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.     

Mechanical properties of the upper airway

The series and shunt components of the impedance of the upper airway (Zuaw) were evaluated from measurements obtained during a Valsalva maneuver by means of a modified forced oscillation technique. When the cheeks are supported, the upper airway can be represented by a single distributed transmission line. The homogeneity of this line was confirmed by measuring separately Zuaw and the impedance of the mouth. Correction of the impedance of the respiratory system, determined by means of the forced oscillations technique, for the shunt properties of Zuaw results in some modifications of the frequency dependence of resistance (Rrs) in healthy adults and in marked changes of the absolute values of Rrs in children and in patients with obstructive lung disease.     

Forced oscillatory impedance of the respiratory system at low frequencies

Respiratory mechanical impedances were determined during voluntary apnea in five healthy subjects, by means of 0.25- to 5-Hz pseudo/random oscillations applied at the mouth. The total respiratory impedance was partitioned into pulmonary (ZL) and chest wall components with the esophageal balloon technique; corrections were made for the upper airway shunt impedance and the compressibility of alveolar gas. Neglect of these shunt effects did not qualitatively alter the frequency dependence of impedances but led to underestimations in impedance, especially in the chest wall resistance (Rw), which decreased by 20-30% at higher frequencies. The total resistance (Rrs) was markedly frequency dependent, falling from 0.47 +/- 0.06 (SD) at 0.25 Hz to 0.17 +/- 0.01 at 1 Hz and 0.15 +/- 0.01 kPa X l-1 X s at 5 Hz. The changes in Rrs were caused by the frequency dependence of Rw almost exclusively between 0.25 and 2 Hz and in most part between 2 and 5 Hz. The effective total respiratory (Crs,e) and pulmonary compliance were computed with corrections for pulmonary inertance derived from three- and five-parameter model fittings of ZL. Crs,e decreased from the static value (1.03 +/- 0.18 l X kPa-1) to a level of approximately 0.35 l X kPa-1 at 2-3 Hz; this change was primarily caused by the frequency-dependent behavior of chest wall compliance.     

A new nasal acoustic reflection technique to estimate pharyngeal cross-sectional area during sleep.

The conventional acoustic reflection technique in which acoustic waves are launched through the mouth cannot be applied during sleep, nor can it be applied to the nasopharynx, which is the major site of occlusion in patients with obstructive sleep apnea syndrome. We propose a new technique of nasal acoustic reflection to measure pharyngeal cross-sectional areas including the nasopharynx. The acoustic waves are introduced simultaneously to both nostrils during spontaneous nasal breathing. A new algorithm takes into account the nasal septum with asymmetric nasal cavities on both sides and assumes prior knowledge of the cross-sectional area of the nasal cavities and the position of the nasal septum. This method was tested on an airway model with a septum and on healthy human subjects. The conventional technique gave inaccurate measurements for pharyngeal cross-sectional areas for an airway model with asymmetric branching, whereas the new technique measured them almost perfectly. The oro- and hypopharyngeal cross-sectional area measurements acquired by the new method were not different from those obtained by the conventional method in normal subjects. This new method can be used as a monitor of upper airway dimensions in nocturnal polysomnography.     

Respiratory impedance measured with head generator to minimize upper airway shunt

A new method for measuring total respiratory input impedance (Zrs), which ensures minimal motion of extrathoracic airway walls, was tested over frequencies of 4-30 Hz in 14 normal subjects and 10 patients with airway obstruction. It consists of applying pressure variations around the head, rather than at the mouth, so that transmural pressure across upper airway walls is equal to the small pressure drop across the pneumotachograph. Compared with reference Zrs values obtained by directly measuring airway wall motion with a head plethysmograph and correcting the data for it, the investigated method provided similar values for respiratory resistance at all frequencies (30 Hz, 3.67 +/- 2.24 cmH2O X 1(-1) X s compared with 3.55 +/- 2.00) but slightly overestimated respiratory reactance at the largest frequencies (30 Hz, 2.82 +/- 1.28 cmH2O X 1(-1) X s compared with 2.52 +/- 1.22, P less than 0.01). In contrast, when the data were not corrected for airway wall motion, resistance was largely underestimated, especially in patients (-48% at 30 Hz, P less than 0.001), and the reactance-frequency curve was shifted to the right. The investigated method is almost as accurate as the reference method, provides equally reproducible data, and is much simpler.     

Low-frequency respiratory mechanical impedance in the rat

A modified forced oscillatory technique was used to determine the respiratory mechanical impedances in anesthetized, paralyzed rats between 0.25 and 10 Hz. From the total respiratory (Zrs) and pulmonary impedance (ZL), measured with pseudorandom oscillations applied at the airway opening before and after thoracotomy, respectively, the chest wall impedance (ZW) was calculated as ZW = Zrs - ZL. The pulmonary (RL) and chest wall resistances were both markedly frequency dependent: between 0.25 and 2 Hz they contributed equally to the total resistance falling from 81.4 +/- 18.3 (SD) at 0.25 Hz to 27.1 +/- 1.7 kPa.l-1 X s at 2 Hz. The pulmonary compliance (CL) decreased mildly, from 2.78 +/- 0.44 at 0.25 Hz to 2.36 +/- 0.39 ml/kPa at 2 Hz, and then increased at higher frequencies, whereas the chest wall compliance declined monotonously from 4.19 +/- 0.88 at 0.25 Hz to 1.93 +/- 0.14 ml/kPa at 10 Hz. Although the frequency dependence of ZW can be interpreted on the basis of parallel inhomogeneities alone, the sharp fall in RL together with the relatively constant CL suggests that at low frequencies significant losses are imposed by the non-Newtonian resistive properties of the lung tissue.     

Early detection of upper airway obstructions by analysis of acoustical respiratory input impedance

Repetitive occurrence of partial or total upper airway obstruction characterizes several respiratory dysfunctions such as the obstructive sleep apnea syndrome (OSAS). In OSAS patients, pharyngeal collapses are linked to a decrease in upper airway muscle activity during sleep which causes decreased upper airway wall stiffness. Continuous positive airway pressure (CPAP) is recommended as the treatment of choice. Advancements in CPAP therapy require early detection of respiratory events in real time to adapt the level of the applied pressure to airway collapsibility. The forced oscillation technique (FOT) is a noninvasive method which reflects patients' airway patency by measuring respiratory impedance. The aim of this study was to evaluate by a mathematical model of the respiratory system if FOT can provide an early detection index of total or partial upper airway obstruction. Furthermore, the simulation should suggest which characteristic features are relevant for early apnea detection in measured clinical data. The respiratory system has been treated as a series of cylindrical segments. The oropharynx analog of the model allows simulation of upper airway collapse, mimicking the situation in patients with OSAS. We calculated the input impedance for different degrees of upper airway obstruction ranging from unobstructed airways to total occlusion. Furthermore, we simulated different upper airway wall compliances. We compared the simulation with real data. The results of the study suggest that FOT is a valuable tool for assessing the degree of upper airway obstruction in patients with OSAS. Especially, the phase angle of the impedance seems to be a potentially useful tool for early apnea detection by assessing the upper airway wall collapsibility. Received: 23 July 1998 / Accepted in revised form: 26 January 1999     

A new technique to demonstrate flow limitation in partial expiratory flow-volume curves in infants

Partial expiratory flow-volume (PEFV) curves in infants are generated by applying a compressive pressure over the chest wall with an inflatable jacket. This study addresses two issues: pressure transmission to and across the chest wall and whether flow limitation can be identified. Eleven infants sedated with chloral hydrate were studied. Pressure transmission to the chest wall, measured with neonatal blood pressure cuffs placed on the infant's body surface, was 72 +/- 4% of jacket pressure during compression maneuvers. The pressure transmission to the air spaces, determined by measuring airway pressure during a compression maneuver against an occluded airway, was 56 +/- 6% of jacket pressure. A significant amount of the applied pressure is therefore lost across both the jacket and chest wall. Rapid pressure oscillations (RPO) were superimposed on static jacket pressures while expiratory flow was measured. Absence of associated oscillations of flow measured at the mouth was taken to indicate that flow was independent of driving pressure and therefore limited. Flow limitation was demonstrable with the RPO technique in all infants for jacket pressures greater than 50 cmH2O; however, it was evident at jacket pressures less than 30 cmH2O jacket pressure in four infants with obstructive airway disease. The RPO technique is a useful adjunct to the compression maneuver utilized to generate PEFV curves in infants because it facilitates the recognition of expiratory flow limitation.     

Alae nasi activation and nasal resistance in healthy subjects

To investigate the effect of alae nasi (AN) activation on nasal resistance, we monitored AN electromyographic (EMG) activity in 17 healthy subjects using surface electrodes placed on either side of the external nares and measured inspiratory nasal resistance utilizing the method of posterior rhinometry. With CO2 inhalation (6 subj), AN EMG activity increased as nasal resistance fell 23 +/- 5% (P less than 0.01). In the same subjects, voluntary flaring of the external nares also increased AN EMG and decreased nasal resistance by 29 +/- 5% (P less than 0.01). Nasal resistance was altered by nasal flaring and CO2 inhalation even after administration of a topical nasal vasoconstrictive spray (8 subj). In six subjects, voluntary nasal flaring or inhibition with the mouth closed produced a 21 +/- 12% change (P less than 0.01) in total airway resistance as measured by body plethysmography. We conclude that activation of the alae nasi will decrease nasal and total airway resistance during voluntary nasal flaring and during CO2 inhalation and thus should be considered in any studies of upper airway resistance.     

Optimized estimation of respiratory impedance by signal averaging in the time domain.

The spontaneous breathing of a subject during measurements of respiratory impedance (Zrs) by the forced oscillation technique (FOT) induces errors that result in biased impedance estimates, especially at low frequencies. Although in standard measurements this bias may be avoided by using special impedance estimators, there are two applications of FOT for which such estimators are not useful: when a head generator is used and when measurements are made during intubation. In this paper we describe a data-processing procedure for unbiased impedance estimation for all FOT setups. The proposed estimator (Z) was devised for pseudorandom excitation and is based on time-domain signal averaging before frequency analysis. The performance of estimator Z was first analyzed by computer simulation of a head generator setup and a setup including an endotracheal tube to measure (2-32 Hz) a resistance-inertance-elastance model mimicking Zrs of a healthy subject. Second, Z was assessed during real measurements in 16 healthy subjects. The results obtained in the simulation (e.g., error in elastance was reduced from 15.6% with most conventional estimators to 3.3% with Z in simulation of head generator setup) and in the measurements in subjects (differences of less than 1.6% between Z and a reference) confirmed the theoretical lack of bias of Z and its practical suitability for the different FOT setups. In addition to its applicability in the situations in which no other unbiased estimators are available, estimator Z is also advantageous in most conventional applications of FOT, since it requires much less computing time and thus allows on-line Zrs measurements.     

Nonhomogeneity of lung response to inhaled histamine assessed with alveolar capsules

To assess the homogeneity of airway responses to inhaled histamine we examined regional alveolar pressure excursions (PA) arising from small-amplitude oscillations applied at the airway opening (Pao). In five anesthetized and vagotomized dogs the sternum was split and the anterior right lung field exposed. PA was sampled using four capsules affixed to the right apical and middle lobes while lung impedance (ZL) and airway impedances (Zaw) were measured during conventional tidal breathing and during forced oscillations (2-60 HZ at 10 cmH2O distending pressure). During tidal breathing after exposure to aerosol histamine regional PA's could be separated into three groups by plotting Lissajous figures of PA vs. Pao: PA in phase with Pao (no looping), PA lagging Pao (moderate looping), and PA decreasing while Pao was increasing and vice versa (paradoxical looping), suggesting unresponsive, responsive, and closed pathways, respectively, between the airway opening and specific alveolar zones. During high-frequency oscillation the corresponding PA spectra were markedly different from control spectra and revealed resonant amplification, overdamped resonance, and marked attenuation, respectively. With induced bronchospasm resonant amplification of PA was damped on average. However, the more obstructed and closed pathways were protected from resonant amplification, and the more open (nonlooping) pathways were subjected to resonant amplification greater than in the control state. In spite of this markedly nonhomogeneous behavior, frequency dependence of ZL was consistent with the model by Mead (J. Appl. Physiol. 26: 670-673, 1969), which ignores nonhomogeneity of peripheral compartments. These data demonstrate that the response of airways to inhaled histamine is nonhomogeneous but that frequency dependence of ZL above 2 Hz is not sufficient to characterize this nonhomogeneity.     

Repeated measurements of airway and parenchymal mechanics in rats by using low-frequency oscillations

For studiesinvestigating the mechanisms underlying the development of allergicconditions such as asthma, noninvasive methodologies for separatingairway and parenchymal mechanics in animal models are required. Todevelop such a method, seven Brown Norway rats were studied on threeoccasions over a 14-day period. After the baseline measurements, on thethird day inhaled methacholine was administered. Once lung functionreturned to the baseline level, a thoracotomy was performed to comparethe lung mechanics in the intact- and open-chest conditions. On eachoccasion, the rats were anesthetized, paralyzed, and intubated.Small-amplitude oscillations between 0.5 and 21 Hz were applied througha wave tube to obtain respiratory impedance (Zrs). Esophageal pressurewas measured to separate Zrs into pulmonary(ZL) and chest wall (Zw)components. A model containing a frequency-independent resistance andinertance and a tissue component, including tissue damping andelastance, was fitted to Zrs,ZL, and Zw spectra. Measurementsof Zrs, ZL, or Zw and the modelparameters calculated from them did not differ among tests. The numberof animals required to show group changes in lung mechanics wassignificantly lower when animals were measured noninvasively than whenthe group changes were calculated from open-chestmeasurements. In conclusion, the method reported in thisstudy can be used to separate airway and lung tissue mechanics noninvasively over a series of tests and can detect pulmonary constrictor responses for the airways and the parenchyma separately.

     

Role of the chest wall in detection of added elastic loads

Changes in respiratory mechanical loads are readily detected by humans. Although it is widely believed that respiratory muscle afferents serve as the primary source of information for load detection, there is, in fact, no convincing evidence to support this belief. We developed a shell that encloses the body, excluding the head and neck. A special loading apparatus altered pressure in proportion to respired volume (elastic load) in one of three ways: 1) at the mouth only (T), producing a conventional load in which respiratory muscles are loaded and airway and intrathoracic pressures are made negative in proportion to volume, 2) both at the mouth and in the shell (AW), where the same pattern of airway and intrathoracic pressure occurs but the muscles are not loaded because Prs (i.e., mouth pressure minus pressure in the shell is unchanged, and 3) positive pressure in proportion to volume at the shell only, loading the chest wall but causing no change in airway or thoracic pressures (CW). The threshold for detection (delta E50) with the three types of application was determined in seven normal subjects: 2.16 +/- 0.22, 2.65 +/- 0.54, and 6.21 +/- 0.85 (SE) cmH2O/l for T, AW, and CW, respectively. Therefore the active chest wall, including muscles, is a much less potent source of information than structures affected by the negative airway and intrathoracic pressure. The latter account for the very low threshold for load detection.     

Arterio-venous heat exchange systems in the Jackass penguin Spheniscus demersus

Extensive arterio-venous associations occur in the head, axillae and legs of the Jackass penguin Spheniscus demersus. These vascular arrangements appear to facilitate counter-current heat exchange. The major heat exchange system in the head is the post orbital rete mirabile formed by the superior orbital artery. Blood from this rete supplies the eye, nasal passages and superficial jaw muscles. Other blood vessels supplying the superficial areas of the head and mouth associate closely with their corresponding veins.
In the axilla the brachial artery divides to form a humeral plexus of parallel running arteries each associating with up to three interlinking veins. Only the marginal vein does not associate with an artery. It appears that a shunt mechanism, which bypasses the veins in the humeral plexus, functions to permit heat loss when required; for instance in a heat-stressed bird breeding or moulting on land.
In both the upper and lower leg all the major arteries and their branches associate closely with corresponding veins.
The development of these arterio-venous associations indicates that Spheniscus demersus is adapted to a cool aquatic environment in which heat retention is of prime importance.     

Assessment of pharyngeal airway stability in normal and micrognathic infants

A current hypothesis for obstructive sleep apnea states that 1) negative airway pressure during inspiration can collapse the pharyngeal airway, and 2) neural control of pharyngeal airway-dilating muscles is important in preventing this collapse. To test this hypothesis we performed nasal mask occlusions to increase negative pharyngeal airway pressures during inspiration in eight normal and five micrognathic infants. Both groups developed midinspiratory pharyngeal obstruction, but obstruction was more frequent in micrognathic infants and varied in some infants with sleep state. The airway usually reopened with the subsequent expiration. The occasional failure to reopen was presumably due to pharyngeal wall adhesion. If airway obstruction occurred in sequential breaths during multiple-breath nasal mask occlusions in normal infants, there was a breath-by-breath change in the airway pressure associated with airway closure (airway closing pressure); the airway closing pressure became progressively more negative. Micrognathic infants showed less ability to improve the airway closing pressure, but this ability increased with age. These findings suggest that nasal mask occlusion can test the competence of the neuromuscular mechanisms that maintain pharyngeal airway patency in infants. Micrognathic infants had spontaneous midinspiratory pharyngeal airway obstructions during snoring. Their episodes of obstructive apnea began with midinspiratory pharyngeal obstruction similar to that seen during snoring and nasal mask occlusions. These findings imply a similar pathophysiology for snoring, spontaneous airway obstruction, and obstruction during snoring.     

Induction of upper airway occlusion in sleeping individuals with subatmospheric nasal pressure

In collapsible biologic conduits, occlusion and cessation of flow occur when upstream pressure falls below a critical pressure (Pcrit). To examine the relationship between Pcrit and the development of upper airway occlusion, we examined the relationship between maximal inspiratory airflow and nasal pressure in seven normal subjects during sleep. At varying levels of subatmospheric pressure applied to a nasal mask during non-rapid-eye-movement (NREM) sleep, maximal inspiratory airflow decreased in proportion to the level of nasal pressure. When nasal pressure fell below a Pcrit, subjects demonstrated upper airway occlusions terminated by arousals. In these normal subjects, the upper airway Pcrit was found to be -13.3 +/- 3.2 (SD) cmH2O. In four subjects who sustained sleep while nasal pressure remained below the Pcrit, recurrent occlusive apneas were demonstrated. The relationship between maximal inspiratory airflow and nasal pressure in each subject was fit by linear regression and demonstrated upper airway Pcrit at the zero-flow intercept that were not significantly different from those observed experimentally. These data demonstrate that the normal human upper airway during sleep is characterized by a negative Pcrit and that occlusion may be induced when nasal pressure is decreased below this Pcrit.     

Control of respiratory activity of the genioglossus muscle in micrognathic infants

The genioglossus (GG) muscle activity of four infants with micrognathia and obstructive sleep apnea was recorded to assess the role of this tongue muscle in upper airway maintenance. Respiratory air flow, esophageal pressure, and intramuscular GG electromyograms (EMG) were recorded during wakefulness and sleep. Both tonic and phasic inspiratory GG-EMG activity was recorded in each of the infants. On occasion, no phasic GG activity could be recorded; these silent periods were unassociated with respiratory embarrassment. GG activity increased during sigh breaths. GG activity also increased when the infants spontaneously changed from oral to nasal breathing and, in two infants, with neck flexion associated with complete upper airway obstruction, suggesting that GG-EMG activity is influenced by sudden changes in upper airway resistance. During sleep, the GG-EMG activity significantly increased with 5% CO2 breathing (P less than or equal to 0.001). With nasal airway occlusion during sleep, the GG-EMG activity increased with the first occluded breath and progressively increased during the subsequent occluded breaths, indicating mechanoreceptor and suggesting chemoreceptor modulation. During nasal occlusion trials, there was a progressive increase in phasic inspiratory activity of the GG-EMG that was greater than that of the diaphragm activity (as reflected by esophageal pressure excursions). When pharyngeal airway closure occurred during a nasal occlusion trial, the negative pressure at which the pharyngeal airway closed (upper airway closing pressure) correlated with the GG-EMG activity at the time of closure, suggesting that the GG muscle contributes to maintaining pharyngeal airway patency in the micrognathic infant.     

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.     

Response of genioglossus muscle activity to nasal airway occlusion in normal sleeping adults

To determine the combined effect of increased subatmospheric upper airway pressure and withdrawal of phasic volume feedback from the lung on genioglossus muscle activity, the response of this muscle to intermittent nasal airway occlusion was studied in 12 normal adult males during sleep. Nasal occlusion at end expiration was achieved by inflating balloon-tipped catheters located within the portals of a nose mask. No seal was placed over the mouth. During nose breathing in non-rapid-eye-movement (NREM) sleep, nasal airway occlusion resulted in multiple respiratory efforts before arousal. Mouth breathing was not initiated until arousal. Phasic inspiratory genioglossus activity was present in eight subjects during NREM sleep. In these subjects, comparison of peak genioglossus inspiratory activity on the first three occluded efforts to the value just before occlusion showed an increase of 4.7, 16.1, and 28.0%, respectively. The relative increases in peak genioglossus activity were very similar to respective increases in peak diaphragm activity. Arousal was associated with a large burst in genioglossus activity. During airway occlusion in rapid-eye-movement (REM) sleep, mouth breathing could occur without a change in sleep state. In general, genioglossus responses to airway occlusion in REM sleep were similar in pattern to those in NREM sleep. A relatively small reflex activation of upper airway muscles associated with a sudden increase in subatmospheric pressure in the potentially collapsible segment of the upper airway may help compromise upper airway patency during sleep.