Upper airway resistance during progressive hypercapnia and progressive hypoxia in normal awake subjects

Ventilatory motor output is known to influence the upper airway. Although inspiratory upper airway resistance decreases during progressive hypoxia or hypercapnia, the effects of hypoxia and hypercapnia on expiratory upper airway resistance remain unknown. In the present study, we attempted to examine whether the expiratory and the inspiratory upper airway resistances were modified in the same way by progressive hyperoxic hypercapnia or by progressive normocapnic hypoxia. Nine healthy subjects (five males, four females, 33+/-9 years) participated in the study. Inspiratory upper airway (iUAR) and expiratory upper airway resistances (eUAR) were calculated at flow 300 ml x s(-1). Both resistances were obtained during a baseline period and during progressive hyperoxic hypercapnia or progressive normocapnic hypoxia. In all subjects, iUAR and eUAR decreased significantly during hypercapnic or hypoxic challenge (P<0.05). eUAR was always lower than iUAR during hypercapnic challenge (P<0.0001) and during hypoxic challenge (P<0.0001). The authors conclude that expiratory upper airway resistance, as with inspiratory resistance, decreases during progressive hypercapnia or during progressive hypoxia. Pharyngeal dilator or constrictor muscle activities may be implicated.     

Moderate alcohol ingestion increases upper airway resistance in normal subjects

Apnea during sleep has been associated with both increased pharyngeal resistance and nasal obstruction. Alcohol can worsen obstructive sleep apnea, but its influence on pharyngeal resistance and nasal patency has not been evaluated. Accordingly, we determined the effects of alcohol on pharyngeal and nasal resistances in 11 normal awake subjects on 2 separate days. Baseline pharyngeal resistance prior to placebo and alcohol was not significantly different. After placebo, pharyngeal resistance did not change significantly. However, after alcohol, pharyngeal resistance increased from 1.9 +/- 0.5 (SEM) to 3.3 +/- 0.8 cm H2O/L/s at 45 min (p less than 0.05) and returned to near baseline level by 90 min. Baseline nasal resistance varied considerably within subjects on the 2 days, but the mean values for baseline nasal resistance on alcohol and placebo days were not significantly different. Nasal resistance did not change after placebo, but after alcohol, nasal resistance increased from 2.4 +/- 0.9 at baseline to 3.7 +/- 0.8 at 45 min (NS) and to 4.3 +/- 1.2 cm H2O/L/s at 90 min (p less than 0.05). We conclude that a decrease in pharyngeal airway size and an increase in nasal resistance may account for alcohol's ability to worsen obstructive sleep apnea.     

A model of obstructive sleep apnea in normal humans. Role of the upper airway

We determined whether upper airway obstruction in normal individuals with intact reflexes could produce the syndrome of obstructive sleep apnea. Upper airway obstruction was produced in 12 normal individuals by lowering nasal pressure to -10 cm H(2)O during sleep. Full night polysomnography was performed during two consecutive nights of sleep with subatmospheric nasal pressure and compared with control nights before and after the negative pressure nights. We found that the application of negative pressure was associated with the development of recurrent obstructive apneas (non-REM-disordered breathing rate, 32.6 +/- 34.8 and 37.8 +/- 29.1 events/h during each of two negative pressure nights; p < 0.001) that were associated with oxyhemoglobin desaturation, arousals from sleep, and alterations in sleep stage distribution. Moreover, the median daytime sleep latency after two nights of sleep with subatmospheric pressure fell from 6.9 +/- 1.1 to 3.4 +/- 0.6 min, and rose significantly again to 8.1 +/- 1.5 min (p < 0.03) after the control night following subatmospheric pressure nights. Our findings suggest that a decrease in the pharyngeal transmural pressure alone is a sufficient condition for the production of the sleep apnea syndrome in normal individuals.     

The upper airway resistance syndrome

Obstructive sleep apnea syndrome has been recognized as a major public health problem. Both its cardiovascular and metabolic comorbidities and symptoms motivate for an accurate diagnosis and appropriate treatment. The main stimulus associated with obstructive sleep apnea (OSA) and explaining deleterious consequences is intermittent hypoxia. The upper airway resistance syndrome (UARS) has been described based on the hypothesis that snoring and repetitive occurrence of respiratory effort-related arousals (RERAs) but not oxygen desaturation might produce a significant disease with symptoms, altered quality of life and cardiovascular morbidity. Diurnal sleepiness remains the main diagnostic criteria, which is often confounded with tiredness in women. UARS patients may also report insomnia and symptoms that closely resemble those of the functional somatic syndromes. Currently, the International Classification of Sleep Disorders does not individualize UARS as a specific entity and reports UARS patients as a subgroup of OSA. However, RERAs are described as unambiguous abnormal respiratory events occurring during sleep and requiring a specific scoring. In this review, the authors attempt to describe the specific characteristics of UARS that are relevant for both clinicians and researchers.     

The upper airway resistance syndrome

The upper airway resistance syndrome (UARS) is a recently described form of sleep-disordered breathing in which repetitive increases in resistance to airflow within the upper airway lead to brief arousals and daytime somnolence. This review will first describe the chronological progression of our understanding of UARS within the broader context of sleep-disordered breathing. The primary symptom, daytime somnolence, appears to result directly from repetitive EEG arousals. The level of negative intrathoracic pressure is the most likely stimulus for arousal, possibly mediated by mechanoreceptors in the upper airway. A general consensus regarding the exact clinical definitions and the physiologic measurement techniques leading to a diagnosis does not exist, although esophageal manometry and pneumotachographic airflow measurements taken during polysomnography are the "gold standard." Less invasive diagnostic modalities have been proposed, but none of them have been well-validated. Aside from daytime somnolence, hypertension is an important sequela of this disorder, likely resulting from autonomic and cardiovascular changes induced by increased negative intrathoracic pressure. Nasal continuous positive airway pressure is the most efficacious form of therapy, although low patient compliance may limit its practical application. The safety and efficacy of surgical treatments are poorly documented in the literature. Palatal tissue reduction by radiofrequency ablation and the use of oral appliances hold promise as safe and effective modalities, but these treatments require further study.     

Effects of upper airway carbon dioxide on upper airway resistance and muscle activity in young guinea-pigs.

The upper airway (UA) of adult animals is known to contain carbon dioxide-sensitive receptors and UA CO2 reflexly affects breathing, UA dilator muscle activity and UA resistance. These effects may function in the control of UA patency. There is evidence that some UA reflexes are stronger in young than in adult animals, but it is not known whether CO2-sensitive receptors are present in the UA of young animals, and the effects of UA CO2 on UA resistance and on UA dilator muscle activity have not been investigated in young animals. The responses of ventilation, UA resistance and geniohyoid muscle electromyographic activity to warm air containing 10% CO2 applied to the isolated UA were measured in anaesthetized, vagotomized young guinea-pigs breathing spontaneously through a low-cervical tracheostomy. Upper airway carbon dioxide caused an increase in ventilation (46.7+/-16.3 to 49.9+/-16.8 mL x min(-1) x 100 g body weight(-1)) and upper airway resistance (56.8+/-14.8 to 63.7+/-17.7 cmH2O x L(-1) x s(-1) x kg body weight(-1)). Similar effects were obtained following vagotomy. Geniohyoid activity became apparent following vagotomy and this activity was reduced by upper airway carbon dioxide. These responses were abolished by topical anaesthesia of the upper airway. This suggests that the reflexes seen are due to carbon dioxide-sensitive receptors in the upper airway.     

睡眠对慢性阻塞性肺疾病患者上气道阻力的影响

目的 探讨睡眠对慢性阻塞性肺疾病(COPD)患者上气道阻力及呼吸动力学的影响.方法 选择19例COPD急性加重期住院患者,治疗后病情稳定,通过食道-胃囊管法,检测气道开口压、食道压和胃内压,层流速仪测呼吸流速和容量改变.同步监测多导睡眠图,采集患者在清醒、睡眠仰卧及侧卧位呼吸动力学的变化.结果 睡眠时吸气峰流速、平均吸...     

Increased upper airway resistance in patients with airway narrowing.

The mean air flow resistance of the orolaryngeal (upper) airway was significantly increased in 7 of 11 patients with chronic airway obstruction, when compared with 6 controls. All the patients had noisy respiration with harsh breath sounds audible by auscultation over the larynx. The increase in resistance was greater during expiration than during inspiration. Since 4 patients had normal upper airway resistance, the signs were not invariably associated with upper airway narrowing and presumably could arise also in the chest. When increased, upper airway resistance was usually more than half the total airway resistance. It is suggested that this increase could only be due to narrowing of the glottis, probably by muscle activity. This narrowing may have had the same function as expiration through pursed lips. On the other hand, when present, the increased resistance through the upper airway during inspiration is unlikely to have had a useful function.     

Alcohol and the response of upper airway resistance to a changing respiratory drive in normal man

We studied the effects of alcohol ingestion on the response of upper airway resistance (UAR) to changing respiratory motor output in 9 normal subjects. Nasal and pharyngeal pressures were measured with two low bias flow catheters placed at the tip of the epiglottis and in the posterior nasopharynx. Respiratory flow was measured with a Fleisch no. 3 pneumotachograph connected to a tightly fitting mask. Breath-by-breath inspiratory upper airway resistances were calculated at isoflow during 1) a CO2 rebreathing (increase in drive), 2) 2 min following five slow vital capacities of 100% O2 (decrease in drive) (Post-O2 period), and 3) 1 min before each procedure (baseline measurements). The respiratory motor output was estimated by the pressure developed 0.1 sec after the onset of inspiration (P0.1) during rebreathing and by the mean inspiratory flow (VT/TI) during the post-O2 period. Measurements were performed before and after the ingestion of 1.5 ml/kg of 40% alcohol. Blood alcohol level rose from 0 to 14.9 +/- 1.8 mmol.L-1 (Mean +/- SD) and total supralaryngeal resistance increased from 2.8 +/- 1.8 cm H2O.L-1.sec to 4.2 +/- 1.8 cm H2O.L-1.sec (P less than 0.001, Student's paired t-test). During CO2 rebreathing UAR decreased exponentially as P0.1 increased both before and after alcohol intake. The slope of the plot Log (pharyngeal resistance) against P0.1 decreased from -17.0 x 10(-3) +/- 9.3 x 10(-3) before alcohol to -11.0 x 10(-3) +/- 6.6 x 10(-3) after alcohol intake (P = 0.03). The slope of the decrease in nasal resistance remained unchanged. A decrease in VT/TI occurred during the Post-O2 period and was accompanied by an exponential increase in UAR at each experiment. The slope of Log (pharyngeal resistance) over VT/TI was significantly higher after (-27.0 x 10(-3) +/- 7.1 x 10(-3)) than before alcohol (-12.0 x 10(-3) +/- 4.2 x 10(-3), P less than 0.001). The slope of the increase in nasal resistance with decreasing VT/TI rose from -8.4 x 10(-3) +/- 6.5 x 10(-3) to -13.0 x 10(-3) +/- 7.4 x 10(-3) after alcohol ingestion (P = 0.06). We conclude that alcohol ingestion depresses the pharyngeal responses to changing central drive in normal subjects.     

Changes in inspiratory muscle electrical activity and upper airway resistance during periodic breathing induced by hypoxia during sleep

We hypothesized that: the balance of electrical activities between the upper airway and chest wall inspiratory muscles affects upper airway inspiratory caliber, and at low levels of central respiratory neural efferent activity, an imbalance between the electrical activities of these 2 inspiratory muscle groups exists that results in a decreased upper airway caliber. These hypotheses were tested during periodic breathing induced by mild hypoxemia in NREM sleep in 9 healthy male subjects. In 6 subjects during periodic breathing as central respiratory neural activity decreased, the tonic and phasic EMG activity of the upper airway inspiratory muscles decreased at a rate greater than that of the chest wall EMG activity. When the ratio of upper airway to chest wall EMG activity decreased below a critical level, which was reproducible across subjects, upper airway inspiratory resistance increased hyperbolically. Resistance at peak inspiratory flow increased from 4.10 +/- 0.97 (mean +/- SEM) to 48.70 +/- 21.00 cmH2O/L/s as tidal volume decreased from 0.79 +/- 0.12 to 0.20 +/- 0.02 L during periodic breathing in these subjects. In the 3 remaining subjects, the ratio of the upper airway to chest wall EMG activity did not decrease below the critical level as the activity of both muscle groups decreased during periodic breathing, and upper airway resistance did not increase. We conclude that within the confines of this study the nonlinear activation of upper airway and chest wall inspiratory muscles contributed to fluctuations in upper airway resistance observed during periodic breathing in sleep.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison between anatomy and resistance of upper airway in normal subjects, snorers and OSAS patients.

Upper airway (UA) anatomical abnormalities are frequently observed in obstructive sleep apnea syndrome (OSAS). The correspondence between UA anatomical modifications and UA resistance (UAR) had not been studied. We aimed to determine if cephalometric characteristics could be related to segmental UAR. In twenty-five patients (21 males) (15 OSAS patients, 10 snorers) and 10 control subjects (8 males), segmental UAR were measured in supine position and cephalometry was performed. Inspiratory and expiratory UAR were calculated at peak flow. Length of the soft palate (LP), posterior airway space (PAS), distance from hyoid bone to mandibular plane and to posterior pharyngeal wall were different between the groups (P<0.01). Inspiratory and expiratory, total and segmental, UAR were higher in OSAS (P<0.001). Segmental UAR were correlated with PAS and distance from hyoid bone to mandibular plane and to pharyngeal posterior wall (P<0.05). In conclusion, OSAS patients had higher UAR depending on anatomical variables, especially the place of the hyoid bone.     

Endogenous opioids and ventilatory responses to hypoxia in normal humans

We studied the putative role of endorphins in modulating hypoxic ventilatory responsiveness. In 12 healthy men, minute ventilation (VE)and mouth occlusion pressure (P0.1) responses to progressive isocapnic hypoxia were determined before and after the intravenous administration of the opioid antagonist naloxone (10 mg) or placebo. Plasma levels of beta-endorphin were measured before and after hypoxia. Naloxone did not affect the slopes or x-intercepts of the relationships between either VE or P0.1 and arterial O2 saturation. There was no correlation between the baseline plasma level of beta-endorphin and any measure of responsiveness to hypoxia. Plasma beta-endorphin levels were not affected by either short-term hypoxia or naloxone alone; however, when hypoxia followed naloxone administration, mean +/- SD beta-endorphin increased from 8.0 +/- 8.9 pg/ml to 20.2 +/- 16.6 pg/ml (p less than 0.005). We concluded that endogenous opioids do not have an important modulating influence on hypoxic ventilatory responsiveness in adult human volunteers.     

Effects of upper airway anaesthesia on respiratory-related evoked potentials in humans.

Cortical potentials evoked by mid-inspiratory occlusion arise from numerous receptors, many of which are probably within the upper airway. Their precise nature is not known. The aim of the current study was to improve knowledge of this by studying the effects of topical upper airway anaesthesia on respiratory-related evoked potentials. Respiratory-related evoked potentials were described through the averaging of electroencephalogram (EEG) epochs following mid-inspiratory occlusions (C3-CZ; C4-CZ). A total of 21 healthy volunteers (13 male, aged 22-52 yrs) were studied during mouth breathing, before and after topical upper airway anaesthesia (lidocaine). Moreover, 15 subjects were studied during nose breathing with and without anaesthesia. Six subjects were studied whilst inhaling L-menthol. Typical potentials were present in all the subjects, their components featuring normal amplitudes and latencies. The route of breathing and upper airway anaesthesia did not modify the EEG responses to inspiratory occlusions, qualitatively or quantitatively, during mouth or nose breathing. L-menthol had no effect. Upper airway receptors sensitive to topical anaesthesia are unlikely to contribute significantly to mid-inspiratory occlusion-evoked potentials. On the contrary, deeper receptors, such as joint and muscle receptors, could contribute dominantly to these potentials.     

Mechanical properties of the rabbit upper airway during hypoxia and hypercapnia

It has been suggested that the response of upper airway muscles to hypoxia may be different from the response of these muscles to hypercapnia. We therefore measured pulmonary ventilation and the mechanical properties of the isolated upper airway in 9 anesthetised rabbits during respiration of hypoxic and hypercapnic gas mixtures. Each animal was exposed to several levels of elevated inspiratory CO2 fraction, FICO2 (0.03 to 0.17) and depressed inspiratory O2 fraction, FIO2 (0.19 to 0.09). The steady-state ventilatory response, the tidal pressure in the upper airway (PTUA) and the upper airway elastance were measured under each condition. Straight lines were calculated by least squares regression relating pulmonary VT to FICO2 and FIO2 and PTUA to FICO2 and FIO2. The PTUA was estimated graphically at two levels of hypoxia and hypercapnia producing equal augmentation of VT. The ratio of PTUA during hypoxia to PTUA during hypercapnia was 1.06 +/- 0.21 (mean +/- 95% C.I.) at low VT and 1.15 +/- 0.25 at high VT. Elastance of the upper airway rose from 6.25 +/- 1.13 cmH2O/ml under control conditions to a maximum of 7.95 +/- 1.24 cmH2O/ml (P less than 0.05) during hypercapnia and to a maximum of 8.02 +/- 1.17 cmH2O/ml (P less than 0.05) during hypoxia. There was no difference between the mean (+/- 95% C.I.) change associated with hypercapnia (1.64 +/- 1.08 cmH2O/ml) and the mean change associated with hypoxia (1.77 +/- 1.26 cmH2O/ml). We concluded that hypoxia did not result in a greater change in upper airway mechanical properties than hypercapnia.     

Effect of hypercapnia on upper airway resistance and collapsibility in anesthetized dogs

The upper airway (UAW) is intrinsically unstable and susceptible to collapse when the negative inspiratory intraluminal pressure exceeds the stabilizing forces which prevent obstruction. In the present study we evaluated mechanisms by which UAW patency is maintained in the presence of increased inspiratory flows when respiration is stimulated. In seven anesthetized dogs breathing spontaneously through a low tracheostomy, the UAW was isolated by a second tracheostomy directed rostrally. UAW pressure-flow relationship and stability against collapse were evaluated during steady flow in the inspiratory direction while the animals were breathing 100% O2 or a hypercapnic gas mixture. The pressure-flow curves of the isolated UAW demonstrated the characteristic pattern of collapsible tubes. Steady state hypercapnia resulted in lower UAW resistance during both inspiration and expiration. UAW resistance decreased linearly as PCO2 and ventilation increased over the course of CO2 rebreathing. In addition, during hypercapnia the critical negative intraluminal pressure required to induce UAW collapse and obstruction increased from -4.3 +/- 0.9 to -8.5 +/- 1.5 SE cm H2O (p less than 0.01), indicating increased stability of the UAW. Since hypercapnia is known to stimulate UAW muscles, our findings suggest that increased UAW muscle activity improves UAW patency both by decreasing their resistance to airflow, and by increasing UAW walls rigidity and stability against collapse.     

Partitioning of upper airway resistance in Friesian and double-muscled calves

Respiratory resistance in calves was partitioned in two components: upper airway resistance and pulmonary resistance. The former one was divided into naso-pharyngeal and laryngeal resistance. A comparison between seven healthy unsedated double-muscled calves of the Belgian White and Blue breed (BWB) and five healthy unsedated Friesian (F) calves was performed. Respiratory resistance was significantly greater in the BWB calves, due to the significantly higher values of the naso-pharyngeal and the laryngeal resistances. This finding might be related to the higher prevalence of laryngitis in this breed.     

Effect of ventilatory drive on upper airway patency in humans during NREM sleep

The pharynx is the site of upper airway obstruction during sleep. As a collapsible tube, pharyngeal patency is determined by transmural pressure and the compliance of the pharyngeal wall. Thus, several factors may influence upper airway patency including the activity of upper airway dilating muscles, the magnitude of caudal traction generated by thoracic inspiratory activity, vascular tone and mucosal surface forces. Changing ventilatory motor output influences upper airway patency primarily by altering dilating muscle activity or caudal traction. Increased ventilatory motor output enhances upper airway patency. Isolated reduction of ventilatory motor output has no significant effect on upper airway patency. However, upper airway narrowing or occlusion occur at the nadir of ventilatory drive during induced periodic breathing and during central apnea. The latter indicates that negative intraluminal pressure is not required for upper airway obstruction during sleep. Therefore, upper airway occlusion during sleep may be due to: (1) passive collapse of a compliant upper airway by gravitational factors or (2) active closure generated by the contraction of the pharyngeal constrictors.     

Influence of upper airway size on volume exhaled under negative pressure during evaluation of upper airway collapsibility

Study objectives  

It has been shown that volume exhaled in the first 0.5 s after application at the mouth of 5 cmH₂O negative pressure (V,NEP_0.5) during wakefulness strongly reflects critical pressure (Pcrit) during sleep but only in males with neck circumference (NC) >37 cm. The aim of this study was to establish the relationship between upper airway (UA) size and V,NEP_0.5, to obtain V,NEP_0.5 values as percent predicted and then correlate them with Pcrit obtained in the same subjects.