Jamie C.M. Lam

Randomised study of three non‐surgical treatments in mild to moderate obstructive sleep apnoea

Background: Patients with mild to moderate obstructive sleep apnoea (OSA) may be managed with different treatment options. This study compared the effectiveness of three commonly used non-surgical treatment modalities. Methods: Subjects with mild to moderate OSA were randomised to one of three treatment groups for 10 weeks: conservative measures (sleep hygiene) only, continuous positive airways pressure (CPAP) in addition to conservative measures or an oral appliance in addition to conservative measures. All overweight subjects were referred to a weight-reduction class. OSA was assessed by polysomnography. Blood pressure was recorded in the morning and evening in the sleep laboratory. Daytime sleepiness was assessed with the Epworth Sleepiness Scale. Health-related quality of life (HRQOL) was assessed with the 36-Item Short-Form Health Survey (SF-36) and Sleep Apnoea Quality of Life Index (SAQLI). Results: 101 subjects with a mean (SEM) apnoea–hypopnoea index (AHI) of 21.4 (1.1) were randomised to one of the three groups. The severity of sleep-disordered breathing was decreased in the CPAP and oral appliance groups compared with the conservative measures group, and the CPAP group was significantly better than the oral appliance group. Relief from sleepiness was significantly better in the CPAP group. CPAP was also better than the oral appliance or conservative measures in improving the “bodily pain” domain, and better than conservative measures in improving the “physical function” domain of SF-36. Both CPAP and the oral appliance were more effective than conservative measures in improving the SAQLI, although no difference was detected between the CPAP and oral appliance groups. CPAP and the oral appliance significantly lowered the morning diastolic blood pressure compared with baseline values, but there was no difference in the changes in blood pressure between the groups. There was also a linear relationship between the changes in AHI and body weight. Conclusion: CPAP produced the best improvement in terms of physiological, symptomatic and HRQOL measures, while the oral appliance was slightly less effective. Weight loss, if achieved, resulted in an improvement in sleep parameters, but weight control alone was not uniformly effective.

Prevalence and recognition of obstructive sleep apnea in Chinese patients with type 2 diabetes mellitus.

BACKGROUNDnObstructive sleep apnea (OSA) is associated with disorders of glucose metabolism. Previous studies revealed a high prevalence of OSA among subjects with type 2 diabetes mellitus (DM). The aims of this study were to determine the prevalence of OSA and associated clinical factors in Chinese patients with DM.nnnMETHODSnAll records of the DM clinic at a teaching hospital in Hong Kong were screened between January 2007 and June 2008. Inclusion criteria for patients were Chinese, aged 18 to 75 years, with type 2 DM. Patients with unstable medical illnesses, gestational diabetes, or on renal replacement therapy were excluded.nnnRESULTSnOf 3,489 records screened, 1,859 subjects were eligible. A random sample of 663 (mean age, 58.2 ± 10.8; mean BMI, 26.0 ± 4.6), except six with known OSA, were invited for polysomnography (PSG). Of 165 subjects on which PSG was performed, OSA was diagnosed (apnea-hypopnea index [AHI] ≥ 5.0/h) in 89 subjects (53.9%, median Epworth Sleepiness Scale, 6 [interquartile range 3, 10]). Fifty-four (32.7%) had moderate/severe OSA (AHI ≥ 15/h). The estimated OSA prevalence in this diabetic cohort was 17.5% (24.7% in men, 10.3% in women). Regression analysis identified that AHI was associated independently with higher BMI, advanced age, male sex, and higher diastolic BP (R(2) = 29.6%). The adjusted OR of requiring three or more antihypertensive drugs in moderate/severe OSA was 2.48 (95% CI, 1.05-5.87). No association between glycemic control (HbA1c) and sleep was identified.nnnCONCLUSIONSnIn conclusion, OSA is more prevalent in Chinese adults with DM than in the general population. A high index of suspicion for OSA in patients with DM is warranted, because they may not have overt daytime sleepiness.

The efficacy of oral appliances in the treatment of severe obstructive sleep apnea

ObjectivesThe purpose of this study is to evaluate the efficacy of oral appliance (OA) treatment for subjects with severe obstructive sleep apnea (OSA) and to determine the dental parameters associated with treatment outcomes.Study designThis study uses a prospective longitudinal design.MethodsConsecutive Chinese subjects with severe OSA who refused continuous positive airway pressure treatment were recruited. Their dental measurements were taken from lateral cephalometric radiographs. Polysomnograms with OA were repeated at 3xa0months and 1xa0year. Blood pressure was taken in the morning after sleep studies.ResultsThirty-four subjects were evaluated at 3xa0months and 1xa0year according to the principle of intention-to-treat analysis. OA reduced AHI significantly in subjects with favorable responses, from 49.3 (37.4–67) to 12.5 (6.1–15.7), pu2009<u20090.001 at 3xa0months and from 47.5 (41.1–72.9) to 13.1 (6.0–14.0), pu2009<u20090.001 at 1xa0year. These OSA subjects had an increased overjet at baseline compared to those with unfavorable responses (pu2009≤u20090.05). Systolic blood pressure was significantly reduced in those hypertensive OSA subjects after 3xa0months and 1xa0year of treatment.ConclusionsOA reduces the severity of sleep apnea, and the effect is maintained at 1xa0year in subjects with retrognathism. OA appears to reduce systolic blood pressure in hypertensive OSA subjects at 3xa0months and 1xa0year.

The efficacy of a brief motivational enhancement education program on CPAP adherence in OSA: a randomized controlled trial.

BACKGROUNDnPoor adherence to CPAP treatment in OSA adversely affects the effectiveness of this therapy. This randomized controlled trial (RCT) examined the efficacy of a brief motivational enhancement education program in improving adherence to CPAP treatment in subjects with OSA.nnnMETHODSnSubjects with newly diagnosed OSA were recruited into this RCT. The control group received usual advice on the importance of CPAP therapy and its care. The intervention group received usual care plus a brief motivational enhancement education program directed at enhancing the subjects knowledge, motivation, and self-efficacy to use CPAP through the use of a 25-min video, a 20-min patient-centered interview, and a 10-min telephone follow-up. Self-reported daytime sleepiness adherence-related cognitions and quality of life were assessed at 1 month and 3 months. CPAP usage data were downloaded at the completion of this 3-month study.nnnRESULTSnOne hundred subjects with OSA (mean ± SD, age 52 ± 10 years; Epworth Sleepiness Scales [ESS], 9 ± 5; median [interquartile range] apnea-hypopnea index, 29 [20, 53] events/h) prescribed CPAP treatment were recruited. The intervention group had better CPAP use (higher daily CPAP usage by 2 h/d [Cohen d = 1.33, P < .001], a fourfold increase in the number using CPAP for ≥ 70% of days with ≥ 4 h/d [P < .001]), and greater improvements in daytime sleepiness (ESS) by 2.2 units (P = .001) and treatment self-efficacy by 0.2 units (P = .012) compared with the control group.nnnCONCLUSIONSnSubjects with OSA who received motivational enhancement education in addition to usual care were more likely to show better adherence to CPAP treatment, with greater improvements in treatment self-efficacy and daytime sleepiness.nnnTRIAL REGISTRYnClinicalTrials.gov; No.: NCT01173406; URL: www.clinicaltrials.gov.

Increased serum levels of advanced glycation end-products is associated with severity of sleep disordered breathing but not insulin sensitivity in non-diabetic men with obstructive sleep apnoea

BACKGROUNDnPatients with diabetes mellitus are known to have increased serum levels of advanced glycation end-products (AGEs), and this is also associated with insulin resistance. This study aimed to investigate the relationship between serum AGEs and insulin sensitivity in non-diabetic subjects with obstructive sleep apnoea (OSA).nnnMETHODSnAdult males with no known comorbidities were recruited from the sleep clinic of a university teaching hospital. They underwent overnight in-laboratory polysomnography. Fasting blood was taken to measure serum AGE and plasma glucose levels. Insulin sensitivity was estimated using the short insulin tolerance test.nnnRESULTSnIn total, 105 subjects with a mean age of 43.5 (standard deviation [SD] 9.2)years, mean body mass index of 27.1 (SD 4.0)kg/m(2), and median apnoea-hypopnoea index (AHI) of 17 (interquartile range 5-46) were analysed. Serum AGE levels were significantly higher in subjects with OSA (AHI ≥5), compared with those without OSA (AHI <5) (3.9 [SD 1.2] vs. 3.2 [SD 0.8]μg/ml, respectively; P=0.037) after adjusting for confounders. AGE levels were positively correlated with AHI (r=0.318, P=0.001), but not with insulin sensitivity. AGE levels decreased in subjects with moderate-to-severe OSA who received continuous positive airway pressure (CPAP) treatment for three months (n=18, P=0.017).nnnCONCLUSIONSnSerum AGE levels correlate with AHI in non-diabetic adult males. This relationship cannot be explained by insulin sensitivity. Supporting the hypothesis of a direct relationship between AHI and AGEs, AGE levels were found to decline with CPAP therapy.

Impact of nephrotic edema of the lower limbs on obstructive sleep apnea: gathering a unifying concept for the pathogenetic role of nocturnal rostral fluid shift

BACKGROUNDnNocturnal rostral fluid shift has been suggested to be a risk factor for obstructive sleep apnea (OSA) in healthy subjects after lower body positive pressurization. It remains unclear whether this may apply to subjects with nephrotic lower limb edema and, if so, whether disease remission may reverse the accompanying OSA.nnnMETHODSnPatients who presented with steroid-responsive primary nephrotic syndrome with lower limb edema as the predominant presenting clinical feature were recruited. They underwent one overnight polysomnography (PSG) before treatment and a repeat testing after achieving remission of the nephrotic edema.nnnRESULTSnAmong 23 consecutive nephrotic subjects, 11 (48%) had polysomnographic evidence of sleep apnea [apnea-hypopnea index (AHI)≥5] upon presentation. After steroid-based treatment, there was remission of proteinuria associated with complete disappearance of lower limb edema, significant reduction of body mass index, waist, hip and calf circumferences and total body water mainly in the extracellular compartment. Repeat PSG, performed 8.1±2.6 months later, showed that the overall (N=23) respiratory disturbance index (RDI) and AHI fell from 17.3±5.0 to 8.7±2.5 (P<0.05) and from 16.3±5.1 to 7.8±2.3 (P=0.057), respectively. Among the 11 subjects with sleep apnea detected at baseline, their AHI and RDI fell from 33.4±7.8 to 15.0±3.7 (P<0.05) and from 34.8±7.6 to 16.5±4.0 (P<0.05), respectively. There was also concomitant improvement in sleep efficiency, mean nocturnal oxygen saturation, shorter duration during sleep with oxygen saturation<95 and <90% and reduced desaturation index. There was also subjective improvement in self-reported daytime sleepiness.nnnCONCLUSIONSnNephrotic lower limb edema is associated with disturbed respiratory breathing and increased propensity to OSA, which was reversed upon remission of the nephrosis. This gathers a unifying concept for the role of nocturnal rostral fluid shift in the pathogenesis of OSA.

Determinants of daytime blood pressure in relation to obstructive sleep apnea in men.

Abstract This study investigated the roles of different potential pathophysiological mechanisms in the determination of blood pressure in relation to obstructive sleep apnea. The study was designed as a cross-sectional study. Consecutive healthy male subjects who were to undergo polysomnography were recruited. Demographic and anthropometric data were collected. Blood pressure measurements were taken in the evening before sleep and the next morning on waking. Overnight urinary samples for catecholamines and fasting blood for cortisol, insulin, glucose, and lipids were taken. Ninety-four men were analyzed, with a mean age of 43.7xa0±xa09.3xa0years and mean apnea–hypopnea index (AHI) of 27.5xa0±xa026.2 events/h. Sixty-nine patients (73%) had obstructive sleep apnea (AHIxa0≥xa05). Urinary catecholamines were positively correlated with severity of sleep apnea, independent of obesity. Blood pressure measurements correlated with age, obesity, severity of sleep apnea, and urinary catecholamines. Regression analysis showed that sleep indices and urinary catecholamines were independent determinants of morning systolic and diastolic blood pressure, respectively, while total cholesterol and waist circumference were respective additional factors. Urinary catecholamines and waist circumference were determinants of evening blood pressure, with morning cortisol being an additional determinant for diastolic blood pressure. Obstructive sleep apnea and related sympathetic activity contributed significantly to the determination of daytime blood pressure in overweight middle-aged men without overt cardiometabolic diseases, and other contributing factors include abdominal obesity, total cholesterol, and cortisol levels.

A pathway underlying the impact of CPAP adherence on intimate relationship with bed partner in men with obstructive sleep apnea

PurposeOur aim was to determine the pathway underlying the effects of continuous positive airway pressure (CPAP) adherence on intimate relationship with bed partner in men with obstructive sleep apnea (OSA). We hypothesized that CPAP with good adherence affected the intimate relationship with bed partner directly and indirectly, and it was mediated through daytime sleepiness and activity level in men with OSA.MethodsData were obtained from an education program for enhancing CPAP adherence. Men who were newly diagnosed of OSA and CPAP therapy naïve were recruited in a tertiary teaching hospital.ResultsSelf-reported quality of life [Functional Outcomes of Sleep Questionnaire], daytime sleepiness [Epworth Sleepiness Scale (ESS)], and negative emotion symptoms [depression, anxiety, stress scale] were assessed before and after CPAP treatment at 1-year assessment. Seventy-three men were included in the data analysis, with a meanu2009±u2009SD age of 52u2009±u200910xa0years, body mass index of 29.0u2009±u20095.2xa0kg/m2, ESS of 9.5u2009±u20095.6, and median [interquartile range(IR)] apnea and hypopnea index of 31 (21, 56) events/h. The median (IR) CPAP daily usage was 4.3(0, 6.1)u2009h/day. From the path analysis, CPAP therapy was shown to improve intimate relationship directly (ßu2009=u20090.185) and indirectly (ßu2009=u20090.050) by reducing daytime sleepiness and increasing activity level. However, negative emotion symptoms were not the mediators between CPAP adherence and the intimate relationship.ConclusionsCPAP therapy with good adherence is related directly and indirectly to a better intimate relationship with bed partner in men with OSA. It was possibly attributed to reduced daytime sleepiness and increased activity level.

Plasma EGFR Mutation Detection Associated With Survival Outcomes in Advanced-Stage Lung Cancer

UNLABELLEDnWe confirmed the performance of an array method for plasma epidermal growth factor receptor (EGFR) mutation detection and showed the association of plasma EGFR mutation with survival outcomes.nnnBACKGROUNDnNoninvasive detection of epidermal growth factor receptor (EGFR) mutation in plasma is feasible and could be adjunct for therapeutic monitoring especially when repeated biopsy of tumor tissue is challenging. The aims of this study were to establish the diagnostic performance of peptide nucleic acid-locked nucleic acid polymerase chain reaction followed by custom array for plasma EGFR mutation and to evaluate the association of detection with clinical characteristics and survival outcomes.nnnMATERIALS AND METHODSnPlasma genomic DNA from consecutive advanced lung cancer subjects was tested for EGFR mutations before anticancer treatment, and compared with mutation status in tumor tissue. Clinical characteristics were compared between patients who were EGFR-mutant and wild type; and within EGFR mutants, whether EGFR mutations could be detected in plasma.nnnRESULTSnIn 74 lung cancer patients, the sensitivity, specificity, and positive and negative predictive values of plasma EGFR detection were 79.1%, 96.8%, 97.1%, and 76.9%, respectively. EGFR mutants with concomitant detection of plasma EGFR mutation showed worse survival compared with mutants with no concomitant plasma mutation detected in biopsy specimens.nnnCONCLUSIONnPlasma EGFR mutation detected using this method demonstrated high diagnostic performance. In EGFR mutants, plasma EGFR mutation detection correlated not only EGFR mutation status in biopsy but was also associated with worse prognosis compared with EGFR mutant without plasma EGFR mutation detection.

Linguistic and psychometric validation of the Chinese version of the self-efficacy measures for sleep apnea questionnaire

OBJECTIVESnThe self-efficacy measure for sleep apnea (SEMSA) questionnaire was shown to be an effective tool to assess adherence-related cognitions on continuous positive airway pressure (CPAP) therapy in obstructive sleep apnea (OSA) subjects. SEMSA helps to solicit fundamental information for formulating strategies to promote CPAP adherence for better treatment outcomes. The objective of our study was to perform a linguistic and psychometric evaluation of a Chinese version of the SEMSA (SEMSA-C).nnnMETHODSnData were obtained from 100 subjects in a randomized controlled trial (RCT) on CPAP education. Subjects were newly diagnosed of OSA and naïve to CPAP therapy.nnnRESULTSnA 26-item SEMSA-C was obtained by a rigorous linguistic validation process. Internal consistency was high with Cronbach α>0.88. One-week test-retest intraclass correlation coefficient (ICC) ranged from 0.70 to 0.82. Principal component factor analysis identified three of the same hypothesized factors (perceived risks, outcome expectancies, and treatment self-efficacy) as in the original version. CPAP adherence was associated with outcome expectancies and treatment self-efficacy at 3-month assessment. Further, SEMSA-C demonstrated an improvement in self-efficacy after CPAP use.nnnCONCLUSIONSnSEMSA-C shows similar psychometric properties as the original English version. It is a reliable and responsive instrument to measure perceived risks, outcome expectancies, and treatment self-efficacy in Chinese subjects with OSA.