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Rationale: Bronchopulmonary dysplasia increases the risk of disability in extremely preterm infants. Although the pathophysiology remains uncertain, prior exposure to intermittent hypoxemia may pla...

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.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.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 score10), 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 (p0.10).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.

Sleep disorders are extremely common and have substantial adverse impacts on both quality of life and mental health. Three of the most common sleep disorders are insomnia, obstructive sleep apnea (OSA), and restless legs syndrome (RLS). Psychiatric disorders such as depression and anxiety are more common in people who have insomnia. Furthermore, chronic insomnia is also a risk factor for the development of psychiatric disorders.1 OSA is a common respiratory sleep disorder characterized by recurrent upper airway collapse during sleep, leading to recurrent asphyxia and sleep fragmentation. Patients with OSA are at increased risk of having motor vehicle crashes, cardiovascular disease, hypertension, and stroke.2,3 Furthermore, OSA is an independent risk factor for the development of incident depression.4 Treatment of OSA leads to substantial improvements in daytime sleepiness, mood, and quality of life.5,6 RLS is a sensorimotor disorder that has a significant impact on sleep. Characteristic symptoms include the desire to move the limbs associated with paresthesia or dysesthesia, which begin or worsen during periods of inactivity predominately in the evening and are relieved by movement.7 A number of studies have demonstrated significant associations between RLS and daytime dysfunction, depression, and anxiety.8–10 Indigenous North American people (American Indian) are a medically vulnerable population with reduced access to healthcare services. They have an increased risk of developing health problems, such as diabetes, cardiovascular disease, obesity, and traumatic injuries.11–13 Furthermore, this population has high rates of depression and other mental health problems.14 The purpose of this study was to assess the prevalence of common sleep symptoms in this population and to determine whether these symptoms are associated with depression. To accomplish this, we performed a community-based survey study of adult indigenous North American people living in the northwestern part of British Columbia, Canada.

Objective To evaluate bronchopulmonary dysplasia (BPD), serious brain injury, and severe retinopathy of prematurity (ROP) as predictors of poor long-term outcome in very low birth weight infants. Study design We examined the associations between counts of the 3 morbidities and long-term outcomes in 1514 of 1791 (85%) infants with birth weights of 500-1250 g who were enrolled in the Caffeine for Apnea of Prematurity trial from October 1999, to October 2004, had complete morbidity data, and were alive at 36 weeks postmenstrual age (PMA). BPD was defined as use of supplemental oxygen at 36 weeks PMA. Serious brain injury on cranial ultrasound included grade 3 and 4 hemorrhage, cystic periventricular leucomalacia, porencephalic cysts, or ventriculomegaly of any cause. Poor long-term outcome was death after 36 weeks PMA or survival to 5 years with 1 or more of the following disabilities: motor impairment, cognitive impairment, behavior problems, poor general health, deafness, and blindness. Results BPD, serious brain injury, and severe ROP occurred in 43%, 13%, and 6% of the infants, respectively. Each of the 3 morbidities was similarly and independently correlated with poor 5-year outcome. Rates of death or disability (95% CI) in children with none, any 1, any 2, and all 3 morbidities were 11.2% (9.0%-13.7%), 22.9% (19.6%-26.5%), 43.9% (35.5%-52.6%), and 61.5% (40.6%-79.8%), respectively. Conclusions In very low birth weight infants who survive to 36 weeks PMA, a count of BPD, serious brain injury, and severe ROP predicts the risk of a late death or survival with disability at 5 years.

To evaluate the mortality and long-term morbidity rates of extremely low birth weight (ELBW) infants admitted to neonatal intensive care units (NICUs).This was a longitudinal cohort study of all admissions born between 1983 and 2003 with birth weight ≤ 800 g at a single tertiary NICU. Trends in survival and neurodevelopmental outcome rates at school entry in four 5-year epochs were analyzed.Of 917 admissions, 552 survived to NICU discharge, with significantly increasing survival rates from 46% in epoch 1 to 71% in epoch 4 (P.0001). Although the overall impairment rate of 30% did not change, the pattern of impairments did. Cognitive (P = .017) and hearing (P = .014) impairment rates increased. Visual impairment rates decreased (P = .042), with a trend toward decreasing cerebral palsy from 20% to 12% (P = .061).Improved survival of low birth weight preterm infants has been associated with different types of neurodevelopmental impairments, including increased cognitive impairment rates.

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).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.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.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.

OBJECTIVE: To determine the extent that social variables influence cognitive development of very low birth weight (VLBW) infants across the preschool years. STUDY DESIGN: Participants were VLBW (500-1250 g) children enrolled in the Caffeine for Apnea of Prematurity randomized trial between 1999 and 2004. We investigated the relationships between 4 potential social advantages: higher maternal education, higher paternal education, caregiver employment, and 2 biologic parents in the same home--and gain in cognitive scores. Cognitive assessments were performed at the corrected ages of 18 months (Mental Development Index score on the Bayley Scales of Infant Development II) and 5 years (Full Scale IQ on the Wechsler Preschool and Primary Scale of Intelligence III). Cognitive gain was computed by subtracting each individual 18-month Mental Development Index score from the corresponding Full Scale IQ at 5 years. RESULTS: Data were available for 1347 children. Mean (SD) cognitive scores were 90.8 (15.7) at 18 months and 98.9 (14.5) at 5 years. Multivariable regression showed that higher maternal education, higher paternal education, and caregiver employment had independent and additive effects of similar size on cognitive gain (P < .001); the mean cognitive gain between 18 months and 5 years increased by 3.6 points in the presence of each of these advantages. When all 3 were present, cognitive scores improved on average by 10.9 points compared with children without any of these advantages. CONCLUSION: In VLBW children, a count of 3 social advantages strongly predicts gains in cognitive scores across the preschool years.