Adaptive pressure support servo-ventilation: a novel treatment for Cheyne-Stokes respiration in heart failure.

Adaptive servo-ventilation (ASV) is a novel method of ventilatory support designed for Cheyne-Stokes respiration (CSR) in heart failure. The aim of our study was to compare the effect of one night of ASV on sleep and breathing with the effect of other treatments. Fourteen subjects with stable cardiac failure and receiving optimal medical treatment were tested untreated and on four treatment nights in random order: nasal oxygen (2 L/min), continuous positive airway pressure (CPAP) (mean 9.25 cm H(2)O), bilevel (mean 13.5/5.2 cm H(2)O), or ASV largely at the default settings (mean pressure 7 to 9 cm H(2)O) during polysomnography. Thermistor apnea + hypopnea index (AHI) declined from 44.5 +/- 3.4/h (SEM) untreated to 28.2 +/- 3.4/h oxygen and 26.8 +/- 4.6/h CPAP (both p < 0.001 versus control), 14.8 +/- 2.3/h bilevel, and 6.3 +/- 0.9/h ASV (p < 0.001 versus bilevel). Effort band AHI behaved similarly. Arousal index decreased from 65.1 +/- 3.9/h untreated to 29.8 +/- 2.8/h oxygen and 29.9 +/- 3.2/h CPAP, to 16.0 +/- 1.3/h bilevel and 14.7 +/- 1.8/h ASV (p < 0.01 versus all except bilevel). There were large increases in slow-wave and rapid eye movement (REM) sleep with ASV but not with oxygen or CPAP. All subjects preferred ASV to CPAP. One night ASV suppresses central sleep apnea and/or CSR (CSA/CSR) in heart failure and improves sleep quality better than CPAP or 2 L/min oxygen.

Two months auto-adjusting versus conventional nCPAP for obstructive sleep apnoea syndrome.

Autoadjusting nasal continuous positive airway pressure (CPAP) greatly reduces the apnoea/hypopnoea index (AHI), and affords a significant reduction in median pressure (P50) compared-with manually titrated conventional nasal CPAP. The aim of the present study was to test whether these benefits were maintained in the medium term at home, in a double-blind crossover study. Ten sequential subjects (mean AHI 52.9 x h(-1)) were enrolled. After a manual titration, subjects were randomly allocated to 2 months autoadjusting nasal CPAP (AutoSet), followed by 2 months with the AutoSet device in fixed pressure mode at the manually titrated pressure, or vice versa. The machine-scored AHI, P50, and median leak were recorded on 12 nights in each arm, and averaged. Mean+/-SEM AHI was 4.0+/-0.3 x h(-1) in auto mode, and 3.7+/-0.3 x h(-1) in manual mode (NS). Mean+/-SEM P50 was 7.2+/-0.4 cmH2O auto, 9.4+/-0.6 cmH2O manual, average reduction 23+/-4% (p<0.0001). Auto "recommended" pressure was (mean+/-SEM) 10.1+/-0.5 cmH2O (p=0.04 with respect to manual) and peak pressure typically 1 cmH2O higher. Median (+/-SEM) leak was 0.181+/-0.006 L x s(-1) auto (and uncorrelated with AHI or pressure), 0.20+/-0.006 L x s(-1) manual (p=0.003). Compliance was 6.3+/-0.4 h in auto mode and 6.1+/-0.5 h in fixed mode (NS). Apnoea/hypopnoea index during 2 months of home autoadjusting nasal continuous positive airway pressure is comparable to that during conventionally titrated fixed pressure continuous positive airway pressure, while affording a 23% reduction in median pressure but no increase in compliance. Leak did not importantly affect autoadjustment.

Effect of mouth leak on effectiveness of nasal bilevel ventilatory assistance and sleep architecture.

Mouth leak is common during nasal ventilatory assistance, but its effects on ventilatory support and on sleep architecture are unknown. The acute effect of sealing the mouth on sleep architecture and transcutaneous carbon dioxide tension (Ptc,CO2) was tested in 9 patients (7 hypercapnic) on longterm nasal bilevel ventilation with symptomatic mouth leak. Patients slept with nasal bilevel ventilation at their usual settings on two nights in random order. On one night, the mouth was taped closed. Leak was measured with a pneumotachograph. Median leak fell from 0.35+/-0.07 (mean +/- SEM) L x s(-1) untaped to 0.06+/-0.03 L x s(-1) taped. Ptc,CO2 fell in 8/9, including all hypercapnic patients. Across all patients, the mean Ptc,CO2 fell by 1.02+/-0.28 kPa (7.7+/-2.1 mm Hg) with taping (p = 0.007). Arousal index fell in every patient. Mean arousal index fell from 35.0+/-3.0 to 13.9+/-1.2 h(-1) (p<0.0001), and rapid eye movement (REM) sleep increased from 12.9+/-1.5% to 21.1+/-1.8% sleep time (p = 0.0016). Slow wave sleep changed inconsistently, from a mean of 13.1+/-1.6% to 19.5+/-2.2% of sleep (p = 0.09). Sleep latency and efficiency were unchanged. In four healthy volunteers ventilator-induced awake hypopharyngeal pressure swing during timed bilevel ventilation fell by 35+/-5% L(-1) x s(-1) of voluntary mouth leak (p<0.0001). Mouth leak reduces effective nasal bilevel ventilatory support, increases transcutaneous carbon dioxide tension, and disrupts sleep architecture.

Detection of apnoeas, hypopnoeas and arousals by the AutoSet in the sleep apnoea/hypopnoea syndrome.

Limited sleep study systems are increasingly being used to diagnose the sleep apnoea/hypopnoea syndrome, but validation is essential and detection of arousal's desirable. One such system (AutoSet) was validated on an event-by-event basis, and the hypothesis that sudden large breaths detected by this system mark arousal from sleep was also examined. Twenty consecutive patients (apnoea/hypopnoea index (AHI) 39+/-6 (SEM)) underwent polysomnography (PSG), which included real-time signals of AutoSet (Version 3.03) scored events. PSG respiratory events were defined using airflow and thoracoabdominal movement and AutoSet events using nasal pressure. All apnoeas were scored by both systems, but 41% more hypopnoeas were scored on PSG and these were clinically significant, with 78% ending in cortical arousal. Twenty per cent of apnoeas and hypopnoeas scored by the AutoSet occurred during wakefulness. Large breaths, defined as a two-thirds increase in ventilation, marked 77% of respiratory-associated but only 9% of spontaneous arousals. Large breaths also marked 48% of "autonomic" arousals following respiratory events without visible electroencephalographic changes. Twenty-seven per cent of large breaths occurred during wakefulness. This study shows that the AutoSet and the standard polysomnographic approach differ in their detection of hypopnoeas. The AutoSet underdetected hypopnoeas during sleep, but also included some hypopnoeas occurring during wakefulness. Detection of large breaths may potentially be useful for identifying respiratory arousals. Detection of periods of wakefulness may improve the accuracy of the system.

AutoSet nasal CPAP titration: constancy of pressure, compliance and effectiveness at 8 month follow-up.

We have previously shown that AutoSet satisfactorily improves sleep-disordered breathing and sleep architecture in subjects with obstructive sleep apnoea (OSA) syndrome. The aim of this study was to determine, in subjects treated with long-term conventional fixed pressure continuous positive airway pressure (CPAP) at the AutoSet recommended pressure, whether: the long-term compliance is satisfactory; the improvement persists once initial rebound is over; the titration pressure is stable with time; and the titration pressure is comparable with manual titration pressure using a similar end-point. Twenty males with OSA, previously studied with full polysomnography on their diagnostic night, at manual and AutoSet titration, and at the AutoSet recommended fixed pressure, were re-studied after a mean of 3 and 8 months of treatment at the recommended fixed pressure. Re-study included home respiratory monitoring (Nellcor EdenTrace), and repeated manual and AutoSet titration with polysomnography. Compliance was assessed with hour-meter readings. Mean (+/-SEM) usage was 5.7 +/- 0.1 h.night-1 at 3 and 8 months. The arousal index remained normalized. Diagnostic respiratory disturbance index (RDI) was 60.3 +/- 5.7 events.h-1. On AutoSet at fixed CPAP, RDI was initially 2.6 +/- 0.7 events.h-1, then rose slightly (p < 0.001) to 4.3 +/- 0.6 events.h-1 at 3 months, and was 3.6 +/- 0.5 events.h-1 at 8 months. AutoSet titration pressure was: 9.9 +/- 0.4 cmH2O initially, 10.6 +/- 0.4 cmH2O at 3 months, and 9.7 +/- 0.5 cmH2O at 8 months (NS). Manual titration pressure at 8 months was 10.4 +/- 0.4 cmH2O. The standard deviation of the discrepancy with AutoSet was 0.84 cmH2O. In conclusion, the AutoSet recommended pressure varies little with time, and closely predicts the final manual titration pressure; the improvement in respiratory disturbance index was largely maintained, and compliance was good, although probably enhanced by close supervision.

[Effect of alcohol on minimal effective nCPAP pressure]. / Die Wirkung von Alkohol auf den minimal effektiven nCPAP-Druck.

Alcohol may have an aggravating effect on sleep disordered breathing. Aim of our study was to test the effect of alcohol on the required nCPAP pressure as determined by the self-adjusting nCPAP-system AutoSet. Ten male subjects (age 54 +/- 9 yrs, body mass index 37 +/- 5 kg/m2) with moderate to severe obstructive sleep apnoea (OSA) were investigated. Full polysomnography was performed on four consecutive days (control night with and without alcohol, nCPAP pressure determination by AutoSet with and without alcohol, in randomised order). Alcohol was given in a single dose of 80 proof vodka (1.5 ml per kg of body weight) one hour prior to bedtime. Alcohol to a deterioration of the respiratory disturbance index (RDI, 56 +/- 23 without vs. 66 +/- 19 with alcohol, p = 0.02), but no significant change was observed in mean or minimal oxygen desaturation, mean or maximal event duration. The 95th percentile of the AutoSet-pressure was not different with or without alcohol (10.7 +/- 2.5 vs. 10.6 +/- 2.5 cm H2O). Moderate alcohol intake in the evening need not be taken into account for CPAP pressure determination in moderate to severe OSA.

Nasal continuous positive airway pressure treatment: current realities and future.

Nasal continuous positive airway pressure (CPAP) is a highly effective treatment for obstructive sleep apnea syndrome. The apnea/hypopnea index (AHI) is reduced 10-fold, but the patient dropout rate is up to 30%, and usage is typically < 5 hours per night. Titration, designed to make the best trade-off between effectiveness and side effects, is expensive. Autotitrating devices make this trade-off on a minute-by-minute basis, potentially reducing mean pressure delivery, reducing side effects, and increasing compliance. The aim of this study was to test the effectiveness of the AutoSet self-adjusting nasal CPAP system (ResMed, Sydney, Australia) in eliminating obstructive events and normalizing the arousal index. Forty-five subjects (41 males and 4 females with AHI) values of > 20/hour were recruited, with written informed consent. Subjects slept for a diagnostic night, followed by a treatment night, in the laboratory, using the AutoSet system with full polysomnographic monitoring of respiratory and sleep variables. Arousals were scored using ASDA criteria. Hypopneas were scored when there was a 50% reduction in ventilation for > 10 seconds, associated with a 4% drop in oxygen saturation. For comparison, the ASDA arousal index in 16 normal subjects (without nasal CPAP) is provided. Results are given as mean +/- standard error of the mean. AHI was reduced from 55 +/- 3 to 1.5 +/- 0.35 events/hour (p < 0.0001). The arousal index was reduced from 65 +/- 3 to 18 +/- 2 events/hour (p < 0.0001), identical to the value in the 16 healthy normal subjects. There was a 158% +/- 21% increase in slow-wave sleep (p = 0.01) and a 186% +/- 27% increase in rapid eye movement sleep (p = 0.013). The AutoSet self-adjusting nasal CPAP system adequately treats obstructive sleep apnea syndrome on the first night under laboratory conditions.

Influence of moderate alcohol consumption on obstructive sleep apnoea with and without AutoSet nasal CPAP therapy.

Snoring worsens with high alcohol consumption. It is unclear whether moderate alcohol intake worsens sleep and breathing in subjects with obstructive sleep apnoea syndrome (OSAS), and whether alcohol increases the pressure requirement for nasal continuous positive airway pressure (CPAP). Fourteen adult males with untreated OSAS but without heart or lung disease were studied (age 53+/-9 yrs, body mass index (BMI) 33+/-5 kg x m(-2) (mean+/-SD). The subjects underwent overnight polysomnography on four occasions: control, alcohol, CPAP, and alcohol + CPAP. On the alcohol nights, the subjects drank 1.5 mL x kg(-1) body weight (BW) vodka (40% alcohol by volume) (blood alcohol with and without CPAP 0.45+/-0.1 and 0.47+/-0.2 mg x mL(-1) (mean+/-SD)). On the CPAP nights, the pressure required to prevent apnoea, snoring, and silent inspiratory airflow limitation was determined using an autotitrating nasal CPAP system (ResCare AutoSet). Alcohol and control nights were performed in random order. Without CPAP, alcohol produced a small non-significant decrease in the percentage of rapid eye movement (REM) sleep (control 11+/-2 vs alcohol 8+/-1% (mean+/-SEM)), but with CPAP there was no such effect (control 15+/-2 vs 17+/-2%; CPA x alcohol interaction p=0.015). With CPAP, slow-wave sleep in the first 2 h increased slightly with alcohol (control 39+/-6 vs alcohol 51+/-4%; p=0.004). Arousal index without CPAP increased slightly with alcohol (control 43+/-5 vs alcohol 49+/-6 events x h(-1); p=0.02). There was little or no effect of alcohol on other sleep stages, arousal index, apnoea index, apnoea/hypopnoea index, mean or longest event duration, mean or worst arterial oxygen saturation, with or without CPAP, either for the full night or for the first 2 h. There was no change in the pressure requirement for CPAP (full night: control 11.9+/-0.9 vs alcohol 12.5+/-0.9 cm H2O; first 2 h: 10.9+/-0.6 vs 11.1+/-0.8 cm H2O). Moderate alcohol intake (in the form of vodka) has little effect on breathing or saturation during sleep in subjects with mild-to-severe obstructive sleep apnoea, and no effect on the pressure required for continuous positive airway pressure in order to prevent apnoea, snoring, and flow limitation. These results cannot be extrapolated to other doses or forms of alcohol, or to subjects with concurrent heart or lung disease.

Influence of maxillary constriction on nasal resistance and sleep apnea severity in patients with Marfan's syndrome.

BACKGROUND: Marfan's syndrome is associated with a high prevalence of obstructive sleep apnea (OSA). As this syndrome is associated with a characteristic constricted maxilla and high-arched palate, we reasoned that nasal airway constriction and resultant high nasal airway resistance (NAR) may contribute to the development of OSA. Therefore, the aim of this study was to measure NAR in patients with Marfan's syndrome. In addition, we aimed to examine the influence of maxillary morphology on both NAR and the severity of OSA. METHOD: We measured NAR in 13 consecutive patients with Marfan's syndrome and 13 control subjects. NAR was measured by posterior rhinomanometry, and expressed as the inspiratory resistance at a flow of 0.5 L/s. Dental impressions were taken to evaluate maxillary arch morphology, allowing measurement of the following distances: intercuspid (ICD), interpremolar (IPD), intermolar (IMD), and maximum hard palate height (MPH). Ten of the patients and four of the control subjects had previously undergone nocturnal polysomnography. RESULTS: Mean NAR for the Marfan group was more than twice that in the control group (7.7 +/- 1.2 vs 2.9 +/- 0.4 cm H2O/L/s; p < 0.005). The patients also had marked constriction of the maxillary arch compared with control subjects. Two of the lateral maxillary measurements were significantly inversely correlated with NAR. There were significant correlations between various maxillary arch measurements (MPH/ICD, MPH/IPD, MPH/IMD) and the apnea/hypopnea index. CONCLUSION: These data suggest that high NAR is a common feature of Marfan's syndrome. Maxillary constriction with a relatively high hard palate appears to be a major reason for the high NAR. The significant correlations between indexes of maxillary constriction and sleep apnea severity suggest that maxillary morphology may play an important role in the pathophysiology of OSA in Marfan's syndrome.

Effect of different levels of hyperoxia on breathing in healthy subjects.

We have recently shown that breathing 50% O2 markedly stimulates ventilation in healthy subjects if end-tidal PCO2 (PETCO2) is maintained. The aim of this study was to investigate a possible dose-dependent stimulation of ventilation by O2 and to examine possible mechanisms of hyperoxic hyperventilation. In eight normal subjects ventilation was measured while they were breathing 30 and 75% O2 for 30 min, with PETCO2 being held constant. Acute hypercapnic ventilatory responses were also tested in these subjects. The 75% O2 experiment was repeated without controlling PETCO2 in 14 subjects, and in 6 subjects arterial blood gases were taken at baseline and at the end of the hyperoxia period. Minute ventilation (VI) increased by 21 and 115% with 30 and 75% isocapnic hyperoxia, respectively. The 75% O2 without any control on PETCO2 led to 16% increase in VI, but PETCO2 decreased by 3.6 Torr (9%). There was a linear correlation (r = 0.83) between the hypercapnic and the hyperoxic ventilatory response. In conclusion, isocapnic hyperoxia stimulates ventilation in a dose-dependent way, with VI more than doubling after 30 min of 75% O2. If isocapnia is not maintained, hyperventilation is attenuated by a decrease in arterial PCO2. There is a correlation between hyperoxic and hypercapnic ventilatory responses. On the basis of data from the literature, we concluded that the Haldane effect seems to be the major cause of hyperventilation during both isocapnic and poikilocapnic hyperoxia.

Automated continuous positive airway pressure titration for obstructive sleep apnea syndrome.

This study tested the effectiveness of the AutoSet self-titrating nasal continuous positive airway pressure (nCPAP) system in treating obstructive sleep apnea (OSA), and choosing a suitable pressure for subsequent conventional fixed-pressure nCPAP therapy. Twenty-one adult men with untreated OSA were studied with full polysomnography on each of four nights: diagnostic, manual and AutoSet nCPAP titration (in random order), and conventional fixed-pressure nCPAP at the pressure recommended by the AutoSet titration. Titration was satisfactorily performed in 20 of 21 subjects. Severe mask leak prevented automated titration in one subject and caused transient unnecessary increases in pressure in three subjects. In the 20 subjects, respiratory disturbance index (RDI) was 60.3 +/- 5.7 events/h (mean +/- SEM) on the diagnostic night. RDI was lower with manual titration (10.1 +/- 3.0, p < 0.001), and lower still with Autoset (2.8 +/- 0.9, p < 0.01) and fixed pressure (2.5 +/- 0.7, p = ns versus AutoSet) nCPAP. There were similar changes in the arousal index, which was 52.7 +/- 4.6 events/h on the diagnostic night, 14.2 +/- 2.4 with manual titration and 8.9 +/- 0.9 with AutoSet titration, and 9.5 +/- 1.0 on the night of conventional fixed-pressure CPAP (p < 0.001 versus diagnostic). We conclude that the AutoSet system is suitable for automated nCPAP pressure titration.

Mouth leak with nasal continuous positive airway pressure increases nasal airway resistance.

Nasal congestion, dry nose and throat, and sore throat affect approximately 40% of patients using nasal continuous positive airway pressure (CPAP). The mechanisms causing nasal symptoms are unclear, but mouth leaks causing high unidirectional nasal airflow may be important. We conducted a study to investigate the effects of mouth leak and the influence of humidification on nasal resistance in normal subjects. Nasal resistance was measured with posterior rhinomanometry in six normal subjects who deliberately produced a mouth leak for 10 min while using nasal CPAP. Nasal resistance was measured regularly for 20 min after the challenge. A series of tests were performed using air at differing temperatures and humidities. There was no change in nasal resistance when subjects breathed through their noses while on CPAP, but a mouth leak caused a large increase in resistance (at a flow of 0.5 L/s) from a baseline mean of 2.21 cm H2O/L/s to a maximum mean of 7.52 cm H2O/L/s at 1 min after the challenge. Use of a cold passover humidifier caused little change in the response (maximum mean: 8.27 cm H2O/L/s), but a hot water bath humidifier greatly attenuated the magnitude (maximum mean: 4.02 cm H2O/L/s) and duration of the response. Mouth leak with nasal CPAP leads to high unidirectional nasal airflow, which causes a large increase in nasal resistance. This response can be largely prevented by fully humidifying the inspired air.

Ventilatory response to isocapnic hyperoxia.

Breathing O2 for up to 1 h has been shown to either not influence or slightly increase (6-13%) minute ventilation. However, end-tidal PCO2 was not kept constant in these experiments. In nine healthy men, we studied the ventilatory, blood pressure, and heart rate responses to 30 min of normobaric hyperoxia (50% O2) at isocapnic conditions. Hyperoxia led to a 60% increase in mean minute ventilation (P = 0.002), largely due to an increase in mean tidal volume from 0.66 +/- 0.04 (SE) to 0.88 +/- 0.05 liter (P = 0.007). Fifteen minutes after the termination of hyperoxia, minute ventilation was still increased (P = 0.02) compared with baseline, although it was reduced compared with hyperoxia (P = 0.02). Arterial blood gas analyses in six subjects before and during hyperoxia showed an increase in arterial PO2 and O2 saturation but no change in arterial PCO2 or pH. Hyperoxia induced no changes in arterial blood pressure or heart rate. We conclude that 1) isocapnic hyperoxia stimulates respiration markedly, an effect that is approximately five times higher than previously measured; 2) the increase in ventilation induced by hyperoxia does not affect arterial blood pressure and heart rate; and 3) in experiments using hyperoxia, its effect on breathing and subsequently on PCO2 has to be taken into account.

Central sleep apnea is associated with increased ventilatory response to carbon dioxide and hypersecretion of growth hormone in patients with acromegaly.

Although obstructive sleep apnea (OSA) occurs commonly in acromegaly, we have recently reported an unexpectedly high prevalence of central sleep apnea (CSA) in these patients. Acromegalic patients with CSA have increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels compared with their counterparts with OSA. Studies in animals, normal humans, and patients with sleep apnea have suggested that CSA is associated with increased gain of the respiratory control system. To examine the relationship between sleep apnea, respiratory control, and hormonal activity in acromegaly, we performed sleep studies and examined ventilatory responses to hypoxia at resting CO2 (HVR) and 8 mm Hg above resting CO2 (HHVR) and hypercapnia (HCVR) in 54 patients with acromegaly who also underwent detailed endocrine evaluation. Patients with CSA (n = 11) had higher HCVR (3.47 +/- 0.57 L/min/mm Hg) than did patients with obstructive sleep apnea (OSA) (1.86 +/- 0.19, n = 33) and patients without sleep apnea (1.77 +/- 0.21, n = 10). Measures of ventilatory control were all correlated with the mean of 12 hourly GH concentrations, but only HCVR was correlated with IGF-1 levels. Multiple linear regression analysis revealed that HCVR, HHVR, and IGF-1 could explain 39% of the variability in the degree of CSA in acromegalic patients with sleep apnea. We conclude that increased ventilatory responsiveness and elevated hormonal parameters of disease activity both contribute to the pathogenesis of central sleep apnea in acromegaly.

Feasibility of a self-setting CPAP machine.

Auto-setting over-prescribed in six of 20 patients due to severe mouth leak. Mouth leak during CPAP has not previously been quantified, and these results, with leaks of 0.3-1.5 l/second, suggest a mechanism for the dry mouth and nasal symptoms commonly observed with CPAP. Obstructive events were reduced to the normal range in 19 of 20 patients and acceptably reduced in the 20th patient. In the nine nonleakers, mean CPAP pressure was reduced to 54% of the traditionally prescribed pressure. These preliminary results suggest that a self-setting CPAP machine, based on subtle indices of partial obstruction, is practicable in patients without severe mouth leaks.

Breathing route and resistive loading: influence on ventilatory response to hypoxia in conscious dogs.

Unlike normal humans, the tracheostomized conscious dog does not show ventilatory adaptation in response to sustained isocapnic hypoxia. To determine whether this phenomenon is a result of the breathing route or the relatively low airflow resistance of tracheostomy breathing, we evaluated the ventilatory response to sustained isocapnic hypoxia (20 min; arterial oxyhemoglobin saturation = 80%) in five awake dogs during nasal-oral (mask) breathing, tracheal breathing, and tracheal breathing with added matched resistance of upper airway breathing. Mask breathing, like unloaded tracheal breathing, was associated with a consistent level of hyperventilation during the entire hypoxic exposure period. However, mask breathing was always less (P < 0.05) than that found during unloaded tracheal breathing. Loaded tracheal breathing during hypoxia resulted in initial hyperventilation similar to that of unloaded tracheal breathing followed by a "roll off" to a lower minute ventilation similar to that of mask breathing. Our findings demonstrate that ventilatory adaptation is only present during loaded tracheal breathing in dogs and suggest that the breathing route and upper airway resistive loading may play roles in ventilatory adaptation.