MEDLINE Abstracts: Treatment of Obstructive Sleep Apnea

December 15, 2003

What's new concerning treatment of obstructive sleep apnea? Find out in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape Pulmonary Medicine.

Wolk R, Shamsuzzaman AS, Somers VK
Hypertension. 2003 Nov 10 [Epub ahead of print]

Obesity has a high and rising prevalence and represents a major public health problem. Obstructive sleep apnea (OSA) is also common, affecting an estimated 15 million Americans, with a prevalence that is probably also rising as a consequence of increasing obesity. Epidemiologic data support a link between obesity and hypertension as well as between OSA and hypertension. For example, untreated OSA predisposes to an increased risk of new hypertension, and treatment of OSA lowers blood pressure, even during the daytime. Possible mechanisms whereby OSA may contribute to hypertension in obese individuals include sympathetic activation, hyperleptinemia, insulin resistance, elevated angiotensin II and aldosterone levels, oxidative and inflammatory stress, endothelial dysfunction, impaired baroreflex function, and perhaps by effects on renal function. The coexistence of OSA and obesity may have more widespread implications for cardiovascular control and dysfunction in obese individuals and may contribute to some of the clustering of abnormalities broadly defined as the metabolic syndrome. From the clinical and therapeutic perspectives, the presence of resistant hypertension and the absence of a nocturnal decrease in blood pressure in obese individuals should prompt the clinician to consider the diagnosis of OSA, especially if clinical symptoms suggestive of OSA (such as poor sleep quality, witnessed apnea, excessive daytime somnolence, and so forth) are also present.

Malow BA, Weatherwax KJ, Chervin RD, et al
Sleep Med. 2003;4:509-515

To determine the effect of treating OSA on seizure frequency in adults and children with epilepsy in a prospective study. Several case series documented an improvement in seizure control with treatment of coexisting OSA, but published series did not sample a clinic population, were not prospective in design, and did not account for concurrent changes in antiepileptic drug (AED) doses or levels. Adult patients and the parents of pediatric patients seen in the University of Michigan Epilepsy and Pediatric Neurology Clinics were given validated questionnaires. Thirteen adults (aged 20-56) and 5 children (aged 14-17) were selected for polysomnography (PSG) based on frequency of seizures and risk for OSA. Seizure frequency was compared during 8-week baseline and treatment phases and AED levels were done to document stability in medication levels. Six of 13 adults and 3 of 5 children met PSG criteria for OSA. Three adults and 1 child were treated with continuous positive airway pressure (CPAP), were tolerant of the device, and had no change in AED doses; all four had at least a 45% reduction in seizure frequency during CPAP treatment. One adult was treated with an oral appliance with a reduction in nocturnal seizures only, and 2 adults and 2 children were intolerant of CPAP. Treatment of OSA in patients with epilepsy may improve seizure control and a large, randomized, placebo-controlled trial appears warranted.

von Kanel R, Dimsdale JE
Chest. 2003;124:1956-1967

Study Objectives: Patients with OSA are at increased risk for coronary artery and cerebrovascular diseases. Numerous studies suggest that a hypercoagulable state is prospectively related to atherothrombotic events. This review explores whether changes in hemostasis may constitute one biological link between OSA and vascular disease.
Design: Ten studies on hemostatic variables in OSA were located by electronic library search and descriptively reviewed. Work on hemostatic function with physiologic conditions similar to those found in OSA (hypoxemia and hyperactivity of the sympathetic nervous system) was considered to discuss potential molecular mechanisms of procoagulant disturbances in OSA.
Measurements and Results: The reviewed data suggest that, as compared to non-OSA control subjects, patients with OSA have elevated plasma fibrinogen levels, exaggerated platelet activity, and reduced fibrinolytic capacity. Although not consistently shown, severity of OSA (ie, apnea-hypopnea index) and plasma epinephrine were independent predictors of platelet activity; and average minimal oxygen saturation was an independent predictor of fibrinogen. In some studies, treatment with CPAP decreased platelet activity, plasma fibrinogen levels, and activity of clotting factor VII.
Conclusions: There is some evidence for a hypercoagulable state in OSA, which might help explain the increased prevalence of vascular diseases in this population. To further confirm such a notion, future studies need to be performed on sufficiently large samples to be able to control for confounders of hemostatic activity. Prospective studies are needed to examine the association between hemostasis molecules and strong vascular end points.

Cahali MB
Laryngoscope. 2003;113:1961-1968

Objective: The role of the lateral pharyngeal muscular walls in the pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS) is crucial. My objective is to describe a surgical procedure for splinting the lateral pharyngeal walls in patients with OSAHS and report the initial results.
Study Design: Prospective, randomized, pilot study performed in an academic tertiary center as part of a doctoral thesis.
Patients and Methods: Ten adults with OSAHS, originally selected for treatment with uvulopalatopharyngoplasty, underwent the lateral pharyngoplasty procedure, which consists of a microdissection of the superior pharyngeal constrictor muscle within the tonsillar fossa, sectioning of this muscle, and suturing of the created laterally based flap of that muscle to the same-side palatoglossus muscle. In addition, a palatopharyngeal Z-plasty is performed to prevent retropalatal collapse.
Results: Lateral pharyngoplasty improved sleep and daytime symptoms related to OSAHS. After at least 6 months of follow-up, the median apnea-hypopnea index decreased from 41.2 to 9.5 (P =.009) and the median total sleep time spent in rapid eye movement (REM) sleep and in stages 3 plus 4 non-REM sleep increased from 14.1% to 22.1% (P =.059) and from 5.3% to 16.3% (P =.037), respectively. Also, there was statistically significant improvement in snoring, daytime sleepiness, and overall impact of the disease on quality of life. Swallowing disturbances lasted a median of 14.5 days after the surgeries, and all patients returned to normal subjective swallowing function in the follow-up.
Conclusions: Lateral pharyngoplasty is a safe and straightforward approach to lateral pharyngeal muscles and has produced appreciable benefits for OSAHS patients.

Mansfield DR, Gollogly NC, Kaye DM, Richardson M, Bergin P, Naughton MT
Am J Respir Crit Care Med. 2003 Nov 3 [Epub ahead of print]

OSA is highly prevalent among patients with congestive heart failure and may contribute to progression of cardiac dysfunction via hypoxia, elevated sympathetic nervous system activity, and systemic hypertension. Our aim was to assess the long-term effect of obstructive sleep apnea treatment with nocturnal CPAP on systolic heart function, sympathetic activity, blood pressure, and quality of life in patients with congestive heart failure. Fifty-five patients with congestive heart failure and OSA were randomized to 3 months of CPAP or control groups. End-points were changes in left ventricular ejection fraction, overnight urinary norepinephrine excretion, blood pressure, and quality of life. Nineteen patients in the CPAP group and 21 control subjects completed the study. Compared with the control group, CPAP treatment was associated with significant improvements in left ventricular ejection fraction (Delta 1.5 ± 1.4 vs 5.0 ± 1.0% respectively, P = .04), reductions in overnight urinary norepinephrine excretion (Delta 1.6 ± 3.7 vs -9.9 ± 3.6 nmol/mmol creatinine, P = .036), and improvements in quality of life. There were no significant changes in systemic blood pressure. In conclusion, treatment of OSA among patients with congestive heart failure leads to improvement in cardiac function, sympathetic activity, and quality of life.

Kao YH, Shnayder Y, Lee KC
Otolaryngol Head Neck Surg. 2003;129:327-335

Objective: Most reports in the literature focus on the efficacy of a single procedure for OSA. We review the overall efficacy of a surgical methodology based on localizing the level of anatomic obstruction for each patient and surgical correction of the nasal, oropharyngeal, or hypopharyngeal obstruction.
Study Design and Setting: Retrospective review of cases performed by a single practitioner using a systematic approach to surgery for OSA with preoperative and postoperative sleep studies.
Results: Forty-two patients with a respiratory disturbance index (RDI) greater than 15 were included in the study. Surgery involved at least 2 levels of obstruction usually performed in 2 stages. All patients reported symptomatic improvement. Overall, 83.3% (35 of 42) of patients were cured according to the accepted RDI criteria of more than 50% reduction and final RDI of less than 20. All 21 patients with mild OSA (RDI, <29), 73% of patients with moderate OSA (RDI, 30 to 49), and 50% of patients with severe OSA (RDI, >50) were cured.
Conclusion: The use of an anatomically based methodology in approaching patients with OSA seems to offer a higher efficacy than a single procedure as reported in the literature.

Qureshi A, Ballard RD
J Allergy Clin Immunol. 2003;112:643-651; quiz 652

OSA is an increasingly well-recognized disease characterized by periodic collapse of the upper airway during sleep. This leads to either complete or partial obstruction of the airway, resulting in apneas, hypopneas, or both. This disorder causes daytime somnolence, neurocognitive defects, and depression. It affects almost every system in the body, resulting in an increased incidence of hypertension, cardiovascular disease, stroke, pulmonary hypertension, cardiac arrhythmias, and altered immune function. It also increases the risk of having an accident, presumably as a result of associated somnolence. The gold standard for the diagnosis of OSA is an overnight polysomnogram. Split-night studies are becoming increasingly common and allow for quicker implementation of therapy at a reduced cost. Treatment options for OSA include weight loss, positional therapy, oral devices, CPAP, and upper airway surgery. CPAP is the most efficacious and widely used therapy. Its complications include nasal congestion or dryness, mask discomfort, and claustrophobia. Heated humidifiers, newer types of masks, and nasal steroids have improved tolerance of this therapy. Bilevel positive-pressure therapy can be considered for patients who find it difficult to exhale against the consistently increased pressure of CPAP. The disease requires aggressive treatment to improve quality of life and prevent its complications.

Bonekat HW, Hardin KA
Clin Rev Allergy Immunol. 2003;25:191-210

Few disorders may manifest with predominantly sleep-related obstructive breathing. 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. 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.

Umlauf MG, Chasens ER
Sleep Med Rev. 2003;7:403-411

Although nocturnal voiding is frequently attributed to urologic disorders, nocturia and enuresis are also important symptoms of sleep-disordered breathing. However, polyuria can be elicited by OSA as well as bedrest, microgravity, and other experimental conditions where the blood volume is shifted centrally to the upper body. The nocturnal polyuria of OSA is an evoked response to conditions of negative intrathoracic pressure due to inspiratory effort posed against a closed airway. The mechanism for this natriuretic response is the release of atrial natriuretic peptide due to cardiac distension caused by the negative pressure environment. This cardiac hormone increases sodium and water excretion and also inhibits other hormone systems that regulate fluid volume, vasopressin, and the rennin-angiotensin-aldosterone complex. Treatment of OSA and airway compromise has been shown to reverse nocturnal polyuria and thereby reduce or eliminate nocturia and enuresis. Thus, careful evaluation of nocturia and enuresis for evidence of nocturnal polyuria can increase the diagnostic certainty of referring primary care providers and sleep specialists. In addition, the resolution of these bothersome symptoms after treatment can contribute to patient satisfaction as well as reinforce treatment compliance.

Rodway GW, Sanders MH
Sleep Med Rev. 2003;7:391-401

Positive airway pressure (PAP) therapy is the most commonly used medical modality to reverse the apneas, hypopneas, and inspiratory flow-limited breaths that result in the oxyhemoglobin desaturation, altered sleep architecture, and daytime sleepiness representing the cardinal features of OSA/hypopnea (OSA/H). Identifying optimal strategies to develop the initial positive airway prescription is of paramount importance to clinicians who evaluate patients with suspected OSA/H. In addition, with the growing appreciation of the clinical and physiologic importance of sleep-disordered breathing, there have been increasing demands on clinical resources to diagnose and treat these patients. The time, hardware, and personnel-intensive nature of in-laboratory polysomnography (PSG) are significant in light of the traditional paradigm that utilizes a full night PSG for a diagnostic evaluation and when indicated, another full night for PAP titration. Efforts to identify time and resource-conserving alternatives to this paradigm have focused on in-laboratory split-night studies, in which the diagnosis of OSA/H can be made, and a positive pressure prescription defined during a single overnight PSG. Case-control studies indicate that, when certain guidelines are applied, split-night PSGs result in prescription efficacy and patient adherence, which are comparable to the traditional two-night strategy. However, prospective, randomized trials designed with adequate power are required to further define the impact of a split-night strategy on clinical outcome. As more information becomes available regarding the factors that determine long-term adherence to positive pressure therapy, the potential for efficient, expeditious treatment, and cost savings with split-night sleep studies will likely receive greater attention.

Weaver TE, Maislin G, Dinges DF, et al
Sleep. 2003;26:727-732

Study Objectives: The purpose of this study was to evaluate the Self-Efficacy Measure for Sleep Apnea (SEMSA) designed to assess adherence-related cognitions.
Design: Subjects completed the questionnaire prior to the initiation of CPAP treatment. Test-retest reliability of the instrument was evaluated by having a subset of subjects complete the SEMSA a second time at home, 1 week later, returning the questionnaire by mail.
Patients: A total of 213 subjects with newly diagnosed OSA were recruited from the clinic populations of 2 sleep disorders centers.
Measurements and Results: Content validity was confirmed by a panel of expert judges. Confirmatory factor analysis validated the 3 a priori sub-scales: risk perception, outcome expectancies, and treatment self-efficacy. The internal consistency of the total instrument was 0.92. Test-retest reliability coefficients (N = 20) were estimated to be 0.68, P = .001, for Perceived Risk; 0.77, P > .0001, for Outcome Expectancies; and 0.71, P = .0005, for the Treatment Self-Efficacy subscale. Subject responses indicated that approximately half of the subjects did not perceive problems with concentration, sexual performance, sleepy driving, or an accident as related to OSA. More than 60% of the subjects acknowledged most of the benefits of CPAP presented to them, but only 53% associated CPAP use with enhanced sexual performance. Frequently identified barriers to treatment use were nasal stuffiness, claustrophobia, and disturbing bed partner sleep.
Conclusion: These findings indicate that the SEMSA has strong psychometric properties and has the potential for identifying patient perceptions that may indicate those most likely to not adhere to treatment.

Fransson AM, Tegelberg A, Leissner L, Wenneberg B, Isacsson G
Sleep Breath. 2003;7:131-142

Objectives: To evaluate subjective discomfort and somnographic measures of patients with OSA and snoring problems who had been treated for 2 years with a mandibular protruding device (MPD).
Methods: The study population comprised 65 patients with a pretreatment diagnosis of OSA (n = 44) or habitual snoring without apnea (n = 21). After a baseline medical and somnographic examination, a functional examination of the stomatognathic system, and a questionnaire focused on sleep-related qualities, each patient received an MPD. Two follow-ups were made 6 months and 2 years after MPD treatment had been initiated, and all initial examinations were repeated.
Results: At the 2-year follow-up, significant subjective improvements were registered in 90% of the patients regarding a reduction of snoring and apneas, in 76% regarding a reduction in daytime tiredness, and in 84% regarding an improvement in the quality of the night sleep (change of ≥ 50% from baseline data). At the 2-year follow-up of the OSA group, the oxygen desaturation index (ODI) had dropped significantly from a mean value of 14.7 (SD, 12.7) to 3.1 (SD, 4.2) (P < .001), and the mean SaO2 nadir rose from 78.2% (SD, 8.1) to 89.0% (SD, 4.7) (P < .001). Only one of the snorers increased his ODI value; the others retained their initial healthy values. The OSA patients significantly reduced the amount of time they snored during their sleep.
Conclusion: MPD treatment is associated with a significant reduction in subjective complaints such as disturbing snoring, apneas, daytime tiredness, and poor quality of night sleep, and with a significant reduction in ODI values in the OSA group. In addition, favorable 6-month results were unchanged after 2 years.

Walker-Engstrom ML, Ringqvist I, Vestling O, Wilhelmsson B, Tegelberg A
Sleep Breath. 2003;7:119-130

The objective of this study was to compare the effect of 2 different degrees of mandibular advancement (MA), 75% versus 50%, on somnographic variables after 6 months of dental appliance treatment in patients with severe OSA. A further purpose was to compare the number of adverse events on the stomatognathic system and the effects of dental appliance treatment on the presence of daytime sleepiness. Eighty-six males with severe OSA (apnea index ≥ 20) were randomly allocated to either 75% or 50% MA. Forty patients in the 75% MA group and 37 patients in the 50% MA group completed the 6-month follow-up. The effectiveness of treatment in terms of normalization (apnea index < 5 and apnea/hypopnea index < 10) with 75% MA was 52%, which was significantly higher (P = .04) than the 31% achieved with 50% MA. The dental appliance had few adverse events on the stomatognathic system regardless of group, and the number of adverse events did not differ between the 2 groups. Finally, the mean value of Epworth Sleepiness Scale scores decreased significantly from 11.6 at baseline to 8.0 at follow-up (P < .001). No significant difference was observed between the 2 groups. The results indicate that a dental appliance could be an alternative treatment for some patients with severe OSA.

Dinges DF, Weaver TE
Sleep Med. 2003;4:393-402

Background: Some patients with OSA/hypopnea syndrome (HS) who are regular users of nasal continuous positive airway pressure (nCPAP) therapy continue to experience daytime sleepiness that impairs performance and quality of life. A randomized, double-blind, placebo-controlled, parallel-group study was conducted to determine the effect of modafinil on sustained attention performance and functional quality of life in OSA/HS patients with residual daytime sleepiness, who were regular users of nCPAP therapy.
Methods: Seventy-seven patients received modafinil (200 mg/day, week 1; 400 mg/day, weeks 2-4) and 80 patients received matching placebo once daily for 4 weeks. Sustained attention performance on the psychomotor vigilance task (PVT) and functional status and quality of life using the Functional Outcomes of Sleep Questionnaire (FOSQ) were measured.
Results: The frequency of lapses of attention during PVT performance was significantly decreased, and both the median and slowest reaction times were significantly improved in patients receiving nCPAP plus modafinil compared with those receiving nCPAP plus placebo (P = .010 for the number of lapses [transformed], P = .023 for the median reaction time, and P = .014 for the reciprocal of the 10% slowest reaction times). Treatment with nCPAP plus modafinil significantly improved the FOSQ total score (weeks 1 and 4), the vigilance subscale score (weeks 1 and 4), and the activity level subscale score (week 4) compared with treatment with nCPAP plus placebo (all P < .05).
Conclusions: Consistent with previous results for objective and subjective measures of sleepiness, modafinil used adjunctively improved performance on a test of behavioral alertness and reduced functional impairments in patients with OSA/HS who were regular users of nCPAP therapy but were still experiencing sleepiness.

Faber CE, Grymer L, Hjorth T
Rhinology. 2003;41:175-181

The aim of this study was to determine the severity of side effects and the influence on snoring and the AHI (apnea-hypopnoea index = number of apneas and hypopneas per hour recording) of an anterior mandibular positioning device (AMP device) for treatment of snoring and OSA. Questionnaires were mailed to a consecutive series of 30 patients who had started treatment with an AMP device. The mean follow-up interval from receiving an AMP device to answering the questionnaire was 22 months. The perceived degree of sore teeth increased statistically significantly (P < .01) as a result of the AMP device treatment, but there was no increase in the degree of facial pain, salivation, or temporomandibular joint pain. The AMP device treatment resulted in a statistically significant reduction (P < .01) of the mean AHI and of the mean percentage of the recording time with loud snoring (P < .05). Twenty-two patients out of 30 were still using the device at the time of follow-up. In conclusion, AMP device treatment was associated with only mild side effects and resulted in a statistically significant reduction of the AHI and of the percentage of the recording time with loud snoring.

Khanna R, Kline LR
Sleep Med. 2003;4:333-338

Objective: To compare efficacy, compliance rates, and side effects of a new strapless oral interface, the Oracle, with available nasal masks over 8 weeks of use for the treatment of obstructive sleep apnea hypopnea syndrome (OSAHS).
Methods: A total of 38 patients with OSAHS (respiratory disturbance index [RDI] ≥ 15/h) were enrolled after the diagnostic polysomnogram for subsequent CPAP therapy. After randomization, therapeutic pressures during a titration study were determined for 21 patients in the oral group and 17 patients in the nasal group. Comparisons for nasal and oral interfaces were made for baseline patient characteristics, average hours of CPAP use, side effects from therapy, and among questionnaires evaluating patients' subjective responses to therapy at months 1 and 2.
Results: No significant difference was observed in the average hours of CPAP use between the oral (4.5 ± 2.1; 5.5 ± 2.6) and nasal groups (4.0 ± 2.6; 4.8 ± 2.5) for either month 1 or 2 (P > .05). The dropout rates were similar for both groups after 8 weeks of therapy. However, patients in the nasal group had higher occurrences of side effects such as nasal congestion, dryness, and air leaks; whereas patients in the oral group experienced more oral dryness and gum pain.
Conclusion: Oral delivery of CPAP with the Oracle is an effective and suitable alternative for patients with OSAHS.

Boeve BF, Silber MH, Ferman TJ
Sleep Med. 2003;4:281-284

Objective: To describe the treatment response with melatonin for REM sleep behavior disorder (RBD) associated with other neurologic disorders.
Background: Clonazepam has been considered the treatment of choice for RBD. However, an alternative treatment is desirable for those with RBD refractory to clonazepam, for those who experience intolerable side-effects with clonazepam, and for those in whom clonazepam precipitates or aggravates OSA. To date, there is minimal published data and limited follow-up regarding the use of melatonin for patients with RBD associated with other neurologic syndromes and disorders.
Design/Methods: The response to melatonin treatment for RBD was reviewed on consecutive patients the investigators treated with this agent at Mayo Clinic Rochester from January 2000 to June 2001. The coexisting neurologic disorders, reasons for using melatonin, effective doses, side-effects, and duration of follow-up were also reviewed on all patients.
Results: Fourteen patients were commenced on melatonin over the specified time period (13 male, median RBD onset age 56 years, range 20-77 years). The coexisting neurologic findings/disorders were dementia with Lewy bodies (n = 7), mild cognitive impairment with mild parkinsonism (n = 2), multiple system atrophy (n = 2), narcolepsy (n = 2), and Parkinson's disease (n = 1). The reasons for using melatonin in these cases were incomplete response of RBD to clonazepam in 6 patients, existing cognitive impairment in 5, intolerable side-effects with clonazepam in 2, and presence of severe OSA and narcolepsy in one. With 7 patients continuing to use clonazepam at 0.5-1.0 mg/night, RBD was controlled in 6 patients, significantly improved in 4, and initially improved but subsequently returned in 2; no improvement occurred in 1 patient and increased RBD frequency/severity occurred in 1 patient. The effective melatonin doses were 3 mg in 2 cases, 6 mg in seven cases, 9 mg in one case, and 12 mg in two cases. Five patients reported side-effects, which included morning headaches (2), morning sleepiness (2), and delusions/hallucinations (1); these symptoms resolved with decreased dosage. The mean duration of follow-up was 14 months (range 9-25 months), with 8 patients experiencing continued benefit with melatonin beyond 12 months of therapy.
Conclusions: In this series, persistent benefit with melatonin beyond 1 year of therapy occurred in most but not all patients. Melatonin can be considered as a possible sole or add-on therapy in select patients with RBD. Prospective, long-term, controlled trials with melatonin are warranted in a larger number of patients with RBD associated with a variety of neurologic symptoms and disorders.


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