Mary S.M. Ip

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.

Alleviation of sleep apnea in patients with chronic renal failure by nocturnal cycler-assisted peritoneal dialysis compared with conventional continuous ambulatory peritoneal dialysis.

Nocturnal hemodialysis has been shown to improve sleep apnea in patients who receive conventional hemodialysis. It was hypothesized that nocturnal peritoneal dialysis (NPD) also is effective in correcting sleep apnea in patients who receive continuous ambulatory PD (CAPD). Overnight polysomnography (PSG) was performed in 46 stable NPD and CAPD patients who were matched for demographic and clinical attributes. The prevalence of sleep apnea, defined as an apnea-hypopnea index (AHI; or frequency of apnea and hypopnea per hour of sleep) > or =15, was 52% for NPD patients and 91% for CAPD patients (P = 0.007). The mean (+/-SD) AHI in NPD and CAPD patients was 31.6 +/- 25.6 and 50.9 +/- 26.4 (P = 0.025), respectively. For validation of the efficacy of NPD in alleviating sleep apnea, a fixed sequence intervention study was performed in which 24 incident PD patients underwent one PSG study during mandatory cycler-assisted NPD while awaiting their turn for CAPD training and a second PSG recording shortly after they were established on stable CAPD. The prevalence of sleep apnea was 4.2% during NPD and 33.3% during CAPD (P = 0.016). AHI increased from 3.4 +/- 1.34 during NPD to 14.0 +/- 3.46 during CAPD (P < 0.001). With the use of bioelectrical impedance analysis, total body water content was significantly lower during stable NPD than CAPD (32.8 +/- 7.37 versus 35.1 +/- 7.35 L; P = 0.004). NPD delivered greater reductions in total body water (-2.81 +/- 0.45 versus -1.34 +/- 0.3 L; P = 0.015) and hydration fraction (-3.63 +/- 0.64 versus -0.71 +/- 0.52%; P = 0.005) during sleep. Pulmonary function tests remained unchanged before and after conversion from NPD to CAPD. These findings suggest that NPD may have a therapeutic edge over CAPD in sleep apnea that is associated with renal failure as a result of better fluid clearance during sleep.

C-Reactive Protein Is Associated With Obstructive Sleep Apnea Independent of Visceral Obesity

BACKGROUND Obstructive sleep apnea (OSA) is associated with adverse cardiovascular outcomes. C-reactive protein (CRP) predicts atherosclerotic complications. Our study evaluates whether OSA is associated with an elevated CRP level, after elimination of known confounders including visceral obesity. METHODS Men without significant chronic medical illness, regular medications, or illness in the preceding 4 weeks were enrolled. Subjects with morbid obesity, newly detected high BP, or fasting glucose were excluded. They underwent polysomnography and MRI of abdomen to quantify visceral fat volume. High-sensitivity CRP levels were measured. RESULTS 111 men with mean body mass index (BMI) 26.3 +/- 3.8 kg/m(2) were evaluated. After adjustment for age, smoking, BMI, waist circumference, and sleep efficiency, CRP correlated positively with the apnea-hypopnea index (AHI) [r = 0.35, p < 0.001], duration of O(2) saturation < 90% (r = 0.29, p = 0.002), and arousal index (r = 0.32, p = 0.001), and it correlated negatively with minimal O(2) saturation (r = -0.29, p = 0.002). These correlations were consistent when adjustment was made for MRI visceral fat volume instead of waist circumference. In the regression model, significant predictors of CRP included AHI, waist circumference, and triglycerides (adjusted R(2), 0.33, p = 0.001, p = 0.002, p = 0.018, respectively). Among the 111 subjects, 32 subjects with no or mild OSA (AHI < 15 events/h) were matched with 32 subjects with moderate-to-severe OSA (AHI > or = 15 events/h) in MRI visceral fat volume. CRP was higher in subjects with moderate-to-severe OSA (median, 1.32; 0.45 to 2.34 mg/L) when compared to subjects with no or mild OSA (median, 0.54; 0.25 to 0.89 mg/L; p = 0.001). CONCLUSIONS In healthy middle-aged men, elevated CRP level is associated with OSA independent of visceral obesity.

Improvement in Sleep Apnea during Nocturnal Peritoneal Dialysis Is Associated with Reduced Airway Congestion and Better Uremic Clearance

BACKGROUND AND OBJECTIVES Among peritoneal dialysis (PD) patients, nocturnal PD (NPD) is known to improve sleep apnea compared with continuous ambulatory peritoneal dialysis (CAPD), but the contributing factors are unclear. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS Thirty-eight incident ESRD patients underwent overnight polysomnography (PSG) during NPD and CAPD. Bioelectrical impedance analysis, magnetic resonance imaging of the upper airway, and urea kinetics (Kt/V) during sleep were measured on both occasions. RESULTS The prevalence of severe sleep apnea (apnea-hypopnea index, AHI > or = 15/h) was 21.1% during NPD, and 42.1% during CAPD. Mean AHI increased from 9.6 +/- 2.7/h during NPD to 21.5 +/- 4.2/h during CAPD. Both obstructive and central apnea worsened after conversion to CAPD. NPD achieved greater reductions in total body water, hydration fraction, and net ultrafiltration than CAPD during sleep. Overnight peritoneal Kt/V and creatinine clearance were lower after conversion. Both peritoneal Kt/V and peritoneal creatinine clearance correlated with AHI, as did their changes after conversion. Volumetric magnetic resonance imaging revealed reduced pharyngeal volumes and cross-sectional area, and tongue enlargement after conversion. CONCLUSIONS Improvement in sleep apnea during NPD versus CAPD is associated with better fluid and uremic clearance and reduced upper airway congestion during sleep.

Mitochondrial transfer of induced pluripotent stem cell-derived mesenchymal stem cells to airway epithelial cells attenuates cigarette smoke-induced damage.

Transplantation of mesenchymal stem cells (MSCs) holds great promise in the repair of cigarette smoke (CS)-induced lung damage in chronic obstructive pulmonary disease (COPD). Because CS leads to mitochondrial dysfunction, we aimed to investigate the potential benefit of mitochondrial transfer from human-induced pluripotent stem cell-derived MSCs (iPSC-MSCs) to CS-exposed airway epithelial cells in vitro and in vivo. Rats were exposed to 4% CS for 1 hour daily for 56 days. At Days 29 and, human iPSC-MSCs or adult bone marrow-derived MSCs (BM-MSCs) were administered intravenously to CS-exposed rats. CS-exposed rats exhibited severe alveolar destruction with a higher mean linear intercept (Lm) than sham air-exposed rats (P < 0.001) that was attenuated in the presence of iPSC-MSCs or BM-MSCs (P < 0.01). The attenuation of Lm value and the severity of fibrosis was greater in the iPSC-MSC-treated group than in the BM-MSC-treated group (P < 0.05). This might have contributed to the novel observation of mitochondrial transfer from MSCs to rat airway epithelial cells in lung sections exposed to CS. In vitro studies further revealed that transfer of mitochondria from iPSC-MSCs to bronchial epithelial cells (BEAS-2B) was more effective than from BM-MSCs, with preservation of adenosine triphosphate contents. This distinct mitochondrial transfer occurred via the formation of tunneling nanotubes. Inhibition of tunneling nanotube formation blocked mitochondrial transfer. Our findings indicate a higher mitochondrial transfer capacity of iPSC-MSCs than BM-MSCs to rescue CS-induced mitochondrial damage. iPSC-MSCs may thus hold promise for the development of cell therapy in COPD.

Effect of Sandostatin® LAR® on sleep apnoea in acromegaly: correlation with computerized tomographic cephalometry and hormonal activity

OBJECTIVES Sleep apnoea has been reported to occur in subjects with acromegaly. This study evaluates the relationship among biochemical activity, sleep apnoeic activity and upper airway anatomic profile in acromegaly, and the effect of Sandostatin® LAR®, a long‐acting somatostatin analogue, on these parameters.

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

BACKGROUND Obstructive 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. METHODS All 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. RESULTS Of 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. CONCLUSIONS In 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.

Clinical profiles of Chinese patients with diffuse panbronchiolitis

BACKGROUND Diffuse panbronchiolitis (DPB), characterised by progressive sinobronchial sepsis, is well characterised in Japanese subjects but not in other ethnic groups. The experience with DPB in seven Chinese patients is described and the clinical profiles compared with those of Japanese subjects. METHODS Seven Chinese patients (three women; mean (SD) age 48(18.6) years, all never smokers) who attended a teaching hospital centre and fulfilled the diagnostic criteria for DPB were assessed prospectively for clinical, radiological, lung function, microbiological, and other “characteristic” laboratory parameters. RESULTS Lung function assessment showed a typical obstructive pattern (n = 5) and air trapping (n = 7). Typical bronchiolar infiltration by lymphocytes and plasma cells and accumulation of foamy macrophages in the intraluminal tissue were detected in open lung biopsy specimens (n = 2). Chest radiographs and high resolution computed tomographic scans revealed hyperinflation, diffuse nodules, bronchial thickening and dilatation, peripheral hypoattenuation, and bronchiolectasis. Radiological improvement, manifest as a reduction in nodular density and bronchial thickening, and persistence of other abnormalities such as air trapping were not accurately depicted by the classical Nakata or Akira classifications. The other “characteristic” features such as HLA-B54, IgG subclass deficiency, raised CD4/CD8 T lymphocyte ratio, cold haemagglutinaemia, raised IgA, IgG, and rheumatoid factor were not present. Treatment with erythromycin led to excellent responses in symptoms, lung function indices, and the radiological picture. A review of the non-Japanese cases in the literature reveals that this absence of typical “additional features” in DPB might also be applicable to non-Japanese patients. CONCLUSIONS We report the only series of non-Japanese Mongoloid patients with well characterised DPB who had uncharacteristic investigation profiles. This experience should help other clinicians in the investigation and management of DPB in non-Japanese patients.

Sleep apnea is a novel risk predictor of cardiovascular morbidity and death in patients receiving peritoneal dialysis.

Sleep apnea syndrome is increasingly recognized in peritoneal dialysis patients; however, its prognostic implication in this population is unknown. To study this, we prospectively followed the clinical outcome of 93 peritoneal dialysis patients with baseline polysomnography. Of these, 51 were diagnosed with the syndrome defined by an apnea-hypopnea index (AHI) of at least 15 per hour. During a median follow-up of 41 months, there were 30 deaths, of which 17 were due to cardiovascular causes. Kaplan-Meier analysis for the entire follow-up period indicated that patients with sleep apnea at baseline had significantly higher all-cause and cardiovascular mortality during follow-up than those without. Minimal nocturnal saturation and desaturation indices were predictors of mortality and cardiovascular events at univariate analysis. Multivariable Cox regression analysis identified significant sleep apnea syndrome at baseline as an independent predictor of increased all-cause mortality independent of age, male gender, and diabetic status. Further, an absolute increase in the AHI was associated with an incremental risk of cardiovascular events. Thus, sleep apnea syndrome, detected at the start of peritoneal dialysis, is a novel risk predictor for subsequent mortality and cardiovascular events.

Manganese superoxide dismutase and catalase genetic polymorphisms, activity levels, and lung cancer risk in Chinese in Hong Kong

Introduction: Antioxidants play an important role in counteracting the effects of potential carcinogens. We investigated the risk of lung cancer development with respect to manganese superoxide dismutase (MnSOD) and catalase genetic polymorphisms and their association with erythrocyte antioxidant activities. Patients and Methods: This was a case-control study involving patients with confirmed lung cancer and age-matched healthy controls. Genotyping of MnSOD and catalase in DNA extracted from peripheral white cells was performed by polymerase chain reaction-based restriction fragment length polymorphism. Erythrocyte superoxide dismutase and catalase activities were measured spectrophotometrically using chemical kinetic reactions. Results: We recruited 240 patients with lung cancer (63% male, aged 55.6 ± 11.9 years, 58% adenocarcinoma, 85% clinical stage III or IV) and 240 age-matched healthy controls. The frequencies of the Val allele of MnSOD gene and the C allele of catalase gene were common (>86% and 90%, respectively), with similar distribution, in both patients with lung cancer and controls. The homozygous variant genotypes of MnSOD and catalase were not associated with increased lung cancer risk. The erythrocyte SOD and catalase activity was significantly lower among all patients with lung cancer as a whole compared with controls, irrespective of genotypes. However, patients with adenocarcinoma and non-adenocarcinoma showed differences in SOD and catalase activity among different genotypes in comparison with controls. Conclusion: The common Val16Ala MnSOD polymorphism and C-T substitution in the promoter region of the catalase gene do not confer increased or reduced risk of lung cancer in Chinese in Hong Kong.