Involvement of upper-airway muscles in extrapyramidal disorders. A cause of airflow limitation

To identify the site and cause of airflow limitation in patients with parkinsonism, we tested pulmonary function in 27 patients with extrapyramidal disorders. In 24 patients, an abnormal flow-volume loop contour, showing either regular (18 patients) or irregular (6 patients) flow oscillations, was found. On direct fiberoptic visualization of the upper airway, these oscillations corresponded to either rhythmic (4 to 8 Hz) or irregular involuntary movements of glottic and supraglottic structures. Ten patients had physiologic evidence of upper-airway obstruction, which was symptomatic in four. We conclude that the upper-airway musculature is frequently involved in extrapyramidal disorders. This causes upper-airway dysfunction that can be severe enough to limit airflow.     

Effect of body posture on dynamic lung functions in young non-obese Indian subjects

Flow volume loop and its various indices can be used to diagnose UAO. Change in posture from sitting to horizontal position per se causes a decrease in effort dependent inspiratory and expiratory flow rates but no significant change in upper airway obstruction indices. Thus, measurement of FVL in supine posture may be used to detect UAO as it may be missed if spirometry is performed in sitting posture.     

Cephalometric analyses and flow-volume loops in obstructive sleep apnea patients

Fifteen patients with obstructive sleep apnea syndrome (OSAS) and 10 controls were studied. Polygraphic monitoring during sleep confirmed the presence or absence of OSAS. Ten OSAS patients and five controls had cephalometric analysis and 12 OSAS patients and five controls had a flow-volume loop study during wakefulness. Seven OSAS patients were submitted to both analyses. Flow-volume loops were unable to detect extrathoracic airway obstruction in six out of 12 OSAS patients. One control was found with positive results. Six out of seven subjects with positive flow-volume loops were overweight (greater than or equal to 30% ideal weight). Cephalograms were very useful in demonstrating mandibular deficiencies in OSAS patients. The length of the soft palate and the position of the hyoid bone, together with the measurement of the posterior airway space, are criteria of great interest in OSAS patients. Cephalometric analysis is recommended in all OSAS patients scheduled for surgical procedure. None of these tests, however, whether alone or in combination, is capable of identifying all cases of OSAS.     

Upper airway EMG responses to acute hypoxia and asphyxia are impaired in streptozotocin-induced diabetic rats

Obstructive sleep apnoea (OSA) is a major clinical disorder that is characterised by multiple episodes of upper airway obstruction due to failure of the upper airway dilator muscles to maintain upper airway patency. The incidence of OSA is high in many endocrine disorders including both insulin-dependent and non-insulin-dependent diabetes but the reasons for this are not known. We wished to test the hypothesis that central respiratory motor output to the upper airway muscles is preferentially impaired in a rat model of diabetes mellitus. Sternohyoid (SH) and diaphragm (DIA) EMG activities were recorded in control and streptozotocin (STZ)-induced diabetic rats during normoxia, hypoxia (7.5% O2 in N2) and asphyxia (7.5% O2 and 3% CO2) under pentobarbitone anaesthesia. SH EMG responses to acute hypoxia and asphyxia were significantly impaired in STZ-induced diabetic rats compared to control animals (+47.1 +/- 5.7 vs. +11.7 +/- 1.9% during hypoxia in control and diabetic animals respectively and +56.5 +/- 7.9 vs. +15.7 +/- 5.0% during asphyxia). However, DIA EMG responses to hypoxia and asphyxia were not different for the two groups. We propose that the higher prevalence of OSA in diabetic patients is related to preferential impairment of cranial motor output to the dilator muscles of the upper airway in response to physiological stimuli.     

Severe upper airway obstruction during sleep

Few disorders may manifest with predominantly sleep-related obstructive breathing. Obstructive sleep apnea (OSA) is a common disorder, varies in severity and is associated with significant cardiovascular and neurocognitive morbidity. It is estimated that between 8 and 18 million people in the United States have at least mild OSA. Although the exact mechanism of OSA is not well-delineated, multiple factors contribute to the development of upper airway obstruction and include anatomic, mechanical, neurologic, and inflammatory changes in the pharynx. OSA may occur concomitantly with asthma. Approximately 74% of asthmatics experience nocturnal symptoms of airflow obstruction secondary to reactive airways disease. Similar cytokine, chemokine, and histologic changes are seen in both disorders. Sleep deprivation, chronic upper airway edema, and inflammation associated with OSA may further exacerbate nocturnal asthma symptoms. Allergic rhinitis may contribute to both OSA and asthma. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA. Treatment with CPAP therapy has also been shown to improve both daytime and nighttime peak expiratory flow rates in patients with concomitant OSA and asthma. It is important for allergists to be aware of how OSA may complicate diagnosis and treatment of asthma and allergic rhinitis. A thorough sleep history and high clinical suspicion for OSA is indicated, particularly in asthma patients who are refractory to standard medication treatments.     

上气道梗阻的肺功能评价

测定了30例上气道梗阻(UAO)的肺功能改变,结果显示胸内型UAO以呼气相早中期流速受限明显,而胸外型UAO以吸气相流速受限尤著,固定型则双相流速均明显受限,肺功能对UAO的评价应按不同类型分别判断,本文并提出了诊断标准,UAO患者的支气管扩张试验阴性,若上气道梗阻得到解除后,反映阻塞性障碍的肺功能指标应得到相应的改善。     

Non-invasive system for applying airway obstructions to model obstructive sleep apnea in mice

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstructions during sleep. The most common animal model of OSA is based on subjecting rodents to intermittent hypoxic exposures and does not mimic important OSA features, such as recurrent hypercapnia and increased inspiratory efforts. To circumvent some of these issues, a novel murine model involving non-invasive application of recurrent airway obstructions was developed. An electronically controlled airbag system is placed in front of the mouse's snout, whereby inflating the airbag leads to obstructed breathing and spontaneous breathing occurs with the airbag deflated. The device was tested on 29 anesthetized mice by measuring inspiratory effort and arterial oxygen saturation (SaO₂). Application of recurrent obstructive apneas (6 s each, 120/h) for 6 h resulted in SaO₂ oscillations to values reaching 84.4 ± 2.5% nadir, with swings mimicking OSA patients. This novel system, capable of applying controlled recurrent airway obstructions in mice, is an easy-to-use tool for investigating pertinent aspects of OSA.     

Obstructive sleep apnoea and upper airway reactivity

Upper airway reactivity was measured in 13 patients with obstructive sleep apnoea (OSA), using transient reflex laryngeal closure in response to dilute inhaled ammonia vapour. Upper airway reactivity was measured before and after 3 months of treatment with nasal continuous positive airway pressure (CPAP). Upper airway reactivity decreased significantly after treatment with nasal CPAP to values which were similar to those seen in normal subjects. We hypothesise that patients with OSA have increased upper airway reactivity, secondary to inflammation of the epithelial lining of the upper airway following the repeated injury of nocturnal airway obstruction, allowing the facilitated passage of inhaled irritants to the subepithelial receptors. Treatment of OSA with nasal CPAP may reverse these changes, although in the absence of a control group, these findings are provisional.     

Upper airway collapsibility evaluated by a negative expiratory pressure test in severe obstructive sleep apnea

OBJECTIVES:

To investigate the usefulness of measuring upper airway collapsibility with a negative expiratory pressure application as a screening test for severe obstructive sleep apnea (OSA).

INTRODUCTION:

OSA is a risk factor for cardiovascular disease, and it may have serious consequences. Its recognition may have important implications during the perioperative period. Increased upper airway collapsibility is one of the main determinants of OSA, and its evaluation could be useful for identifying this condition.

METHODS:

Severe OSA and normal subjects (24 in each group) were matched by body mass index and referred to our sleep laboratory. The subjects were enrolled in an overnight sleep study, and a diurnal negative expiratory pressure test was performed. Flow drop (ΔV̇) and expiratory volume were measured in the first 0.2 s (V_0.2) of the negative expiratory pressure test.

RESULTS:

ΔV̇ and V_0.2 (%) values were statistically different between normal and OSA subjects. OSA patients showed a greater decrease in flow than normal subjects. In addition, severely OSA patients exhaled during the first 0.2 s of the negative expiratory pressure application was an average of only 11.2% of the inspired volume compared to 34.2% for the normal subjects. Analysis of the receiver operating characteristics showed that V_0.2 (%) and ΔV̇ could accurately identify severe OSA in subjects with sensitivities of 95.8% and 91.7%, respectively, and specificities of 95.8% and 91.7%, respectively.

CONCLUSIONS:

V_0.2 (%) and ΔV̇ are highly accurate parameters for detecting severe OSA. The pharyngeal collapsibility measurement, which uses negative expiratory pressure during wakefulness, is predictive of collapsibility during sleep.     

Nasal continuous positive airway pressure changes blood pressure "non-dippers" to "dippers" in patients with obstructive sleep apnea

To evaluate the circadian pattern of blood pressure (BP) and the effects of nasal continuous positive airway pressure (CPAP) on patients with obstructive sleep apnea (OSA), we examined 24-hour BP in 38 male OSA patients with and without nasal CPAP. We measured the BP at 30-min intervals during daytime (800 to 2200) and nighttime (2200 to 800) hours. A "dipper" was defined as a patient who showed an average reduction of at least 10 mm Hg systolic and 5 mm Hg diastolic between daytime and nighttime values. The subjects were predominantly "non-dipper" (22 of 38 patients, 58%). Daytime hypertension (>160/95 mm Hg) was present in 11 of 38 patients (4 "dippers" and 7 "non-dippers"). After nasal CPAP treatment for 3 days, the average BP decreased significantly during the day and night in all subjects (p<0.05). Fifteen of 22 subjects who were "non-dippers" before treatment reversed to become "dippers." And daytime hypertension was detected in only 5 of these patients during nasal CPAP treatment (4 "dippers" and 1 "non-dipper"). These results showed that the "non-dipper" status was common in patients with OSA, and that nasal CPAP restored the normal circadian "dipper" pattern. We suggest that nasal CPAP may contribute to an improved prognosis in patients with OSA because of a reduction in cardiovascular risk factors in "non-dipper" with severe OSA.     

Ten years experience of the sleep laboratory at the Institute of Tuberculosis and Lung Disease in Warsaw

Between 1991-2000 2052 patients (81% men and 19% women) were referred to our Sleep Laboratory because of OSA suspision. In 1194 (58%) subjects (88% men and 12% women) diagnosis of obstructive sleep apnoea (OSA, AHI > 10) was confirmed. In 430 of them (36%) mild OSA (AHI 11-25), in 243 (20%) moderate OSA (AHI 26-40), and in 521 (44%) severe OSA (AHI > 40) was diagnosed. Epworth sleepiness scale score in those groups was 10.4, 10.5 and 13.0 points respectively. 908 (76%) of patients with OSA were submitted to nCPAP treatment. Effective CPAP pressure ranged from 5 to 20 milibars, mean 8.4 mbars. In 21 patients upper airway resistance syndrome (UARS) was diagnosed. Central sleep apnoea, most frequently of Cheyne-Stokes respiration type was diagnosed in 13 patients. The most common diseases accompanying OSA were: systemic hypertension (46%), coronary heart disease (29%), diabetes (12%), and COPD (9%). Majority of OSA patients (61%) were obese (BMI > 30 kg/m2), 32% were over weight (BMI 25-30 kg/m2). Only 7% had normal body weight (BMI 20-25 kg/m2). Long-term (more than one year) compliance to treatment was found in 70% of patients prescribed CPAP.     

The cholinergic system may play a role in the pathophysiology of residual excessive sleepiness in patients with obstructive sleep apnea

Obstructive sleep apnea (OSA) is a prevalent condition characterized by momentary cessations in breathing during sleep due to intermittent obstruction of the upper airway. OSA has been frequently associated with a number of medical comorbidities. CPAP (continuous positive airway pressure) is the gold standard treatment and is known to improve OSA symptoms, including excessive sleepiness. However, 12–14% of CPAP-treated patients continue to complain of sleepiness despite normalization of ventilation during sleep, and 6% after exclusion of other causes of EDS. This is of great concern because EDS is strongly associated with systemic health disorders, lower work performance, and a high risk of accidents. We hypothesized that decreased central cholinergic activity plays a role in the pathophysiology of residual excessive sleepiness in patients with OSA treated with CPAP. Acetylcholine (Ach) plays a large role in wakefulness physiology, and its levels are reduced in sleepiness. Herein, we discuss the potential role of the cholinergic system in this new clinical condition.     

Pattern of snoring in obstructive sleep apnea patients and in heavy snorers.

We measured respiratory mechanical characteristics during sleep in five heavy, nonapneic snorers (HS) and in five obstructive sleep apnea (OSA) patients. In two HS and in two OSA patients we obtained lateral pharyngeal cineradiographic images during sleep while snoring. Flow limitation preceded all snores in both HS and OSA. Pattern of snoring, hysteresis and temporal relationship between supraglottic pressure (Psg) and flow rate were different in HS and OSA. Maximal flow during snoring was less (p less than 0.05) in OSA (0.18 +/- 0.07 liter/second) than in HS (0.36 +/- 0.06 liter/second). Linear supraglottic resistance during inspiratory snoring was higher, though not significantly, in OSA patients (7.11 +/- 3.01 cm H2O/liter/second) than in HS (4.80 +/- 2.83 cm H2O/liter/second). We conclude that: 1) Snoring is characterized by high frequency oscillations of the soft palate, pharyngeal walls, epiglottis and tongue. 2) Flow limitation appears to be a sine qua non for snoring during sleep. 3) The pattern of snoring is different in OSA and HS. 4) Pharyngeal size during snoring is probably larger in HS than in OSA patients.     

Sleep apnea is associated with bronchial inflammation and continuous positive airway pressure-induced airway hyperresponsiveness

BACKGROUND: Obstructive sleep apnea syndrome (OSA) is associated with systemic and upper airway inflammation. Pharyngeal inflammation has a potential role in upper airway collapse, whereas systemic inflammation relates to cardiovascular morbidity. However, the presence of an inflammatory involvement of lower airway has been poorly investigated. OBJECTIVE: The aim of the study was to demonstrate an inflammatory process at the bronchial level in patients with OSA and to analyze effects of continuous positive airway pressure (CPAP) application and humidification on bronchial mucosa. METHODS: The study was conducted by using sequential induced sputum for cell analysis and IL-8 production, nitric oxide exhalation measurement, and methacholine challenge before and after CPAP. RESULTS: Bronchial neutrophilia and a high IL-8 concentration were observed in untreated OSA compared with controls (75% +/- 20% vs 43% +/- 12%, P < .05; and 25.02 +/- 9.43 ng/mL vs 8.6 +/- 3.7 ng/mL, P < .001, respectively). IL-8 in sputum supernatant was correlated to apnea hypopnea index (P < .01; r = 0.81). After 1 month of CPAP, this inflammatory pattern remained unchanged, and an increase in airway hyperresponsiveness (AHR) was observed (P < .001). CONCLUSION: Obstructive sleep apnea syndrome is associated with bronchial inflammation. Our data demonstrate CPAP effect on the development of AHR, possibly facilitated by the pre-existing inflammation. Both issues should be evaluated during long-term CPAP use. CLINICAL IMPLICATIONS: Results showing a spontaneous bronchial inflammation in OSA and the development of a CPAP-related AHR require a long-term follow-up to evaluate consequences on chronic bronchial obstruction.     

Surgical modifications of the upper airway for obstructive sleep apnea in adults: a systematic review and meta-analysis

A substantial portion of patients with obstructive sleep apnea (OSA) seek alternatives to positive airway pressure (PAP), the usual first-line treatment for the disorder. One option is upper airway surgery. As an adjunct to the American Academy of Sleep Medicine (AASM) Standards of Practice paper, we conducted a systematic review and meta-analysis of literature reporting outcomes following various upper airway surgeries for the treatment of OSA in adults, including maxillomandibular advancement (MMA), pharyngeal surgeries such as uvulopharyngopalatoplasty (UPPP), laser assisted uvulopalatoplasty (LAUP), and radiofrequency ablation (RFA), as well as multi-level and multi-phased procedures. We found that the published literature is comprised primarily of case series, with few controlled trials and varying approaches to pre-operative evaluation and post-operative follow-up. We include surgical morbidity and adverse events where reported but these were not systematically analyzed. Utilizing the ratio of means method, we used the change in the apnea-hypopnea index (AHI) as the primary measure of efficacy. Substantial and consistent reductions in the AHI were observed following MMA; adverse events were uncommonly reported. Outcomes following pharyngeal surgeries were less consistent; adverse events were reported more commonly. Papers describing positive outcomes associated with newer pharyngeal techniques and multi-level procedures performed in small samples of patients appear promising. Further research is needed to better clarify patient selection, as well as efficacy and safety of upper airway surgery in those with OSA.     

Does episodic hypoxia affect upper airway dilator muscle function? Implications for the pathophysiology of obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is characterised by repetitive collapse of the upper airway during sleep owing to a sleep-related decrement in upper airway muscle activity with consequent failure of the pharyngeal dilator muscles to oppose the collapsing pressure that is generated by the diaphragm and accessory muscles during inspiration. The causes of upper airway obstruction during sleep are multi-factorial but there is evidence implicating intrinsic upper airway muscle function and impaired central regulation of the upper airway muscles in the pathophysiology of OSA. The condition is associated with episodic hypoxia due to recurrent apnoea. However, despite its obvious importance very little is known about the effects of episodic hypoxia on upper airway muscle function. In this review, we examine the evidence that chronic intermittent hypoxia can affect upper airway muscle structure and function and impair CNS control of the pharyngeal dilator muscles. We review the literature and discuss results from our laboratory showing that episodic hypoxia/asphyxia reduces upper airway muscle endurance and selectively impairs pharyngeal dilator EMG responses to physiological stimulation. Our observations lead us to speculate that episodic hypoxia--a consequence of periodic airway occlusion--is responsible for progression of OSA through impairment of the neural control systems that regulate upper airway patency and through altered respiratory muscle contractile function, leading to the establishment of a vicious cycle of further airway obstruction and hypoxic insult that chronically exacerbates and perpetuates the condition. We conclude that chronic intermittent hypoxia/asphyxia contributes to the pathophysiology of sleep-disordered breathing.     

Effects of nicotine on rat sternohyoid muscle contractile properties

Obstructive sleep apnoea (OSA) is a major clinical disorder characterised by recurring episodes of pharyngeal collapse during sleep. At present, there remains no satisfactory treatment for OSA. Pharmacological therapies as a potential treatment for the disorder are an attractive option and include agents that increase the contractility of the pharyngeal muscles. The aim of the present study was to examine the effects of nicotine on upper airway muscle contractile properties. In vitro isometric contractile properties were determined using strips of rat sternohyoid muscle in physiological salt solution containing nicotine (0-100 microg/ml) at 25 degrees C. Isometric twitch and tetanic tension, contraction time, half-relaxation time and tension-frequency relationship were determined by electrical field stimulation with platinum electrodes. Fatigue was induced by stimulation at 40 Hz with 300 ms trains at a frequency of 0.5 Hz for 5 min. Nicotine at a concentration of 1 microg/ml was associated with a significant increase in sternohyoid muscle specific tension compared to control data. Dose-dependent increases in contractile tension were not observed. Nicotine had effects on tension-frequency relationship and endurance properties of the sternohyoid muscle at some but not all doses. A leftward shift in the tension-frequency relationship was observed at low stimulus frequencies (20-30 Hz) for nicotine at a concentration of 1 and 5 microg/ml and a significant increase in fatigue resistance was observed with nicotine at a concentration of 10 microg/ml. As fatigue of the upper airway muscles has been implicated in obstructive airway conditions, a pharmacological agent that improves muscle endurance may prove useful as a potential treatment for such disorders. Therefore, further studies of the effects of nicotinic agonists on upper airway function are warranted.     

Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders

Positive airway pressure (PAP) devices are used to treat patients with sleep related breathing disorders (SRBD) including obstructive sleep apnea (OSA). Currently, PAP devices come in three forms: (1) continuous positive airway pressure (CPAP), (2) bilevel positive airway pressure (BPAP), and (3) automatic self-adjusting positive airway pressure (APAP). After a patient is diagnosed with OSA, the current standard of practice involves performing full, attended polysomnography during which positive pressure is adjusted to determine optimal pressure for maintaining airway patency. This titration is used to find a fixed single pressure for subsequent nightly usage. A task force of the Standards of Practice Committee of the American Academy of Sleep Medicine reviewed the available literature. Based on this review, the Standards of Practice Committee developed these practice parameters as a guideline for using CPAP and BPAP appropriately (an earlier review and practice parameters for APAP was published in 2002). Major conclusions and current recommendations are as follows: 1) A diagnosis of OSA must be established by an acceptable method. 2) CPAP is effective for treating OSA. 3) Full-night, attended studies performed in the laboratory are the preferred approach for titration to determine optimal pressure; however, split-night, diagnostic-titration studies are usually adequate. 4) CPAP usage should be monitored objectively to help assure utilization. 5) Initial CPAP follow-up is recommended during the first few weeks to establish utilization pattern and provide remediation if needed. 6) Longer-term follow-up is recommended yearly or as needed to address mask, machine, or usage problems. 7) Heated humidification and a systematic educational program are recommended to improve CPAP utilization. 8) Some functional outcomes such as subjective sleepiness improve with positive pressure treatment in patients with OSA. 9) CPAP and BPAP therapy are safe; side effects and adverse events are mainly minor and reversible. 10) BPAP may be useful in treating some forms of restrictive lung disease or hypoventilation syndromes associated with hypercapnia.     

The length-force relationship of the human genioglossus in patients with obstructive sleep apnea

During sleep, patients with obstructive sleep apnea (OSA) have repetitive episodes of upper airway collapse, which are terminated by increased activity of upper airway dilator muscles. The repetitive activation of the genioglossus (GG) may result in muscle remodeling. We hypothesized that OSA patients have an altered length-force relationship, increased force generation and/or decreased force maintenance as compared with control subjects. The GG length-force relationship was determined in 12 patients with OSA and 12 normal control subjects. The optimum length of the GG (LO) was at a longer muscle length in OSA patients than in control subjects. At longer muscle lengths, OSA patients produced greater percentages of their maximum protrusion force than control subjects. Force maintenance was not significantly different between the two groups. We conclude that in OSA patients relative to normal controls, the length-force relationship of the GG is altered, specifically at longer muscle lengths. We speculate that the GG is remodeled in OSA patients and that this facilitates airway re-opening to terminate obstructive events.     

Effect of Body Posture on Pharyngeal Shape and Size in Adults With and Without Obstructive Sleep Apnea

Study Objectives:

In patients with obstructive sleep apnea (OSA), the severity and frequency of respiratory events is increased in the supine body posture compared with the lateral recumbent posture. The mechanism responsible is not clear but may relate to the effect of posture on upper airway shape and size. This study compared the effect of body posture on upper airway shape and size in individuals with OSA with control subjects matched for age, BMI, and gender.

Participants:

11 males with OSA and 11 age- and BMI-matched male control subjects.

Results:

Anatomical optical coherence tomography was used to scan the upper airway of all subjects while awake and breathing quietly, initially when supine, and then in the lateral recumbent posture. A standard head, neck, and tongue position was maintained during scanning. Airway cross-sectional area (CSA) and anteroposterior (A-P) and lateral diameters were obtained in the oropharyngeal and velopharyngeal regions in both postures. A-P to lateral diameter ratios provided an index of regional airway shape. In equivalent postures, the ratio of A-P to lateral diameter in the velopharynx was similar in OSA and control subjects. In both groups, this ratio was significantly less for the supine than for the lateral recumbent posture. CSA was smaller in OSA subjects than in controls but was unaffected by posture.

Conclusions:

The upper airway changes from a more transversely oriented elliptical shape when supine to a more circular shape when in the lateral recumbent posture but without altering CSA. Increased circularity decreases propensity to tube collapse and may account for the postural dependency of OSA.

Citation:

Walsh JH; Leigh MS; Paduch A; Maddison KJ; Armstrong JJ; Sampson DD; Hillman DR; Eastwood PR. Effect of body posture on pharyngeal shape and size in adults with and without obstructive sleep apnea. SLEEP 2008;31(11):1543–1549.