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1.  Adiposity, serum lipid levels, and allergic sensitization in Chinese men and women 
Background
Obesity and allergic diseases have increased dramatically in recent decades. While adiposity has been associated with asthma, associations with allergic sensitization have been inconsistent.
Objective
To examine the association of adiposity and lipid profiles with allergic sensitization.
Methods
This study included 1,187 rural Chinese twins (653 men) aged 18-39 years, with skin prick tests (SPT), anthropometric and DEXA-assessed adiposity measures, and lipid assessments. Allergic sensitization was defined as positive SPT to ≥1 allergen (9 foods and 5 aeroallergens tested). We applied gender-stratified generalized estimating equations to assess the association of adiposity and serum lipids with allergic sensitization, and structural equation models to estimate the genetic/environmental influences on any observed associations.
Results
Males had lower percent body fat (%BF) (13.9% vs. 28.8%) but higher rates of allergic sensitization (56.2% vs. 36.7%) than females. Males in the highest %BF quartile were 2.1 times more likely sensitized than the lowest quartile (95%CI 1.3-3.5, P-trend=0.003). In males, the risk of allergic sensitization increased with HDL<40 mg/dl (OR=4.0, 95%CI 1.8-9.2) and higher LDL quartiles (P-trend=0.007). This appeared to be partially explained by shared genetic factors between serum lipid levels and allergic sensitization. In females, lower HDL was associated with increased risk of allergic sensitization.
Conclusions
In this relatively lean Chinese population, higher %BF, lower HDL and higher LDL were associated with greater risk of allergic sensitization, most notable in males. The observed associations between adiposity, serum lipids and allergic sensitization in males appear to be partially explained by common genetic influences on these traits.
doi:10.1016/j.jaci.2008.11.032
PMCID: PMC2697621  PMID: 19135238
DEXA; Body mass index; Adiposity; Serum lipids; Sensitization
2.  The Association of Short and Long Sleep Durations with Insulin Sensitivity In Adolescents 
The Journal of pediatrics  2010;158(4):617-623.
Objective
To characterize the relationship between insulin sensitivity, assessed by the homeostasis model of insulin (HOMA), and objective measurements of sleep duration in adolescents.
Study design
Cross-sectional analysis from two examinations conducted in the Cleveland Children’s Sleep and Health Cohort (n=387; 43% minorities). Biochemical and anthropometry measurements made in a Clinical Research Unit. Sleep duration measured by actigraphy.
Results
Decreased sleep duration was associated with increased adiposity and minority race. Sleep duration had a quadratic “u-shape” association with HOMA. When adjusted for age, sex, race, preterm status and activity, adolescents who slept 7.75 hours had the lowest predicted HOMA (1.96 [95% CI: 1.82, 2.10]), and adolescents who slept 5.0 hours or 10.5 hours had HOMA indices that were about 20% higher (2.36 [95% CI: 1.94, 2.86] and 2.41 [95% CI: 1.93, 3.01], respectively). After adjusting for adiposity, the association between shorter sleep and HOMA was appreciably attenuated, but the association with longer sleep persisted.
Conclusions
Shorter and longer sleep durations are associated with decreased insulin sensitivity in adolescents. Whereas the association between shorter sleep duration with insulin sensitivity is likely explained by the association between short sleep and obesity, association between longer sleep and insulin sensitivity is independent of obesity.
doi:10.1016/j.jpeds.2010.09.080
PMCID: PMC3076647  PMID: 21146189
Sleep; insulin resistance; obesity
3.  SLEEP DURATION AND AMBULATORY BLOOD PRESSURE IN BLACK AND WHITE ADOLESCENTS 
Hypertension  2012;59(3):747-752.
Self-reported short sleep duration is linked to higher blood pressure and incident hypertension in adults. Few studies have examined sleep and blood pressure in younger samples. We evaluated the associations between actigraphy-assessed time spent asleep and ambulatory blood pressure in adolescents. Participants were 246 black and white adolescents (mean age = 15.7) who were free from cardiovascular or kidney disease and were not taking sleep, cardiovascular, or psychiatric medications. Sleep duration and efficiency were assessed with in-home wrist actigraphy and sleep diaries across one week; ambulatory blood pressure monitoring was used to obtain 24-hour, sleep, wake blood pressure, and sleep-wake blood pressure ratios across two full days and nights. Results showed that shorter actigraphy-assessed sleep across one week was related to higher 48-hour blood pressure and higher nighttime blood pressure. Shorter sleep was also related to a higher systolic blood pressure sleep-wake ratio. These results were independent of age, race, sex, and body mass index. Follow-up analyses by race revealed that associations between sleep duration and blood pressure were largely present in white, but not black, adolescents. These data are consistent with the hypothesis that the cardiovascular consequences of short sleep may begin as early as adolescence.
doi:10.1161/HYPERTENSIONAHA.111.184770
PMCID: PMC3314491  PMID: 22275538
ambulatory blood pressure; sleep duration; actigraphy; adolescent; race
4.  HIGH PREVALENCE OF AEROALLERGEN SENSITIZATION AMONG INFANTS OF ATOPIC PARENTS 
The Journal of pediatrics  2006;149(4):505-511.
Objective
To present methodology to identify atopic parents and determine the prevalence of sensitization to 15 aeroallergens in their infant offspring.
Study design
A birth cohort of infants was identified from birth records; an infant was enrolled if 1 of the parents reported allergy respiratory symptoms and had a positive skin prick test (SPT) to a common aeroallergen. At age 1 year, these infants were tested to the same aeroallergens.
Results
Of the 680 enrolled infants, 28.4% were SPT+ to 1 or more aeroallergens and/or food, and 18.0% were positive to 1 or more aeroallergens. By category of allergens, 9.7% were sensitized to pollens, 7.5% to molds, 4.3% to house dust mite and/or cockroach, and 3.4% to dog and/or cat. Of the infants who were positive to an aeroallergen, 65.7% remained positive at age 2 years.
Conclusions
Infants born to atopic parents with percutaneous sensitization to aeroallergens are at increased risk for aeroallergen sensitization during infancy, which persists to age 2 years. These findings suggest that current clinical practices, which generally avoid skin testing before age 2 years, be reassessed in this population of high-risk children.
doi:10.1016/j.jpeds.2006.06.035
PMCID: PMC2233934  PMID: 17011322
5.  Temporal daily associations between pain and sleep in adolescents with chronic pain versus healthy adolescents 
Pain  2010;151(1):220-225.
Adolescents with chronic pain frequently report sleep disturbances, particularly short sleep duration, night wakings, and poor sleep quality. Prior research has been limited by assessment of subjectively reported sleep only and lack of data on daily relationships between sleep and pain. The current study utilized multilevel modeling to compare daily associations between sleep and pain in adolescents with chronic pain and healthy adolescents. Ninety-seven adolescents (n=39 chronic pain; n=58 healthy) aged 12–18, 70.1% female participated. Adolescents completed pain diary ratings (0–10 NRS) and actigraphic sleep monitoring for 10 days. Actigraphic sleep variables (duration, efficiency, WASO) and self-reported sleep quality were tested as predictors of next-day pain, and daytime pain was tested as a predictor of sleep that night. Effects of age, gender, study group, and depressive symptoms on daily associations between sleep and pain were also tested. Multivariate analyses revealed that nighttime sleep (p<.001) and minutes awake after sleep onset (WASO) (p<.05) predicted next-day pain, with longer sleep duration and higher WASO associated with higher pain. Contrary to hypotheses, neither nighttime sleep quality nor sleep efficiency predicted pain the following day. The interaction between nighttime sleep efficiency and study group was significant, with adolescents with pain showing stronger associations between sleep efficiency and next day pain than healthy participants (p=.05). Contrary to hypotheses, daytime pain did not predict nighttime sleep. Daily associations between pain and sleep suggest that further work is needed to identify specific adolescent sleep behaviors (e.g., compensatory sleep behaviors) that may be targeted in interventions.
doi:10.1016/j.pain.2010.07.016
PMCID: PMC2939216  PMID: 20719433
pain; chronic pain; actigraphy; adolescents; sleep; multilevel-modeling
6.  Sleep Duration, Sleep Regularity, Body Weight, and Metabolic Homeostasis in School-aged Children 
Pediatrics  2011;127(2):e345-e352.
OBJECTIVE:
The goal was to explore the effects of duration and regularity of sleep schedules on BMI and the impact on metabolic regulation in children.
METHODS:
Sleep patterns of 308 community-recruited children 4 to 10 years of age were assessed with wrist actigraphs for 1 week in a cross-sectional study, along with BMI assessment. Fasting morning plasma levels of glucose, insulin, lipids, and high-sensitivity C-reactive protein also were measured for a subsample.
RESULTS:
Children slept 8 hours per night, on average, regardless of their weight categorization. A nonlinear trend between sleep and weight emerged. For obese children, sleep duration was shorter and showed more variability on weekends, compared with school days. For overweight children, a mixed sleep pattern emerged. The presence of high variance in sleep duration or short sleep duration was more likely associated with altered insulin, low-density lipoprotein, and high-sensitivity C-reactive protein plasma levels. Children whose sleep patterns were at the lower end of sleep duration, particularly in the presence of irregular sleep schedules, exhibited the greatest health risk.
CONCLUSIONS:
Obese children were less likely to experience “catch-up” sleep on weekends, and the combination of shorter sleep duration and more-variable sleep patterns was associated with adverse metabolic outcomes. Educational campaigns, aimed at families, regarding longer and more-regular sleep may promote decreases in obesity rates and may improve metabolic dysfunction trends in school-aged children.
doi:10.1542/peds.2010-0497
PMCID: PMC3025425  PMID: 21262888
sleep duration; obesity; children; lipids; insulin resistance; inflammation
7.  Genetic and Environmental Contributions to Allergen Sensitization in a Chinese Twin Study 
Background:
Allergic disease is on the rise worldwide. Effective prevention of allergic disease requires comprehensive understanding of the factors that contribute to its intermediate phenotypes, such as sensitization to common allergens.
Objective:
To estimate the degree of genetic and environmental contributions to sensitization to food or aeroallergens.
Methods:
Sensitization was defined as a positive skin prick test to an allergen. We calculated the zygosity-specific concordance rates and odds ratios (ORs) for sensitization to food and aeroallergens in 826 Chinese twin pairs (472 MZ and 354 DZ) aged 12 to 28 years. We also applied structural equation modeling procedures to estimate genetic and environmental influences on sensitization.
Results:
The concordance rates and risk of sensitization in one twin given the presence vs. the absence of sensitization in the other twin were higher in MZ twins than those in DZ twins. However, a large number of MZ twins were discordant in sensitization to common allergens. These observations suggest both genetic and environmental factors influence sensitization. Consistently, the estimated heritability and individual environmental components of the liability to sensitization ranged from 0.51 to 0.68 and 0.32 to 0.49, respectively, based on the best-fitted structural equation model. We also observed high phenotypic correlations between sensitization to two aeroallergens (cockroach and dust mite: 0.83) and two food allergens (peanut and shellfish: 0.58), but only moderate correlations for the pairs between sensitization to a food and an aeroallergen (0.31-0.46). The shared genetic and environmental factors between paired sensitizations contribute to the observed correlations.
Conclusion:
We demonstrated that sensitization to common food and aeroallergens were influenced by both genetic and environmental factors. Moreover, we found that paired allergen sensitizations might share some common sets of genes and environmental factors. This study underscores the need to further delineate unique and/or pleiotropic genetic and environmental factors for allergen sensitization.
doi:10.1111/j.1365-2222.2009.03228.x
PMCID: PMC2756049  PMID: 19302247
Twin; sensitization; positive SPT; structural equation modeling; heritability; environmental factors
8.  Sleep Patterns Among Rural Chinese Twin Adolescents 
Sleep medicine  2008;10(4):479-489.
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 8.6 hours on weekdays and 9.4 hours 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.
doi:10.1016/j.sleep.2008.04.011
PMCID: PMC2753967  PMID: 18752997
Age; gender; puberty; Tanner stages; sleep patterns; wake-up time; bedtime; total sleep time
9.  A faded bedtime with response cost protocol for treatment of multiple sleep problems in children. 
The sleep-wake cycles of 4 developmentally delayed individuals with longstanding severe sleep disturbances were regulated using a faded bedtime procedure with response cost. Bedtimes were systematically delayed for each individual, thus increasing the probability of short latency to sleep onset. The response cost component, consisting of removing the individual from bed for 1 hour, was implemented when an individual did not experience short latency to sleep onset. A fading procedure was then applied successfully to advance the bedtimes and to gradually increase durations of sleep. Specifically, all 4 individuals had decreased amounts of nighttime sleep that increased following treatment. Two of the 4 individuals showed excessive daytime sleep that decreased following treatment. Three of the 4 individuals experienced decreases in night wakings following treatment. Both environmental and biological manipulations of the sleep-wake cycle are hypothesized as mechanisms of treatment. The relative advantages of this procedure over other procedures for the treatment of pediatric sleep disorders are discussed, as are directions for future research.
doi:10.1901/jaba.1991.24-129
PMCID: PMC1279554  PMID: 2055796
10.  Short Sleep Duration Is Associated with Insulin Resistance Independent of Adiposity in Chinese Adult Twins 
Sleep medicine  2011;12(9):914-919.
Objective
To investigate the association between sleep duration and insulin resistance in rural Chinese adults and examine whether any such associations are independent of adiposity.
Methods
This is a cross-sectional analysis of 854 men and 640 women aged 20 to 70 years from the Anqing Twin Cohort. The following measures were obtained for each subject: Body mass index (BMI) and percentage of trunk fat (%TF), fasting plasma glucose, homeostatic model assessment of insulin resistance index (HOMA-IR), self-reported sleep duration, and measures of snoring and sleep disturbance from the Pittsburgh Sleep Quality Indices (PSQI) questionnaire modified for a Chinese population. Multivariate linear regressions were applied to examine the association of sleep duration with HOMA-IR, with and without adjustment for adiposity variables, along with other relevant covariates.
Results
In this sample of relatively lean rural Chinese adults, short sleep duration was associated with HOMA-IR in women but not in men. In women, short (≤7 hrs/night) sleep duration was associated with a higher HOMA-IR (p=0.003) compared with normal sleep duration (>7 to ≤8 hrs/night) after adjustment for all the covariates except adiposity. Further adjustment for BMI or %TF attenuated the sleep-HOMA-IR association, but the association remained significant upon adjustment for BMI (p=0.013); and upon adjustment for %TF (p=0.026). Long sleep duration (>8 hrs/night) was not significantly associated with HOMA-IR.
Conclusion
In this rural Chinese cohort, short sleep duration is independently associated with increased insulin resistance among women only, even after adjusting for adiposity and other potential confounders.
doi:10.1016/j.sleep.2011.04.006
PMCID: PMC3210935  PMID: 21940204
sleep duration; insulin resistance; adiposity; gender; rural; adults
11.  Dissociation between the Prevalence of Atopy and Allergic Disease in Rural China among Children and Adults 
Background
The prevalence of allergic diseases is increasing worldwide, but the reasons are not well understood. Previous studies suggest that this trend may be associated with lifestyle and urbanization.
Objective
To describe patterns of sensitization and allergic disease in an unselected agricultural Chinese population.
Methods
The data was derived from a community-based twin study in Anqing, China. Skin prick testing was performed to foods and aeroallergens. Atopy was defined as sensitization to ≥1 allergen. Allergic disease was ascertained by self-report. The analysis was stratified by sex and age (children [11-17 years] and adults [≥18 years]) and included 1059 same-sex twin pairs.
Results
Of 2118 subjects, 57.6% were male (n=1220). Ages ranged from 11-71 years; 43.3% were children (n=918). Atopy was observed in 47.2% (n=999) of participants. The most common sensitizing foods were shellfish (16.7%) and peanut (12.3%). The most common sensitizing aeroallergens were dust mite (30.6%) and cockroach (25.2%). Birth order and zygosity had no effect on sensitization rates. Multivariate logistic regression models revealed risk factors for sensitization include age for foods and sex for aeroallergens. The rates of food allergy and asthma were estimated to be <1%.
Conclusions
Atopic sensitization was common in this rural farming Chinese population, particularly to shellfish, peanut, dust mite, and cockroach. The prevalence of allergic disease, in contrast, was quite low.
Clinical Implications
Allergen sensitization was far more common than the rate of self-reported allergic disease in this community. Evidence of sensitization is an inadequate marker of allergic disease and better correlates with clinical disease are needed.
Capsule summary
Among this large unselected Chinese rural farming community, atopy was observed in nearly half of the study subjects, but the rate of allergic disease was comparatively very low.
doi:10.1016/j.jaci.2008.08.009
PMCID: PMC2747487  PMID: 18805578
aeroallergens; rural; farming community; Chinese; food allergens; prevalence; sensitization; skin prick tests
12.  Role of sleep duration in the regulation of glucose metabolism and appetite 
Sleep curtailment has become a common behavior in modern society. This review summarizes the current laboratory evidence indicating that sleep loss may contribute to the pathophysiology of diabetes mellitus and obesity. Experimentally-induced sleep loss in healthy volunteers decreases insulin sensitivity without adequate compensation in beta-cell function, resulting in impaired glucose tolerance and increased diabetes risk. Lack of sleep also down-regulates the satiety hormone leptin, up-regulates the appetite-stimulating hormone ghrelin, and increases hunger and food intake. Taken together with the epidemiologic evidence for an association between short sleep and the prevalence or incidence of diabetes mellitus and/or obesity, these results support a role for reduced sleep duration in the current epidemic of these metabolic disorders. Screening for habitual sleep patterns in patients with “diabesity” is therefore of great importance. Studies are warranted to investigate the putative therapeutic impact of extending sleep in habitual short sleepers with metabolic disorders.
doi:10.1016/j.beem.2010.07.005
PMCID: PMC3018785  PMID: 21112019
Sleep deprivation; glucose metabolism; appetite regulation; diabetes; obesity
13.  Disrupted sleep without sleep curtailment induces sleepiness and cognitive dysfunction via the tumor necrosis factor-α pathway 
Background
Sleepiness and cognitive dysfunction are recognized as prominent consequences of sleep deprivation. Experimentally induced short-term sleep fragmentation, even in the absence of any reductions in total sleep duration, will lead to the emergence of excessive daytime sleepiness and cognitive impairments in humans. Tumor necrosis factor (TNF)-α has important regulatory effects on sleep, and seems to play a role in the occurrence of excessive daytime sleepiness in children who have disrupted sleep as a result of obstructive sleep apnea, a condition associated with prominent sleep fragmentation. The aim of this study was to examine role of the TNF-α pathway after long-term sleep fragmentation in mice.
Methods
The effect of chronic sleep fragmentation during the sleep-predominant period on sleep architecture, sleep latency, cognitive function, behavior, and inflammatory markers was assessed in C57BL/6 J and in mice lacking the TNF-α receptor (double knockout mice). In addition, we also assessed the above parameters in C57BL/6 J mice after injection of a TNF-α neutralizing antibody.
Results
Mice subjected to chronic sleep fragmentation had preserved sleep duration, sleep state distribution, and cumulative delta frequency power, but also exhibited excessive sleepiness, altered cognitive abilities and mood correlates, reduced cyclic AMP response element-binding protein phosphorylation and transcriptional activity, and increased phosphodiesterase-4 expression, in the absence of AMP kinase-α phosphorylation and ATP changes. Selective increases in cortical expression of TNF-α primarily circumscribed to neurons emerged. Consequently, sleepiness and cognitive dysfunction were absent in TNF-α double receptor knockout mice subjected to sleep fragmentation, and similarly, treatment with a TNF-α neutralizing antibody abrogated sleep fragmentation-induced learning deficits and increases in sleep propensity.
Conclusions
Taken together, our findings show that recurrent arousals during sleep, as happens during sleep apnea, induce excessive sleepiness via activation of inflammatory mechanisms, and more specifically TNF-α-dependent pathways, despite preserved sleep duration.
doi:10.1186/1742-2094-9-91
PMCID: PMC3411474  PMID: 22578011
TNF-α; Sleep fragmentation; Neurocognitive impairments; Sleep apnea; ATP
14.  Shorter sleep may be a risk factor for impaired bone mass accrual in childhood 
The purpose of the study was to investigate whether sleep duration during early childhood was associated with fat mass and bone mineral content (BMC). BMC and fat mass were measured by dual-energy x-ray absorptiometry (DXA) in children (n=336) ages 4–12 years. Sleep was quantified according to parental report of hours slept at night and napping. The relationship between sleep pattern and body composition was tested using ANOVA including confounding factors. Based on the sample distribution, children were grouped into tertiles of sleep duration. BMC was greater in children with longer sleep duration (p=0.02). Age was inversely associated with sleep duration; therefore the sample was analyzed by age category using seven years old as the cut-point. The relationship remained significant only among younger children. Napping was positively associated with BMC (p=0.001). Sleep duration was not associated with fat parameters. Longer sleep duration, may allow for optimal energy resource partitioning in which bone is favored. Sleep duration of less than 8 hours may impair bone mass accrual, particularly during periods of rapid growth.
doi:10.1016/j.jocd.2011.06.005
PMCID: PMC3208825  PMID: 22051093
sleep curtailment; bone mineral content; growth; pediatric
15.  Adolescent Sleep, Risk Behaviors, and Depressive Symptoms: Are They Linked? 
Objective
To explore how weekday and weekend sleep patterns are related to adolescent substance use, depressive symptoms, and school truancy.
Methods
Self-report surveys of 242 youth (93.4% white, mean age 16.4 years).
Results
Longer weekday sleep duration was inversely associated with depressive symptoms, past month alcohol use, and drunkenness. Later weekend bedtime and wake-times, compared to those of weekdays, were associated with increased substance use and truancy.
Conclusions
Weekday sleep duration appears to be protective for substance use, depression and school truancy for teenagers. However, inconsistent sleep patterns between weekdays and weekends were associated with a range of markers for adolescent risk.
PMCID: PMC3086400  PMID: 19814603
adolescents; sleep; risk behaviors; depressive symptoms
16.  Influence of degree of specific allergic sensitivity on severity of rhinitis and asthma in Chinese allergic patients 
Respiratory Research  2011;12(1):95.
Background
The association between sensitizations and severity of allergic diseases is controversial.
Objective
This study was to investigate the association between severity of asthma and rhinitis and degree of specific allergic sensitization in allergic patients in China.
Method
A cross-sectional survey was performed in 6304 patients with asthma and/or rhinitis from 4 regions of China. Patients completed a standardized questionnaire documenting their respiratory and allergic symptoms, their impact on sleep, daily activities, school and work. They also underwent skin prick tests with 13 common aeroallergens. Among the recruited subjects, 2268 provided blood samples for serum measurement of specific IgE (sIgE) against 16 common aeroallergens.
Results
Significantly higher percentage of patients with moderate-severe intermittent rhinitis were sensitized to outdoor allergens while percentage of patients sensitized to indoor allergens was increased with increasing severity of asthma. Moderate-severe intermittent rhinitis was associated with the skin wheal size and the level of sIgE to Artemisia vulgaris and Ambrosia artemisifolia (p < 0.001). Moderate-severe asthma was associated with increasing wheal size and sIgE response to Dermatophagoides (D.) pteronyssinus and D. farinae (p < 0.001). Moderate-severe rhinitis and asthma were also associated with increase in number of positive skin prick test and sIgE.
Conclusions
Artemisia vulgaris and Ambrosia artemisifolia sensitizations are associated with the severity of intermittent rhinitis and D. pteronyssinus and D. farinae sensitizations are associated with increasing severity of asthma in China. Increase in number of allergens the patients are sensitized to may also increase the severity of rhinitis and asthma.
doi:10.1186/1465-9921-12-95
PMCID: PMC3145577  PMID: 21831329
sensitization; aeroallergens; disease severity; allergic rhinitis; asthma; association.
17.  211 Influence of Degree of Specific Allergic Sensitivity on Severity of Rhinitis and Asthma in Chinese Allergic Patients 
Background
The associations between sensitizations and severity of allergic diseases are controversial. This study was to investigate the association between severity of asthma and rhinitis and degree of specific allergic sensitivity in allergic patients in China.
Methods
A cross-sectional survey was performed in 6,304 patients with asthma and/or rhinitis from 4 regions of China. Patients completed a standardized questionnaire related to the respiratory and allergic symptoms, their impact on sleep, daily activities, school and work. They also underwent skin prick tests with 13 common aeroallergens. 2,268 of them were taken blood for serum specific IgE (sIgE) measurements for 16 common aeroallergens.
Results
Significantly higher percentage of patients with moderate-severe intermittent rhinitis were sensitized to outdoor allergens while percentage of patients sensitized to indoor allergens was increased with increasing severity of asthma. Moderate-severe intermittent rhinitis was related to skin wheal size and sIgE to Artemisia vulgaris and Ambrosia artemisifolia (P < 0.001). Moderate-severe asthma was associated with increasing in skin and sIgE response to Dermatophagoides (D.) pteronyssinus and D. farinae (P < 0.001). Moderate-severe rhinitis and asthma were also associated with increasing in number of skin and sIgE sensitized allergens.
Conclusions
Outdoor allergen sensitizations are significantly associated with severity of intermittent rhinitis and indoor allergen sensitizations are significantly associated with severity of asthma in patients in China. Number of allergen sensitization is also related to severity of rhinitis and asthma.
doi:10.1097/01.WOX.0000411968.40276.b5
PMCID: PMC3512821
18.  Sleep Insufficiency, Sleep Health Problems and Performance in High School Students 
A survey on sleep schedule, sleep health, school performance and school start times was conducted in 1,941 adolescents. A high level of early and circadian-disadvantaged sleep/wake schedules during weekdays was observed. Shorter sleep duration on weekdays was reported, especially in upper classmen. Complaints of inadequate sleep and sleepiness during weekdays, alarm clock use, and napping were prevalent. Night awakening and prolonged sleep onset were common and associated with poor school performance. Students with a sleep length of less than 7 hours on both weekdays and weekends exhibited poorer performance, while those who made up this sleep loss on weekends did not. The total number of poor sleep factors in an individual also correlated with poor school performance. Earlier school start times were associated with a perception of poor sleep quality, shorter sleep duration and more sleep health problems. We conclude that sleep inadequacies and sleep health problems were prevalent in this population, especially in those who started school earlier in the morning, and that these poor sleep factors were associated with school performance.
doi:10.4137/CCRPM.S7955
PMCID: PMC3212860  PMID: 22084618
sleep deprivation; sleep health problem; adolescents; performance; school start time
19.  Sleep, aging, and lifespan in Drosophila 
BMC Neuroscience  2010;11:56.
Background
Epidemiological studies in humans suggest that a decrease in daily sleep duration is associated with reduced lifespan, but this issue remains controversial. Other studies in humans also show that both sleep quantity and sleep quality decrease with age. Drosophila melanogaster is a useful model to study aging and sleep, and inheriting mutations affecting the potassium current Shaker results in flies that sleep less and have a shorter lifespan. However, whether the link between short sleep and reduced longevity exists also in wild-type flies is unknown. Similarly, it is unknown whether such a link depends on sleep amount per se, rather than on other factors such as waking activity. Also, sleep quality has been shown to decrease in old flies, but it remains unclear whether aging-related sleep fragmentation is a generalized phenomenon.
Results
We compared 3 short sleeping mutant lines (Hk1, HkY and Hk2) carrying a mutation in Hyperkinetic, which codes for the beta subunit of the Shaker channel, to wild-type siblings throughout their entire lifespan (all flies kept at 20°C). Hk1 and HkY mutants were short sleeping relative to wild-type controls from day 3 after eclosure, and Hk2 flies became short sleepers about two weeks later. All 3 Hk mutant lines had reduced lifespan relative to wild-type flies. Total sleep time showed a trend to increase in all lines with age, but the effect was most pronounced in Hk1 and HkY flies. In both mutant and wild-type lines sleep quality did not decay with age, but the strong preference for sleep at night declined starting in "middle age". Using Cox regression analysis we found that in Hk1 and HkY mutants and their control lines there was a negative relationship between total sleep amount during the first 2 and 4 weeks of age and hazard (individual risk of death), while no association was found in Hk2 flies and their wild-type controls. Hk1 and HkY mutants and their control lines also showed an association between total daily wake activity over the first 2 and 4 weeks of age and hazard. However, when both sleep duration and wake activity were used in the same regression, the effects of activity were much reduced, while most of the sleep effects remained significant. Finally, Hk1 flies and wild-type siblings were also tested at 25°C, and results were similar to those at 20°C. Namely, Hk1 mutants were short sleeping, hyperactive, and short lived relative to controls, and sleep quality in both groups did not decrease with age.
Conclusions
Different Hk mutations affect the sleep phenotype, and do so in an age-dependent manner. In 4 of the 6 lines tested sleep associates significantly with lifespan variation even after any effect of activity is removed, but activity does not associate significantly with lifespan after the effects of sleep are removed. Thus, in addition to environmental factors and genetic background, sleep may also affect longevity. Sleep quality does not necessarily decay as flies age, suggesting that aging-related sleep fragmentation may also depend on many factors, including genetic background and rearing conditions.
doi:10.1186/1471-2202-11-56
PMCID: PMC2871268  PMID: 20429945
20.  Sleep Phenotyping in a Mouse Model of Extreme Trait Anxiety 
PLoS ONE  2012;7(7):e40625.
Background
There is accumulating evidence that anxiety impairs sleep. However, due to high sleep variability in anxiety disorders, it has been difficult to state particular changes in sleep parameters caused by anxiety. Sleep profiling in an animal model with extremely high vs. low levels of trait anxiety might serve to further define sleep patterns associated with this psychopathology.
Methodology/Principal Findings
Sleep-wake behavior in mouse lines with high (HAB), low (LAB) and normal (NAB) anxiety-related behaviors was monitored for 24 h during baseline and recovery after 6 h sleep deprivation (SD). The amounts of each vigilance state, sleep architecture, and EEG spectral variations were compared between the mouse lines. In comparison to NAB mice, HAB mice slept more and exhibited consistently increased delta power during non-rapid eye movement (NREM) sleep. Their sleep patterns were characterized by heavy fragmentation, reduced maintenance of wakefulness, and frequent intrusions of rapid eye movement (REM) sleep. In contrast, LAB mice showed a robust sleep-wake rhythm with remarkably prolonged sleep latency and a long, persistent period of wakefulness. In addition, the accumulation of delta power after SD was impaired in the LAB line, as compared to HAB mice.
Conclusions/Significance
Sleep-wake patterns were significantly different between HAB and LAB mice, indicating that the genetic predisposition to extremes in trait anxiety leaves a biological scar on sleep quality. The enhanced sleep demand observed in HAB mice, with a strong drive toward REM sleep, may resemble a unique phenotype reflecting not only elevated anxiety but also a depression-like attribute.
doi:10.1371/journal.pone.0040625
PMCID: PMC3394752  PMID: 22808211
21.  Sleep Quality and Elevated Blood Pressure in Adolescents 
Circulation  2008;118(10):1034-1040.
Background
We assessed whether insufficient sleep is associated with pre-hypertension in healthy adolescents.
Methods and Results
Cross-sectional analysis of 238 adolescents, all without sleep apnea or severe co-morbidities. Participants underwent multiple day wrist actigraphy at home to provide objective estimates of sleep patterns. In a clinical research facility, overnight polysomnography, anthropometry, and 9 blood pressure (BP) measurements over 2 days were made. Exposures were actigraphy-defined low weekday sleep efficiency, an objective measure of sleep quality (low sleep efficiency ≤85%) and short sleep duration (≤6.5 hrs). The main outcome was pre-hypertension (≥90th%ile for age, sex, and height), with systolic and diastolic BP as continuous measures as secondary outcomes. Pre-hypertension, low sleep efficiency, and short sleep duration occurred in 14%, 26%, and 11% of the sample, respectively. In unadjusted analyses, the odds of pre-hypertension was increased 4.5-fold (95% CI: 2.1, 9.7) in adolescents with low sleep efficiency and 2.8-fold (95% CI: 1.1,7.3) in those with short sleep. In analyses adjusted for gender, BMI percentile and socioeconomic status, the odds of pre-hypertension was increased 3.5-fold (95% CI: 1.5. 8.0) for low sleep efficiency and 2.5 fold (95% CI: 0.9, 6.9) for short sleep. Adjusted analyses showed that adolescents with low sleep efficiency, on average, had a 4.0 ± 1.2 mm Hg higher systolic BP compared to other children(p<0.01).
Conclusions
Poor sleep quality is associated with pre-hypertension in healthy adolescents. Associations are not explained by socioeconomic status, obesity, sleep apnea or known co-morbidities, suggesting that inadequate sleep quality is associated with elevated blood pressure.
doi:10.1161/CIRCULATIONAHA.108.766410
PMCID: PMC2798149  PMID: 18711015
blood pressure; epidemiology; pediatrics
22.  Prevalence, Patterns, and Persistence of Sleep Problems in the First 3 Years of Life 
Pediatrics  2012;129(2):e276-e284.
OBJECTIVE:
Examine the prevalence, patterns, and persistence of parent-reported sleep problems during the first 3 years of life.
METHODS:
Three hundred fifty-nine mother/child pairs participated in a prospective birth cohort study. Sleep questionnaires were administered to mothers when children were 6, 12, 24, and 36 months old. Sleep variables included parent response to a nonspecific query about the presence/absence of a sleep problem and 8 specific sleep outcome domains: sleep onset latency, sleep maintenance, 24-hour sleep duration, daytime sleep/naps, sleep location, restlessness/vocalization, nightmares/night terrors, and snoring.
RESULTS:
Prevalence of a parent-reported sleep problem was 10% at all assessment intervals. Night wakings and shorter sleep duration were associated with a parent-reported sleep problem during infancy and early toddlerhood (6–24 months), whereas nightmares and restless sleep emerged as associations with report of a sleep problem in later developmental periods (24–36 months). Prolonged sleep latency was associated with parent report of a sleep problem throughout the study period. In contrast, napping, sleep location, and snoring were not associated with parent-reported sleep problems. Twenty-one percent of children with sleep problems in infancy (compared with 6% of those without) had sleep problems in the third year of life.
CONCLUSIONS:
Ten percent of children are reported to have a sleep problem at any given point during early childhood, and these problems persist in a significant minority of children throughout early development. Parent response to a single-item nonspecific sleep query may overlook relevant sleep behaviors and symptoms associated with clinical morbidity.
doi:10.1542/peds.2011-0372
PMCID: PMC3357046  PMID: 22218837
sleep problems; infants; toddlers; prevalence; persistence
23.  Factors Associated with Sleep Duration in Korean Adults: Results of a 2008 Community Health Survey in Gwangju Metropolitan City, Korea 
Journal of Korean Medical Science  2011;26(9):1124-1131.
Short (≤ 6 hr) and long (≥ 9 hr) sleep durations are both associated with risk factors for cardiovascular diseases and diabetes, depression, learning problems, accidents and excess mortality. However, little is known about factors associated with sleep duration in Korean adults. This study examined sleep patterns in Korean adults and identified factors associated with short and long sleep durations. This study analyzed cross-sectional data collected from 4,411 Korean adults aged 19 yr and older who participated in a community health survey conducted in Gwangju, Korea. Multinomial logistic regression analysis was used to identify associations between socio-demographic and health-related factors and short or long sleep durations. Of the population, 37.2% and 4.0% reported short and long sleep, respectively. Short sleep was associated with older age, lower levels of income, night or shift work, heavy smoking, and depression or anxiety; long sleep was associated with younger age, being divorced or widowed, heavy smoking, underweight, depression or anxiety, and poorer self-reported health. In conclusion, a relatively high prevalence of short sleep duration is identified in this population of Korean adults. Factors associated with short or long sleep may act as potential confounders of the relationship between sleep duration and health outcomes.
doi:10.3346/jkms.2011.26.9.1124
PMCID: PMC3172647  PMID: 21935265
Sleep; Health Behavior; Socioeconomic Factors
24.  Sleep Restriction for 1 Week Reduces Insulin Sensitivity in Healthy Men 
Diabetes  2010;59(9):2126-2133.
OBJECTIVE
Short sleep duration is associated with impaired glucose tolerance and an increased risk of diabetes. The effects of sleep restriction on insulin sensitivity have not been established. This study tests the hypothesis that decreasing nighttime sleep duration reduces insulin sensitivity and assesses the effects of a drug, modafinil, that increases alertness during wakefulness.
RESEARCH DESIGN AND METHODS
This 12-day inpatient General Clinical Research Center study included 20 healthy men (age 20–35 years and BMI 20–30 kg/m2). Subjects spent 10 h/night in bed for ≥8 nights including three inpatient nights (sleep-replete condition), followed by 5 h/night in bed for 7 nights (sleep-restricted condition). Subjects received 300 mg/day modafinil or placebo during sleep restriction. Diet and activity were controlled. On the last 2 days of each condition, we assessed glucose metabolism by intravenous glucose tolerance test (IVGTT) and euglycemic-hyperinsulinemic clamp. Salivary cortisol, 24-h urinary catecholamines, and neurobehavioral performance were measured.
RESULTS
IVGTT-derived insulin sensitivity was reduced by (means ± SD) 20 ± 24% after sleep restriction (P = 0.001), without significant alterations in the insulin secretory response. Similarly, insulin sensitivity assessed by clamp was reduced by 11 ± 5.5% (P < 0.04) after sleep restriction. Glucose tolerance and the disposition index were reduced by sleep restriction. These outcomes were not affected by modafinil treatment. Changes in insulin sensitivity did not correlate with changes in salivary cortisol (increase of 51 ± 8% with sleep restriction, P < 0.02), urinary catecholamines, or slow wave sleep.
CONCLUSIONS
Sleep restriction (5 h/night) for 1 week significantly reduces insulin sensitivity, raising concerns about effects of chronic insufficient sleep on disease processes associated with insulin resistance.
doi:10.2337/db09-0699
PMCID: PMC2927933  PMID: 20585000
25.  A preliminary study of sleep in adolescents with bipolar disorder, ADHD, and non-patient controls 
Bipolar disorders  2011;13(4):425-432.
Objectives
To compare the sleep of adolescents with bipolar disorder (BD) to groups of adolescents with attention-deficit hyperactivity disorder–combined type (ADHD-C) and those without psychopathology.
Methods
A sample of 13 adolescents diagnosed with BD who were not in the midst of a mood episode, 14 adolescents with ADHD-C, and 21 healthy controls, all between the ages of 11 and 17 years served as participants. They were psychiatrically evaluated using a structured diagnostic interview and completed four nights of in-home sleep monitoring using actigraphy and sleep diaries.
Results
Sleep diary estimates of sleep indicated that participants with BD experienced more awakenings than their peers with ADHD, whereas actigraphic estimates revealed that participants with BD slept longer and with less wakefulness than their peers.
Conclusions
In between mood episodes, adolescents with BD experience their sleep as more fragmented than that of their peers but do not exhibit more disturbed sleep as estimated by actigraphy. The possible influence of psychotropic medication is an important consideration when assessing sleep in the context of BD.
doi:10.1111/j.1399-5618.2011.00933.x
PMCID: PMC3158129  PMID: 21843282
actigraphy; ADHD; adolescent; bipolar disorder; sleep

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