Measurement of total respiratory impedance in calves by the forced oscillation technique

We have determined the resistance (Rrs) and the reactance (Xrs) of the total respiratory system in unsedated spontaneously breathing calves at various frequencies. A pseudorandom noise pressure wave was produced at the nostrils of the animals by means of a loudspeaker adapted to the nose by a tightly fitting mask. A Fourier analysis of the pressure in the nostrils and flow signals yielded mean Rrs and Xrs, over 16 s, at frequencies of 2-26 Hz. A good correlation was found between values of pulmonary resistances measured by the isovolume method at the respiratory frequency of animals and values obtained at a frequency of 6 Hz by use of our technique. The linearity of the respiratory system, the reproducibility of the technique, and the effects of upper airways on results have been studied. In healthy calves, Rrs increases with frequency. Mean resonant frequency is 7.5 Hz. Bronchospasm was induced in six calves by administration of intravenous organophosphates. Rrs tended to decrease with increasing frequency. Resonant frequency exceeded 26 Hz. All parameters returned to initial values after administration of atropine. In healthy calves, atropine produces a decrease in Rrs, especially at low frequencies. Values of resonant frequency are not modified.     

Measurement of total respiratory impedance in infants by the forced oscillation technique

The forced oscillation technique according to Làndsér et al. (J. Appl. Physiol. 41:101-106, 1976) was modified for use in infants. Adaptations, including a flexible tube to connect the infant to the measuring system and a bias flow to avoid rebreathing, did not influence impedance values. The linearity of the respiratory system was assessed and confirmed by 1) applying pseudo-random noise oscillations at three different amplitudes to 7 infants and 2) comparing in 12 infants impedance values obtained with pseudo-random noise and with sinusoidal oscillations at 12 and 32 Hz. Intersubject variability, averaged for all frequencies, was 6%. In 17 infants the relative error (+/- SD) between two series of five measurements within a time interval of 15 min was 0.5 +/- 5.7%. No statistically significant difference was found between impedance values before and after repositioning of the infant's head, whereas rotation resulted in a decrease in resistance and no effect on reactance. Our results indicate that the infant-adapted forced pseudo-random noise oscillation technique has the potential to give valuable information about ventilatory lung function in infants.     

A modified measurement of respiratory resistance by forced oscillation during normal breathing.

We have modified the measurements of the resistance of the respiratory system, Rrs, by the forced oscillation technique and we have developed equipment to automatically compute Rrs. Flow rate and mouth pressure are treated by selective averaging filters that remove the interference of the subject's respiratory flow on the imposed oscillations. The filtered mean Rrs represents a weighted ensemble average computer over both inspiration and expiration. This method avoids aberrant Rrs values, decreases the variability, and yields an unbiased mean Rrs. Rrs may be measured during slow or rapid spontaneous breathing, in normals and in obstructive patients, over a range of 3-9 Hz. A good reproducibility of Rrs at several days' interval was demonstrated. Frequency dependence of Rrs was found in patients with obstructive lung disease but not in healthy nonsmokers.     

Evaluation of a forced oscillation method to measure thoracic gas volume

The purposeof this study was to test a plethysmographic method of measuringthoracic gas volume (TGV) that, contrary to the usual panting method,would not require any active cooperation from the subject. It is basedon the assumption that the out-of-phase component of airway impedancevaries linearly with frequency. By using that assumption, TGV may becomputed by combining measurements of total respiratory impedance (Zrs)and of the relationship between the plethysmographic signal (Vpl) andairway flow () during forcedoscillations at several frequencies. Zrs and Vpl/were measured at 10 noninteger multiple frequencies ranging from 4 to29 Hz in 15 subjects breathing gas in nearlyBTPS conditions. Forced oscillationmeasurements were immediately followed by determination of TGV by thestandard method. The data were analyzed on different frequency ranges,and the best agreement was seen in the 6- to 29-Hz range. Within thatrange, forced oscillation TGV and standard TGV differed little(3.92 ± 0.66 vs. 3.83 ± 0.73 liters,n = 77, P < 0.05) and were stronglycorrelated (r = 0.875); thedifferences were not correlated to the mean of the two estimates, andtheir SD was 0.35 liter. In seven subjects the differences weresignificantly different from zero, which may, in part, be due toimperfect gas conditioning. We conclude that the method is not highlyaccurate but could prove useful when, for lack of sufficientcooperation, the panting method cannot be used. The results of computersimulation, however, suggest that the method would be unreliable in thepresence of severe airway inhomogeneity or peripheral airwayobstruction.

     

Estimation of alveolar pressure during forced oscillation of the respiratory system.

A method for obtaining a continuous estimate of alveolar pressure (PAlv) during periodic flow is described; it was developed to improve the precision of measurements of airway and respiratory tissue impedance using the improved resolution of relatively high-frequency (approximately 5 Hz) singlas. The respiratory system was modulated with a piston pump, and lung volume and the volume change due to compression and expansion of alveolar gas were measured plethysmorgraphically; these signals and an analog divider were used to obtain a continuous solution of Boyle's law during flow. The plethysmorgraph was of the "flow" type; with it volume changes at frequencies up to 10 Hz and with rates of change up to 6 l/s were measured without amplitude or phase distortion. The method permits control of frequency and flow amplitude during PAlv measurement and calibration of PAlv in the absence of an active chest wall. However, it is technically complex.     

Evaluating the forced oscillation technique in the detection of early smoking-induced respiratory changes

Background  

Early detection of the effects of smoking is of the utmost importance in the prevention of chronic obstructive pulmonary disease (COPD). The forced oscillation technique (FOT) is easy to perform since it requires only tidal breathing and offers a detailed approach to investigate the mechanical properties of the respiratory system. The FOT was recently suggested as an attractive alternative for diagnosing initial obstruction in COPD, which may be helpful in detecting COPD in its initial phases. Thus, the purpose of this study was twofold: (1) to evaluate the ability of FOT to detect early smoking-induced respiratory alterations; and (2) to compare the sensitivity of FOT with spirometry in a sample of low tobacco-dose subjects.     

Frequency dependence of forced oscillatory respiratory mechanics in horses with heaves

Young, S. S., D. Tesarowski, and L. Viel. Frequencydependence of forced oscillatory respiratory mechanics in horses withheaves. J. Appl. Physiol. 82(3):983-987, 1997.The effect of measurement frequency on respiratorymechanics was investigated in six horses with reversible allergicairway disease. Total respiratory impedance was measured at 1.5, 2.0, 3.0, and 5.0 Hz by using the forced oscillation technique with thehorses in remission, after acute antigenic challenge producing clinicalheaves, and with heaves but after the administration of 2 mg fenoterolby inhalation. The slopes of the magnitude(|Zrs|) and real part (R) of total respiratoryimpedance over the frequency range 1.5-3 Hz changed significantlyafter antigenic challenge and fenoterol. The ratio of R at 2 Hz to R at3 Hz, however, discriminated better among the three conditions.Compliance and resonant frequency (calculated by using a three-elementmodel) changed significantly after antigenic challenge and fenoterol,but inertance did not. We concluded that horses with heaves showedfrequency dependence of R and |Zrs| atfrequencies up to 3 Hz and that parameters derived from a three-element model were useful indicators of small airway obstruction in the horse.

     

Flow and volume dependence of expiratory resistance in anesthetized cats

In five anesthetized paralyzed cats, mechanically ventilated with tidal volumes of 36-48 ml, the isovolume pressure-flow relationships of the lung and respiratory system were studied. The expiratory pressure was altered between 3 and -12 cmH2O for single tidal expirations. Isovolume pressure-flow plots for three lung volumes showed that the resistive pressure-flow relationships were curvilinear in all cases, fitting Rohrer's equation: P = K1V + K2V2, where P is the resistive pressure loss, K1 and K2 are Rohrer's coefficients, and V is flow. Values of K1 and K2 declined with lung inflation, consistent with the volume dependence of pulmonary (RL) and respiratory system resistances (Rrs). During lung deflation against atmospheric pressure, RL and Rrs tended to remain constant through most of expiration, resulting in a nearly linear volume-flow relationship. In the presence of a fixed respiratory system elastance, the shape of the volume-flow profile depended on the balance between the volume and the flow dependence of RL and Rrs. However, the flow dependence of RL and Rrs indicates that their measured values will be affected by all factors that modify expiratory flow, e.g., respiratory system elastance, equipment resistance, and the presence of respiratory muscle activity.     

Flow and volume dependence of pulmonary mechanics in anesthetized cats

The effects of inspiratory flow rate and inflation volume on pulmonary mechanics were investigated in six anesthetized-paralyzed cats ventilated by constant-flow inflation. Pulmonary mechanics were assessed using the technique of rapid airway occlusion during constant-flow inflation which allows measurement of the intrinsic pulmonary resistance (RLmin) and of the overall "pulmonary flow resistance" (RLmax), which includes the additional pulmonary pressure losses due to time constant inequalities within the lung and/or stress adaptation. We observed that, at fixed inflation volume, 1) RLmin fitted Rohrer's equation, 2) RLmax was higher at low than intermediate flows, and 3) RLmax-RLmin decreased progressively with increasing flow. At fixed flow, RLmax increased, whereas RLmin decreased with increasing volume. We conclude that during eupneic breathing in cats, the pulmonary flow resistance as conventionally measured includes a significant component reflecting stress adaptation.     

Respiratory resistance with histamine challenge by single-breath and forced oscillation methods

Relaxed expirations were obtained from five anesthetized dogs under control conditions and during various rates of intravenous infusion of histamine. All volume vs. time curves obtained from 20 ms to 2 s after the start of expiration were poorly described by a single exponential function but were fitted very well by a biexponential function. The resistance of the respiratory system as a function of frequency from 2 to 26 Hz was also determined by the forced oscillation method in the same dogs. Three two-compartment models of the respiratory system were identified from the exponentials fitted to the relaxed expiration data, and the one that had the most plausible parameter values under control conditions consisted of a homogeneous lung compartment connected to a viscoelastic compartment. Although a two-compartment model is arguably appropriate for describing relaxed expirations in normal dogs, physiological considerations suggest that there should be more than two interacting components with histamine infusion. We cannot identify all these components from our data, however. The equivalent complex impedance of the respiratory system was also calculated from the biexponential curves and showed significant variation in resistance over the frequency range from 0 to 2 Hz and negligible variation above 2 Hz. The calculated resistances at 2 Hz were consistently higher than those obtained by the forced oscillation method, which may be due to the nonlinear behavior of the respiratory system during relaxed expiration. We conclude that the single-breath and forced oscillation methods should be viewed as providing complimentary information about respiratory resistance.     

Combined forced oscillation and forced expiration measurements in mice for the assessment of airway hyperresponsiveness

Background

Acute exacerbations contribute to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD). This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations.

Methods

Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N = 573) or placebo (N = 584) once a day for 5 days. Treatment was repeated every 8 weeks for a total of six courses. Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks' follow-up.

Results

At 48 weeks the odds ratio (OR) for suffering an exacerbation favoured moxifloxacin: per-protocol (PP) population (N = 738, OR 0.75, 95% confidence interval (CI) 0.565-0.994, p = 0.046), intent-to-treat (ITT) population (N = 1149, OR 0.81, 95% CI 0.645-1.008, p = 0.059), and a post-hoc analysis of per-protocol (PP) patients with purulent/mucopurulent sputum production at baseline (N = 323, OR 0.55, 95% CI 0.36-0.84, p = 0.006). There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George's Respiratory Questionnaire (SGRQ) total scores. There was, however, a significant difference in favour of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs -3.8, p = 0.009; PP: -8.8 vs -4.4, p = 0.006). Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility. There were more treatment-emergent, drug related adverse events with moxifloxacin vs placebo (p < 0.001) largely due to gastrointestinal events (4.7% vs 0.7%).

Conclusions

Intermittent pulsed therapy with moxifloxacin reduced the odds of exacerbation by 20% in the ITT population, by 25% among the PP population and by 45% in PP patients with purulent/mucopurulent sputum at baseline. There were no unexpected adverse events and there was no evidence of resistance development.

Trial registration

ClinicalTrials.gov number, NCT00473460 (ClincalTrials.gov).     

The mechanical properties and molecular dynamics of plant cell wall polysaccharides studied by Fourier-transform infrared spectroscopy

Polarized one- and two-dimensional infrared spectra were obtained from the epidermis of onion (Allium cepa) under hydrated and mechanically stressed conditions. By Fourier-transform infrared microspectroscopy, the orientation of macromolecules in single cell walls was determined. Cellulose and pectin exhibited little orientation in native epidermal cell walls, but when a mechanical stress was placed on the tissue these molecules showed distinct reorientation as the cells were elongated. When the stress was removed the tissue recovered slightly, but a relatively large plastic deformation remained. The plastic deformation was confirmed in microscopic images by retention of some elongation of cells within the tissue and by residual molecular orientation in the infrared spectra of the cell wall. Two-dimensional infrared spectroscopy was used to determine the nature of the interaction between the polysaccharide networks during deformation. The results provide evidence that cellulose and xyloglucan associate while pectin creates an independent network that exhibits different reorientation rates in the wet onion cell walls. The pectin chains respond faster to oscillation than the more rigid cellulose.