Yoshiro Toyama

Flexible positive airway pressure improves treatment adherence compared with auto-adjusting PAP.

STUDY OBJECTIVES There are no clinical data comparing adherence and quality of life between auto-adjusting positive airway pressure (APAP) and two different flex positive airway pressure (PAP) devices (A-Flex, C-Flex) in patients with obstructive sleep apnea (OSA). DESIGN AND SETTING Ninety-three patients in whom OSA was newly diagnosed were randomly assigned to receive 3 mo of APAP (n = 31), APAP with C-Flex (n = 31), or APAP with A-Flex (n = 31). Objective adherence was determined after 3 mo of CPAP treatment, and the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Calgary Sleep Apnea Quality of Life Index (SAQLI) were examined at baseline and after 3 mo. After 3 mo, patients in the APAP with A-Flex group and those in the APAP with C-Flex group were crossed over and those in the APAP group were switched to A-Flex for an additional 3 mo. MEASUREMENTS AND RESULTS The groups were similar demographically. Treatment adherence during the first 3 mo was significantly greater in the APAP with C-Flex group (APAP with C-Flex: 5.19 ± 1.84 h/night versus APAP: 3.96 ± 1.66 h/night versus APAP with A-Flex: 4.27 ± 2.12 h/night, P = 0.04). There was a significant improvement in two of four of the SAQLI domain scores and in the ESS and PSQI in the APAP with C-Flex group. Adherence significantly improved among the poor compliers (< 4 h/night of use) in the APAP group after change to APAP with A-Flex (P = 0.01). CONCLUSIONS Of these three modes of PAP delivery, adherence was greatest with APAP with C-Flex. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00873977.

Association Between Sleep Apnea, Sleep Duration, and Serum Lipid Profile in an Urban, Male, Working Population in Japan

BACKGROUND Dyslipidemia is often comorbid with obstructive sleep apnea (OSA), but few population-based studies have investigated their relationship. Short sleep duration is associated with hypertension and diabetes; however, its association with dyslipidemia is not well known. We investigated relationships among OSA, sleep duration, and the lipid profile in a community-based study. METHODS We measured the respiratory disturbance index (RDI) and sleep duration by a type 3 portable device and actigraph in 275 men in a Japanese company. Fasting blood parameters were obtained from periodic inspection data. RESULTS According to Japanese criteria, 143 subjects had dyslipidemia. Percent sleep time of oxygen saturation as measured by pulse oximetry (SpO2) < 90% and prevalence of severe OSA were greater and sleep duration and mean SpO2 during sleep were lower in subjects with dyslipidemia than in those without. Univariate analysis showed that the RDI was positively correlated with serum triglyceride (TG) levels (ρ = 0.20, P < .01), and sleep duration was negatively correlated with serum total cholesterol (TC) levels (γ = -0.13, P = .03) and serum low-density lipoprotein cholesterol levels (γ = -0.12, P = .04). Stepwise multiple regression analysis revealed that TG was correlated with RDI (β = 0.14, P = .02), BMI (β = 0.20, P < .01), and alcohol intake (β = 0.20, P < .01), and that TC was correlated with sleep duration (β = -0.13, P = .03), age (β = 0.15, P = .02), and waist/hip ratio (β = 0.15, P = .02). CONCLUSIONS Short sleep duration was associated with TC levels and RDI was positively associated with TG levels among working-aged men in an urban Japanese company. Correcting the status of OSA and/or short sleep duration might improve the lipid profile and cardiovascular consequences.

Association between Plasma Neutrophil Gelatinase Associated Lipocalin Level and Obstructive Sleep Apnea or Nocturnal Intermittent Hypoxia

Background Both obstructive sleep apnea (OSA) and a novel lipocalin, neutrophil gelatinase associated lipocalin (Ngal), have been reported to be closely linked with cardiovascular disease and loss of kidney function through chronic inflammation. However, the relationship between OSA and Ngal has never been investigated. Objectives To evaluate the relationship between Ngal and OSA in clinical practice. Methods In 102 patients, polysomnography was performed to diagnose OSA and plasma Ngal levels were measured. The correlations between Ngal levels and OSA severity and other clinical variables were evaluated. Of the 46 patients who began treatment with continuous positive airway pressure (CPAP), Ngal levels were reevaluated after three months of treatment in 25 patients. Results The Ngal level correlated significantly with OSA severity as determined by the apnea hypopnea index (r = 0.24, p = 0.01) and 4% oxygen desaturation index (ODI) (r = 0.26, p = 0.01). Multiple regression analysis showed that the Ngal level was associated with 4%ODI independently of other clinical variables. Compliance was good in 13 of the 25 patients who used CPAP. Although the OSA (4%ODI: 33.1±16.7 to 1.1±1.9/h, p<0.01) had significantly improved in those with good compliance, the Ngal levels were not significantly changed (60.5±18.1 before CPAP vs 64.2±13.9 ng/ml after CPAP, p = 0.27). Conclusions Plasma Ngal levels were positively associated with the severity of OSA. However, the contribution rate of OSA to systemic Ngal secretion was small and changes in Ngal levels appeared to be influenced largely by other confounding factors. Therefore, it does not seem reasonable to use the Ngal level as a specific biomarker of OSA in clinical practice.

Obesity hypoventilation syndrome in Japan and independent determinants of arterial carbon dioxide levels.

Obesity hypoventilation syndrome (OHS) prevalence was previously estimated at 9% in patients with obstructive sleep apnoea (OSA) in Japan. However, the definition of OSA in that study was based on an apnoea‐hypopnoea index (AHI) of ≥ 20/h rather than ≥ 5/h. Therefore, the prevalence of OHS in OSA was not measured in the same way as for Western countries. Our study objectives were to investigate the characteristics of Japanese patients with OHS.

Differences in associations between visceral fat accumulation and obstructive sleep apnea by sex.

RATIONALE The difference in mortality from obstructive sleep apnea (OSA) by sex is an important issue. Visceral fat, a significant risk factor for cardiovascular disease, was reported to be closely related to OSA. OBJECTIVES To assess the different associations between OSA and visceral fat area (VFA) by sex, which might account for the different prognosis in men and women with OSA. METHODS Participants were 271 men and 100 women consecutively hospitalized for examination of OSA from October 2008 to December 2010. Among the 371 participants, relationships were analyzed between fat areas by computed tomography, comorbidity, polysomnographic data, arterial blood gas, pulmonary function, and venous blood data. Multiple regression analyses were performed to identify variables independently associated with VFA and subcutaneous fat area for each sex. MEASUREMENTS AND MAIN RESULTS Despite similar body mass index (BMI) and waist circumference, men had larger VFA, more severe OSA, and more severe dyslipidemia than women. Multiple regression analyses revealed that in men, not only age and BMI but also minimal oxygen saturation (contribution rate [R(2)], 4.6%) during sleep, and alveolar-arterial oxygen difference (R(2) = 7.6%) were independently associated with VFA. Conversely, VFA was associated only with BMI in women. CONCLUSIONS Only in men was OSA independently associated with VFA. The lesser associations between OSA and visceral fat in women might account for the lower impact of OSA on cardiovascular disease or mortality in women.

A urine biomarker for severe obstructive sleep apnoea patients: lipocalin-type prostaglandin D synthase

Lipocalin-type prostaglandin D synthase (L-PGDS), which is responsible for the biosynthesis of prostaglandin D2, has been reported to have a close connection with cardiovascular disease and sleep regulation. This study aimed to test the hypothesis that the L-PGDS level is a useful marker to identify patients with obstructive sleep apnoea. 64 subjects were enrolled in this prospective study. Urinary concentrations of L-PGDS were measured in the morning. Measurements were made every 4 h in 25 of the 64 patients. Endothelial function was assessed by the reactive hyperaemia peripheral arterial tone index. Circadian variations in L-PGDS concentrations had a significant time-dependent fluctuation (p = 0.0002). L-PGDS was higher in the subjects with severe obstructive sleep apnoea (median 784.7 ng per mg of creatinine, n = 23) than in control subjects (262.1 ng per mg of creatinine, n = 16; p = 0.004) and in those with moderate obstructive sleep apnoea (371.7 ng per mg of creatinine, n = 25; p = 0.0008). After 2 days of continuous positive airway pressure treatment, L-PGDS concentrations in severe obstructive sleep apnoea subjects (n = 12) decreased significantly (p = 0.02) to levels present in control subjects whereas endothelial function did not change significantly. Morning urinary L-PGDS concentrations had significant correlations with the apnoea/hypopnoea index (R2 = 13.9%) and serum high-density lipoprotein cholesterol (R2 = 6.2%), but not with sleepiness. Urinary L-PGDS might be a moderately useful marker to identify patients with severe obstructive sleep apnoea. Urinary lipocalin-type prostaglandin D synthase might be a moderately useful marker to identify patients with severe OSA http://ow.ly/pBuac

The additive impact of periodic limb movements during sleep on inflammation in patients with obstructive sleep apnea.

RATIONALE Both periodic limb movements during sleep (PLMS) and obstructive sleep apnea (OSA) are major causes of sleep disorders and have been associated with systemic inflammation and cardiovascular events. However, it is uncertain whether in combination they promote a higher inflammatory response and greater risk of cardiovascular events than each condition alone. OBJECTIVES To investigate whether the presence of PLMS is associated with increased inflammation in patients suspected of having OSA. METHODS In 342 patients who underwent polysomnography to diagnose OSA, plasma C-reactive protein (CRP) and fibrinogen levels were measured. MEASUREMENTS AND MAIN RESULTS OSA was found in 254 patients, with 46 also having PLMS. Among the 88 patients who did not have OSA, 8 had PLMS. Plasma CRP and fibrinogen levels in the group with both PLMS and OSA were higher than in patients with neither OSA nor PLMS and in patients with OSA only (CRP: 0.20 ± 0.48 vs. 0.09 ± 0.15 vs. 0.13 ± 0.18 mg/dl, P = 0.03; fibrinogen: 298.2 ± 76.1 vs. 269.0 ± 57.1 vs. 270.0 ± 52.6 mg/dl, P < 0.01). Multivariate analysis showed that the presence of PLMS was associated with higher plasma CRP levels (β = 0.1401, P < 0.01) and fibrinogen levels (β = 0.1359, P = 0.01) independently from other clinical variables such as body mass index and the severity of OSA. CONCLUSIONS PLMS were positively associated with plasma CRP and fibrinogen levels in patients suspected of having OSA. Because plasma levels of these proteins have been established as predictive factors of future cardiovascular events, the presence of PLMS may be a useful clinical sign to identify patients with OSA at high risk of cardiovascular events.

Measurement of dyspnea in patients with obstructive sleep apnea.

PurposePatients with obstructive sleep apnea (OSA) frequently complain of exertional dyspnea. We aimed to assess its related factors and the significance of its measurement in OSA.MethodsWe evaluated 301 subjects with suspected OSA for dyspnea during activities of daily living using the Medical Research Council (MRC) scale. We analyzed the relationships between MRC grades and various subjective and objective indices. Further, the relationship of disease severity based on the apnea/hypopnea index (AHI) with these indices was examined. Results were compared between those obtained using MRC grades and the AHI.ResultsOf 301 subjects, 265 were diagnosed with OSA. Their MRC scores were worse than in non-OSA patients. Among OSA patients, 125 had MRC grade 1 (mild), 121 had MRC grade 2 (moderate), and 19 had MRC grade 3 or more (severe) dyspnea. Various measurements differed significantly between groups categorized according to the MRC scale although determinants between mild and moderate groups and between moderate and severe groups differed. AHI categorizations were not significantly related to patient-reported measurements such as the Medical Outcomes Study 36-item short form, Pittsburgh Sleep Quality Index, and Hospital Anxiety and Depression Scale scores, unlike categorization based on the MRC scale.ConclusionsDyspnea is an important outcome in OSA although dyspnea in OSA patients is unrelated to the sleep disorder per se. Measurement of dyspnea in patients with OSA might provide further insights into the health of these patients and clinical manifestations of this disease.

Impact of Obstructive Sleep Apnea on Liver Fat Accumulation According to Sex and Visceral Obesity.

Rationale Associations between obstructive sleep apnea (OSA) and liver fat accumulation have been frequently investigated because both morbidities are common. Visceral fat was reported to be closely related to OSA and liver fat accumulation. Recently, sex differences in the association between OSA and mortality have gained much attention. Objectives To investigate the associations among OSA, liver fat accumulation as determined by computed tomography, and visceral fat area and their sex differences. Methods Studied were 188 males and 62 females who consecutively underwent polysomnography and computed tomography. Results Although the apnea-hypopnea index was positively correlated with liver fat accumulation in the total males, none of the OSA-related factors was independently associated with liver fat accumulation in either the total male or female participants in the multivariate analyses. When performing subanalyses using a specific definition for Japanese of obesity or visceral obesity (body mass index (BMI) ≥25 kg/m2 or visceral fat area ≥100 cm2), in only males without visceral obesity, percent sleep time with oxygen saturation <90%, in addition to BMI, insulin resistance, and serum triglyceride values, was independently correlated with liver fat accumulation (R2 = 15.1%, P<0.001). In males, percent sleep time of oxygen saturation <90% was also a determining factor for alanine aminotransferase values regardless of visceral fat area. In contrast, OSA was not associated with liver fat accumulation or alanine aminotransferase values in females whether or not visceral obesity was absent. Conclusions Sex differences in the visceral fat-dependent impact of OSA on liver fat accumulation existed. Although the mechanisms are not known and ethnic differences may exist in addition to the specific criteria of visceral obesity in Japan, the treatment of male patients with OSA might be favorable from the viewpoint of preventing liver fat accumulation and liver dysfunction even in patients without obvious visceral fat accumulation.