Chikara Yoshimura

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 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.

Cumulative Hypoxemia During Sleep Predicts Vascular Endothelial Dysfunction in Patients With Sleep-Disordered Breathing

BACKGROUND Sleep-disordered breathing (SDB) is associated with repeated intermittent hypoxemia, and it is known as one of the risk factors for cardiovascular diseases. Previous studies assessing the effects of frequency and depth of hypoxemia on cardiovascular diseases have shown conflicting results. The aim of the current study was to clarify what SDB-related parameters most predict endothelial dysfunction to better understand the pathogenesis of endothelial dysfunction in patients with SDB. METHODS We conducted polysomnography (PSG) and measured flow-mediated vasodilation response (%FMD) in 50 outpatients suspected of SDB. Evaluated indices included: apnea-hypopnea index (AHI), 3% oxygen desaturation index (3%ODI), averaged arterial oxygen saturation (averaged SpO2), lowest arterial oxygen saturation (lowest SpO2), ratio of arterial oxygen saturation <90% (<SpO2 90%), and averaged time desaturation summation index (TDS: [100%-averaged SpO2] × total sleep time). RESULTS Significant differences were observed only in the TDS between the first and third (P = 0.03) and between the first and forth (P = 0.04) quartile groups, stratified by %FMD. The %FMD showed a significant relationship with TDS (β = -0.47, P = 0.001), even after adjusting for confounding factors (β = -0.33, P = 0.02). In contrast, AHI, 3%ODI, averaged SpO2, lowest SpO2, and <SpO2 90% showed no significant relationships. CONCLUSIONS This study shows the validity of TDS in predicting endothelial damage in patients with SDB. Cumulative hypoxemia, rather than the frequency of hypoxemic events presented as AHI, may be a greater contributing factor in causing endothelial dysfunction. A simple index like TDS may be a useful and novel indicator of the influence of SDB on the vasculature.

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.

Associations among Chronic Obstructive Pulmonary Disease and Sleep-Disordered Breathing in an Urban Male Working Population in Japan

Background: There are few reports about sleep disturbances in patients with chronic obstructive pulmonary disease (COPD) in Asian countries. Objectives: To investigate the associations between sleep-disordered breathing (SDB) with hypoxemia and sleep quality, including sleep duration, in patients with COPD, we measured SDB and sleep quality including the objective sleep duration determined by an actigraph and portable monitoring. Methods: A cross-sectional epidemiological health survey of 303 male employees (means ± SD: age 43.9 ± 8.2 years; BMI 24.0 ± 3.1) was conducted. Sleep quality was measured using the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). A respiratory disturbance index (RDI) ≥5 indicated SDB. Results: Nineteen subjects (6.3%) had COPD. Among these, 11 (3.6%) had COPD with SDB (overlap syndrome). Sleep duration, ESS, and PSQI scores were not significantly different between COPD patients and normal control subjects. However, COPD patients had significantly longer sleep latency (p = 0.019), a lower sleep efficiency (p = 0.017), and a higher sleep fragmentation index (p = 0.041) and average activity (p = 0.0097) during sleep than control subjects. They also had a significantly higher RDI and more severe desaturation during sleep than control subjects (p < 0.01). The differences remained after adjustment for age and BMI but disappeared following adjustment for RDI. Conclusions: COPD patients with even mild-to-moderate airflow limitations had nocturnal desaturation and RDI-related impaired sleep quality without significant symptoms.

Prevalence of Sleep Disordered Breathing among Patients with Nocturia at a Urology Clinic

OBJECTIVE We assessed the prevalence of sleep disordered breathing (SDB) and characteristics among patients who visited a urology clinic complaining of nocturia (URO group) and those who visited a sleep apnea (SA) clinic complaining of excessive daytime sleepiness (EDS) (SA group). Additionally, we evaluated the effects of continuous positive airway pressure (CPAP) therapy in the URO group patients with nocturia and SDB resistant to conventional therapy for nocturia. METHODS Questionnaires were used to assess EDS, nocturia and lower urinary tract symptoms in 34 URO group patients and 49 age-matched SA group patients. We also compared these factors in the male patients in both groups and the male and female patients in the SA group. Significant SDB was diagnosed as a 3% oxygen desaturation index (3%ODI) on pulse oximeter of >5/h. The treatment response was analyzed in six URO group patients treated with CPAP after not responding to the conventional medical treatment. RESULTS SDB was found in 91.8% of the SA group patients and 70.6% of the URO group patients. The level of EDS and lower urinary tract symptoms were similar in both groups. The SA group showed higher 3%ODI values, while the frequency of urination during bedtime was higher in the URO group. The frequency of nocturnal urination was reduced after CPAP in the subjects resistant to conventional therapy. CONCLUSION SDB is as prevalent in patients who visit a urology clinic complaining of nocturia as in those who visit a sleep apnea clinic. Patients who complains of nocturia must be assessed for SDB before starting therapy for nocturia.