Naricha Chirakalwasan

Clinical and polysomnographic data of positional sleep apnea and its predictors

IntroductionIn Asian population, facial structure may contribute to the primary pathophysiology of obstructive sleep apnea (OSA). We hypothesized that sleep position may have more effect on OSA in Asians compared to the Western population. If this hypothesis is accurate, positional therapy will have a major impact on treatment of OSA among Asians.Patients/methodsWe reviewed 263 polysomnographic studies from our laboratory from January 1, 2010 to June 30, 2010. Criteria for positional and non-positional OSA were (1) supine respiratory disturbance index (RDI)/non-supine RDI ≥2 and total RDI ≥5 and (2) supine RDI/non-supine RDI <2 and total RDI ≥5, respectively. We aimed to determine the difference in baseline characteristics, polysomnographic findings, and predictors for positional OSA.ResultsWe found 144 patients diagnosed with OSA (RDI ≥5), and 96 patients met the criteria for positional OSA (67%), in which in almost half of these patients (47%), RDI was normalized (RDI < 5) in non-supine position. Snoring frequency were significantly lower among positional OSA and OSA was less severe indicated by lower RDI and arousal index, higher mean and nadir oxygen saturation, and higher %NREM3. We also found that low snoring frequency (less than 20% of total sleep time) was a significant predictor for positional OSA (odd ratio of 3.27; p = 0.011), contrarily to low mean oxygen saturation (<95%) which was found to be a negative predictor (odd ratio of 0.31; p = 0.009). Among OSA patients, low RDI (<15) was a significant predictor for normalization of RDI in non-supine position (odd ratio of 8.77; p = < 0.001), contrarily to low mean oxygen saturation (<95%) which was also found to be a negative predictor (odd ratio of 0.13; p = 0.001).ConclusionPositional OSA is very prevalent and noted in almost 70% of our patients. Low snoring frequency was noted to be a positive predictor for positional OSA, contrarily to low mean oxygen saturation which was found to be a negative predictor. These findings are encouraging that positional therapy can be very beneficial as the treatment modality for OSA among Asians.

Sleep characteristics in type 1 diabetes and associations with glycemic control: systematic review and meta-analysis

OBJECTIVES The association between inadequate sleep and type 2 diabetes has garnered much attention, but little is known about sleep and type 1 diabetes (T1D). Our objectives were to conduct a systematic review and meta-analysis comparing sleep in persons with and without T1D, and to explore relationships between sleep and glycemic control in T1D. METHODS Studies were identified from Medline and Scopus. Studies reporting measures of sleep in T1D patients and controls, and/or associations between sleep and glycemic control, were selected. RESULTS A total of 22 studies were eligible for the meta-analysis. Children with T1D had shorter sleep duration (mean difference [MD] = -26.4 minutes; 95% confidence interval [CI] = -35.4, -17.7) than controls. Adults with T1D reported poorer sleep quality (MD in standardized sleep quality score = 0.51; 95% CI = 0.33, 0.70), with higher scores reflecting worse sleep quality) than controls, but there was no difference in self-reported sleep duration. Adults with TID who reported sleeping >6 hours had lower hemoglobin A1c (HbA1c) levels than those sleeping ≤6 hours (MD = -0.24%; 95% CI = -0.47, -0.02), and participants reporting good sleep quality had lower HbA1c than those with poor sleep quality (MD = -0.19%; 95% CI = -0.30, -0.08). The estimated prevalence of obstructive sleep apnea (OSA) in adults with TID was 51.9% (95% CI = 31.2, 72.6). Patients with moderate-to-severe OSA had a trend toward higher HbA1c (MD = 0.39%, 95% CI = -0.08, 0.87). CONCLUSION T1D was associated with poorer sleep and high prevalence of OSA. Poor sleep quality, shorter sleep duration, and OSA were associated with suboptimal glycemic control in T1D patients.

Comparison of Polysomnographic and Clinical Presentations and Predictors for Cardiovascular-Related Diseases between Non-Obese and Obese Obstructive Sleep Apnea among Asians

INTRODUCTION Unlike Caucasians, many Asians with obstructive sleep apnea (OSA) are non-obese but are affected by the disease due to predisposing craniofacial structure. Therefore, non-obese and obese OSA may represent different disease entities. The associated risk factors for developing cardiovascular-related diseases, consequently, may be considered separately for the two types of OSA. METHOD We reviewed polysomnographic studies performed in adults (aged ≥ 18 years) diagnosed with OSA (respiratory disturbance index [RDI] ≥ 5). We divided the patients into obese (body mass index [BMI] ≥ 25) and non-obese (BMI < 25) groups. We aimed to determine the differences between these two groups in terms of clinical presentations, polysomno-graphic findings, and association with cardiovascular-related diseases including hypertension, diabetes mellitus, coronary artery disease, and/or cerebrovascular disease. RESULTS Among 194 patients with OSA (RDI ≥ 5), 63.4% were non-obese and 36.6% were obese. Compared with obese OSA patients, non-obese OSA patients were noted to have smaller neck size, less prevalence of hypertension, and less history of frequent nocturia (> 3-4/week), with equal prevalence of excessive daytime sleepiness. Overall, non-obese OSA patients were noted to have milder disease indicated by lower total, supine, and non-supine, NREM RDI and higher mean and nadir oxygen saturations. In the non-obese group, only total obstructive apnea index (OAI) was noted to be a predictor for developing any of the cardiovascular-related diseases after controlling for age, sex, and RDI (odds ratio = 9.7). However, in the obese OSA group, frequent snoring (> 50% of total sleep time), low sleep efficiency (≤ 90%), and low mean oxygen saturation (< 95%) were noted to be significant predictors of cardiovascular-related diseases (odds ratios = 12.3, 4.2, and 5.2, respectively). CONCLUSION Among Asians, most OSA patients were not obese. Compared to obese OSA patients, non-obese OSA patients were noted to have less prevalence of hypertension and less history of nocturia. They were also noted to have overall milder OSA. Only OAI was noted to be a significant predictor for cardiovascular-related disease in the non-obese OSA group.

Relationships among sleep timing, sleep duration and glycemic control in Type 2 diabetes in Thailand.

There is evidence that the sleep and circadian systems play a role in glucose metabolism. In addition to physiological factors, sleep is also affected by behavioral, environmental, cultural and social factors. In this study, we examined whether morning or evening preference, sleep timing and sleep duration are associated with glycemic control in patients with type 2 diabetes residing in Thailand. Two hundred and ten type 2 diabetes patients who were not shift workers completed an interview and questionnaires to collect information on diabetes history, habitual sleep duration and sleep timing. Chronotype, an individual’s tendency for being a “morning” or “evening” person, was assessed using the Composite Score of Morningness (CSM), which reflects an individual’s subjective preference for activities in the morning or evening, as well as mid-sleep time on weekend nights (MSF), which reflects their actual sleep behavior. Most recent hemoglobin A1c (HbA1c) values were retrieved from medical records. Evening preference (as indicated by lower CSM), later bedtime on weekends, and shorter sleep duration correlated with higher HbA1c (r = −0.18, p = 0.01; r = 0.17, p = 0.01 and r = −0.17, p = 0.01, respectively), while there was no association between MSF or wake up time and glycemic control. In addition, later bedtime on weekends significantly correlated with shorter sleep duration (r = −0.34, p < 0.001). Hierarchical regression analyses adjusting for age, sex, body mass index, insulin use and diabetes duration revealed that later bedtime on weekends was significantly associated with poorer glycemic control (B = 0.018, p = 0.02), while CSM was not. Mediation analysis revealed that this association was fully mediated by sleep duration. In summary, later bedtime on weekends was associated with shorter sleep duration and poorer glycemic control in patients with type 2 diabetes. It is likely that patients with later weekend bedtimes curtail their sleep by waking up earlier. Exploring the potential reasons for this phenomenon (e.g. cultural influences, metropolitan lifestyle, environmental factors, family and social obligations) specific to a Thai population may help identify behavioral modifications (i.e. earlier bedtime and/or sleep duration extension) that could possibly lead to improved glycemic control in this population.

Associations between nocturnal urinary 6-sulfatoxymelatonin, obstructive sleep apnea severity and glycemic control in type 2 diabetes.

ABSTRACT Reduced nocturnal secretion of melatonin, a pineal hormone under circadian control, and obstructive sleep apnea have been both identified as risk factors for the development of type 2 diabetes mellitus. Whether they interact to impact glycemic control in patients with existing type 2 diabetes is not known. Therefore, this study explores the relationships between obstructive sleep apnea, melatonin and glycemic control in type 2 diabetes. As diabetic retinopathy may affect melatonin secretion, we also explore the relationship between retinopathy, melatonin and glycemic control. Fifty-six non-shift workers with type 2 diabetes, who were not using beta-blockers, participated. Most recent hemoglobin A1c (HbA1c) levels and the results of ophthalmologic examinations were obtained from medical records. Obstructive sleep apnea was diagnosed using an ambulatory device. Sleep duration and fragmentation were recorded by 7-day wrist actigraphy. The urinary 6-sulfatoxymelatonin/creatinine ratio, an indicator of nocturnal melatonin secretion, was measured in an overnight urine sample. Mediation analyses were applied to explore whether low nocturnal urinary 6-sulfatoxymelatonin/creatinine ratio could be a causal link between increasing obstructive sleep apnea severity [as measured by an Apnea Hypopnea Index (AHI)] and poorer glycemic control, and between the presence of retinopathy and glycemic control. AHI and HbA1c were log-scale (ln) transformed. Obstructive sleep apnea was found in 76.8%, and 25.5% had diabetic retinopathy. The median (interquartile range) of urinary 6-sulfatoxymelatonin/creatinine ratio was 12.3 (6.0, 20.1) ng/mg. Higher lnHbA1c significantly correlated with lower 6-sulfatoxymelatonin/creatinine ratio (p = 0.04) but was not directly associated with OSA severity. More severe obstructive sleep apnea (lnAHI, p = 0.01), longer diabetes duration (p = 0.02), retinopathy (p = 0.01) and insulin use (p = 0.03) correlated with lower urinary 6-sulfatoxymelatonin/creatinine ratio, while habitual sleep duration and fragmentation did not. A mediation analysis revealed that lnAHI negatively correlated with urinary 6-sulfatoxymelatonin/creatinine ratio (coefficient = −2.413, p = 0.03), and urinary 6-sulfatoxymelatonin/creatinine negatively associated with lnHbA1c (coefficient = −0.005, p = 0.02), after adjusting for covariates. Mediation analysis indicated that the effect of lnAHI on lnHbA1c was indirectly mediated by urinary 6-sulfatoxymelatonin/creatinine ratio (B = 0.013, 95% CI: 0.0006, 0.0505). In addition, having retinopathy was significantly associated with reduced nocturnal urinary 6-sulfatoxymelatonin/creatinine ratio, and an increase in HbA1c by 1.013% of its original value (B = −0.013, 95% CI: −0.038, −0.005). In conclusion, the presence and severity of obstructive sleep apnea as well as the presence of diabetic retinopathy were associated with lower nocturnal melatonin secretion, with an indirect adverse effect on glycemic control. Intervention studies are needed to determine whether melatonin supplementation may be beneficial in type 2 diabetes patients with obstructive sleep apnea.

Severity of Obstructive Sleep Apnea in Patients With and Without Cardiovascular-Related Diseases

BACKGROUND: Previous studies have often investigated the association of obstructive sleep apnea (OSA) with cardiovascular morbidity and mortality, but the possibility of reverse causation has not been clearly defined. OBJECTIVE: To examine if the presence of any of the cardiovascular-related diseases, including hypertension, diabetes mellitus, coronary artery disease, and/or cerebrovascular disease, correlates with more severe OSA. METHODS: This was a retrospective study where all patients age ≥ 18 years referred to our sleep laboratory for suspected OSA were included. The data from the full-night baseline and split-night polysomnographic reports were reviewed. Data were then evaluated by logistic regression analysis to compare between 2 groups, the severity of OSA (respiratory disturbance index [RDI] < 15 vs RDI ≥ 15, and RDI < 5 vs RDI ≥ 5), other polysomnographic variables and daytime sleepiness score (Epworth Sleepiness Scale [ESS] score < 10 and ≥ 10). RESULTS: 190 patients were analyzed. The patients with any of the cardiovascular-related diseases were noted to have more severe sleep apnea (RDI ≥ 15), with an adjusted odds ratio of 3.24. Sleep efficiency ≥ 90% and mean oxygen saturation ≥ 95% were observed less commonly in the patients with any of the cardiovascular-related diseases (adjusted odds ratios of 0.45 and 0.36, respectively). There was no statistically significant difference in ESS score. CONCLUSIONS: Patients with any of the cardiovascular-related diseases are at a higher risk of having moderate to severe OSA without significant increase in daytime sleepiness. Therefore, we suggest that patients with any of the cardiovascular-related diseases should be screened for OSA, even if they are asymptomatic.

Continuous Positive Airway Pressure Therapy in Gestational Diabetes With Obstructive Sleep Apnea: A Randomized Controlled Trial

STUDY OBJECTIVES Obstructive sleep apnea (OSA) is associated with gestational diabetes mellitus (GDM). This study assessed the effects of continuous positive airway pressure (CPAP) in obese pregnant females with GDM and OSA. METHODS A randomized controlled trial was conducted (April 2014 - June 2016). Obese females at 24 to 34 weeks gestation and with diet-controlled GDM were screened for OSA. Those with OSA were randomly assigned to receive 2 weeks nightly CPAP or be part of a waitlist control group. After 2 weeks, all patients were offered CPAP. The primary outcome was glucose metabolism, obtained from an oral meal tolerance test (MTT) at baseline and 2 weeks. Pregnancy outcomes were collected. RESULTS Eighteen patients were randomized to CPAP and 18 to control groups. There were no significant changes between groups in fasting glucose, glucose response to MTT, and insulin sensitivity or secretion after 2 weeks. Those adherent to CPAP had significantly improved insulin secretion (P = .016) compared to the control group. When a counterfactual instrumental variable approach was applied to deal with nonadherence, the CPAP group had significantly improved insulin secretion (P = .002) and insulin sensitivity (P = .015). Lower rates of preterm delivery (P = .002), unplanned cesarean section (P = .005), and neonatal intensive care unit admissions (P < .001) were observed among those who used CPAP longer than 2 weeks. CONCLUSIONS Two weeks of CPAP in females with GDM and OSA did not result in improved glucose levels, but insulin secretion improved in those adherent to CPAP. Continued CPAP use was possibly associated with improved pregnancy outcomes. CLINICAL TRIAL REGISTRATION Registry: ClinicalTrials.gov; Title: Obstructive Sleep Apnea and Gestational Diabetes: Incidence and Effects of Continuous Positive Airway Pressure Treatment on Glucose Metabolism; Identifier: NCT02108197; URL: https://clinicaltrials.gov/ct2/show/NCT02108197.

Obstructive sleep apnea and diet-controlled gestational diabetes

BACKGROUND Obstructive sleep apnea (OSA) was shown to be associated with gestational diabetes mellitus (GDM). However, prevalence of OSA in GDM women, its relationship to metabolic control, and predictive factors have not been studied. MATERIAL AND METHODS Eighty-two obese pregnant women with diet-controlled GDM between 24 and 34 weeks of gestation participated. The Berlin questionnaire was used to assess OSA symptoms. OSA was diagnosed using an overnight monitor. Fasting glucose and hemoglobin A1c (HbA1c) were obtained. Those with OSA underwent meal tolerance test (MTT) to assess their metabolic parameters. Classification tree analysis was used to develop a screening tool for OSA. RESULTS At a median gestational age of 29 weeks, OSA was diagnosed in 52.4% of the women, with a median apnea hypopnea index of 9.4 (interquartile range 6.4, 12.4). More severe OSA was significantly correlated with higher fasting glucose but not HbA1c. For those with OSA, sleep parameters related to oxygen desaturation significantly correlated with higher fasting insulin resistance and more severe β-cell dysfunction, as evaluated by MTT. A screening tool involving two variables, neck circumference and Berlin Questionnaire score, was developed. The sensitivity and specificity were 86% and 51%, respectively. The overall accuracy was 70%. CONCLUSION OSA is prevalent in obese pregnant women with diet-controlled GDM in the late second to early third trimester. OSA severity, especially the degree of oxygen desaturation, correlated with fasting glucose, insulin resistance, and β-cell function. A simple screening tool involving the Berlin Questionnaire and neck circumference can aid in predicting OSA in this patient group.

Effect of Heated Humidification on CPAP Therapy Adherence in Subjects With Obstructive Sleep Apnea With Nasopharyngeal Symptoms

BACKGROUND: The addition of heated humidification to CPAP has been shown to improve nasal adverse effects in subjects with obstructive sleep apnea (OSA). However, current data regarding improvement in CPAP adherence is conflicting. Furthermore, there are no data from a tropical climate area with a high humidity level. METHODS: In this prospective randomized crossover study conducted in Thailand, subjects with moderate to severe OSA with nasopharyngeal symptoms post-split-night study were enrolled in the study. Subjects were randomly assigned to receive CPAP with or without heated humidification for 4 weeks and then crossed over. Information on CPAP adherence, quality of life assessed by the Functional Outcomes of Sleep Questionnaire, nasopharyngeal symptoms assessed by a modified XERO questionnaire, and bedroom ambient humidity and temperature data were obtained. RESULTS: Data were collected on 20 subjects with OSA during the period of January to December 2014. Although the addition of heated humidification appeared to improve average hours of use for all days when compared with conventional CPAP, the difference was not statistically significant (CPAP with heated humidification = 4.6 ± 1.7 h/night; conventional CPAP = 4.0 ± 1.7 h/night, P = .1). However, the addition of heated humidification improved CPAP adherence on the days of use (5.5 ± 1.5 h/night) compared with conventional CPAP (5.2 ± 1.4 h/night), P = .033. Quality of life was also improved according to the Functional Outcomes of Sleep Questionnaire score (median 17.6 [interquartile range 3.5]) in the heated humidification group compared with conventional CPAP group (median 17.6 [interquartile range 4.5]), P = .046. Significant reduction in the dry throat/sore throat symptom was noted only when CPAP with heated humidification was used. CONCLUSIONS: Even in a tropical climate area, CPAP adherence and quality of life appeared to improve when heated humidification was employed in subjects with moderate to severe OSA with nasopharyngeal symptoms post-split-night polysomnography. The improvement may be related to a reduction in the dry throat/sore throat symptom.

Immunoglobulin G4-related disease: a rare steroid-responsive disease: IgG4-related disease

A 70‐year‐old man presented with progressive dyspnoea and weight loss. Physical examination revealed only mild pale conjunctiva. The workup showed mild anaemia, mild impaired renal function, and high globulin level. Multiple myeloma was excluded by normal serum protein electrophoresis. The chest radiography and computed tomography (CT) revealed bilateral multifocal patchy infiltration with mediastinal adenopathy. Bronchoscopy was performed. Bronchoalveolar lavage (BAL) fluid examination was negative for infection and malignancy. Tissue pathology revealed diffuse lymphoplasmacytic cell infiltration. Immunohistochemistry revealed positive highlight for CD38, immunoglobulin G (IgG), and IgG4. Serum IgG subclass was requested and showed an IgG4 level of 7230 mg/dL. Examination of bone marrow and submental lymph node pathology were also positive for IgG4. IgG4‐related disease with pulmonary involvement was diagnosed. Treatment with prednisolone (30 mg/day) resulted in improvement in his dyspnoea and almost complete resolution of the pulmonary infiltration on repeated CT at 6 month. This case highlighted a rare occurrence of IgG4‐related disease which was successfully treated with steroid.