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Sleep apnea & automobile crashes.

BACKGROUND: As a group, patients with obstructive sleep apnea (OSA) are at increased risk of having automobile accidents. Previous studies using actual accident data have used only small numbers of subjects. OBJECTIVE: To determine the rate of automobile accidents in a large population of OSA patients using objective data from the Ministry of Transportation of Ontario (MTO). DESIGN: Retrospective study SETTING: Academic sleep disorders clinic and laboratory. PARTICIPANTS: All cases of OSA polygraphically confirmed between June 1990 and June 1994. INTERVENTIONS: Cases of OSA were a priori divided into groups based on apnea-hypopnea index (AHI): (OSA1 - AHI 10-25, OSA2 - AHI 26-40, OSA3 - AHI>40) and driving records were obtained from the MTO. Age and sex matched controls were selected at random from drivers in the MTO driver database who hold passenger vehicle licences. Analysis was restricted to drivers with the same licence class. MAIN OUTCOME MEASURES: Primary outcome measure was accidents in the five years preceding diagnosis. Secondary outcome was citations during the same period. RESULTS: There were 155 of 460 OSA patients with one or more accidents compared with 150 of 581 Controls for the same time period (x2=7.7,p<0.01). The rate of accidents/year, for the preceding five years, was 0.07+/-0.14 for Controls versus 0.09+/-0.14 for OSA (p <0.05). This difference could all be accounted for by increased accident rate in OSA patients with the highest AHI (OSA3) (MVA/yr: 0.11+/-0.15, 0.08+/-0.12, 0.06+/-0.14 for OSA groups 3,2,1 respectively) as there was no differences among Control, OSA1 and OSA2 accident rates. OSA patients had twice as many citations as Controls (1.74+/-2.13 vs 0.86+/-1.43 p<0.001) although the types of citation were the same. CONCLUSIONS: Increased automobile accidents in OSA may be restricted to cases with more severe apnea (AHI >40). Despite the large sample size (an order of magnitude greater than previous reports using accident data) further study is needed with even larger numbers, including more measures of disease severity and rigorously controlling for driving exposure.

Accidents, Traffic↗

Procedural skill learning in obstructive sleep apnea syndrome.

STUDY OBJECTIVES: To better characterize the cognitive deficits observed in obstructive sleep apnea syndrome (OSAS) by examining procedural skill learning abilities. DESIGN: Procedural skill learning was assessed using Mirror Tracing and Rotary Pursuit skill learning tasks. Subjects also completed a comprehensive neuropsychological test battery. SETTING: Cognitive testing was performed during the day following the second of two consecutive nights during which sleep and respiratory variables were recorded. PARTICIPANTS: Two groups (28 OSAS patients and 18 normal controls) with equivalent mean age and education levels. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: No significant differences in learning rates were observed between the groups on the Rotary Pursuit Task. On the Mirror Tracing Task, overall learning of the skill and transfer to a new figure or to the reverse tracing direction was similar in the OSAS and NC groups. However, there was a subgroup of OSAS subjects (n=11) who showed marked difficulties in the initial acquisition of the Mirror Tracing Task. This subgroup's performance was no longer significantly different from that of controls and OSAS subjects without initial adaptation difficulty in the subsequent trials. Performance of subjects who had difficulty with initial adaptation on the Mirror Tracing was also significantly lower on tests of frontal executive function, but not on episodic memory tests. Sleep and respiratory variables did not distinguish between the two subgroups of OSAS patients. However, none of the young OSAS subjects (<40 years) presented this deficit. CONCLUSION: Results indicate that contrary to this study's hypothesis, OSAS patients did not show procedural skill learning deficits. A subgroup of OSAS patients, however, did show deficits in initial skill adaptation and difficulties on other neuropsychological tests. Frontal dysfunction and decrement in psychomotor efficiency and vigilance appeared to be the most consistent explanation for characterizing the profile of neuropsychological test results among the OSAS patients.

Adult↗

Evidence for lipid peroxidation in obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea syndrome (OSA) is associated with an increased rate of cardiovascular morbidity, which has been suggested to be related to oxidative stress. The present study investigated the concentration of lipid peroxidation biomarkers in patients with OSA in comparison with nonapneic controls and the effects of treatment with nasal continuous positive airway pressure (nCPAP) on these biomarkers. DESIGN: In Experiment 1, morning plasma levels of the oxidative-stress biomarkers, thiobarbituric reactive substances (TBARS) and peroxides (PD), and of the antioxidant protective enzyme paraxonase-1 (PON1), were measured in OSA patients with and without cardiovascular disease (CVD) and in nonapneic controls after an overnight fasting. The concentrations of the biomarkers were compared between patients and controls and were correlated with respiratory disturbance index (RDI). In Experiment 2, TBARS and PD were measured at hourly intervals during sleep in sleep-apnea patients before and after nCPAP treatment as well as in controls. PATIENTS: In the first experiment, 114 consecutive patients with sleep apnea, 55 without (+OSA/-CVD) and 59 with CVD (+OSA/+CVD), and 30 nonapneic controls were investigated. Nine patients and 6 controls participated in Experiment 2. Five of the patients were also studied 9.3 +/- 3.9 months after nCPAP treatment. MEASUREMENTS AND RESULTS: Morning levels of TBARS and PD were found to be significantly higher in both groups of OSA patients than in controls. The PON1 was lower in +OSA/+CVD patients than in controls and +OSA/-CVD patients, but the difference between the 2 OSA groups bordered on statistical significance. The concentrations of TBARS and PD were significantly positively correlated with RDI (.43, P < .0001 and .36, P < .0002, respectively), while a negative correlation was found between RDI and PON1 activity (-.24, P < .01). Stepwise regression analysis revealed that RDI was an independent significant predictor of all 3 lipid-peroxidation biomarkers. In the second experiment, nocturnal levels of TBARS and PD were significantly higher in sleep-apnea patients than in controls and were significantly lowered by nCPAP treatment. CONCLUSIONS: These results support the existence of an increased state of oxidative stress in OSA and its possible involvement in cardiovascular morbidity.

Adult↗

Disturbed angiogenic activity in sera from obstructive sleep apnea patients.

It is increasingly recognized that obstructive sleep apnea (OSA) syndrome is a systematic rather than local disorder. There is also growing evidence that apart from the syndrome's major features: intermittent hypoxia and sleep fragmentation, functional activity of the immune system is altered in OSA patients, with several cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) taking active part in sleep regulation. Little is known about the effects exerted by chronic intermittent hypoxia combined with persistent pro-inflammatory activity of the immune system on the vascular micro milieu in OSA. In this study we attempted to confirm the hypothesized imbalance between pro- and anti-angiogenic factors by evaluating direct and indirect angiogenic activity of OSA patients' sera in the in vivo serum-induced angiogenesis (SIA) and leukocyte-induced (LIA) assays, respectively, in mice. Both tests revealed significantly inhibited angiogenic activity of OSA patients' sera compared with healthy controls (P<0.001). Moreover, differences related to the subject's weight regarding in the mean number of newly-formed vessels were observed with a significantly greater inhibition in the normal-weighing apneic subjects than in the overweight or obese ones (P<0.01). The angiogenesis inhibition index was positively related to the serum IL-6 level (r=0.35; P<0.05) in the OSA group, but not to TNF-alpha, fasting serum leptin, or OSA syndrome severity as assessed by the AHI index. Our results demonstrate that OSA is accompanied by disturbed serum angiogenic activity, apparently resulting from an imbalance between pro- and anti-angiogenic factors, some of them being produced by the adipose tissue. The disordered angiogenic activity might be related to the pathophysiology of OSA and should be considered an important causative factor for the increased prevalence of cardiovascular diseases in OSA patients.

Adipose Tissue↗

[Obstructive sleep apnoea syndrome in younger and older age groups--differences and similarities].

UNLABELLED: The prevalence of OSA rises with age, however it is also diagnosed in patients below the age of 35 years. Aim of the paper was the camparison of the severity and clinical features of OSA in young and elderly subjects. The study was a retrospective analysis of 561 subjects aged > 65 yrs and 319 subjects aged < 35 yrs who were investigated in our Sleep Laboratory between 1992-2005 due to snoring or daytime sleepiness. They all underwent full polisomnography or a limited recording. In patients with diagnosed OSA (AHI > 10) we initiated CPAP therapy. RESULTS: OSA was diagnosed in 383 (63,3%) older patients and in 144 (45,1%) younger patients. BMI was significantly higher in younger subjects than in older (32,2+/-6,9 vs 28,9+/-5,1 kg/m2). The prevalence of OSA among women was significantly higher in older patients than in younger (26,4 vs 5,8%). Younger patients with OSA had a significantly higher AHI (42,7+/-32,1 vs 32,2+/-18,4) and a longer duration of apneas expressed as percentage of total sleep time spent in apnea (31,6+/-23,2 vs 26,5+/-17,7%). CPAP therapy was initiated in 185 older patients and 41% of them continue therapy. In younger group patients CPAP therapy was started in 51 patients and 47% of them continue therapy. The mean therapeutic pressure was significantly higher in younger patients with OSA (9,2+/-2,2 vs 8,2+/-2,2 cmH2O). CONCLUSIONS: 1/ OSA is more frequent in elderly patients ; 2/ in young patients OSA is more severe and requires higher pressures in CPAP therapy; 3/ OSA among women is four time more frequent in older patients than in younger.

Adult↗

Obstructive sleep apnea in children with Down syndrome.

Children with Down syndrome have many predisposing factors for the obstructive sleep apnea syndrome (OSAS), yet the type and severity of OSAS in this population has not been characterized. Fifty-three subjects with Down syndrome (mean age 7.4 +/- 1.2 [SE] years; range 2 weeks to 51 years) were studied. Chest wall movement, heart rate, electroculogram, end-tidal PO2 and PCO2, transcutaneous PO2 and PCO2, and arterial oxygen saturation were measured during a daytime nap polysomnogram. Sixteen of these children also underwent overnight polysomnography. Nap polysomnograms were abnormal in 77% of children; 45% had obstructive sleep apnea (OSA), 4% had central apnea, and 6% had mixed apneas; 66% had hypoventilation (end-tidal PCO2 greater than 45 mm Hg) and 32% desaturation (arterial oxygen saturation less than 90%). Overnight studies were abnormal in 100% of children, with OSA in 63%, hypoventilation in 81%, and desaturation in 56%. Nap studies significantly underestimated the presence of abnormalities when compared to overnight polysomnograms. Seventeen (32%) of the children were referred for testing because OSAS was clinically suspected, but there was no clinical suspicion of OSAS in 36 (68%) children. Neither age, obesity, nor the presence of congenital heart disease affected the incidence of OSA, desaturation, or hypoventilation. Polysomnograms improved in all 8 children who underwent tonsillectomy and adenoidectomy, but they normalized in only 3. It is concluded that children with Down syndrome frequently in have OSAS, with OSA, hypoxemia, and hypoventilation. Obstructive sleep apnea syndrome is seen frequently in those children in whom it is not clinically suspected. It is speculated that OSAS may contribute to the unexplained pulmonary hypertension seen in children with Down syndrome.

Adenoidectomy↗

Lung volume-related changes in the pharyngeal area of obese females with and without obstructive sleep apnoea.

The majority of male patients with obstructive sleep apnoea (OSA) have an abnormal pharyngeal structure and function, with episodic complete airway occlusion during sleep. Since OSA is less common in females than in males, it is possible that other abnormalities are active in female patients with OSA. Consequently, we measured pharyngeal area and its lung volume-related changes (LVRC) from functional residual capacity (FRC) to residual volume (RV) in overweight females, 14 with OSA and 14 without OSA. Pharyngeal areas were measured using the acoustic reflection technique. While there were no significant differences in pharyngeal area between the OSA and control groups at either FRC (mean +/- SD, 3.49 +/- 0.46 cm2 vs 3.08 +/- 0.63 cm2) or RV (2.86 +/- 0.47 cm2 vs 2.67 +/- 0.49 cm2), the reduction in pharyngeal area between FRC and RV was significantly greater in the OSA group (0.63 +/- 0.23 cm2 vs 0.33 +/- 0.32 cm2, p less than 0.05). Furthermore, although the expiratory reserve volume (ERV) was not significantly different between the two groups (0.4 +/- 0.2 l vs 0.4 +/- 0.3 l), LVRC, defined as the reduction in pharyngeal area normalized by ERV, was significantly higher in the females with OSA than in the non-apnoeic controls (2.68 +/- 2.24 cm2.l-1 vs 1.17 +/- 1.23 cm2.l-1, p less than 0.02). We conclude that females with OSA have abnormal pharyngeal mechanics similar to males with OSA.

Adult↗

Polygenic scores for obstructive sleep apnoea reveal pathways contributing to cardiovascular disease.

BACKGROUND: Obstructive sleep apnoea (OSA) is a common chronic condition, with obesity its strongest risk factor. Polygenic scores (PGSs) summarise the genetic liability to phenotype and can provide insights into relationships between phenotypes. Recently, large datasets that include genetic data and OSA status became available, providing an opportunity to utilise PGS approaches to study the genetic relationship between OSA and other phenotypes, while differentiating OSA-specific from obesity-specific genetic factors. METHODS: Using race/ethnic diverse samples from over 1.2 million individuals from the Million Veteran Program, FinnGen, TOPMed, All of Us (AoU), Geisinger's MyCode, MGB Biobank, and the Human Phenotype Project, we developed and assessed PGSs for OSA, both without (BMIunadjOSA-PGS) and with adjustment for the genetic contributions of BMI (BMIadjOSA-PGS). FINDINGS: Adjusted odds ratios (ORs) for OSA per 1 standard deviation of the PGSs ranged from 1.38 to 2.75. The associations of BMIadjOSA- and BMIunadjOSA-PGSs with CVD outcomes in AoU shared both common and distinct patterns. Only BMIunadjOSA-PGS was associated with type 2 diabetes, heart failure, and coronary artery disease, while both BMIadjOSA- and BMIunadjOSA-PGSs were associated with hypertension and stroke. Sex stratified analyses revealed that BMIadjOSA-PGS association with hypertension was driven by females (OR = 1.1, p-value = 0.002, OR = 1.01 p-value = 0.2 in males). OSA PGSs were also associated with body fat measures with some sex-specific associations. INTERPRETATION: Distinct components of OSA genetic risk are related and independent of obesity. Sex-specific associations with body fat distribution measures may explain differing OSA risks and associations with cardiometabolic morbidities between sexes. FUNDING: R01AG080598.

Humans↗

Do patients with obstructive sleep apnea wake up with headaches?

BACKGROUND: There is a controversy regarding the association of obstructive sleep apnea (OSA) and morning headaches. This study investigates whether this relationship exists. METHODS: This is a retrospective study of 80 consecutive patients with OSA who underwent sleep polysomnography from December 1996 to March 1997. Patients were interviewed about their headache history. Headaches were classified according to International Headache Society criteria and the severity graded by the Chronic Pain Index. Headache characteristics were compared with those of 22 control patients with periodic limb movement disorder. Headache response to continuous positive airway pressure or uvulopalatopharyngoplasty in the patients with OSA was also assessed. RESULTS: Forty-eight (60%) patients had headaches in the year prior to study. Twenty-five of the 48 patients had headaches that did not fit any category. Of these 25 patients, 23 (48% of total group) reported awakening headaches. These awakening headaches were significantly more common in the OSA group compared with the periodic limb movement disorder group, 9 (41%) of whom had headaches, none of which occurred on awakening. The proportion of common types of headaches in both groups was similar. The awakening headaches were brief (shorter than 30 minutes), and their occurrence and severity correlated with OSA severity. Of the 29 patients with OSA who were treated with continuous positive airway pressure or uvulopalatopharyngoplasty, awakening headaches improved by a mean of 80% compared with minimal improvement of migraine, tension, and cervicogenic headaches. CONCLUSIONS: Awakening headaches are associated with OSA. These headaches are of brief duration, and their occurrence and severity increase with increasing OSA severity. Treatment of OSA with continuous positive airway pressure or uvulopalatopharyngoplasty can reduce these headaches.

Adult↗

Sleepiness and sleep in patients with both systolic heart failure and obstructive sleep apnea.

BACKGROUND: Adverse effects of obstructive sleep apnea (OSA), including sleep deprivation, can contribute to the progression of heart failure. The usual indication to diagnose and treat sleep apnea is subjective sleepiness. Previous studies suggest that patients with both heart failure and obstructive sleep apnea often do not complain of sleepiness, albeit their sleep time may be reduced. Therefore, we tested the hypothesis that patients with heart failure have less sleepiness and sleep less compared with subjects without heart failure for a given severity of OSA. METHODS: Sleepiness assessed with the Epworth Sleepiness Scale and sleep structure measured with polysomnography were compared among 155 consecutive patients with heart failure and from a random community sample (n = 1139) according to categories of the apnea-hypopnea index (<5, no OSA; 5-14, mild OSA; and > or =15, moderate to severe OSA). RESULTS: Compared with the community sample, for any given severity of OSA, patients with heart failure had lower mean +/- SE Epworth Sleepiness Scale scores (7.1 +/- 0.4 vs 8.3 +/- 0.2 [P = .005]; 6.7 +/- 0.7 vs 9.2 +/- 0.3 [P < .001]; and 7.8 +/- 0.7 vs 9.8 +/- 0.4 [P = .01]), indicating less sleepiness despite sleeping less (total sleep time mean +/- SE [in minutes]: 306 +/- 7 vs 384 +/- 2, 295 +/- 19 vs 384 +/- 5, and 285 +/- 13 vs 359 +/- 7 for no, mild, and moderate to severe OSA, respectively; P < .001 for all comparisons). CONCLUSIONS: Patients with heart failure have less subjective daytime sleepiness compared with individuals from a community sample, despite significantly reduced sleep time, whether or not they have OSA. In patients with heart failure, the absence of subjective sleepiness is not a reliable means of ruling out OSA.

Body Mass Index↗

Snoring and obstructive sleep apnea in children: a 6-month follow-up study.

BACKGROUND: Snoring children may present symptoms suggestive of obstructive sleep apnea syndrome (OSAS). Different and controversial methods to establish the diagnosis and to choose the treatment modalities have been proposed. OBJECTIVES: To study children with symptoms raising the suspicion of OSAS with overnight polysomnography (PSG). To evaluate the efficacy of adenotonsillectomy as treatment of pediatric OSAS and to elucidate the natural history of OSAS and primary snoring. DESIGN: A controlled, prospective, nonrandomized clinical trial. SETTING: Academic medical center. SUBJECTS: Fifty-eight snoring but otherwise healthy children aged 3 to 10 years with symptoms suggestive of OSAS underwent PSG twice, 6 months apart. Thirty healthy children served as controls. RESULTS: Twenty-seven children had OSAS with an obstructive apnea/hypopnea index greater than 1, while 31 had primary snoring. There were statistical differences in the symptoms and signs among the 3 study groups. Adenotonsillectomy was curative in the 21 children with OSAS who were operated on. Obstructive apneas and hypopneas in the healthy, nonsnoring children were almost nonexistent in this study. CONCLUSIONS: Half of the children or fewer with symptoms suggestive of OSAS actually had the condition. Clinical symptoms may raise the suspicion, but it is not possible to establish the diagnosis without PSG. Because snoring and obstructive symptoms may resolve over time, a normal PSG finding may help the clinician decide on an observation period. Adenotonsillectomy is curative in most cases of pediatric OSAS. Obstructive symptoms may continue after adenoidectomy alone.

Adenoidectomy↗

The familial aggregation of pediatric obstructive sleep apnea syndrome.

OBJECTIVE: To determine the role of genetic mechanisms in the development of pediatric obstructive sleep apnea syndrome (OSAS). DESIGN: Genetic-epidemiologic survey of families of index children with laboratory-confirmed OSAS. SETTING: Tertiary care academic medical center. PARTICIPANTS: Six-hundred nap polysomnograms performed in our institution's pediatric sleep laboratory over a 6-year period (1994-2000) were reviewed, and the 497 children who tested positive for OSAS were selected. A caretaker of 200 of these index patients was contacted, and 115 were enrolled in the study. INTERVENTION AND MAIN OUTCOME MEASURE: Questionnaire-type telephone interviews were conducted with the current caretakers of the index patients to assess the distribution of sleep-disordered breathing in the first-degree relatives. RESULTS: Data were collected for 445 first-degree relatives (256 adults and 189 children) of the 115 index patients. Habitual snoring was found in 194 (43.6%) of the family members, while symptoms highly suggestive of OSAS (nighttime "gasping for air" or "cessation of breathing") were found in 91(20.4%). Sixty-eight (26.6%) of the adult first-degree relatives and 23 (12.2%) of the pediatric first-degree relatives had symptoms highly suggestive of OSAS. Of the 115 index children, 50 (43.5%) had at least 1 relative with symptoms highly suggestive of OSAS; 6 (1.3%) of the first-degree relatives had sleep study results positive for OSAS, 4 (0.9%) were using nasal continuous positive airway pressure, and 21 (4.7%) had prior surgery for the treatment of OSAS. CONCLUSION: Considering the established prevalence of OSAS in the general population (2%-4%), the results of this study support a familial basis for this disorder.

Adolescent↗

Obstructive sleep apnea: implications for cardiac and vascular disease.

CONTEXT: Obstructive sleep apnea (OSA) has been increasingly implicated in the initiation and progression of cardiovascular diseases. OBJECTIVE: To systematically review the interactions of OSA with cardiovascular pathophysiology and diseases. DATA SOURCES AND STUDY SELECTION: The MEDLINE database from January 1966 to March 2003 was searched using the Medical Subject Headings sleep, sleep apnea, obesity, hypertension, heart failure, cardiac arrhythmia, coronary artery disease, stroke, sympathetic activity, endothelium, inflammation, and continuous positive airway pressure (CPAP) to identify peer-reviewed studies of OSA. Priority was given to large prospective cohort studies and to randomized controlled trials. DATA EXTRACTION: We identified 154 original investigations and reviews of sleep-related breathing disorders. Data from these studies were examined for relevance and extracted by one of the authors. DATA SYNTHESIS: Approximately 1 in 5 adults has at least mild OSA (apnea-hypopnea index [ie, the number of apneic and hypopneic events per hour], 5-15), and 1 in 15 adults has at least moderate OSA (apnea-hypopnea index, 15-30). Repetitive apneic events disrupt the normal physiologic interactions between sleep and the cardiovascular system. Such sleep fragmentation, as well as abnormalities evident in patients with OSA (eg, increased sympathetic activation, vascular endothelial dysfunction, increased oxidative stress, inflammation, increased platelet aggregability, metabolic dysregulation), may be implicated in the initiation and progression of cardiac and vascular disease. Persuasive data implicate OSA in the development of hypertension, and OSA also may contribute to cardiac ischemia, congestive heart failure, cardiac arrhythmias, and perhaps also to cerebrovascular disease and stroke. CONCLUSIONS: Obstructive sleep apnea is common, readily diagnosed, and usually treatable. It frequently coexists undiagnosed in patients with cardiovascular disease, activates disease mechanisms known to elicit cardiac and vascular damage, and may be implicated in progression of cardiovascular disease and resistance to conventional therapeutic strategies. In the absence of definitive evidence from large-scale trials and a better understanding of potential cost-effectiveness, the likely benefits of diagnosis and treatment of OSA are presently best appraised on an individualized patient basis.

Cardiovascular Diseases↗

Drug therapy for obstructive sleep apnoea in adults.

BACKGROUND: The treatment of choice for moderate to severe obstructive sleep apnoea (OSA) is continuous positive airways pressure (CPAP) via a mask during sleep. However this is not tolerated by all patients and its role in mild OSA is not proven. Drug therapy has been proposed as an alternative to CPAP in some patients with mild to moderate sleep apnoea and could be of value in patients intolerant of CPAP. A number of mechanisms have been proposed by which drugs could reduce the severity of OSA. These include an increase in tone in the upper airway dilator muscles, an increase in ventilatory drive, a reduction in the proportion of REM sleep, an increase in cholinergic tone during sleep, a reduction in airway resistance and a reduction in surface tension in the upper airway. OBJECTIVES: To determine the efficacy of drug therapies in the treatment of sleep apnoea. SEARCH STRATEGY: We carried out searches on the Cochrane Airways Group Specialised Register of trials. Searches were current as of July 2005. SELECTION CRITERIA: Randomised, placebo controlled trials involving adult patients with confirmed OSA . We excluded trials if continuous positive airways pressure, mandibular devices or oxygen therapy were used. No restriction was placed upon publication language or trial duration. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for inclusion, undertook data extraction according to pre-specified entry criteria, and quality assessment of studies. No response for further information was forthcoming from study authors. Results were expressed as mean differences and 95% Confidence Intervals (CI). MAIN RESULTS: Twenty-six trials of 21 drugs, involving 394 participants contributed data to the review. Most of the studies were small and many trials had methodological limitations. Each of the studies states that the subjects had OSA but diagnostic criteria were not always explicit and it is possible that some patients with central apnoeas may have been recruited. Six drugs had some impact on OSA severity and two altered daytime symptoms. One study reported that apnoea hypopnea index (AHI) was lower following treatment with intranasal fluticasone compared with placebo (23.3 versus 30.3) in 24 participants with sleep apnoea and rhinitis. Subjective alertness in the daytime also improved. Physostigmine gave an AHI of 41 compared to 54 on placebo (10 participants) and in a similar study Mirtazipine 15 mg produced an AHI of 13 compared to 23.7 for placebo (10 participants). Topical nasal lubricant given twice overnight resulted in an AHI of 14 compared to 24 with placebo (10 participants). These three latter studies were of single night crossover design and so there are no data on the acceptability of these treatments or their effect on symptoms. Paroxetine was shown to reduce AHI to 23.3 compared to 30.3 for placebo, most of the 20 participants tolerated the treatment but there was no improvement in daytime symptoms. Acetazolamide also reduced the AHI (one crossover trial of nine patients, mean difference 24 (95% CI 4 to 44). However there was no symptomatic benefit from the drug and it was poorly tolerated in the long term. Protriptyline led to a symptomatic improvement (improved versus not improved) in two out of three crossover trials (13 participants, Peto Odds Ratio 29.2 (95% CI 2.8 to 301.1) but there was no change in the apnoea frequency. In one trial naltrexone did reduce AHI, but total sleep time favoured placebo. No significant beneficial effects were found for medroxy progesterone, clonidine, mibefradil, cilazapril, buspirone, aminophylline, theophylline doxapram, ondansetron or sabeluzole. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend the use of drug therapy in the treatment of OSA. Small studies have reported positive effects of certain agents on short-term outcome. Certain agents have been shown to reduce the AHI in largely unselected populations with OSA by between 24 and 45%. For fluticasone, mirtazipine, physostigmine and nasal lubricant, studies of longer duration are required to establish whether this has an impact on daytime symptoms. Individual patients had more complete responses to particular drugs. It is likely that better matching of drugs to patients according to the dominant mechanism of their OSA will lead to better results and this also needs further study.

Humans↗

Sleep and breathing on the first night after adenotonsillectomy for obstructive sleep apnea.

Adenotonsillectomy (T&A) has established effectiveness for the treatment of obstructive sleep apnea (OSA). However, more than 20% of children with OSA have respiratory compromise requiring medical intervention in the postoperative period. The reasons for this complication are not well-defined. We aimed to compare the nature and severity of sleep-disordered breathing in children with mild and severe OSA on the first night following adenotonsillectomy. Ten children were classified into groups of mild and severe OSA, based on preoperative testing. On the first night after T&A, they underwent polysomnography, including electroencephalograph, submental electromyography, bilateral electro-oculograms, monitoring of respiratory movements, heart rate, ECG, and oxygen saturation. Sleep-disordered breathing was assessed by the apnea-hypopnea index, the SaO(2) nadir, and the desaturation index, including dips in saturation below 90% (DI(90)). Sleep quality was assessed by sleep efficiency, time spent in each sleep state, and respiratory arousal index. Obstructive events occurred postoperatively in all children, but were more frequent in those with severe OSA preoperatively: the median (interquartile range) mixed/obstructive apnea/hypopnea indicies were 6.9 (2.2-9.8) events/hr and 21.5 (15.1-112.1) events/hr for the mild OSA group and the severe OSA group, respectively (P = 0.009). Obstructive events were the major cause of desaturation during sleep postoperatively. Sleep quality was severely disrupted in both groups, with reductions in both slow-wave sleep and rapid eye movement sleep. In conclusion, despite removal of obstructing lymphoid tissue, upper airway obstruction occurred on the first postoperative night in children with OSA. This study is the first to demonstrate the mechanism of respiratory compromise after adenotonsillectomy, a common postoperative complication in children with severe OSA.

Adenoids↗

Partial prevention of long-term femoral bone loss in aged ovariectomized rats supplemented with choline-stabilized orthosilicic acid.

Silicon (Si) deficiency in animals results in bone defects. Choline-stabilized orthosilicic acid (ch-OSA) was found to have a high bioavailability compared to other Si supplements. The effect of ch-OSA supplementation was investigated on bone loss in aged ovariectomized (OVX) rats. Female Wistar rats (n = 58, age 9 months) were randomized in three groups. One group was sham-operated (sham, n = 21), and bilateral OVX was performed in the other two groups. OVX rats were supplemented orally with ch-OSA over 30 weeks (OVX1, n = 20; 1 mg Si/kg body weight daily) or used as controls (OVX0, n = 17). The serum Si concentration and the 24-hour urinary Si excretion of supplemented OVX rats was significantly higher compared to sham and OVX controls. Supplementation with ch-OSA significantly but partially reversed the decrease in Ca excretion, which was observed after OVX. The increase in bone turnover in OVX rats tended to be reduced by ch-OSA supplementation. ch-OSA supplementation increased significantly the femoral bone mineral content (BMC) in the distal region and total femoral BMC in OVX rats, whereas lumbar BMC was marginally increased. Femoral BMD was significantly increased at two sites in the distal region in OVX rats supplemented with ch-OSA compared to OVX controls. Total lumbar bone mineral density was marginally increased by ch-OSA supplementation. In conclusion, ch-OSA supplementation partially prevents femoral bone loss in the aged OVX rat model.

Absorptiometry, Photon↗

NT-pro-BNP in obstructive sleep apnea syndrome is decreased by nasal continuous positive airway pressure.

OBJECTIVE: The aim of this study was to evaluate the impact of obstructive sleep apnea syndrome (OSAS) on B-type natriuretic peptide (BNP) and to determine the effect of nasal continuous positive airway pressure (nCPAP) treatment on BNP levels. BACKGROUND: Increased sympathetic activity, repetitive rises in blood pressure, and apnea-induced wall stress may contribute as a trigger to release BNP in OSAS. However, there is uncertainty about whether OSAS affects BNP and whether application of nasal continuous positive airway pressure (nCPAP) ventilation affects release of BNP. PATIENTS AND METHODS: A prospective study in 69 consecutive patients with suspected sleep disordered breathing referred to our sleep laboratory was conducted. OSAS was confirmed in 26 normotensive and 34 hypertensive patients and ruled out in nine normotensive patients (controls) by polysomnography (PSG). RESULTS: Baseline N-terminal fragment of BNP prohormone (NT-pro-BNP) did not differ significantly between OSAS patients (hypertensive: mean +/-SEM 60.8+/-9.9 pg/ml, normotensive: 43.2+/-6.8 pg/ml) and controls (36.5+/-8.5 pg/ml). Application of CPAP resulted in a significant decrease of NT-pro-BNP in hypertensive (60.8+/-9.9 pg/ml to 47.6+/-7.4 pg/ml, p=0.023) and normotensive OSAS (43.2+/-6.8 pg/ml to 29.6+/-5.3 pg/ml, p=0.0002). In contrast, controls showed no significant differences in NT-pro-BNP after a second PSG (36.5+/-8.5 pg/ml to 40.7+/-12.3 pg/ml, p=0.597). CONCLUSIONS: Normotensive and hypertensive OSAS was not associated with a significant elevation of NT-pro-BNP. Application of nCPAP decreased NT-pro-BNP levels significantly in normotensive and, in particular, hypertensive OSAS. These findings may provide further evidence of the potential for nCPAP to improve cardiovascular comorbidity and co-mortality in OSAS and sleep disordered breathing, in general.

Continuous Positive Airway Pressure↗

Effect of oral intake of choline-stabilized orthosilicic acid on skin, nails and hair in women with photodamaged skin.

Chronic exposure of the skin to sunlight causes damage to the underlying connective tissue with a loss of elasticity and firmness. Silicon (Si) was suggested to have an important function in the formation and maintenance of connective tissue. Choline-stabilized orthosilicic acid ("ch-OSA") is a bioavailable form of silicon which was found to increase the hydroxyproline concentration in the dermis of animals. The effect of ch-OSA on skin, nails and hair was investigated in a randomized, double blind, placebo-controlled study. Fifty women with photodamaged facial skin were administered orally during 20 weeks, 10 mg Si/day in the form of ch-OSA pellets (n=25) or a placebo (n=25). Noninvasive methods were used to evaluate skin microrelief (forearm), hydration (forearm) and mechanical anisotropy (forehead). Volunteers evaluated on a virtual analog scale (VAS, "none=0, severe=3") brittleness of hair and nails. The serum Si concentration was significantly higher after a 20-week supplementation in subjects with ch-OSA compared to the placebo group. Skin roughness parameters increased in the placebo group (Rt:+8%; Rm: +11%; Rz: +6%) but decreased in the ch-OSA group (Rt: -16%; Rm: -19%; Rz: -8%). The change in roughness from baseline was significantly different between ch-OSA and placebo groups for Rt and Rm. The difference in longitudinal and lateral shear propagation time increased after 20 weeks in the placebo group but decreased in the ch-OSA group suggesting improvement in isotropy of the skin. VAS scores for nail and hair brittleness were significantly lower after 20 weeks in the ch-OSA group compared to baseline scores. Oral intake of ch-OSA during the 20 weeks results in a significant positive effect on skin surface and skin mechanical properties, and on brittleness of hair and nails.

Administration, Oral↗