Hung-Mo Lin

IL-6 and Its Circadian Secretion in Humans

Interleukin-6 (IL-6) is a pleiotropic cytokine produced by numerous types of immune and nonimmune cells and is involved in many pathophysiologic mechanisms in humans. Many studies suggest that IL-6 is a putative ‘sleep factor’ and its circadian secretion correlates with sleep/sleepiness. IL-6 is elevated in disorders of excessive daytime sleepiness such as narcolepsy and obstructive sleep apnea. It correlates positively with body mass index and may be a mediator of sleepiness in obesity. Also the secretion of this cytokine is stimulated by total acute or partial short-term sleep loss reflecting the increased sleepiness experienced by sleep-deprived individuals. Studies that evaluated the 24-hour secretory pattern of IL-6 in healthy young adults suggest that IL-6 is secreted in a biphasic circadian pattern with two nadirs at about 08.00 and 21.00, and two zeniths at about 19.00 and 05.00 h. In contrast, following sleep deprivation or in disorders of sleep disturbance, e.g., insomnia, IL-6 peaks during the day and, based on the level of stress system activity, i.e., cortisol secretion, contributes to either sleepiness and deep sleep (low cortisol) or feelings of tiredness and fatigue and poor sleep (high cortisol). In order to address concerns about the potential impact of differences of IL-6 levels between the beginning and the end of the 24-hour blood-drawing experiment, we proceeded with a cosinor analysis of ‘detrended’ data in young and old healthy individuals. This new analysis did not affect the biphasic circadian pattern of IL-6 secretion in young adults, while it augmented the flattened circadian pattern in old individuals in whom the difference was greater. Finally, IL-6 appears to be somnogenic in rats and exhibits a diurnal rhythm that follows the sleep/wake cycle in these animals. We conclude that IL-6 is a mediator of sleepiness and its circadian pattern reflects the homeostatic drive for sleep.

Insomnia in central Pennsylvania.

OBJECTIVEnEstablish the association between insomnia and various physical and mental health symptoms as well as objective measures of sleep disturbance while controlling for age, gender and BMI in a large random sample of the general public.nnnMETHODSnA subsample (N=1741) was selected for a single-night sleep laboratory evaluation from a larger random sample (N=16,583) of the general public (20-100 years old).nnnRESULTSnThe prevalence of insomnia was 7.5% and difficulty sleeping an additional 22.4%. The complaints were more frequent in women and in non-Caucasian minorities. A multivariate logistic regression analysis indicated that depression was the single strongest factor followed by female gender associated with either insomnia or difficulty sleeping. Minority status and a history of colitis, hypertension and anemia were also associated, but to a lesser degree. The final model did not include age, BMI as well as any of the sleep laboratory findings.nnnCONCLUSIONnThese findings support the conclusion that mental health variables have the primary independent association with a complaint of insomnia. Other factors including minorities and hypertension are also independently associated, though to a lesser degree. Other primary sleep disorders, e.g., sleep apnea, do not seem to play a major role in insomnia. These findings underscore the fact that insomnia is a symptom associated with a wide variety of mental and physical health problems requiring a proper psychiatric and medical management.

Short sleep duration and obesity: the role of emotional stress and sleep disturbances

Objective: Many epidemiologic studies have reported that obesity is associated with short sleep duration. How the degree of obesity or other clinical characteristics of the obese individuals, such as sleep disturbances or emotional stress, define this relation is not known.Design: We studied a random sample of 1300 middle-aged men and women from the Penn State Cohort in the sleep laboratory for one night. Sleep disturbances were recorded as insomnia, excessive daytime sleepiness (EDS) or sleep difficulty. Chronic emotional stress was determined by the Minnesota Multiphasic Personality Inventory-2 (MMPI-2).Results: Obese individuals (body mass index, BMI>30) reported shorter duration of sleep, had a higher incidence of subjective sleep disturbances (47.4 vs 25.5%; P<0.01) and scored higher for chronic emotional stress than nonobese subjects. However, there was no difference in self-reported sleep duration between obese and nonobese individuals without subjective sleep disturbances, while both obese men and women with sleep complaints scored higher in the MMPI-2 compared to obese individuals without sleep complaints. The shortest sleep duration was reported by the obese insomniac patients (5.9u2009h), followed by obese with EDS (6.3u2009h) or sleep difficulty (6.6u2009h). The effect of chronic emotional stress was stronger than that of the BMI on the reported sleep duration, with a synergistic joint effect. The presence of a sleep disturbance was associated with a reduction of reported sleep by 18u2009min for men and 42u2009min in women, whereas a 10u2009kgu2009m−2 increase of BMI was associated with a 16 and 6u2009min decrease of sleep in men and women, respectively. Interestingly, there was no association between objective sleep duration and BMI.Conclusion: Self-reported short sleep duration in obese individuals may be a surrogate marker of emotional stress and subjective sleep disturbances, whose detection and management should be the focus of our preventive and therapeutic strategies for obesity.

GIS Approaches for the Estimation of Residential-Level Ambient PM Concentrations

Spatial estimations are increasingly used to estimate geocoded ambient particulate matter (PM) concentrations in epidemiologic studies because measures of daily PM concentrations are unavailable in most U.S. locations. This study was conducted to a) assess the feasibility of large-scale kriging estimations of daily residential-level ambient PM concentrations, b) perform and compare cross-validations of different kriging models, c) contrast three popular kriging approaches, and d ) calculate SE of the kriging estimations. We used PM data for PM with aerodynamic diameter ≤10 μm (PM10) and aerodynamic diameter ≤ 2.5 μm (PM2.5) from the U.S. Environmental Protection Agency for the year 2000. Kriging estimations were performed at 94,135 geocoded addresses of Women’s Health Initiative study participants using the ArcView geographic information system. We developed a semiautomated program to enable large-scale daily kriging estimation and assessed validity of semivariogram models using prediction error (PE), standardized prediction error (SPE), root mean square standardized (RMSS), and SE of the estimated PM. National- and regional-scale kriging performed satisfactorily, with the former slightly better. The average PE, SPE, and RMSS of daily PM10 semivariograms using regular ordinary kriging with a spherical model were 0.0629, −0.0011, and 1.255 μg/m3, respectively; the average SE of the estimated residential-level PM10 was 27.36 μg/m3. The values for PM2.5 were 0.049, 0.0085, 1.389, and 4.13 μg/m3, respectively. Lognormal ordinary kriging yielded a smaller average SE and effectively eliminated out-of-range predicted values compared to regular ordinary kriging. Semiautomated daily kriging estimations and semivariogram cross-validations are feasible on a national scale. Lognormal ordinary kriging with a spherical model is valid for estimating daily ambient PM at geocoded residential addresses.

Blood Pressure Associated With Sleep-Disordered Breathing in a Population Sample of Children

The current criteria for sleep-disordered breathing (SDB) in children are not based on a clinically relevant outcome. The purpose of this study was to assess the association of blood pressure with SDB in a random sample of the local elementary school children (kindergarten through grade 5) using a 2-phased strategy. During phase 1, a brief questionnaire was completed for all of the children (N=5740) with a response rate of 78.5%. During phase 2, 700 randomly selected children from phase 1 with a response rate of 70.0% were assessed with a full polysomnograph and a history/physical, including an ECG; ear, nose, and throat; and pulmonary evaluation. We observed a significantly elevated systolic blood pressure associated with the apnea hypopnea index (AHI): AHI ≥1 (2.9 mm Hg); AHI ≥3 (7.1 mm Hg); and AHI ≥5 (12.9 mm Hg). The SDB and blood pressure association remained significant after adjusting for age, sex, race, body mass index percentile or waist circumference, sleep efficiency, percentage of rapid eye movement sleep, and snoring. In addition, older age, body mass index percentile, waist circumference, and snoring were significantly associated with blood pressure, independent of SDB. Based on these findings, our study suggests that SDB is significantly associated with higher levels of systolic blood pressure in children aged 5 to 12 years even after adjusting for the various confounding factors. Clinically, the data support the threshold of AHI ≥5 for the initiation of treatment for SDB. Additional research is indicated to assess the efficacy of SDB treatment on reducing blood pressure.

Selective effects of CPAP on sleep apnoea-associated manifestations

Backgroundu2003 Visceral adiposity and obstructive sleep apnoea (OSA) may be independently associated with daytime sleepiness/low performance, insulin resistance, hypercytokinaemia, and/or hypertension. The objectives of this study are to simultaneously test these associations at baseline and after 3 months of continuous positive airway pressure (CPAP) therapy.

Association of criteria pollutants with plasma hemostatic/inflammatory markers: a population-based study

To elucidate the health effects of air pollution, the short-term association of criteria pollutants (particles <10u2009μm in diameter [PM10], O3, CO, NO2, and SO2) with hemostatic and inflammatory markers were examined using a population-based sample of 10,208 middle-age males and females of the biracial cohort of Atherosclerosis Risk in Communities (ARIC) study. For each participant, we calculated the following pollutant exposures 1–3 days prior to the randomly allocated cohort examination date: PM10, CO, NO2, and SO2 as 24-h averages, and O3 as an 8-h average of the hourly measures. The hemostatic/inflammatory factors included fibrinogen, factor VIII-C, von Willebrand factor (vWF), albumin, and white blood cell count (WBC). Linear regression models were used to adjust for cardiovascular disease (CVD) risk factors, demographic and socioeconomic variables, and relevant meteorological variables. One standard deviation (SD) increment of PM10 (12.8u2009μg/m3) was significantly (P<0.05) associated with 3.93% higher of vWF among diabetics and 0.006u2009g/dl lower of serum albumin among persons with a history of CVD. One SD increment of CO (0.60u2009p.p.m.) was significantly (P<0.01) associated with 0.018u2009g/dl lower of serum albumin. Significant curvilinear associations, indicative of threshold effects, for PM10 with factor VIII-C, O3 with fibrinogen and vWF, and SO2 with factor VIII-C, WBC, and serum albumin were found. This population-based study suggest that the hemostasis/inmflammation markers analyzed, which are linked to higher risk of CHD, are associated adversely with environmentally relevant ambient pollutants, with the strongest associations in the upper range of the pollutant distributions, and in persons with a positive history of diabetes and CHD.

High Temperatures Enhanced Acute Mortality Effects of Ambient Particle Pollution in the “Oven” City of Wuhan, China

Background We investigated whether the effect of air pollution on daily mortality is enhanced by high temperatures in Wuhan, China, using data from 2001 to 2004. Wuhan has been called an “oven” city because of its hot summers. Approximately 4.5 million permanent residents live in the 201-km2 core area of the city. Method We used a generalized additive model to analyze pollution, mortality, and covariate data. The estimates of the interaction between high temperature and air pollution were obtained from the main effects and pollutant–temperature interaction models. Results We observed effects of consistently and statistically significant interactions between particulate matter ≤ 10 μm (PM10) and temperature on daily nonaccidental (p = 0.014), cardiovascular (p = 0.007), and cardiopulmonary (p = 0.014) mortality. The PM10 effects were strongest on extremely high-temperature days (daily average temperature, 33.1°C), less strong on extremely low-temperature days (2.2°C), and weakest on normal-temperature days (18.0°C). The estimates of the mean percentage of change in daily mortality per 10-μg/m3 increase in PM10 concentrations at the average of lags 0 and 1 day during hot temperature were 2.20% (95% confidence interval), 0.74–3.68) for nonaccidental, 3.28% (1.24–5.37) for cardiovascular, 2.35% (−0.03 to 4.78) for stroke, 3.31% (−0.22 to 6.97) for cardiac, 1.15% (−3.54% to 6.07) for respiratory, and 3.02% (1.03–5.04) for cardiopulmonary mortality. Conclusions We found synergistic effects of PM10 and high temperatures on daily nonaccidental, cardiovascular, and cardiopulmonary mortality in Wuhan.

Metabolic syndrome, its preeminent clusters, incident coronary heart disease and all-cause mortality--results of prospective analysis for the Atherosclerosis Risk in Communities study.

Objective.u2002 To investigate the prospective association between Metabolic Syndrome (MetS) and coronary heart disease (CHD) and all‐cause mortality.

Women sleep objectively better than men and the sleep of young women is more resilient to external stressors: effects of age and menopause

The aims of this study were to: (i) assess gender differences of objective sleep patterns in a general population sample; (ii) evaluate the effects of menopause and hormone treatment (HT) on the sleep of the same cohort; and (iii) examine gender differences in sleep resilience towards external stressors. The participants were (i) 1324 subjects without sleep complaints, recruited from the general population of Central Pennsylvania that spent one night in the sleep laboratory and (ii) 66 young, healthy volunteers whose sleep was disturbed during night four by an external stressor, i.e. 24‐h blood drawing (average of nights 2 and 3 versus night 4). Women compared with men in the general population sample had significantly higher percentage of sleep time, lower percentage of stage 1, and higher percentage of slow wave sleep. Also, menopause, in the absence of HT, was associated with prolonged sleep latency and decreased deep sleep. Finally, young, healthy women compared with men experienced less sleep disturbance because of blood draws as indicated by a significantly smaller change in per cent sleep time, and percentage of stage 1 sleep. These findings suggest that women without sleep complaints sleep objectively better across age than men and the sleep of young women is more resistant to external stressors. Also, gonadal hormones exert a beneficial effect on women’s sleep. This gender dimorphism in sleep regulation may have been to protect women from the demands of infant and child care, and in part, might contribute to women’s lower cardiovascular risks and greater longevity.