Effects of 10 days of modest intermittent hypoxia on circulating measures of inflammation in healthy humans.

PURPOSE: Obstructive sleep apnea (OSA) is a common disease which is associated with elevated inflammatory markers and adhesion molecules, possibly due to nightly intermittent hypoxia (IH). The purpose of this study was to test the hypothesis that IH would increase systemic inflammatory markers in healthy human males. METHODS: Healthy, young male subjects (n = 9; 24 ± 2 years) were exposed to a single daily isocapnic hypoxia exposure (oxyhemoglobin saturation = 80%, 1 h/day) for 10 consecutive days. Serum granulocyte macrophage colony-stimulating factor, interferon-γ, interleukin-1ß, interleukin-6, interleukin-8, leptin, monocyte chemotactic protein-1, vascular endothelial growth factor, intracellular adhesion molecule-1, and vascular cell adhesion molecule-1 were measured before and following the 10 days of IH using Luminex. RESULTS: Nine subjects completed the study (24 ± 2 years; 24 ± 2 kg/m(2)). The mean oxyhemoglobin saturation was 80.8 ± 1.6% during the hypoxia exposures. There was no significant change in any of the markers of inflammation (paired t test, P > 0.2 all cytokines). CONCLUSIONS: These findings suggest that (1) a more substantial or a different pattern of hypoxemia might be necessary to activate systemic inflammation, (2) the system may need to be primed before hypoxic exposure, or (3) increases in inflammatory markers in patients with OSA may be more related to other factors such as obesity or nocturnal arousal.

Pro-atherogenic cytokine profile of patients with suspected obstructive sleep apnea.

PURPOSE: Systemic inflammation is important in the pathogenesis of cardiovascular disease (CVD). We sought to characterize the systemic inflammatory profile associated with obstructive sleep apnea (OSA). METHODS: Adult patients referred for suspected OSA at the University of British Columbia Hospital Sleep Disorders Program were recruited for our study. Patients using HMG CoA inhibitors or a history of CVD were excluded. Fasting serum samples were obtained the morning after their diagnostic polysomnograms. Samples were tested for the following circulating inflammatory mediators: interferon gamma; interleukins 1B, 6, and 8; intercellular and vascular cell adhesion molecules (sICAM-1 and sVCAM-1); and leptin using a multiplex Luminex System. RESULTS: There were 176 patients; 68% were male, mean age = 50 +/- (SD) 11 years, mean apnea/hyponea index (AHI) = 22.9 +/- 22/h, mean desaturation (i.e. % of sleep time spent below an oxyhemoglobin saturation of 90%) = 5.4% +/- 15, and mean body mass index (BMI) = 32.2 +/- 8 kg/m(2). In univariate analyses, only leptin, sVCAM-1, and sICAM-1 were significantly associated with indices of OSA severity (i.e. AHI and/or desaturation). In multivariate linear regression analyses that controlled for BMI, gender, age, and current smoking; desaturation persisted as a significant independent predictor for elevated sVCAM-1 and leptin. CONCLUSIONS: We did not find significant associations between OSA and markers of activated innate immunity (IL-1B, 6, and 8). However, OSA severity was independently associated with serum levels of sVCAM-1 and leptin; these may represent mechanisms involved in the pathogenesis of OSA-related CVD.

Intensive nursing work schedules and the risk of hypoglycaemia in critically ill patients who are receiving intravenous insulin.

RATIONALE: Nurses in the intensive care unit (ICU) commonly work frequent 12 h shifts, potentially leading to fatigue and reduced vigilance. The authors hypothesised that rates of hypoglycaemia in patients receiving an insulin infusion would be associated with the intensity of work of the bedside nurse in the preceding 72 h. METHODS: The authors identified ICU patients who had hypoglycaemia (glucose ≤3.5 mmol/l, 63 mg/dl) between October 2006 and June 2007. The number of shifts worked in the previous 72 h was calculated for the nurse caring for the patient when the event occurred (case shift). For each case shift, the authors identified up to three control shifts (24, 48 and 72 h before the event in the same patient) and calculated the number of shifts worked by nurses on these shifts in the previous 72 h. Conditional logistic regression was used to determine whether the number of shifts worked was associated with hypoglycaemia. RESULTS: There were 41 events (32 patients). Each additional shift worked in the previous 72 h was associated with a significantly increased risk of hypoglycaemia (OR = 1.65/shift, 95% CI 1.01 to 2.68, p = 0.04) after controlling for nurse age and experience. The association was greater for the 23 events associated with an error in management according to the insulin protocol (OR = 2.93/shift, 1.15 to 7.44, p = 0.02) compared with events not associated with an error (OR = 1.34/shift, 0.73 to 2.45, p = 0.34). CONCLUSIONS: Intensive nursing work schedules are associated with hypoglycaemic events in ICU patients.

Clinical manifestations and consequences of obstructive sleep apnea.

Obstructive sleep apnea is a common respiratory disorder that is underdiagnosed and associated with a variety of adverse health and safety consequences. Treatment is effective in improving quality of life and reducing morbidity. This underscores the importance of considering the diagnosis in suitable patients, verifying the diagnosis, and initiating prompt, effective therapy. In this review, the risk factors, symptoms and signs, diagnosis, clinical consequences, and treatment of obstructive sleep apnea are discussed.

The impact of CPAP on cardiovascular biomarkers in minimally symptomatic patients with obstructive sleep apnea: a pilot feasibility randomized crossover trial.

BACKGROUND: Previous, largely uncontrolled studies demonstrated the substantial effects of continuous positive airway pressure ventilation (CPAP) on a variety of physiologic and biochemical markers known to be risk factors for cardiovascular disease in patients with obstructive sleep apnea (OSA). In this pilot crossover study, we assessed (1) the feasibility of using CPAP in a group of minimally symptomatic patients with OSA, assessed through patient compliance and (2) CPAP therapy's effect on biomarkers in these patients. METHODS: We studied patients with minimal daytime sleepiness who were referred to the University of British Columbia's Hospital Sleep Clinic with suspected OSA and an apnea-hypopnea index (AHI) > 15 events/h. Patients were randomized to either CPAP or no therapy for 4 weeks followed by a washout of 4 weeks, and then a crossover to the other intervention. Fasting morning blood and urine, 24-h blood pressure (BP) measurements, and endothelial function (peak flow-mediated dilation to nitroglycerin-mediated dilation ratio) were assessed before and after each study intervention. RESULTS: Nine adult male and four female patients were studied. Mean (SD) age was 55 (7) years, mean AHI = 27.9/h, mean Epworth Sleepiness Score = 6.8 (11/13 had a score < 10), and mean BMI = 31.1 kg/m(2). Mean compliance with CPAP therapy was 5.53 h/night. Compared to no therapy, potential improvements were observed with CPAP for urinary microalbumin, norepinephrine, and epinephrine to creatinine ratios (decreased by 3.51 mg/mmol, 1.70 nmol/mmol, and 0.95 nmol/mmol, respectively); 24-h BP (systolic decreased by 3.60 mmHg, diastolic by 0.70 mmHg); homeostasis model for insulin resistance score (decreased by 1.11); and endothelial function (increased by 7.4%). However, none of the above differences was significant (p > 0.10). CONCLUSION: In this pilot study there were potential improvements in a variety of cardiovascular biomarkers with CPAP. CPAP compliance was reasonably good even though patients were not particularly sleepy. Accordingly, larger randomized controlled trials in this area appear feasible and warranted.

Depression and sleep-related symptoms in an adult, indigenous, North American population.

STUDY OBJECTIVES: Symptoms related to sleep disorders are common and may have substantial adverse impacts on mental health. Indigenous North Americans (American Indian) are a medically vulnerable population with reduced access to healthcare services. The purposes of this study were to assess (1) the prevalence of sleep symptoms and (2) the relationships between symptoms and depression in this population. METHODS: We performed a community-based, door-to-door, cross-sectional survey of 3 indigenous North American groups (Gitxsan, Nisga'a and Tsimshian) living in the northwestern part of British Columbia. Between May and September of 2006, subjects completed a comprehensive questionnaire that included questions about sleep habits, medical history, subjective sleepiness (Epworth Sleepiness Scale), and depression (Personal Health Questionnaire [PHQ-9]). Weights and heights were also measured. RESULTS: Four hundred thirty adults participated in the study (response rate = 42%). Their mean age was 43.2 years. Three hundred ninety-three agreed to have heights and weights measured. Their mean body mass index (BMI) was 31.0 +/- 9.2 kg/m2; 45% of them (177/393) were obese (BMI > 30 kg/m2), and 11% (43/393) were morbidly obese (BMI > 40 kg/m2). The prevalence of sleep complaints was high; insomnia symptoms was reported by 17.2%, symptoms of restless legs syndrome (RLS) by 17.7%, and frequent witnessed apneas reported (i.e., being told they stopped breathing at least 3 nights per week) by 7.6%. Of the 76 patients who had RLS symptoms, only 3 (3.9%) reported having received a diagnosis of RLS from a physician. Thirty-three subjects reported having frequent witnessed apneas, but only 5 of them (15.1%) reported having received a diagnosis of OSA from a physician. The mean PHQ9 score was 4.86 +/- 5.13 (reported by 389 subjects). Twenty-eight subjects (7.20%) had moderate to severe depression, with a PHQ-9 score of 15 or greater. In multivariable linear regression analysis, insomnia symptoms, witnessed apneas, and RLS symptoms were independently associated with an increase in PHQ9 score; frequent witnessed apneas were associated with an increase in PHQ9 by 2.46 (95% confidence interval: 0.47-4.46), insomnia symptoms by 4.49 (95% confidence interval: 3.14-5.83), and RLS symptoms by 1.82, (95% confidence interval: 0.53-3.12). CONCLUSIONS: Sleep symptoms and depression are common in the indigenous North American population of northern British Columbia. Sleep-related symptoms (insomnia symptoms, witnessed nocturnal apneas, and RLS symptoms) are independently associated with depression scores. Improving access to sleep-related diagnostic and therapeutic services may substantially improve mental health in this vulnerable patient population.