained in OA0.1: significant Raw, G, and H values in survivors; rapid and significantly higher responses in all three parameters in non-survivors. Extremely large parameter values were measured in OA0.3. We found that OA caused dose-related increases in WW, DW and WW/DW. Highly significant correlations were found between the degree of edema and G or H, but not Raw. This study demonstrates that low dose of OA had only transient lung mechanical effects; however, it resulted in mild edema. The higher dose elicited significant airway and tissue changes (smaller responses in survivors than in non-survivors), and severe edema. The strong correlation between lung tissue parameters and the degree of edema suggests that the OA-induced acute lung injury is manifested primarily in the alterations in parenchymal mechanics.