Kimihiko Murase

Changes in Energy Metabolism after Continuous Positive Airway Pressure for Obstructive Sleep Apnea

RATIONALE Disrupted energy homeostasis in obstructive sleep apnea (OSA) may lead to weight gain. Paradoxically, treating OSA with continuous positive airway pressure (CPAP) may also promote weight gain, although the underlying mechanism remains unclear. OBJECTIVES To explore the underlying mechanism by which patients with OSA gain weight after CPAP. METHODS A comprehensive assessment of energy metabolism was performed in 63 newly diagnosed OSA study participants (51 men; 60.8 ± 10.1 yr; apnea-hypopnea index >20 h(-1)) at baseline, CPAP initiation, and at a 3-month follow-up. Measurements included polysomnography, body weight, body composition, basal metabolic rate (BMR), hormones (norepinephrine, cortisol, leptin, ghrelin, insulin-like growth factor-1), dietary intake, eating behavior, and physical activity. MEASUREMENTS AND MAIN RESULTS BMR significantly decreased after CPAP (1,584 kcal/d at baseline, 1,561 kcal/d at CPAP initiation, and 1,508 kcal/d at follow-up; P < 0.001), whereas physical activity and total caloric intake did not significantly change. In multivariate regression, baseline apnea-hypopnea index, Δurine norepinephrine, and CPAP adherence were significant predictors of ΔBMR. The weight gainers had higher leptin levels, lower ghrelin levels, and higher eating behavior scores than the non-weight gainers, indicating a positive energy balance and disordered eating behavior among the weight gainers. Among the parameters related to energy metabolism, increased caloric intake was a particularly significant predictor of weight gain. CONCLUSIONS Although a reduction in BMR after CPAP predisposes to a positive energy balance, dietary intake and eating behavior had greater impacts on weight change. These findings highlight the importance of lifestyle modifications combined with CPAP. Clinical trial registered with http://www.umin.ac.jp/english/ (UMIN000012639).

The use of non-invasive ventilation for life-threatening asthma attacks: Changes in the need for intubation.

Background and objective:  Although non‐invasive ventilation (NIV) has been shown to be effective in a wide variety of respiratory diseases, its role in severe asthma attacks remains uncertain. The aim of this study was to clarify the effectiveness of NIV in patients experiencing severe attacks of asthma.

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.

Gastroesophageal reflux disease symptoms and dietary behaviors are significant correlates of short sleep duration in the general population: the Nagahama Study.

STUDY OBJECTIVES To examine relationships among gastroesophageal reflux disease (GERD) symptoms, dietary behaviors, and sleep duration in the general population. DESIGN Cross-sectional. SETTING Community-based. PARTICIPANTS There were 9,643 participants selected from the general population (54 ± 13 y). INTERVENTIONS None. MEASUREMENTS AND RESULTS Sleep duration, sleep habits, and unfavorable dietary behaviors of each participant were assessed with a structured questionnaire. Participants were categorized into five groups according to their sleep duration: less than 5 h, 5 to less than 6 h, 6 to less than 7 h, 7 to less than 8 h, and 8 or more h per day. GERD was evaluated using the Frequency Scale for the Symptoms of GERD (FSSG) and participants having an FSSG score of 8 or more or those under treatment of GERD were defined as having GERD. Trend analysis showed that both the FSSG score and the number of unfavorable dietary habits increased with decreasing sleep duration. Further, multiple logistic regression analysis showed that both the presence of GERD (odds ratio = 1.19, 95% confidence interval (CI) = 1.07-1.32) and the number of unfavorable dietary behaviors (odds ratio = 1.19, 95% CI = 1.13-1.26) were independent and potent factors to identify participants with short sleep duration even after controlling for other confounding factors. CONCLUSION The current study showed that both GERD symptoms and unfavorable dietary behaviors were significant correlates of short sleep duration independently of each other in a large sample from the general population.

Use of noninvasive ventilation for pediatric patients after liver transplantation: Decrease in the need for reintubation

Noninvasive ventilation (NIV) refers to ventilation delivered through a noninvasive interface (a nasal or face mask) rather than an invasive interface (an endotracheal tube or tracheostomy). The role of NIV in preventing reintubation after abdominal surgery in pediatric patients is uncertain. Therefore, we evaluated the role of NIV for this purpose in pediatric patients after liver transplantation. We successfully started using NIV for respiratory complications (RCs) in pediatric patients undergoing liver transplantation in 1999. For this report, we screened all medical records of patients under the age of 12 years who underwent liver transplantation between 2001 and 2009, and we retrieved data for cases at high risk of extubation failure. We retrospectively compared the clinical outcomes of patients who received NIV during their intensive care unit (ICU) stay and patients who did not. Data for 94 cases (92 patients) were included in this analysis. NIV was used in 47 patients during their ICU stay. The rate of reintubation for RCs was significantly lower in NIV patients versus non‐NIV patients [3/47 (6.4%) versus 11/47 (23.4%), P = 0.02]. Furthermore, the discharge rate from the ICU was significantly better for NIV patients versus non‐NIV patients. The use of NIV after extubation prevented the worsening of atelectasis and stabilized respiratory conditions in this cohort. No major changes in operative procedures or other treatments during the examined period were found. In conclusion, NIV is acceptable and promising for the respiratory management of pediatric patients undergoing liver transplantation. Its use may stabilize respiratory conditions and decrease the need for reintubation in pediatric liver transplant patients, and it may also facilitate an early ICU discharge. Liver Transpl 18:1217–1225, 2012.

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

Plasma Incretin Levels and Dipeptidyl Peptidase-4 Activity in Patients with Obstructive Sleep Apnea

RATIONALE Incretin hormones, namely glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide/glucose-dependent insulinotropic polypeptide (GIP), and dipeptidyl peptidase-4 (DPP-4) activity are important factors in glucose metabolism and have not been investigated in patients with obstructive sleep apnea (OSA). OBJECTIVES The objective of this study was to investigate the association between OSA and incretin and DPP-4 activity. METHODS This study included 96 consecutive patients without diabetes who were suspected of having OSA. We investigated the fasting and post-prandial incremental area under the curve (IAUC) of GLP-1, GIP serum levels, and serum DPP-4 activity levels, as well as their association with OSA. Changes in clinical variables were evaluated in the 43 patients who continued continuous positive airway pressure therapy for 3 months. MEASUREMENTS AND MAIN RESULTS Apnea-hypopnea index was an independent determining factor for fasting GLP-1 (β = 0.31; P = 0.0019) and IAUC GIP (β = -0.21; P = 0.037) after adjusting for known confounding factors. In those with very severe OSA (apnea-hypopnea index ≥50), the IAUCs for GLP-1 and GIP were significantly decreased, while fasting GLP-1 and fasting GIP were significantly increased. DPP-4 activity had no relation to OSA parameters or severity, while body mass index was significantly higher in those with severe OSA. Although significant changes in incretin secretion were not seen for 3 months after onset of continuous positive airway pressure therapy, the fasting GLP-1 level in the treated patients with severe OSA decreased to the same level as in untreated patients with normal to moderately severe OSA. CONCLUSIONS OSA is associated with elevated serum levels of the incretin hormones GLP-1 (fasting) and GIP (post-prandial) in patients without diabetes. A significant association between body mass index and DPP-4, which is said to exist in healthy persons, was not found in the patients with OSA. Fasting GLP-1 in patients without diabetes with OSA may influence fasting glucose levels.