Neurobiology of sleep.

The neurobiology of sleep is introduced in the context of interacting wake and sleep systems. Specifically, the transitions from wake to sleep and from non-rapid eye movement to rapid eye movement sleep are discussed based on the flip-flop switch hypothesis. Regulation of wake and sleep according to the opposing homeostatic and circadian systems are also presented.

Hyperinflation is associated with lower sleep efficiency in COPD with co-existent obstructive sleep apnea.

Prior research has shown that individuals with obstructive lung disease are at risk for sleep fragmentation and poor sleep quality. We postulated that patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (known as overlap syndrome) who have more severe lung disease, as measured by lung hyperinflation (inspiratory capacity/total lung capacity), would have greater sleep disturbances independent of traditional measures of sleep apnea. We performed a retrospective chart review of consecutive patients evaluated and treated in an academic pulmonary clinic for overlap syndrome. Pulmonary function tests and polysomnogram data were collected. Thirty patients with overlap syndrome were included in the analysis. We found significant univariable associations between sleep efficiency and apnea/hypopnea index (beta = -0.285, p = 0.01) and between sleep efficiency and lung hyperinflation (beta = 0.654, p = 0.03). Using multivariable linear regression, the relationship between sleep efficiency and lung hyperinflation remained significant (beta = 1.13, p = 0.02) after adjusting for age, sex, body mass index, apnea/hypopnea index, FEV(1)% predicted, oxygen saturation nadir, medications, and cardiac disease. We conclude that increased severity of hyperinflation is associated with worse sleep efficiency, independent of apnea and nocturnal hypoxemia. The mechanisms underlying this observation are uncertain. We speculate that therapies aimed at reducing lung hyperinflation may improve sleep quality in patients with overlap syndrome.

Sleep patterns among rural Chinese twin adolescents.

OBJECTIVE: To examine sleep patterns and influencing factors (age, gender, Tanner Stage, weekday vs. weekend, and pre-sleep activity) among rural Chinese adolescents. METHODS: This is a prospective study among 621 adolescents aged 11-20 years (341 males) using both a questionnaire and sleep diary to obtain bedtime, wake-up time, sleep latency, and total sleep time (TST). RESULTS: The median TST was 8.6h on weekdays and 9.4h on weekends. Despite absence of late night social pressure and computers, a U-shaped TST pattern was observed across age and Tanner Stage, with a nadir around age 15-16 years or Tanner IV. Bedtimes became progressively later with age and Tanner Stage, while wake-up time was considerably earlier for school students or up to Tanner IV. Later wake-up times and longer TST on weekends were seen in school students, but not in non-school adolescents (>17 years). Pre-sleep activity, like reading or studying, was related to later bedtime, earlier wake-up time, and shorter TST in both genders. CONCLUSIONS: Age, Tanner Stage, and pre-sleep activity affected sleep patterns in this sample of rural Chinese adolescents. Later bedtime coupled with earlier wake-up time associated with academic demand appear to be important contributors to sleep loss among school students.

Short sleep duration and adiposity in Chinese adolescents.

OBJECTIVE: To investigate the relationship between sleep duration and adiposity measurements in rural Chinese adolescents. METHODS: This report is based on a cross-sectional analysis of 500 Chinese adolescent twins. Anthropometric measurements and direct adiposity measurements using dual-energy X-ray absorptiometry (DEXA) were taken for all subjects. Standard sleep questionnaires and a 7-day diary were administered to assess sleep duration. RESULTS: Sleep duration decreased with increasing age during adolescence, reaching a nadir at approximately 15 years of age. While BMI and body fat increased through the entire range of adolescence for both genders, after the age of 12, females had much higher amounts of total and truncal fat than males. Graphic plots showed that among females, both long and short sleepers tended to have higher adiposity measures than medium duration sleepers. The association of short sleep duration with higher adiposity measures was significant even after adjustment for covariates. This association was stronger for total and truncal fat and waist circumference (P < 0.05) than for BMI (P = 0.06). In contrast, consistent relationships between sleep duration and adiposity measures were not seen in males. CONCLUSION: Even in this relatively lean Chinese adolescent cohort, short sleep duration was significantly associated with higher adiposity measures and lower lean body mass in females. The results of this study indicate that the observed association between short sleep duration and higher BMI is most likely mediated by factors associated with total and central adiposity rather than lean body mass.

Circadian rhythm sleep disorders.

Humans exhibit endogenous circadian rhythms that are regulated by the master circadian clock of the body, the suprachiasmatic nucleus. These endogenous circadian rhythms are aligned to the outside world by social and environmental cues. Circadian rhythm sleep disorders (CRSD) occur when there is an alteration of the internal timing mechanism or a misalignment between sleep and the 24-h social and physical environment. CRSD are often underrecognized yet should be considered in the differential of patients presenting with symptoms of insomnia and/or hypersomnia. Because behavioral and environmental factors often are involved in the development and maintenance of these conditions, a multimodal treatment approach of behavioral and/or pharmacologic approaches is usually required to synchronize a patient's circadian rhythm to the 24-h environment, consolidate sleep, and improve alertness. Rapid advances in our understanding of the physiologic, cellular, and molecular basis of circadian rhythm and sleep regulation will likely lead to improved diagnostic tools and treatments for CRSD.

Sequential gene expression profiling in lung transplant recipients with chronic rejection.

STUDY OBJECTIVES: Chronic allograft rejection is the leading cause of morbidity and mortality for long-term survivors of lung transplantation. Previous studies have implicated only isolated genes in the development of chronic rejection and have not examined multiple pathways in an individual concurrently. Using microarray technology, we identified and compared gene expression profiling in lung transplant recipients with and without chronic rejection, and follow sequential expression of genes differentially expressed between the two groups. DESIGN: Prospective, cohort study. SETTING: Single lung transplant center. PATIENTS OR PARTICIPANTS: Eleven transplant recipients with chronic rejection were matched with 9 control transplant recipients. INTERVENTIONS: All recipients underwent surveillance bronchoscopies at predetermined times to rule out infection and/or acute rejection. Gene expression profiling was obtained from hybridizing BAL fluid cell RNA to a 96-gene microarray. MEASUREMENTS AND RESULTS: Fifteen genes were found to be significantly differentially expressed between the two patient groups, and they are involved in inflammatory, fibrotic, and apoptotic pathways. Temporal expression of the significant genes demonstrated a change in their levels at the onset of chronic rejection, with normalization to prerejection levels as rejection continued. CONCLUSIONS: We conclude that microarray technology is valuable in studying the mechanism of chronic lung rejection, and the expression of genes in multiple pathways is elevated in patients with chronic lung rejection.

Lung transplantation for interstitial lung disease.

Lung transplantation remains the only therapeutic option shown to improve survival for many end-stage interstitial lung diseases. Although idiopathic pulmonary fibrosis is the most common indication, transplantation has been performed for many other diseases. This article reviews the current indications and outcomes for the procedure and problems encountered in lung transplantation for interstitial lung diseases. The role of transplant for specific diseases also is discussed.