Comparison of Collapsibility of the Human Upper Airway During Anesthesia and During Sleep.

BACKGROUND: The propensities for the upper airway to collapse during anesthesia and sleep are related, although much of our understanding of this relationship has been inferred from clinical observation and indirect measures such as the apnea-hypopnea index. The aim of this study was to use an identical, rigorous, direct measure of upper airway collapsibility (critical closing pressure of the upper airway) under both conditions to allow the magnitude of upper airway collapsibility in each state to be precisely compared. METHODS: Ten subjects (8 men and 2 women; mean ± SD: age, 40.4 ± 12.1 years; body mass index, 28.5 ± 4.0 kg/m) were studied. Critical closing pressure of the upper airway was measured in each subject on separate days during (1) propofol anesthesia and (2) sleep. RESULTS: Critical closing pressure of the upper airway measurements were obtained in all 10 subjects during nonrapid eye movement sleep and, in 4 of these 10 subjects, also during rapid eye movement sleep. Critical closing pressure of the upper airway during anesthesia was linearly related to critical closing pressure of the upper airway during nonrapid eye movement sleep (r = 0.64 [95% CI, 0.02-0.91]; n = 10; P = .046) with a similar tendency in rapid eye movement sleep (r = 0.80 [95% CI, -0.70 to 0.99]; n = 4; P = .200). However, critical closing pressure of the upper airway during anesthesia was systematically greater (indicating increased collapsibility) than during nonrapid eye movement sleep (2.1 ± 2.2 vs -2.0 ± 3.2 cm H2O, respectively, n = 10; within-subject mean difference, 4.1 cm H2O [95% CI, 2.32-5.87]; P < .001) with a similar tendency during rapid eye movement sleep (1.6 ± 2.4 vs -1.9 ± 4.3 cm H2O, respectively, n = 4; unadjusted difference, 3.5 cm H2O [95% CI, -0.95 to 7.96]; P = .087). CONCLUSIONS: These results demonstrate that the magnitude of upper airway collapsibility during anesthesia and sleep is directly related. However, the upper airway is systematically more collapsible during anesthesia than sleep, suggesting greater vulnerability to upper airway obstruction in the anesthetized state.

Effects on upper airway collapsibility of presence of a pharyngeal catheter.

Catheters that traverse the pharynx are often in place during clinical or research evaluations of upper airway function. The purpose of this study was to determine whether the presence of such catheters affects measures of upper airway collapsibility itself. To do so, pharyngeal critical closing pressure (Pcrit) and resistance upstream of the site of collapse Rus) were assessed in 24 propofol-anaesthetized subjects (14 men) with and without a multi-sensor oesophageal catheter (external diameter 2.7 mm) in place. Anaesthetic depth and posture were maintained constant throughout each study. Six subjects had polysomnography(PSG)-defined obstructive sleep apnea (OSA) and 18 either did not have or were at low risk of OSA. Airway patency was maintained with positive airway pressure. At intervals, pressure was reduced by varying amounts to induce varying degrees of inspiratory flow limitation. The slope of the pressure flow relationship for flow-limited breaths defined Rus. Pcrit was similar with the catheter in and out (-1.5 ± 5.4 cmH2 O and -2.1 ± 5.6 cmH2O, respectively, P = 0.14, n = 24). This remained the case both for those with PSG-defined OSA (3.9 ± 2.2 cmH2O and 2.6 ± 1.4 cmH2O, n = 6) and those at low risk/without OSA (-3.3 ± 4.9 cmH2O and -3.7 ± 5.6 cmH2O, respectively, n = 18). Rus was similar with the catheter in and out (20.0 ± 12.3 cmH2O mL(-1) s(-1) and 16.8 ± 10.1 cmH2O mL(-1) s(-1), P = 0.22, n = 24). In conclusion, the presence of a small catheter traversing the pharynx had no significant effect on upper airway collapsibility in these anaesthestized subjects, providing reassurance that such measures can be made reliably in their presence.

Pharyngeal dysphagia in inflammatory muscle diseases resulting from impaired suprahyoid musculature.

Dysphagia has previously been reported in the inflammatory myopathies (IMs): inclusion body myositis (IBM), dermatomyositis (DM), and polymyositis (PM). Patients report coughing, choking, and bolus sticking in the pharynx. Myotomy has been the treatment of choice, with variable success reported. We sought to determine underlying causes of dysphagia in IM patients using instrumental evaluation. Eighteen subjects participated in the study: four with DM, six with PM, and eight with IBM. They underwent simultaneous videofluoroscopy and manometry, yielding 214 swallows for analysis regarding function of the upper esophageal sphincter (UES), swallow initiation, hyolaryngeal excursion, and pharyngeal residue. Penetration and aspiration were also recorded. UES failed to relax in two participants. High incidence of pharyngeal dysphagia was noted; 72% of participants demonstrated abnormalities, including delayed swallow initiation (24%), decreased hyolaryngeal excursion (22%), pyriform residue (17%), and penetration (22%). Dysphagia in IM patients appears to be more due to impaired muscle contraction and reduced hyolaryngeal excursion than the often held belief of failed UES relaxation. The distinction between mechanisms causing patients' dysphagia should be examined, particularly if CP myotomy is being considered as it may be contraindicated for patients with normal UES relaxation. More studies investigating IM patients pre- and post-myotomy are needed.

Elastic properties of the central airways in obstructive lung diseases measured using anatomical optical coherence tomography.

RATIONALE: Our understanding of how airway remodeling affects regional airway elastic properties is limited due to technical difficulties in quantitatively measuring dynamic, in vivo airway dimensions. Such knowledge could help elucidate mechanisms of excessive airway narrowing. OBJECTIVES: To use anatomical optical coherence tomography (aOCT) to compare central airway elastic properties in control subjects and those with obstructive lung diseases. METHODS: After bronchodilation, airway lumen area (Ai) was measured using aOCT during bronchoscopy in control subjects (n = 10) and those with asthma (n = 16), chronic obstructive pulmonary disease (COPD) (n = 9), and bronchiectasis (n = 8). Ai was measured in each of generations 0 to 5 while airway pressure was increased from -10 to 20 cm H(2)O. Airway compliance (Caw) and specific compliance (sCaw) were derived from the transpulmonary pressure (Pl) versus Ai curves. MEASUREMENTS AND MAIN RESULTS: Caw decreased progressively as airway generation increased, but sCaw did not differ appreciably across the generations. In subjects with asthma and bronchiectasis, Caw and sCaw were similar to control subjects and the Pl-Ai curves were left-shifted. No significant differences were observed between control and COPD groups. CONCLUSIONS: Proximal airway elastic properties are altered in obstructive lung diseases. Although central airway compliance does not differ from control subjects in asthma, bronchiectasis, or COPD, Ai is lower in asthma and the Pl-Ai relationship is left-shifted in both asthma and bronchiectasis, suggesting that airways are maximally distended at lower inflating pressures. Such changes reflect alteration in the balance between airway wall distensibility and radial traction exerted on airways by surrounding lung parenchyma favoring airway narrowing. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN12607000624482).

Gastro-oesophageal reflux symptoms are related to the presence and severity of obstructive sleep apnoea.

Repetitive airway occlusion during sleep in patients with obstructive sleep apnoea (OSA) results in the generation of negative intrathoracic pressures and ends in arousal, both of which may predispose to reflux during sleep (nocturnal reflux). We aimed to determine and compare the prevalence of nocturnal reflux symptoms and their sleep-associated risk factors in untreated OSA patients, OSA patients using continuous positive airway pressure (CPAP) therapy, and the general population. Gastro-oesophageal reflux and sleep questionnaires were completed by 1116 patients with polysomnography diagnosed OSA and by 1999 participants of the 2007 Busselton population health survey. Of the OSA patients, 137 completed the reflux questionnaire before and after treatment. Risk of OSA in the general population was assessed using the Berlin score. The prevalence of frequent (>weekly) nocturnal reflux symptoms was increased (P<0.001) in OSA patients (10.2%) versus the general population (5.5%), in individuals from the general population at high (8.7%) versus low risk (4.3%) of OSA and in patients with severe (13.9%) versus mild OSA (5.1%). Frequent nocturnal reflux symptoms were associated with high risk (general population) (OR 1.9, P<0.01) and severity of OSA (OSA population) OR 3.0, severe versus mild OSA, P<0.001) after correcting for age, gender and body mass index. Treatment with CPAP decreased the prevalence of reflux symptoms significantly. In conclusion, the prevalence of nocturnal reflux symptoms is increased in those with or suspected of having OSA. This association is independent of other risk factors including age, gender and body mass index, suggesting a causal relationship between OSA and nocturnal reflux.

Obstructive sleep apnoea and nocturnal gastroesophageal reflux are common in lung transplant patients.

BACKGROUND AND OBJECTIVE: Gastroesophageal reflux (GOR) has been implicated in the pathogenesis of bronchiolitis obliterans syndrome (BOS), possibly due to pulmonary aspiration of refluxed acid. Risk of aspiration of gastric contents is increased during sleep due to decreased oesophageal clearance mechanisms and may be further increased by the presence of OSA. This study investigated the relationship between nocturnal GOR, OSA and BOS in a group of lung transplant patients. METHODS: Fourteen lung transplant patients underwent overnight polysomnography with simultaneous dual oesophageal pH monitoring. RESULTS: Patients had an FEV(1) of 84 +/- 15% of their best post-transplant FEV(1). Six of the 14 patients were in various stages of BOS. The average proportion of time spent overnight with a pH of <4 was 1.7 +/- 3.1%. Increased GOR was evident in 8/14 patients during the postprandial period and/or overnight in the distal and/or proximal oesophagus. All patients had OSA (AHI >5 events per hour). There were no relationships between severity of OSA or GOR and severity of BOS. CONCLUSION: Both nocturnal GOR and OSA were common in this group of patients but their occurrences were not related. Neither was there any relationship between the presence of nocturnal GOR or OSA and severity of BOS.

Modulation of upper and lower esophageal sphincter tone during sleep.

BACKGROUND AND PURPOSE: The pressures generated within the upper esophageal sphincter (P(UES)) and lower esophageal sphincter (P(LES)) reflect the integrity of these barriers to gastroesophageal and pharyngoesophageal reflux, respectively. This study sought to describe the effects of sleep, respiration and posture on the function of the UES and the LES and the pressure differentials developed across them. METHODS: Ten healthy volunteers (7M, 3F: 38+/-10 yr) without a history of sleep-disordered breathing or reflux underwent overnight polysomnography with simultaneous measurement of P(LES) and P(UES) using a purpose-built sleeve device (Dentsleeve). Posture was recorded but not controlled. RESULTS: Subjects slept for 4.3+/-1.6h. Compared to waking values, both end-inspiratory and end-expiratory Pues were significantly less during slow wave sleep (SWS) (p<0.05). However, P(LES) was unaffected by sleep stage. During wakefulness and all stages of sleep, both P(UES) and P(LES) were greater at end-inspiration than end-expiration (p<0.05). Similar relationships were observed whether subjects were supine or in the lateral decubitus position. CONCLUSION: Sleep decreases the effectiveness of the UES to act as a barrier to pharyngoesophageal reflux, particularly during slow wave sleep (SWS). UES pressure varies with respiration, with minimal values observed during expiration. Hence, barrier function of the UES appears most impaired during SWS, in the expiratory phase of the respiratory cycle. The LES pressure and its barrier pressure also vary with respiration, being least during expiration. However, unlike the UES, the function of the LES was unaffected by sleep.

The impact of continuous positive airway pressure on the lower esophageal sphincter.

The lower esophageal sphincter (LES) is the primary barrier to gastroesophageal reflux. Reflux is associated with periods of LES relaxation, as occurs during swallowing. Continuous positive airway pressure (CPAP) has been shown to reduce reflux in individuals with and without sleep apnea, by an unknown mechanism. The aim of this study was to determine the effect of CPAP on swallow-induced LES relaxation. Measurements were made in 10 healthy, awake, supine individuals. Esophageal (Pes), LES (Ples), gastric (Pg), and barrier pressure to reflux (Pb = Ples - Pg) were recorded using a sleeve catheter during five swallows of 5 ml of water. This was repeated at four levels of CPAP (0, 5, 10, and 15 cmH(2)O). Pressures were measured during quiet breathing and during the LES relaxation associated with a swallow. Duration of LES relaxation was also recorded. During quiet breathing, CPAP significantly increased end-expiratory Pes, Ples, Pg, and Pb (P < 0.05). The increase in Pb was due to a disproportionate increase in Ples compared with Pg (P < 0.05). During a swallow, CPAP increased nadir Ples, Pg, and Pb and decreased the duration of LES relaxation (4.1 s with 0-cmH(2)O CPAP to 1.6 s on 15-cmH(2)O CPAP, P < 0.001). Pb increased with CPAP by virtue of a disproportionate increase in Ples compared with Pg. This may be due to either reflex activation of LES smooth muscle, or nonspecific transmission of pressure to the LES. The findings suggest CPAP may make the LES less susceptible to reflux by increasing Pb and decreasing the duration of LES relaxation.

Relationship between upper airway and inspiratory pump muscle force in obstructive sleep apnea.

BACKGROUND: Upper airway (UA) patency during inspiration is determined by the balance between dilating forces generated by UA dilator muscle activity and collapsing forces related to the decreased intraluminal pressure that accompanies flow generated by inspiratory muscle activity. It is possible that the relative strengths of UA dilator and inspiratory pump muscles could be an important determinant of the susceptibility to UA collapse during sleep (ie, obstructive sleep apnea [OSA]). METHODS: Measurements of tongue protrusion (TP) force and maximum inspiratory pressure (Pimax) were obtained in 94 patients admitted for overnight polysomnography for suspected OSA, quantified by apnea-hypopnea index (AHI). RESULTS: There was a direct linear relationship between TP force and Pimax (r(2) = 0.37, p < 0.001). A high ratio of TP force to Pimax (greater than group 90th percentile, 0.027 kg/cm H(2)O) appeared to protect against OSA, as moderate-to-severe OSA (AHI > 20/h) was not observed in any individual with a ratio above this threshold. AHI was not linearly related to TP force, Pimax, or the ratio of TP force to Pimax. CONCLUSIONS: UA muscle strength is linearly related to inspiratory pump muscle strength. The ratio of UA muscle strength (TP force) and inspiratory pump muscle strength (Pimax) was not different between individuals with and without OSA; however, a high wakeful ratio of TP force to Pimax appears to be associated with a reduced propensity to moderate-to-severe OSA.

Function of the lower esophageal sphincter during and after high-intensity exercise.

INTRODUCTION: Gastroesophageal reflux is commonly reported during high-intensity endurance exercise in otherwise healthy asymptomatic individuals. Although the mechanisms underlying this exercise-induced reflux are unknown, it most likely reflects a failure of the primary barrier to reflux, the lower esophageal sphincter (LES). The aim of this study was to determine the influence of exercise with and without ingestion of fluid on the LES barrier pressure in asymptomatic individuals. METHODS: Seven recreational cyclists (five males) performed four 5-min bouts of cycle exercise at 90% VO2max, each separated by 1-3 min. Before, during, and after exercise, measurements were made of esophageal pressure (Pes), LES pressure (Ples), and gastric pressure (Pg). LES barrier pressure (Pb) was defined as the difference between Ples and Pg. Following exercise bouts 2 and 3, subjects ingested 600 and 200 mL of a sports drink, respectively. RESULTS: Pb before exercise was 13.1 +/- 5.2 cm H2O (+/- SD), decreased to 6.5 +/- 4.6 cm H2O during each of the four bouts of high-intensity exercise (P < 0.05), and remained decreased at 7.4 +/- 3.5 cm H2O after exercise (P < 0.05). CONCLUSIONS: High-intensity exercise reduces LES Pb during exercise in asymptomatic individuals. The magnitude of this exercise-induced impairment in LES function is unaffected by ingestion of a sports drink.

Contractile physiology and response to temperature changes of the tunica dartos muscle of the rat.

We show here that explants of tunica dartos smooth muscle from the rat scrotum contract in response to cooling. The tension developed during cooling was potentiated by the presence of the overlying skin. This potentiation remained even if direct connection between the muscle and skin was severed by cutting the skin from the muscle but leaving the muscle and skin in contact. The potentiation did not depend on any inherent response of the skin since isolated skin showed no change in tension with cooling. The muscle exhibited a sigmoid dose response to noradrenaline with an EC(50) (dose for 50% contractile response) of 1.03+/-0.02 x 10(-6) M. Acetylcholine altered neither resting tone or the sustained contraction induced by a submaximal dose of noradrenaline. The contractile response to an EC(50) and maximal dose of noradrenaline was attenuated at both 15 and 40 degrees C relative to the response observed at 33 degrees C. We hypothesise that the potentiation of tunica dartos muscle contraction with cooling caused by the presence of the scrotal skin depends on some soluble agent released from the skin and affecting the underlying muscle. Noradrenaline release from the skin, or some molecule with alpha-receptor activity, may account for a small proportion of the potentiation. The remainder of the effect does not depend on prostaglandins, or other products of the cyclooxygenase cascade, or the nitric oxide system.

Heterogeneous activity of the human genioglossus muscle assessed by multiple bipolar fine-wire electrodes.

Genioglossus (GG) electrical activity [measured by electromyogram (EMGgg)] is best measured by intramuscular electrodes; however, the homogeneity of EMGgg is undefined. We investigated the relationships between EMGgg and the site from which activity was measured to determine whether and to what extent inhomogeneity in activity occurred. Eight healthy human volunteers underwent ultrasound to determine GG depth and width. Four pairs of electrodes were then inserted percutaneously into the left and right GG muscle, anteriorly and posteriorly. Additional configurations were obtained by connecting electrodes across the midline and along each muscle belly. EMGgg activity was simultaneously recorded from these 10 configurations at rest and during various respiratory maneuvers. Heterogeneous behavior of the GG was evidenced by 1) the variable presence of phasic EMGgg at rest, which was undetectable in two subjects but evident in 65% of configurations in six subjects and present in all configurations in all subjects during voluntary hyperventilation; 2) a greater amplitude of EMGgg response to pharyngeal square-wave negative pressure in anterior than posterior configurations (14.1 +/- 7.1 vs. 8.5 +/- 5.1% of maximum, P < 0.05); and 3) variable (linear and alinear) relationships between EMGgg and lingual force within and between subjects. We hypothesize that regional differences in density and type of muscle fiber are the most likely sources of heterogeneity in these responses.