Symptoms of sleep disordered breathing: Association with the apnea-hypopnea index and somatic arousal.

We investigated the association of typical symptoms of obstructive sleep apnea with a measure of daytime somatic arousal and with the apnea-hypopnea index. We extended the finding of an association between sleepiness, fatigue and somatic arousal previously reported in a US sleep apnea population to a German sleep apnea population (n = 374) and to other typical sleep apnea symptoms, insomnia, anxiety, daytime alertness and non-restorative sleep. Somatic arousal was measured using the body sensation questionnaire (BSQ). Correlations of apnea-hypopnea index and BSQ were computed with values of polysomnographic variables derived from overnight sleep studies and with severity of OSA symptoms. Apnea-hypopnea index and BSQ scores showed only a small negative correlation with each other; each correlated independently with the Epworth Sleepiness Scale score. Controlling for BSQ score, the apnea-hypopnea index was found to affect sleepiness only when it exceeded 50/h. Severity of all other sleep apnea symptoms did not increase with increasing apnea-hypopnea index. In contrast, severity of all symptoms of sleep apnea increased consistently with increasing BSQ scores. Thus, autonomic stress associated with obstructive sleep apnea may be the driving force behind sleep apnea symptoms rather than the sleep fragmentation associated with obstructive sleep apnea severity (apnea-hypopnea index). These findings support previously reported correlations by Gold and associates between the levels of somatic arousal, sleepiness and fatigue. Using the apnea-hypopnea index and BSQ together renders a more comprehensive assessment of sleep apnea than apnea-hypopnea index alone, which appears to impact only on sleepiness and only when it exceeds 50/h. More work is needed to elucidate the source of the chronic stress, which appears to arise endogenously in affected individuals, likely as a function of sleep disordered breathing, such as snoring/inspiratory flow limitation.

Differences in clinical features of upper airway resistance syndrome, primary snoring, and obstructive sleep apnea/hypopnea syndrome.

BACKGROUND: The clinical features of patients with upper airway resistance syndrome (UARS) have previously been compared to patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). No data regarding differences between patients with primary snoring (PS) or patients with obstructive sleep apnea/hypopnea without daytime sleepiness (OSAH) are available. We conducted a study to investigate clinical features of UARS, comparing them to those in patients with PS, OSAH, and OSAHS. METHODS: Retrospective chart analysis of 157 patients with PS, 424 patients with UARS, 562 patients with OSAH, and 1610 patients with OSAHS seen in two sleep disorders clinics between 1996 and 2006. All patients had a diagnostic polysomnography (PSG) and a comprehensive clinical history taken by board-certified sleep specialists. RESULTS: PS and UARS patients were significantly younger, less overweight and had lower weight gain during the past 5years. The female-to-male ratio was highest in the UARS group. UARS patients had significantly less stage non-rapid eye movement sleep (NREM) 1 and NREM 2 and significantly more NREM 3 and NREM 4 sleep than OSAH and OSAHS patients. Arousal indices between PS/UARS and OSAH/OSAHS patients were significantly lower, with no significant difference within these diagnostic categories. Patients with UARS presented the highest degree of subjective impairment. CONCLUSIONS: UARS patients share some clinical features of patients with OSAHS and PS, although these two groups differ in their presentation of clinical sleepiness. Patients with UARS were most impaired in terms of their daily functioning and perception of sleep quality. This finding could not be corroborated by objective measures.

Comparison of pleural pressure and transcutaneous diaphragmatic electromyogram in obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Based on studies of the impact of esophageal pressure on cardiovascular variables during sleep, this signal can be used to refine the severity level in the clinical diagnosis of obstructive sleep apnea syndrome. We hypothesized that relative changes in diaphragmatic electromyogram (EMG) can reflect short-term changes in esophageal pressure durng obstructive apneas and hypopneas. DESIGN: Diaphragmatic EMG was sampled at 0.25 kHz; diaphragmatic EMG waveform was band-pass filtered and digitally converted; the electrocardiogram artifact was eliminated; using a gating procedure, the waveform was fast-Fourier transformed and digitally rectified; and a moving average of 200 milliseconds was calculated. For each inspiratory effort during apnea or hypopnea, we calculated maximum diaphragmatic EMG and esophageal pressure. Data were normalized calculating the percentage difference between the first obstructed and each subsequent inspiratory effort during the respiratory event. SETTING: Sleep disorders laboratory. PATIENTS: 9 patients with moderate obstructive sleep apnea syndrome presenting with apneas and hypopneas during sleep. INTERVENTION: None. MEASUREMENTS AND RESULTS: 861 respiratory events were scored, and the evolution between esophageal pressure and diaphragmatic EMG were compared. Normalized data showed a good correlation between the 2 measures during apneas and hypopneas. There was a significant difference between the percentage increase in esophageal pressure and diaphragmatic EMG for apneas and hypopneas (esophageal pressure, apnea: 118.1% +/- 118.5%, hypopnea: 76.1% +/- 74.3%, P = .000; diaphragmatic EMG, 123.5% +/- 131.7%, hypopnea: 73.3% +/- 74.2%, P = .000). No significant differences for apnea or hypopnea were noted between the 2 measures under investigation. CONCLUSION: Diaphragmatic EMG may be clinically useful to describe relative changes in respiratory effort under conditions of apnea and hypopnea during sleep and to reliably dissociate central from obstructive events where esophageal pressure monitoring is not readily available.

Long-term effects of nasal continuous positive airway pressure on vasodilatory endothelial function in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is associated with a dysfunction of vascular endothelial cells. The aim of this study was to investigate long-term improvement of endothelial dysfunction in OSAS with nasal continuous positive airway pressure (nCPAP) treatment. We investigated endothelium-dependent and endothelium-independent vasodilatory function in patients with OSAS using the hand vein compliance technique. Dose-response curves to endothelium-dependent vasodilator bradykinin were obtained in 16 subjects with OSAS before and after 6 months of nCPAP therapy and in 12 control subjects without OSAS. Maximum dilation (Emax) to bradykinin, being impaired in all OSAS patients, was completely restored with nCPAP. Mean Emax to bradykinin rose from 54.9+/-18.5 to 108.2+/-28.7% with 164.4+/-90.0 nights of nCPAP therapy (p<0.0001; Emax healthy controls, 94.8+/-9.5%). At treatment follow-up, endothelium-dependent vasodilatory capacity was not significantly different in nCPAP-treated OSAS patients vs healthy controls. Mean vasodilation with endothelium independently acting nitroglycerin was not altered initially and did not change with nCPAP therapy indicating that nCPAP restored endothelial cell function and not unspecific, endothelium-independent factors. These results suggest that regular nocturnal nCPAP treatment leads to a sustained restoration of OSAS-induced impaired endothelium-dependent nitric oxide-mediated vasodilation, suggesting an improvement of systemic endothelial dysfunction in patients studied.

Reaction time performance in upper airway resistance syndrome versus obstructive sleep apnea syndrome.

BACKGROUND: Patients with obstructive sleep apnea syndrome (OSAS) are known to have an increased risk for motor vehicle crashes. They suffer from sleep-related respiratory abnormality causing repetitive arousal leading to daytime sleepiness. In turn, it has been demonstrated that sleepiness can impair human psychomotor performance causing slowing of reaction times (RTs). Patients with OSAS present with RTs comparable to young adults under the influence of blood alcohol concentrations above the legally permitted level to drive a motor vehicle. Vigilance related risk levels in patients with upper airway resistance syndrome (UARS) and potential deficits in psychomotor performance are unknown. METHODS: We designed a study to compare psychomotor performance in UARS and compared it to patients with OSAS. Forty-seven UARS patients were matched by gender and age with 47 OSAS patients. All subjects completed a standardized vigilant attention task utilizing reaction time before undergoing polygraphic sleep studies. RESULTS: Patients with UARS presented worse psychomotor performance on most test metrics than patients with OSAS. CONCLUSIONS: Our study results may suggest that patients with UARS may also present an increased risk for motor vehicle crashes as previously demonstrated in OSAS patients.

Antihypertensive treatment and endothelium-dependent venodilation in sleep-disordered breathing.

Sleep-disordered breathing (SDB) is associated with nitric oxide-mediated endothelial dysfunction and increased risk and prevalence of cardiovascular disease, namely, arterial hypertension. A substantial number of patients do not comply with nasal continuous positive airway pressure (nCPAP) treatment. These individuals have a persisting increased cardiovascular risk. Antihypertensive drugs have shown to improve nitric oxide-mediated endothelial dysfunction. We therefore designed a study to test the hypothesis that antihypertensive drug treatment in hypertensive patients with SDB can have beneficial effects on nitric oxide-mediated endothelial function in the absence of treatment with nCPAP. Six patients with SDB and treated arterial hypertension, six normotensive patients with SDB, and six healthy controls received sleep studies and an assessment of venodilation using the dorsal hand vein technique. Polygraphic measures using standard overnight sleep studies and dose-response curves to the endothelium-dependent vasodilator bradykinin were obtained. Maximum nitric-oxide-mediated dilation to bradykinin was significantly higher in patients with SDB who had received antihypertensive drug treatment compared to normotensive SDB patients. Nitric oxide-mediated dilation in hypertensive patients with SDB was similar to nitric oxide-mediated dilation in healthy controls. After treatment of normotensive patients with SDB using nCPAP, nitric oxide-mediated dilation in normotensive SDB patients was comparable to nitric oxide-mediated dilation in SDB patients with antihypertensive drug treatment and normal controls. Hypertensive patients with SDB present a normal nitric oxide-mediated endothelial function under antihypertensive treatment.

Effect of iron depletion in carbohydrate-intolerant patients with clinical evidence of nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Increased body iron, genetic hemochromatosis (GH) mutations, and nonalcoholic fatty liver disease (NAFLD) tend to cluster in carbohydrate-intolerant patients. In an attempt to further clarify the interrelationships among these conditions, we studied 42 carbohydrate-intolerant patients who were free of the common GH mutations C282Y and H63D, and had a serum iron saturation lower than 50%. METHODS: We measured body iron stores, and induced iron depletion to a level of near-iron deficiency (NID) by quantitative phlebotomy. RESULTS: In the 17 patients with clinical evidence of NAFLD, we could not demonstrate supranormal levels of body iron (1.6 +/- 0.2 vs. 1.4 +/- 0.2 g; P = 0.06). However, at NID, there was a 40%-55% improvement (P = 0.05-0.0001) of both fasting and glucose-stimulated plasma insulin concentrations, and near-normalization of serum alanine aminotransferase activity (from 61 +/- 5 to 32 +/- 2 IU/L; P < 0.001). CONCLUSIONS: These results reflect the insulin-sparing effect of iron depletion and indicate a key role of iron and hyperinsulinemia in the pathogenesis of NAFLD.

Abnormal blood pressure in prepubertal children with sleep-disordered breathing.

The purpose of this study was to investigate the association between low blood pressure (BP) with mild symptoms of orthostatism, sleep-disordered breathing (SDB) and tilt test results in 7- to 12-y-old children. A retrospective chart review of 301 children, ages 7 to 12 y, was initially performed to evaluate the frequency of abnormal BP measurements. Then a prospective study was performed on 7- to 12-y-old prepubertal children with SDB, looking for both abnormal BP and mild orthostatism. All children had polysomnography. Those identified with abnormal (high or low) BP measurements (called "BP outliers") were studied with a new polysomnogram followed by a head-up tilt test as an indicator of autonomic activity. Four of the children with low BP were treated with nasal continuous positive airway pressure and received a second head-up tilt test 3.5 to 7 mo after starting treatment. The prospective study included 78 children, eight of whom were BP outliers. Seven of these outliers had low BP. Compared with all of the SDB subjects, SDB subjects with low BP and indicators of mild orthostatic hypotension had a significantly higher incidence of craniofacial dysmorphism, symptoms of SDB early in life, chronically cold extremities, and dizziness on standing up (chi2, p = 0.01 to 0.0001). They had a significantly greater drop in BP without evidence of autonomic neuropathy than all other children on head-up tilt testing (Kruskal-Wallis ANOVA with Bonferroni adjustment, p = 0.001 to 0.0001). However, the normotensive SDB controls also had significantly different BP drops than the normal controls (p = 0.0001). The four children placed on nasal continuous positive airway pressure had a nonsignificant trend toward normalization of tilt test response. SDB in prepubertal children can lead to different abnormal stimulation of the autonomic nervous system, with different impacts on BP. The severity and frequency of oxygen saturation drops during sleep, nonhypoxic increases in respiratory effort, and the duration of abnormal breathing are suspected of playing a role in the difference in autonomic nervous system stimulation.