Decrease In Upper Airway Resistance Research Articles

Expiratory Resistance Increases End-Expiratory Lung Volume during Sleep

A 37-year-old man with severe obstructive sleep apnea presented to our sleep disorders research laboratory and was instrumented with an epiglottic catheter, pneumotachograph, and magnetometers (to measure relative changes in lung volume) as part of an ongoing study. During the night there were periods of spontaneous, sustained increases in upper airway resistance during expiration (Figure 1A). During these periods, expiratory positive airway pressure developed at the level of the epiglottis (epiglottic pressure channel). Note that although epiglottic pressure increases during expiration, there is no corresponding increase in flow or mask pressure, suggesting a choke point between the epiglottis and airway opening. Expiratory positive airway pressure was associated with an increase in end-expiratory lung volume (rib cage, abdomen, and change in lung volume channels) according to the total respiratory system compliance (Figure 1B). Although other factors may be important, such as upper airway muscle activation, the increase in end-expiratory lung volume was generally associated with a decrease in upper airway resistance (increased flow despite less negative epiglottic pressure) (Figure 1C). Figure 1. Nasal expiratory resistance valves may improve obstructive sleep apnea in a subset of patients, but the mechanism of action is not known (1, 2). Expiratory resistance valves increase end-expiratory lung volume during wakefulness, which might stabilize the upper airway, but this phenomenon has not been clearly demonstrated during sleep. This spontaneously occurring example provides proof of concept that expiratory resistance acts to increase end-expiratory lung volume during sleep via generation of expiratory positive airway pressure. Furthermore, it suggests that such increased end-expiratory lung volume can stabilize the upper airway during inspiration. This image has not been previously published in any form.

Anatomical and functional changes in the upper airways of sleep apnea patients due to mandibular repositioning: A large scale study

The obstructive sleep apnea-hypopnea syndrome (OSAHS) is a sleep related breathing disorder. A popular treatment is the use of a mandibular repositioning appliance (MRA) which advances the mandibula during the sleep and decreases the collapsibility of the upper airway. The success rate of such a device is, however, limited and very variable within a population of patients. Previous studies using computational fluid dynamics have shown that there is a decrease in upper airway resistance in patients who improve clinically due to an MRA. In this article, correlations between patient-specific anatomical and functional parameters are studied to examine how MRA induced biomechanical changes will have an impact on the upper airway resistance. Low-dose computed tomography (CT) scans are made from 143 patients suffering from OSAHS. A baseline scan and a scan after mandibular repositioning (MR) are performed in order to study variations in parameters. It is found that MR using a simulation bite is able to induce resistance changes by changing the pharyngeal lumen. The change in minimal cross-sectional area is the best parameter to predict the change in upper airway resistance. Looking at baseline values, the ideal patients for MR induced resistance decrease seem to be women with short airways, high initial resistance and no baseline occlusion.

Ventilatory long-term facilitation in non-snoring subjects during NREM sleep

We hypothesized that very brief episodes of hypoxia (<1 min) would evoke long-term facilitation (LTF) in individuals free of inspiratory flow limitation (IFL). We studied 12 healthy participants who were self-reported non-snorers and confirmed the absence of IFL. We induced 15 brief episodes of hypoxia during non-REM sleep, reducing arterial oxygen saturation to 84-85%, followed by 1 min of room air. Ventilatory variables and resistance were measured during the control period, hypoxic trials, room air controls, and for 20 min following the last hypoxic episode. There was a significant increase in minute ventilation (108+/-1.3% of control, P < 0.05) and tidal volume (105+/-1.7% of control, P < 0.05) and a significant decrease in upper airway resistance (88+/-9.8% control, P < 0.05) during the recovery period. However, there were no significant changes in any variable during sham studies. We have shown for the first time that LTF can be elicited in sleeping humans free of IFL.

Activation of Orexin B receptors in the pontine Kölliker-Fuse nucleus modulates pre-inspiratory hypoglossal motor activity in rat

Orexins (splice variants A and B) are hypothalamic neuropeptides that have essential functions in control of arousal and nutrition. Lack of Orexins is strongly associated with narcolepsy and sleep disordered breathing. However, the role of Orexins and particularly that of Orexin-B (OXB), in respiratory centres controlling upper-airway patency are less defined. In the present study we performed microinjections of OXB into the pontine Kölliker-Fuse nucleus (KF) of the dorsolateral pons, since this nucleus is particularly involved in the pre-motor control of upper airway muscles. The OXB mediated effects on heart, phrenic (PNA) and hypoglossal (XII-A) nerve activities were analysed in an in situ perfused brainstem preparation. Injection of OXB into the KF evoked significant augmentation of the respiratory frequency. Importantly, OXB provoked particularly prolonged pre-inspiratory discharge of the XII nerve, while no cardiovascular response was observed after KF microinjections. In summary, OXB in the KF exerts an excitatory effect on XII pre-motoneurones. Since pre-inspiratory activity of the XII is important for the decrease in upper airway resistance during inspiration, we conclude that OXB release in the KF has strong implications in the state-dependent control of upper airway patency under physiological and pathophysiological conditions.

Functional imaging using computational fluid dynamics to predict treatment success of mandibular advancement devices in sleep-disordered breathing

Mandibular advancement devices (MADs) have emerged as a popular alternative for the treatment of sleep-disordered breathing. These devices bring the mandibula forward in order to increase upper airway (UA) volume and prevent total UA collapse during sleep. However, the precise mechanism of action appears to be quite complex and is not yet completely understood; this might explain interindividual variation in treatment success. We examined whether an UA model, that combines imaging techniques and computational fluid dynamics (CFD), allows for a prediction of the treatment outcome with MADs. Ten patients that were treated with a custom-made mandibular advancement device (MAD), underwent split-night polysomnography. The morning after the sleep study, a low radiation dose CT scan was scheduled with and without the MAD. The CT examinations allowed for a comparison between the change in UA volume and the anatomical characteristics through the conversion to three-dimensional computer models. Furthermore, the change in UA resistance could be calculated through flow simulations with CFD. Boundary conditions for the model such as mass flow rate and pressure distributions were obtained during the split-night polysomnography. Therefore, the flow modeling was based on a patient specific geometry and patient specific boundary conditions. The results indicated that a decrease in UA resistance and an increase in UA volume correlate with both a clinical and an objective improvement. The results of this pilot study suggest that the outcome of MAD treatment can be predicted using the described UA model.

Continuous Positive Airway Pressure and Lung Inflation in Sleep Apnea Patients

Background: It was shown in normals that an important decrease in upper airway resistance can be obtained with continuous positive airway pressure (CPAP). It was suggested that lung inflation in patients with sleep apnea syndrome (SAS) could also be a mechanism of action of CPAP. Objective: In the present study we wanted to evaluate the effects of nocturnal CPAP on the daytime lung function pattern in patients with SAS. Methods: We measured arterial blood gases and possible changes in static lung volumes in 57 SAS patients (37 with normal lung function, 10 with COPD and 10 with restrictive lung disease) after at least one month of CPAP therapy. Results: A significant increase in PaO₂ (from 79 to 84 mm Hg, p = 0.01) and a decrease in AaDO₂ (from 23 ± 1 to 16 ± 1, p < 0.01) was only observed in SAS patients with normal lung function. This improved gas exchange was parallelled by a small but non significant change in the FRC (from 96.5 ± 3.2 to 105.4 ± 3.7%pred, p = 0.07) and TLC (from 101.3 ± 1.7 to 104.1 ± 1.4%pred, p = 0.15). Similar changes in TLC and FRC were also observed in SAS patients with obstructive and restrictive lung disease. Conclusions: Chronic nocturnal CPAP therapy can improve daytime gas exchange and may influence lung inflation during the daytime. The small changes seem to be a functional effect but of no clinical relevance.

Ventilatory dynamics of transient arousal in patients with obstructive sleep apnea

The hyperpnea that accompanies arousal at the end of obstructive apnea is believed to be due to the progressive build-up in chemical drive during the apnea and a state-related decrease in upper airway resistance. We postulated the existence of a third component: a state-related transient increase in neural drive to the ventilatory pump muscles. To quantify this contribution, we measured the ventilatory response to arousal (VRA) in eight patients with obstructive sleep apnea (OSA) during continuous positive airway pressure (CPAP) therapy, applied at individually titrated levels. CPAP application reduced total pulmonary resistance (R l) to approximately normal levels, stabilizing ventilation and sleep state. Transient arousal from stage 2 sleep was induced using 5-sec tones (60–90 dB). Mean inspiratory flow increased above control on the second and third post-arousal breaths ( P<0.05), with a peak increase of 7.8±2.9 L/min while the accompanying changes in R l were significant. The time-course of VRA measured in three normal subjects under CPAP was similar to that observed in the OSA patients. However, elimination of CPAP prolonged the VRA time-course. Taken together, these findings demonstrate that: (1) during arousal, the increase in state-related neural respiratory drive is short-lived but not substantial; and (2) the resulting VRA time-course is shaped by the dynamics of the upper airway response to arousal.

Respiratory mechanics of horses during stepwise treadmill exercise tests, and the effect of clenbuterol pretreatment on them

Normal Standardbred horses were given an incremental exercise test on a horizontal treadmill to evaluate the influence of exercise on gas exchange, resistance, dynamic compliance and inertance of the respiratory system. The exercise test consisted of 2 min exercise steps at each of the following speeds: 2.4 m/sec (walk), 4.5 m/sec (slow trot), 7.0 m/sec (fast trot) and 10 m/sec (gallop). At rest and after 1 min of exercise at each step, airflow, tidal volume, respiratory frequency, pharyngeal, mid-oesophageal and transdiaphragmatic pressures and arterial blood gas tensions were measured. The same horses were subsequently treated intravenously with clenbuterol (0.8 microgram/kg) and an identical exercise test and measurement performed 10 min after clenbuterol injection. In response to exercise, there were large increases in tidal volume, respiratory frequency, airflow and pressures. Exercise was associated with a decrease in upper airway resistance but total pulmonary resistance was unchanged. Exercise did not alter inertance or dynamic compliance, horses became hypoxaemic, and at 10 m/sec (galloping) also developed hypercarbia. Treatment with clenbuterol did not alter any of these measurements in response to exercise. These data suggest that dilation of upper airways occurs during exercise, and that inertial forces are important in strenuously exercising horses and may influence the accuracy of dynamic compliance determinations at high exercise intensities.

Influence of Progressive and of Transient Hypoxia on Upper Airway Resistance in Normal Humans

In order to evaluate the influence of hypoxia on upper airway patency, we measured the response of upper airway resistance (UAR) to progressive (P) normocapnic hypoxia (Rebuck's method) and transient (T) hypoxia (three to five breaths to 100% N2) in 11 normal men. Breath-by-breath inspiratory UAR was calculated at isoflow during exclusive nasal breathing. The UAR response to hypoxia was characterized by the changes in nasal resistance and pharyngeal resistance (PR) as a function of SaO2, mean inspiratory flow (VT/Tl), and changes in the end-expiratory lung volume (EELV) measured with an inductance vest. The ventilatory response to hypoxia was greater during T (-0.31 +/- 0.03 L/min/%SaO2; mean +/- SEM) than during P (-0.27 +/- 0.03 L/min/%SaO2, p = 0.05). UAR decreased as SaO2 decreased; this decrease was steeper during T than during P hypoxia (delta PR/%SaO2: 3.9 +/- 0.5 during P and 2.5 +/- 0.2 during T, p = 0.05). For the whole group, there was no difference in the slope of the decrease in UAR with increasing VT/Tl between the two hypoxic tests (delta PR/delta VT/Tl: -0.85 +/- 0.1 during P and -0.70 +/- 0.1 during T, p greater than 0.05). However, in four subjects, the slope of the relationship PR/VT/Tl during T remained steeper than during P. EELV increased as SaO2 decreased, with a greater increase during progressive than during transient hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Responses to negative pressure surrounding the neck in anesthetized animals

Continuous positive pressure applied at the nose has been shown to cause a decrease in upper airway resistance. The present study was designed to determine whether a similar positive transmural pressure gradient, generated by applying a negative pressure at the body surface around the neck, altered upper airway patency. Studies were performed in nine spontaneously breathing anesthetized supine dogs. Airflow was measured with a pneumotachograph mounted on an airtight muzzle placed over the nose and mouth of each animal. Upper airway pressure was measured as the differential pressure between the extrathoracic trachea and the inside of the muzzle. Upper airway resistance was monitored as an index of airway patency. Negative pressure (-2 to -20 cmH2O) was applied around the neck by using a cuirass extending from the jaw to the thorax. In each animal, increasingly negative pressures were transmitted to the airway wall in a progressive, although not linear, fashion. Decreasing the pressure produced a progressive fall in upper airway resistance, without causing a significant change in respiratory drive or respiratory timing. At -5 cmH2O pressure, there occurred a significant fall in upper airway resistance, comparable with the response of a single, intravenous injection of sodium cyanide (0.5-3.0 mg), a respiratory stimulant that produces substantial increases in respiratory drive. We conclude that upper airway resistance is influenced by the transmural pressure across the airway wall and that such a gradient can be accomplished by making the extraluminal pressure more negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary mechanical responses to cholinesterase inhibitor

Lung static and dynamic compliances, and lung and upper airway resistances were measured in pentobarbital-anesthetized dogs before and after intravenous administration of 2 LD50 of the organophosphate cholinesterase inhibitor pinacolyl methylphosphonofluoridate (GD), followed by 1 mg of atropine 8 min later. Dynamic compliances and resistances were estimated by a linear regression model and by a Fourier analysis technique, with the two methods giving comparable results. GD caused a maximum increase in lung resistance of about 20 times control values, and about an 80% decrease in lung dynamic compliance. Frequency dependence of lung compliance and resistance was increased by GD administration. Following GD administration, upper airway opening pressure increased, indicating the presence of laryngospasm. Upper airway resistance during the latter portion of the breath, when the airway was open, decreased after GD administration, concurrent with the increase in carinal pressure that occurred as the result of increased lung impedance. These results suggest that the GD-induced decrease in upper airway resistance was due to passive distension of the upper airway. Physiological deadspace decreased by a maximum of about 65% following GD administration. Administration of atropine resulted in a prompt and almost complete reversal of all of the GD-induced effects on pulmonary mechanical properties and ventilation. The results of this study suggest that the major pulmonary mechanical effects of GD in the dog are caused by constriction of smooth muscle at different levels of the respiratory tract.

Effect of salicylate on upper airway dilating muscles in anesthetized dogs.

It is well documented that salicylate given in large doses stimulates ventilation. As increased ventilatory drive is often associated with augmented upper airway dilating muscle activity, we evaluated in anesthetized dogs the effect of salicylate on the electrical activity of three upper airway muscles, the alae nasi, the genioglossus, and the posterior cricoarytenoid. The electromyograms of these muscles were compared with those of the diaphragm before and at 15-min intervals after intravenous salicylate administration (250 mg/kg). Salicylate induced a gradual increase in ventilation and in the electrical activity of all muscles examined (p less than 0.001). Compared to baseline activity, salicylate increased the electrical activity of the genioglossus more than that of the diaphragm (p less than 0.01). The increase in upper airway muscle activity was observed also in vagotomized dogs, and was not accounted for by changes in arterial blood gases or pH. Increases in upper airway muscle electrical activity were associated with a significant decrease in upper airway resistance to airflow (mean reduction of 62 +/- 7% SE, p less than 0.01). The preferential increase in genioglossus electrical activity and the decrease in upper airway resistance observed in this study with salicylate suggest that salicylate, and possibly other pharmacologic agents that stimulate ventilation, may improve upper airway patency.

Effects of sodium cyanide and nicotine on upper airway resistance in anesthetized dogs

The purpose of this study was to determine whether pharmacologic interventions which increase respiratory drive could also reduce flow resistance in the upper airway. Studies were performed in twelve anesthetized supine dogs. In six animals breathing spontaneously through the intact upper airway, intravenous administration of respiratory stimulants (sodium cyanide and nicotine) produced a dose-related decrease in upper airway resistance. In nine animals, upper airway resistance was measured across the isolated upper airway. The stimulants produced a dose-related decrease in upper airway resistance. In both preparations inspiratory resistance fell at lower doses than expiratory resistance. Eventually a dose could be given which resulted in comparable, minimal values of resistance during both inspiration and expiration. Mechanisms for changes in resistance were clarified using lateral radiographs of the neck and transbronchoscopic views of the upper airway. Pharmacologic challenge resulted in a change in the route of airflow (from nose only to nose-and-mouth breathing) as well as a change in caliber of the airway at the level of the naso-pharynx and hyoid apparatus. In anesthetized dogs, respiratory stimulants will decrease upper airway resistance by increasing activation of upper airway muscles which may enlarge the airway, change the route of flow, and thus overcoming collapsing forces produced by increased chest wall muscle activation.

Increased upper airway resistance to breathing during sleep in the cat

At the onset of sleep, upper airway resistance shifted to higher levels which were maintained throughout sleep. With each inspiration, there was a decrease in upper airway resistance. These respiratory changes in resistance were smaller in wakefulness (on low baseline resistances) than those in nonrapid eye movement sleep (on high baseline resistances). In rapid eye movement sleep, modulations with inspiration were diminished and were intermittently absent, and baseline resistance was high.

Control of the duration of expiration

We recorded tidal volume, inspiratory and expiratory durations, upper airway resistance, abdominal pressure and diaphragmatic electromyograms in resting, unanesthetized cats. During air breathing expiratory duration (spontaneous t e) exceeded the time required for passive collapse of the intubated respiratory system (passive t e). This difference between spontaneous and passive t e values resulted from the influence of two factors that retard expiratory flow: post-inspiratory activity of the diaphragm and the resistance of the upper airway. Hypercapnia consistently led to a decrease in spontaneous t e, accompanied by a decrease in upper airway resistance, an increase in abdominal expiratory muscle activity and, in some animals, a decrease in post-inspiratory activity of the diaphragm. In cats studied 1–4 weeks after bilateral cervical vagotomy, t e was generally increased, a change that is consistent with the operation of a volume-related feedback system controlling t e in the intact animal. Our analysis of the factors that regulate expiratory flow indicates the importance of variations in upper airway resistance brought about by movements of the vocal cords. We propose that by this mechanism, via the operation of volume-related feedback, the larynx is a significant determinant of t e and the respiratory frequency.