@article {715, title = {Sleep and sleep-disordered breathing in adults with predominantly mild obstructive airway disease.}, journal = {Am J Respir Crit Care Med}, volume = {167}, year = {2003}, month = {2003 Jan 01}, pages = {7-14}, abstract = {

Neither the association between obstructive airways disease (OAD) and sleep apnea-hypopnea (SAH) nor the sleep consequences of each disorder alone and together have been characterized in an adult community setting. Our primary aims were (1) to determine if there is an association between OAD and SAH and (2) identify predictors of oxyhemoglobin desaturation during sleep in persons having OAD with and without SAH. Polysomnography and spirometry results from 5,954 participants in the Sleep Heart Health Study were analyzed. OAD was defined by a FEV1/FVC value less than 70\%. Assessment of SAH prevalence in OAD was performed using thresholds of respiratory disturbance index (RDI) greater than 10 and greater than 15. A total of 1,132 participants had OAD that was predominantly mild (FEV1/FVC 63.81 +/- 6.56\%, mean +/- SD). SAH was not more prevalent in participants with OAD than in those without OAD (22.32 versus 28.86\%, with and without OAD, respectively, at RDI threshold values greater than 10; and 13.97 versus 18.63\%, with and without OAD, respectively, at RDI threshold value greater than 15). In the absence of SAH, the adjusted odds ratio for sleep desaturation (> 5\% total sleep time with saturation < 90\%) was greater than 1.9 when FEV1/FVC was less than 65\%. Participants with both OAD and SAH had greater sleep perturbation and desaturation than those with one disorder. Generally mild OAD alone was associated with minimally altered sleep quality. We conclude that (1) there is no association between generally mild OAD and SAH; (2) exclusive of SAH and after adjusting for demographic factors and awake oxyhemoglobin saturation, an FEV1/FVC value less than 65\% is associated with increased risk of sleep desaturation; (3) desaturation is greater in persons with both OAD and SAH compared with each of these alone; and (4) individuals with generally mild OAD and without SAH in the community have minimally perturbed sleep.

}, keywords = {Aged, Cohort Studies, Female, Forced Expiratory Volume, Humans, Male, Middle Aged, Oxyhemoglobins, Polysomnography, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Sleep, Sleep Apnea, Obstructive, Spirometry, Vital Capacity}, issn = {1073-449X}, doi = {10.1164/rccm.2203046}, author = {Sanders, Mark H and Newman, Anne B and Haggerty, Catherine L and Redline, Susan and Lebowitz, Michael and Samet, Jonathan and O{\textquoteright}Connor, George T and Punjabi, Naresh M and Shahar, Eyal} } @article {839, title = {Predictors of heartburn during sleep in a large prospective cohort study.}, journal = {Chest}, volume = {127}, year = {2005}, month = {2005 May}, pages = {1658-66}, abstract = {

BACKGROUND AND AIMS: Nocturnal gastroesophageal reflux, which may result in nocturnal heartburn, has been demonstrated to be associated with a more severe form of gastroesophageal reflux disease (GERD). The aim of this study was to determine the clinical predictors of heartburn during sleep in a large prospective cohort study.

METHODS: Study subjects were members of the parent cohorts from which the Sleep Heart Health Study (SHHS) recruited participants. SHHS is a multicenter, longitudinal, cohort study of the cardiovascular consequences of sleep-disordered breathing. As part of the recruitment process, parent cohort members completed a questionnaire that permitted an assessment of the relationships between heartburn during sleep, and patient demographics, sleep abnormalities, medical history, and social habits in nine community-based parent cohorts across the United States. All variables, significant at the p < 0.05 level, were included as independent variables in multivariate logistic regression models with heartburn during sleep status included as the dependent variable

RESULTS: A total of 15,314 subjects completed the questions about heartburn during sleep, and of these, 3,806 subjects (24.9\%) reported having this symptom. In four increasingly comprehensive multivariate models, increased body mass index (BMI), carbonated soft drink consumption, snoring and daytime sleepiness (Epworth sleepiness scale score), insomnia, hypertension, asthma, and usage of benzodiazepines were strong predictors of heartburn during sleep. In contrast, college education decreased the risk of reporting heartburn during sleep.

CONCLUSIONS: Heartburn during sleep is very common in the general population. Reports of this type of symptom of GERD are strongly associated with increased BMI, carbonated soft drink consumption, snoring and daytime sleepiness, insomnia, hypertension, asthma, and usage of benzodiazepines. Overall, heartburn during sleep may be associated with sleep complaints and excessive daytime sleepiness.

}, keywords = {Aged, Body Mass Index, Carbonated Beverages, Cohort Studies, Educational Status, Female, Gastroesophageal Reflux, Heartburn, Humans, Male, Middle Aged, Multivariate Analysis, Prospective Studies, Sleep, Surveys and Questionnaires}, issn = {0012-3692}, doi = {10.1378/chest.127.5.1658}, author = {Fass, Ronnie and Quan, Stuart F and O{\textquoteright}Connor, George T and Ervin, Ann and Iber, Conrad} } @article {989, title = {Genome-wide association of sleep and circadian phenotypes.}, journal = {BMC Med Genet}, volume = {8 Suppl 1}, year = {2007}, month = {2007 Sep 19}, pages = {S9}, abstract = {

BACKGROUND: Numerous studies suggest genetic influences on sleepiness and circadian rhythms. The Sleep Heart Health Study collected questionnaire data on sleep habits and sleepiness from 2848 Framingham Heart Study Offspring Cohort participants. More than 700 participants were genotyped using the Affymetrix 100K SNP GeneChip, providing a unique opportunity to assess genetic linkage and association of these traits.

METHODS: Sleepiness (defined as the Epworth Sleepiness Scale score), usual bedtime and usual sleep duration were assessed by self-completion questionnaire. Standardized residual measures adjusted for age, sex and BMI were analyzed. Multipoint variance components linkage analysis was performed. Association of SNPs to sleep phenotypes was analyzed with both population-based and family-based association tests, with analysis limited to 70,987 autosomal SNPs with minor allele frequency > or =10\%, call rate > or =80\%, and no significant deviation from Hardy-Weinberg equilibrium (p > or = 0.001).

RESULTS: Heritability of sleepiness was 0.29, bedtime 0.22, and sleep duration 0.17. Both genotype and sleep phenotype data were available for 749 subjects. Linkage analysis revealed five linkage peaks of LOD >2: four to usual bedtime, one to sleep duration. These peaks include several candidate sleep-related genes, including CSNK2A2, encoding a known component of the circadian molecular clock, and PROK2, encoding a putative transmitter of the behavioral circadian rhythm from the suprachiasmatic nucleus. Association tests identified an association of usual bedtime with a non-synonymous coding SNP in NPSR1 that has been shown to encode a gain of function mutation of the neuropeptide S receptor, whose endogenous ligand is a potent promoter of wakefulness. Each copy of the minor allele of this SNP was associated with a 15 minute later mean bedtime. The lowest p value was for association of sleepiness with a SNP located in an intron of PDE4D, which encodes a cAMP-specific phosphodiesterase widely expressed in human brain. Full association results are posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite.

CONCLUSION: This analysis confirms prior reports of significant heritability of sleepiness, usual bedtime, and usual sleep duration. Several genetic loci with suggestive linkage to these traits are identified, including linkage peaks containing circadian clock-related genes. Association tests identify NPSR1 and PDE4D as possible mediators of bedtime and sleepiness.

}, keywords = {Adult, Alleles, Cardiovascular Diseases, Circadian Rhythm, Cohort Studies, Female, Gene Frequency, Genetic Linkage, Genome, Human, Genotype, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Sleep, Surveys and Questionnaires}, issn = {1471-2350}, doi = {10.1186/1471-2350-8-S1-S9}, author = {Gottlieb, Daniel J and O{\textquoteright}Connor, George T and Wilk, Jemma B} } @article {1202, title = {Associations of PM10 with sleep and sleep-disordered breathing in adults from seven U.S. urban areas.}, journal = {Am J Respir Crit Care Med}, volume = {182}, year = {2010}, month = {2010 Sep 15}, pages = {819-25}, abstract = {

RATIONALE: Sleep-disordered breathing (SDB), the recurrent episodic disruption of normal breathing during sleep, affects as much as 17\% of U.S. adults, and may be more prevalent in poor urban environments. SDB and air pollution have been linked to increased cardiovascular diseases and mortality, but the association between pollution and SDB is poorly understood.

OBJECTIVES: We used data from the Sleep Heart Health Study (SHHS), a U.S. multicenter cohort study assessing cardiovascular and other consequences of SDB, to examine whether particulate air matter less than 10 μm in aerodynamic diameter (PM(10)) was associated with SDB among persons 39 years of age and older.

METHODS: Using baseline data from SHHS urban sites, outcomes included the following: the respiratory disturbance index (RDI); percentage of sleep time at less than 90\% O(2) saturation; and sleep efficiency, measured by overnight in-home polysomnography. We applied a fixed-effect model containing a city effect, controlling for potential predictors. In all models we included both the 365-day moving averages of PM(10) and temperature (long-term effects) and the differences between the daily measures of these two predictors and their 365-day average (short-term effects).

MEASUREMENTS AND MAIN RESULTS: In summer, increases in RDI or percentage of sleep time at less than 90\% O(2) saturation, and decreases in sleep efficiency, were all associated with increases in short-term variation in PM(10). Over all seasons, we found that increased RDI was associated with an 11.5\% (95\% confidence interval: 1.96, 22.01) increase per interquartile range increase (25.5{\textdegree}F) in temperature.

CONCLUSIONS: Reduction in air pollution exposure may decrease the severity of SDB and nocturnal hypoxemia and may improve cardiac risk.

}, keywords = {Adult, Aged, Aged, 80 and over, Air Pollutants, Air Pollution, Cities, Cohort Studies, Female, Humans, Male, Middle Aged, Multicenter Studies as Topic, Particle Size, Particulate Matter, Polysomnography, Seasons, Severity of Illness Index, Sleep, Sleep Apnea Syndromes, Temperature, United States, Urban Health}, issn = {1535-4970}, doi = {10.1164/rccm.200912-1797OC}, author = {Zanobetti, Antonella and Redline, Susan and Schwartz, Joel and Rosen, Dennis and Patel, Sanjay and O{\textquoteright}Connor, George T and Lebowitz, Michael and Coull, Brent A and Gold, Diane R} }