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1.  Habitual Snoring in school-aged children: environmental and biological predictors 
Respiratory Research  2010;11(1):144.
Background
Habitual snoring, a prominent symptom of sleep-disordered breathing, is an important indicator for a number of health problems in children. Compared to adults, large epidemiological studies on childhood habitual snoring and associated predisposing factors are extremely scarce. The present study aimed to assess the prevalence and associated factors of habitual snoring among Chinese school-aged children.
Methods
A random sample of 20,152 children aged 5.08 to 11.99 years old participated in a cross-sectional survey, which was conducted in eight cities of China. Parent-administrated questionnaires were used to collect information on children's snoring frequency and the possible correlates.
Results
The prevalence of habitual snoring was 12.0% (14.5% for boys vs. 9.5% for girls) in our sampled children. Following factors were associated with an increased risk for habitual snoring: lower family income (adjusted odds ratio [OR] = 1.46), lower father's education (OR = 1.38 and 1.14 for middle school or under and high school of educational level, respectively), breastfeeding duration < 6 months (OR = 1.17), pregnancy maternal smoking (OR = 1.51), obesity (OR = 1.50), overweight (OR = 1.35), several respiratory problems associated with atopy and infection, such as chronic/allergic rhinitis (OR = 1.94), asthma (OR = 1.43), adenotonsillar hypertrophy (OR = 2.17), and chronic otitis media (OR = 1.31), and family history of habitual snoring (OR = 1.70).
Conclusion
The prevalence of habitual snoring in Chinese children was similar to that observed in other countries. The potential predisposing factors covered socioeconomic characteristics, environmental exposures, chronic health problems, and family susceptibility. Compared to socioeconomic status and family susceptibility, environmental exposures and chronic health problems had greater impact, indicating childhood habitual snoring could be partly prevented by health promotion and environmental intervention.
doi:10.1186/1465-9921-11-144
PMCID: PMC2967531  PMID: 20955625
2.  Increased Cerebral Blood Flow Velocity in Children with Mild Sleep-Disordered Breathing 
Pediatrics  2006;118(4):e1100-e1108.
Objective
Sleep-disordered breathing describes a spectrum of upper airway obstruction in sleep from simple primary snoring, estimated to affect 10% of preschool children, to the syndrome of obstructive sleep apnea. Emerging evidence has challenged previous assumptions that primary snoring is benign. A recent report identified reduced attention and higher levels of social problems and anxiety/depressive symptoms in snoring children compared with controls. Uncertainty persists regarding clinical thresholds for medical or surgical intervention in sleep-disordered breathing, underlining the need to better understand the pathophysiology of this condition. Adults with sleep-disordered breathing have an increased risk of cerebrovascular disease independent of atherosclerotic risk factors. There has been little focus on cerebrovascular function in children with sleep-disordered breathing, although this would seem an important line of investigation, because studies have identified abnormalities of the systemic vasculature. Raised cerebral blood flow velocities on transcranial Doppler, compatible with raised blood flow and/or vascular narrowing, are associated with neuropsychological deficits in children with sickle cell disease, a condition in which sleep-disordered breathing is common. We hypothesized that there would be cerebral blood flow velocity differences in sleep-disordered breathing children without sickle cell disease that might contribute to the association with neuropsychological deficits.
Design
Thirty-one snoring children aged 3 to 7 years were recruited from adenotonsillectomy waiting lists, and 17 control children were identified through a local Sunday school or as siblings of cases. Children with craniofacial abnormalities, neuromuscular disorders, moderate or severe learning disabilities, chronic respiratory/cardiac conditions, or allergic rhinitis were excluded. Severity of sleep-disordered breathing in snoring children was categorized by attended polysomnography. Weight, height, and head circumference were measured in all of the children. BMI and occipitofrontal circumference z scores were computed. Resting systolic and diastolic blood pressure were obtained. Both sleep-disordered breathing children and the age- and BMI-similar controls were assessed using the Behavior Rating Inventory of Executive Function (BRIEF), Neuropsychological Test Battery for Children (NEPSY) visual attention and visuomotor integration, and IQ assessment (Wechsler Preschool and Primary Scale of Intelligence Version III). Transcranial Doppler was performed using a TL2-64b 2-MHz pulsed Doppler device between 2 PM and 7 PM in all of the patients and the majority of controls while awake. Time-averaged mean of the maximal cerebral blood flow velocities was measured in the left and right middle cerebral artery and the higher used for analysis.
Results
Twenty-one snoring children had an apnea/hypopnea index <5, consistent with mild sleep-disordered breathing below the conventional threshold for surgical intervention. Compared with 17 nonsnoring controls, these children had significantly raised middle cerebral artery blood flow velocities. There was no correlation between cerebral blood flow velocities and BMI or systolic or diastolic blood pressure indices. Exploratory analyses did not reveal any significant associations with apnea/hypopnea index, apnea index, hypopnea index, mean pulse oxygen saturation, lowest pulse oxygen saturation, accumulated time at pulse oxygen saturation <90%, or respiratory arousals when examined in separate bivariate correlations or in aggregate when entered simultaneously. Similarly, there was no significant association between cerebral blood flow velocities and parental estimation of child’s exposure to sleep-disordered breathing. However, it is important to note that whereas the sleep-disordered breathing group did not exhibit significant hypoxia at the time of study, it was unclear to what extent this may have been a feature of their sleep-disordered breathing in the past. IQ measures were in the average range and comparable between groups. Measures of processing speed and visual attention were significantly lower in sleep-disordered breathing children compared with controls, although within the average range. There were similar group differences in parental-reported executive function behavior. Although there were no direct correlations, adjusting for cerebral blood flow velocities eliminated significant group differences between processing speed and visual attention and decreased the significance of differences in Behavior Rating Inventory of Executive Function scores, suggesting that cerebral hemodynamic factors contribute to the relationship between mild sleep-disordered breathing and these outcome measures.
Conclusions
Cerebral blood flow velocities measured by noninvasive transcranial Doppler provide evidence for increased cerebral blood flow and/or vascular narrowing in childhood sleep-disordered breathing; the relationship with neuropsychological deficits requires further exploration. A number of physiologic changes might alter cerebral blood flow and/or vessel diameter and, therefore, affect cerebral blood flow velocities. We were able to explore potential confounding influences of obesity and hypertension, neither of which explained our findings. Second, although cerebral blood flow velocities increase with increasing partial pressure of carbon dioxide and hypoxia, it is unlikely that the observed differences could be accounted for by arterial blood gas tensions, because all of the children in the study were healthy, with no cardiorespiratory disease, other than sleep-disordered breathing in the snoring group. Although arterial partial pressure of oxygen and partial pressure of carbon dioxide were not monitored during cerebral blood flow velocity measurement, assessment was undertaken during the afternoon/early evening when the child was awake, and all of the sleep-disordered breathing children had normal resting oxyhemoglobin saturation at the outset of their subsequent sleep studies that day. Finally, there is an inverse linear relationship between cerebral blood flow and hematocrit in adults, and it is known that iron-deficient erythropoiesis is associated with chronic infection, such as recurrent tonsillitis, a clinical feature of many of the snoring children in the study. Preoperative full blood counts were not performed routinely in these children, and, therefore, it was not possible to exclude anemia as a cause of increased cerebral blood flow velocity in the sleep-disordered breathing group. However, hemoglobin levels were obtained in 4 children, 2 of whom had borderline low levels (10.9 and 10.2 g/dL). Although there was no apparent relationship with cerebral blood flow velocity in these children (cerebral blood flow velocity values of 131 and 130 cm/second compared with 130 and 137 cm/second in the 2 children with normal hemoglobin levels), this requires verification. It is of particular interest that our data suggest a relationship among snoring, increased cerebral blood flow velocities and indices of cognition (processing speed and visual attention) and perhaps behavioral (Behavior Rating Inventory of Executive Function) function. This finding is preliminary: a causal relationship is not established, and the physiologic mechanisms underlying such a relationship are not clear. Prospective studies that quantify cumulative exposure to the physiologic consequences of sleep-disordered breathing, such as hypoxia, would be informative.
doi:10.1542/peds.2006-0092
PMCID: PMC1995426  PMID: 17015501
sleep disordered breathing; cerebral blood flow; transcranial Doppler; executive function; neuropsychological function
3.  Snoring in primary school children and domestic environment: A Perth school based study 
Respiratory Research  2004;5(1):19.
Background
The home is the predominant environment for exposure to many environmental irritants such as air pollutants and allergens. Exposure to common indoor irritants including volatile organic compounds, formaldehyde and nitrogen dioxide, may increase the risk of snoring for children. The aim of this study was to investigate domestic environmental factors associated with snoring in children.
Methods
A school-based respiratory survey was administered during March and April of 2002. Nine hundred and ninety six children from four primary schools within the Perth metropolitan area were recruited for the study. A sub-group of 88 children aged 4–6 years were further selected from this sample for domestic air pollutant assessment.
Results
The prevalences of infrequent snoring and habitual snoring in primary school children were 24.9% and 15.2% respectively. Passive smoking was found to be a significant risk factor for habitual snoring (odds ratio (OR) = 1.77; 95% confidence interval (CI): 1.20–2.61), while having pets at home appeared to be protective against habitual snoring (OR = 0.58; 95% CI: 0.37–0.92). Domestic pollutant assessments showed that the prevalence of snoring was significantly associated with exposure to nitrogen dioxide during winter. Relative to the low exposure category (<30 μg/m3), the adjusted ORs of snoring by children with medium (30 – 60 μg/m3) and high exposures (> 60 μg/m3) to NO2 were 2.5 (95% CI: 0.7–8.7) and 4.5 (95% CI: 1.4–14.3) respectively. The corresponding linear dose-response trend was also significant (P = 0.011).
Conclusion
Snoring is common in primary school children. Domestic environments may play a significant role in the increased prevalence of snoring. Exposure to nitrogen dioxide in domestic environment is associated with snoring in children.
doi:10.1186/1465-9921-5-19
PMCID: PMC535337  PMID: 15527500
4.  Effect of asthma on the risk of obstructive sleep apnea syndrome in atopic women 
Background
Obstructive sleep apnea syndrome is associated with significant morbidity and remains underdiagnosed in women. Identification of high-risk groups among women is important for early detection and treatment.
Objective
To describe the prevalence of snoring in young women with atopy and to determine the risk factors for snoring in these individuals.
Methods
The Cincinnati Childhood Allergy and Air Pollution Study is an ongoing prospective birth cohort study of infants with at least 1 atopic parent. Mothers of study participants were evaluated by questionnaire for snoring, respiratory symptoms, and smoking status. Women who snored were compared with those who did not snore. Logistic regression analysis was performed to determine risk factors for snoring.
Results
Data were available on 677 women who had at least 1 live birth. Of these 677 women, 546 (81%) were white, 122 (18%) were African American, and 9 (1%) were biracial or Asian. The mean ± SD age of the cohort at the time of evaluation for snoring was 29.6 ± 5.6 years. Of the 677 women, 231 (34%) reported snoring at least 1 night per week, and snoring almost always (5–7 nights per week) was reported by 85 (13%). An almost 2-fold risk of snoring was associated with asthma (diagnosis and current symptoms) (odds ratio, 1.8; 95% confidence interval, 1.1–2.8) and African American race (odds ratio, 1.6; 95% confidence interval, 1.04–2.6) after controlling for income level and smoking status.
Conclusions
We found a high prevalence of snoring in young women with atopy and a significant association with asthma.
PMCID: PMC2233949  PMID: 16937757
5.  Excessive daytime sleepiness among rural residents in Saskatchewan 
Obstructive sleep apnea and its sequelae are emerging public health issues in North America, and symptoms are often under-recognized or under-reported. Although several patient factors have been identified, limited data regarding the prevalence of and predictors for excessive daytime sleepiness in rural or remote populations area available. Accordingly, this study used Epworth Sleepiness Scale scores to evaluate daytime sleepiness in a large rural population participating in the Saskatchewan Rural Health Study.
BACKGROUND:
Obstructive sleep apnea (OSA) is a common diagnosis in clinical practice. Excessive daytime sleepiness may be a warning for possible OSA.
OBJECTIVES:
To assess the prevalence of excessive daytime sleepiness as measured by the Epworth Sleepiness Scale (ESS) in a rural community population; potential risk factors for OSA were also assessed.
METHODS:
In 2010, a baseline respiratory health questionnaire within the Saskatchewan Rural Health Study was mailed to 11,982 households in Saskatchewan. A total of 7597 adults within the 4624 (42%) respondent households completed the ESS questionnaire. Participants were categorized according to normal or high (>10) ESS scores. Data obtained included respiratory symptoms, doctor-diagnosed sleep apnea, snoring, hypertension, smoking and demographics. Body mass index was calculated. Multivariable logistic regression analysis examined associations between high ESS scores and possible risk factors. Generalized estimating equations accounted for the two-tiered sampling procedure of the study design.
RESULTS:
The mean age of respondents was 55.0 years and 49.2% were male. The prevalence of ESS>10 and ‘doctor diagnosed’ OSA were 15.9% and 6.0%, respectively. Approximately 23% of respondents reported loud snoring and 30% had a body mass index >30 kg/m2. Of those with ‘doctor-diagnosed’ OSA, 37.7% reported ESS>10 (P<0.0001) and 47.7% reported loud snoring (P<0.0001). Risk of having an ESS>10 score increased with age, male sex, obesity, lower socioeconomic status, marriage, loud snoring and doctor-diagnosed sinus trouble.
CONCLUSIONS:
High levels of excessive daytime sleepiness in this particular rural population are common and men >55 years of age are at highest risk. Examination of reasons for residual sleepiness and snoring in persons with and without sleep apnea is warranted.
PMCID: PMC4173890  PMID: 24791255
Epworth Sleepiness Scale; Farm; Nonfarm; Obesity; Rural; Sleep apnea; Snoring; Socioeconomic
6.  Natural history of snoring and related behaviour problems between the ages of 4 and 7 years. 
In 1989-90 a survey was carried out of the prevalence of snoring and related symptoms in 782 4 to 5 year old children. Two years later, in 1992, the same group of children was studied to gather information on the natural history of snoring and the related behaviour problems. A total of 507/782 (64.8%) completed questionnaires were received. Comparison of the responses with the 1989-90 survey showed that those who did not reply to the questionnaire were no different from the respondents in terms of the prevalence of snoring, daytime sleepiness, hyperactivity, and restless sleep. The overall prevalence of habitual snoring did not change between the two surveys (12.1% in 1989-90 v 11.4% in 1992), though more than half of the children who snored habitually in the original survey no longer did so. There was little change in the prevalence of hyperactivity (24.2% in 1989-90 v 20.7% in 1992) or restless sleep (both 39%) among the 507 who responded to the present survey. The prevalence of daytime sleepiness, however, did decrease substantially (20.7% in 1989-90 v 10.2% in 1992). There was moderate agreement between the individual questionnaire responses for the 1989-90 and 1992 surveys for snoring (weighted kappa 0.52), but poor agreement for the other symptoms (daytime sleepiness 0.37, hyperactivity 0.35, and restless sleep 0.38). Trend analysis showed that the increasing prevalence of sleepiness, hyperactivity, and restless sleep across the snoring categories was highly significant. Daytime sleepiness, hyperactivity, and restless sleep were all significantly more common in the habitual snorers than in those who never snored. Relative risks (95% confidence interval) were as follows: daytime sleepiness 6.13 (2.5 to 14.9), hyperactivity 2.78 (1.6 to 4.7), and restless sleep 2.3 (1.6 to 3.2). Though habitual snoring and the associated behaviour problems resolved spontaneously over two years in about half of the children with these symptoms, there is still the same overall percentage with these problems due to the emergence of new cases.
PMCID: PMC1029917  PMID: 8067797
7.  Comparative Effects of Snoring Sound between Two Minimally Invasive Surgeries in the Treatment of Snoring: A Randomized Controlled Trial 
PLoS ONE  2014;9(5):e97186.
Background
Minimally invasive surgeries of the soft palate have emerged as a less-invasive treatment for habitual snoring. To date, there is only limited information available comparing the effects of snoring sound between different minimally invasive surgeries in the treatment of habitual snoring.
Objective
To compare the efficacy of palatal implant and radiofrequency surgery, in the reduction of snoring through subjective evaluation of snoring and objective snoring sound analysis.
Patients and Method
Thirty patients with habitual snoring due to palatal obstruction (apnea-hypopnea index ≤15, body max index ≤30) were prospectively enrolled and randomized to undergo a single session of palatal implant or temperature-controlled radiofrequency surgery of the soft palate under local anesthesia. Snoring was primarily evaluated by the patient with a 10 cm visual analogue scale (VAS) at baseline and at a 3-month follow-up visit and the change in VAS was the primary outcome. Moreover, life qualities, measured by snore outcomes survey, and full-night snoring sounds, analyzed by a sound analytic program (Snore Map), were also investigated at the same time.
Results
Twenty-eight patients completed the study; 14 received palatal implant surgery and 14 underwent radiofrequency surgery. The VAS and snore outcomes survey scores were significantly improved in both groups. However, the good response (postoperative VAS ≤3 or postoperative VAS ≤5 plus snore outcomes survey score ≥60) rate of the palatal implant group was significantly higher than that of the radiofrequency group (79% vs. 29%, P = 0.021). The maximal loudness of low-frequency (40–300 Hz) snores was reduced significantly in the palatal implant group. In addition, the snoring index was significantly reduced in the radiofrequency group.
Conclusions
Both palatal implants and a single-stage radiofrequency surgery improve subjective snoring outcomes, but palatal implants have a greater effect on most measures of subjective and objective snoring. Multi-stage radiofrequency surgery was not tested.
Trial Registration
ClinicalTrials.gov NCT01955083
doi:10.1371/journal.pone.0097186
PMCID: PMC4016275  PMID: 24816691
8.  Snoring during pregnancy and its relation to sleepiness and pregnancy outcome - a prospective study 
Background
The incidence of snoring and sleepiness is known to increase during pregnancy, and this might impact maternal health and obstetric outcome. However, the association between snoring and sleepiness during pregnancy is not fully understood. This study was aimed at investigating the development of snoring during pregnancy and prospectively assessing if there is an association between snoring and sleepiness or adverse pregnancy outcomes, such as preeclampsia, mode of delivery, and fetal complications.
Methods
Consecutively recruited pregnant women (n = 500) received a questionnaire concerning snoring and sleep at the 1st and 3rd trimester of pregnancy. The women who had rated their frequency of snoring at both occasions (n = 340) were divided into subgroups according to the development of snoring they reported and included in the subsequent analyses. Additional medical data were collected from the medical records.
Results
The frequency of snoring was 7.9% in the 1st trimester and increased to 21.2% in the 3rd trimester of pregnancy. The women who snored already in early pregnancy had significantly higher baseline BMI (p = 0.001) than the women who never snored, but snoring was not associated with the magnitude of weight gain during pregnancy. Snoring women were more likely to experience edema in late pregnancy than the non-snorers. Women who started to snore during pregnancy had higher Epworth Sleepiness Scores than the non snorers in both early and late pregnancy. No significant association between obstetric outcome and snoring was found.
Conclusion
Snoring does increase during pregnancy, and this increase is associated with sleepiness, higher BMI at the start of pregnancy and higher prevalence of edema, but not with weight gain.
doi:10.1186/1471-2393-14-15
PMCID: PMC3893487  PMID: 24418321
Pregnancy; Snoring; Sleepiness; Epworth sleepiness score; Body mass index; Edema; Pregnancy outcome
9.  Markers for severity of illness associated with decreased snoring in toddlers born ELGA 
Aim
To describe the prevalence of paediatric sleep disordered breathing (SDB) symptoms in extremely low gestational age infants and identify neonatal risk factors, including early exposure to hypoxia and hyperoxia.
Methods
Patients <28 weeks gestation were monitored with high-resolution pulse oximetry. Hypoxia/hyperoxia variables were defined as percentage time of first 4 weeks of life that SaO2 < 80% or SaO2 > 98%, respectively. Parents completed part of the OSA-18 questionnaire for symptoms of SDB at 18–22 months. Logistic regression was used to test the association between risk factors and sleep symptoms.
Results
Of 182 patients recruited, 138 (76%) completed the questionnaire. The mean gestation was 26 weeks, and mean birth weight 887 grams. Loud snoring (21%) and restless sleep (24%) were the most prevalent symptoms. Female sex was associated with an increased risk of loud snoring (OR, 2.7; CI, 1.13–6.5). Prolonged mechanical ventilation, necrotizing enterocolitis and prolonged caffeine use, however, were inversely correlated with loud snoring. Neither neonatal hypoxia nor hyperoxia were associated with sleep symptoms.
Conclusions
While the prevalence of sleep disordered breathing symptoms is similar to reported rates, we found a sex difference not previously reported. Interestingly, markers for severity of illness show a pattern of being protective against loud snoring.
doi:10.1111/apa.12033
PMCID: PMC3650629  PMID: 23009601
Snoring; Sleep disordered breathing; Prematurity
10.  Prevalence of Sleep Abnormalities and Their Association with Metabolic Syndrome among Asian Indians: Chennai Urban Rural Epidemiology Study (CURES – 67) 
Objective
To estimate the prevalence of sleep abnormalities and their association with glucose intolerance and metabolic syndrome (MS) in the normal-weight urban South Indian population.
Methods
This population-based, cross-sectional study was carried out in 358 subjects aged 20–76 years randomly selected from the Chennai Urban Rural Epidemiology Study in South India. A validated questionnaire assessing various sleep abnormalities (snoring, daytime sleepiness, lack of refreshing sleep, and number of hours of sleep) was administered. All subjects underwent an oral glucose tolerance test, and anthropometric biochemical measurements were obtained to assess cardiometabolic risk factors including glucose intolerance. Diabetes risk was assessed using a previously validated Indian Diabetes Risk Score (IDRS).
Results
The overall prevalence of snoring and daytime sleepiness was 40% and 59%, respectively. Snorers were more male, older, smokers, and had higher levels of cardiometabolic risk factors. Subjects with daytime sleepiness had higher body mass index (BMI) and abdominal obesity. Both snoring (50.9% vs 30.2%, p < 0.001) and daytime sleepiness (68% vs 49.7%, p < 0.001) were more prevalent among subjects with impaired glucose metabolism compared to those with normal glucose metabolism. Both sleep measures were associated with higher diabetes risk scores, as assessed by the IDRS (snoring: trend χ2, 11.14, p = 0.001; daytime sleepiness: trend χ2, 5.12, p = 0.024). Metabolic syndrome was significantly associated with snoring even after adjusting for age, sex, family history of diabetes, physical activity, smoking, and alcohol.
Conclusion
The prevalence of snoring and daytime sleepiness is high among urban South Indians and these two sleep measures are associated with glucose intolerance, MS, and higher diabetes risk scores.
PMCID: PMC3005066  PMID: 21129351
sleep abnormalities; snoring; daytime sleepiness; cardiometabolic risk factors; metabolic syndrome; Asian Indians
11.  Clinical Screening of School Children for Polysomnography to Detect Sleep-Disordered Breathing—the Tucson Children’s Assessment of Sleep Apnea Study (TuCASA) 
Study Objectives
This report describes the associations, specificities, sensitivities, and positive likelihood ratios of clinical symptoms to a finding of sleep-disordered breathing (SDB) on polysomnography in children.
Methods
Four hundred eighty unattended home polysomnograms were completed in a community-based cohort of children 6 to 11 years of age (50% boys, 42.3% Hispanic, and 52.9% between the ages of 6 and 8 years). SDB was present if the child had a respiratory disturbance index of ≥ 1 event per hour.
Measurements and Results
Boys were twice as likely as girls to have SDB (p<.01); however, witnessed apnea, ethnicity, age, obesity, and air-way size (based on clinical evaluation) were not significantly different between those with SDB and without SDB. The sensitivity of any individual or combined clinical symptoms was poor, with male sex (60%) and snoring (29.5%) having the greatest proportion of SDB children. However, high specificities for snoring (89.5%), excessive daytime sleepiness (86.3%), and learning problems (95.9%) were noted. Combinations of symptoms such as snoring+male sex (95.1%), snoring+excessive daytime sleepiness (97.0%), and snoring+learning problems (98.9%) had specificities approaching 1. Positive likelihood ratios for snoring (2.8), learning (2.8), and symptoms combined with snoring such as snoring+male sex(3.9), snoring+learning problems (4.0), and snoring+excessive daytime sleepiness (2.9) were observed.
Conclusions
Snoring, excessive daytime sleepiness, and learning problems are each highly specific, but not sensitive, for SDB in 6- to 11-year old children. However, specificities and positive likelihood ratios for the combination of some of these symptoms is sufficiently high to suggest that some children may not require a polysomnogram for the diagnosis of SDB.
PMCID: PMC1307497  PMID: 16429591
Sleep; children; sleep-disordered breathing; sleep apnea; respiratory disturbance index
12.  Persistent Snoring in Preschool Children: Predictors and Behavioral and Developmental Correlates 
Pediatrics  2012;130(3):382-389.
OBJECTIVE:
To clarify whether persistent snoring in 2- to 3-year-olds is associated with behavioral and cognitive development, and to identify predictors of transient and persistent snoring.
METHODS:
Two hundred forty-nine mother/child pairs participated in a prospective birth cohort study. Based upon parental report of loud snoring ≥2 times weekly at 2 and 3 years of age, children were designated as nonsnorers, transient snorers (snored at 2 or 3 years of age, but not both), or persistent snorers (snored at both ages). We compared groups by using validated measures of behavioral and cognitive functioning. Potential predictors of snoring included child race and gender, socioeconomic status (parent education and income), birth weight, prenatal tobacco exposure (maternal serum cotinine), childhood tobacco exposure (serum cotinine), history and duration of breast milk feeding, and body mass relative to norms.
RESULTS:
In multivariable analyses, persistent snorers had significantly higher reported overall behavior problems, particularly hyperactivity, depression, and inattention. Nonsnorers had significantly stronger cognitive development than transient and persistent snorers in unadjusted analyses, but not after demographic adjustment. The strongest predictors of the presence and persistence of snoring were lower socioeconomic status and the absence or shorter duration of breast milk feeding. Secondary analyses suggested that race may modify the association of childhood tobacco smoke exposure and snoring.
CONCLUSIONS:
Persistent, loud snoring was associated with higher rates of problem behaviors. These results support routine screening and tracking of snoring, especially in children from low socioeconomic backgrounds; referral for follow-up care of persistent snoring in young children; and encouragement and facilitation of infant breastfeeding.
doi:10.1542/peds.2012-0045
PMCID: PMC3428758  PMID: 22891224
sleep-disordered breathing; behavior problems; preschool; environmental tobacco smoke; breastfeeding; overweight
13.  Snoring and risk for obstructive sleep apnea among nigerians with heart failure: Prevalence and clinical correlates 
Background:
Heart failure is an important cause of morbidity and mortality in developing nations like Nigeria. Sleep apnea and snoring has recently been recognized to be a cardiovascular risk factor. Sleep apnea is yet to be well studied among Africans with heart failure. We aimed to determine the prevalence of snoring and high risk for obstructive sleep apnea among Nigerians with stable heart failure.
Materials and Methods:
We studied 103 subjects that included 62 patients with heart failure and 41 control subjects. Demographic parameters and clinical examination were performed on the participants. The Berlin score and the Epworth Sleepiness Scale were administered for each participant. Echocardiography was done on all participants. Statistical analysis was done using Statistical Package for Social Sciences (SPSS) 17.0.
Results:
Snoring was reported in 48.4% of subjects with heart failure compared to 22.0% of control subjects ( P < 0.005). High risk for obstructive sleep apnea using the Berlin score was documented in 51.6% of heart failure subjects compared to 7.31% of controls. Excessive daytime somnolence occurred more in heart failure patients (51.6% vs. 9.8%, P < 0.05). Snorers tended to be older and were more likely to be obese than nonsnorers. Systolic blood pressure and fasting blood sugar were significantly higher among heart failure subjects with snoring than those without snoring (131.9 ± 19.2 vs. 119.2 ± 15.7 and 6.0 ± 0.8 vs. 5.4 ± 2.7, P < 0.005).
Conclusion:
Heart failure seems to be associated with snoring and a high risk for obstructive sleep apnea among Africans with heart failure. Assessment for sleep disordered breathing should be incorporated into their routine clinical workup.
doi:10.4103/1995-705X.107115
PMCID: PMC3621219  PMID: 23580920
Clinical correlates; heart failure; Nigeria; prevalence; sleep apnea; snoring
14.  Obstructive Sleep Apnea and Risk of Cardiovascular Events and All-Cause Mortality: A Decade-Long Historical Cohort Study 
PLoS Medicine  2014;11(2):e1001599.
Tetyana Kendzerska and colleagues explore the association between physiological measures of obstructive sleep apnea other than the apnea-hypopnea index and the risk of cardiovascular events.
Please see later in the article for the Editors' Summary
Background
Obstructive sleep apnea (OSA) has been reported to be a risk factor for cardiovascular (CV) disease. Although the apnea-hypopnea index (AHI) is the most commonly used measure of OSA, other less well studied OSA-related variables may be more pathophysiologically relevant and offer better prediction. The objective of this study was to evaluate the relationship between OSA-related variables and risk of CV events.
Methods and Findings
A historical cohort study was conducted using clinical database and health administrative data. Adults referred for suspected OSA who underwent diagnostic polysomnography at the sleep laboratory at St Michael's Hospital (Toronto, Canada) between 1994 and 2010 were followed through provincial health administrative data (Ontario, Canada) until May 2011 to examine the occurrence of a composite outcome (myocardial infarction, stroke, congestive heart failure, revascularization procedures, or death from any cause). Cox regression models were used to investigate the association between baseline OSA-related variables and composite outcome controlling for traditional risk factors. The results were expressed as hazard ratios (HRs) and 95% CIs; for continuous variables, HRs compare the 75th and 25th percentiles. Over a median follow-up of 68 months, 1,172 (11.5%) of 10,149 participants experienced our composite outcome. In a fully adjusted model, other than AHI OSA-related variables were significant independent predictors: time spent with oxygen saturation <90% (9 minutes versus 0; HR = 1.50, 95% CI 1.25–1.79), sleep time (4.9 versus 6.4 hours; HR = 1.20, 95% CI 1.12–1.27), awakenings (35 versus 18; HR = 1.06, 95% CI 1.02–1.10), periodic leg movements (13 versus 0/hour; HR = 1.05, 95% CI 1.03–1.07), heart rate (70 versus 56 beats per minute [bpm]; HR = 1.28, 95% CI 1.19–1.37), and daytime sleepiness (HR = 1.13, 95% CI 1.01–1.28).The main study limitation was lack of information about continuous positive airway pressure (CPAP) adherence.
Conclusion
OSA-related factors other than AHI were shown as important predictors of composite CV outcome and should be considered in future studies and clinical practice.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder, particularly among middle-aged and elderly people. It is characterized by apnea—a brief interruption in breathing that lasts at least 10 seconds—and hypopnea—a decrease of more than 50% in the amplitude of breathing that lasts at least 10 seconds or clear but smaller decrease in amplitude associated with either oxygen desaturation or an arousal. Patients with OSA experience numerous episodes of apnea and hypopnea during the night; severe OSA is defined as having 30 or more episodes per hour (an apnea-hypopnea index [AHI] of >30). These breathing interruptions occur when relaxation of the upper airway muscles decreases the airflow, which lowers the amount of oxygen in the blood. As a result, affected individuals frequently wake from deep sleep as they struggle to breathe. Symptoms of OSA include loud snoring and daytime sleepiness. Treatments include lifestyle changes such as losing weight (excess fat around the neck increases airway collapse) and smoking cessation. For severe OSA, doctors recommend continuous positive airway pressure (CPAP), in which a machine blows pressurized air through a face mask into the airway to keep it open.
Why Was This Study Done?
OSA can be life-threatening. Most directly, daytime sleepiness can cause accidents, but OSA is also associated with an increased risk of developing cardiovascular disease (CVD, disease that affects the heart and the circulation). To date, studies that have investigated the association between OSA and the risk of myocardial infarction (heart attack), congestive heart failure, stroke, and other CVDs have used the AHI to diagnose and categorize the severity of OSA. However, by focussing on AHI, clinicians and researchers may be missing opportunities to improve their ability to predict which patients are at the highest risk of CVD. In this historical cohort study, the researchers investigate the association between other OSA-related variables (for example, blood oxygen saturation and sleep fragmentation) and the risk of cardiovascular events and all-cause mortality (death). A historical cohort study examines the medical records of groups of individuals who have different characteristics at baseline for the subsequent occurrence of specific outcomes.
What Did the Researchers Do and Find?
The researchers used administrative data (including hospitalization records and physicians' claims for services supplied to patients) to follow up adults referred for suspected OSA who underwent diagnostic polysomnography (a sleep study) at a single Canadian hospital between 1994 and 2010. A database of the polysomnography results provided information on OSA-related variables for all the study participants. Over an average follow-up of about 6 years, 11.5% of the 10,149 participants were hospitalized for a myocardial infarction, stroke, or congestive heart failure, underwent a revascularization procedure (an intervention that restores the blood supply to an organ or tissue after CVD has blocked a blood vessel), or had died from any cause. After adjusting for multiple established risk factors for CVD such as smoking and age in Cox regression models (a statistical approach that examines associations between patient variables and outcomes), several OSA-related variables (but not AHI) were significant predictors of CVD. The strongest OSA-related predictor of cardiovascular events or all-cause mortality was total sleep time spent with oxygen saturation below 90%, which increased the risk of a cardiovascular event or death by 50%. Other statistically significant OSA-related predictors (predictors that were unlikely to be associated with the outcome through chance) of cardiovascular events or death included total sleep time, number of awakenings, frequency of periodic leg movements, heart rate, and daytime sleepiness.
What Do These Findings Mean?
These findings indicate that OSA-related factors other than AHI are important predictors of the composite outcome of a cardiovascular event or all-cause mortality. Indeed, although AHI was significantly associated with the researchers' composite outcome in an analysis that did not consider other established risk factors for CVD (“confounders”), the association became non-significant after controlling for potential confounders. The accuracy of these findings, which need to be confirmed in other settings, is likely to be limited by the lack of information available about the use of CPAP by study participants and by the lack of adjustment for some important confounders. Importantly, however, these findings suggest that OSA-related factors other than AHI should be considered as predictors of CVD in future studies and in clinical practice.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001599.
The US National Heart Lung and Blood Institute has information (including several videos) about obstructive sleep apnea (in English and Spanish), sleep studies, heart disease, and other cardiovascular diseases (some information in English and Spanish)
The UK National Health Service Choices website provides information (including personal stories) about sleep apnea and about cardiovascular disease
The not-for-profit American Sleep Apnea Association provides detailed information about sleep apnea for patients and health-care professionals, including personal stories about the condition
The MedlinePlus encyclopedia has pages on obstructive sleep apnea and on polysomnography; MedlinePlus provides links to further information and advice about obstructive sleep apnea, heart diseases, and vascular diseases (in English and Spanish)
doi:10.1371/journal.pmed.1001599
PMCID: PMC3913558  PMID: 24503600
15.  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
16.  Snoring and obstructive sleep apnoea syndrome among hypertensive Nigerians: Prevalence and clinical correlates 
Background
Obstructive sleep apnoea (OSA) syndrome is a common disorder in the community. Association between hypertension and sleep apnoea and /or snoring has been described. The Berlin questionnaire is a validated instrument that is used to identify individuals who are at risk for OSA. The study aim to describe the prevalence of snoring and OSA among hypertensive subjects in South Western, Nigeria.
Methods
This was a descriptive study conducted at the Cardiology clinic of Ladoke Akintola University of Technology LAUTECH Teaching Hospital, Osogbo, South West Nigeria. One hundred consecutive hypertensive patients were recruited from the clinic. The Berlin questionnaire and the Epworth sleepiness scale (ESS) were used to determine excessive daytime sleepiness and the risk of having OSA. Statistical analysis was done using SPSS 16.0. Data were summarized as means ± S.D and percentages.
Results
The study participants consisted of 40 males (40.0%). The demographic data were similar between both genders except that females had higher mean body mass index than males. The prevalence of snoring was 50.0%. 52% were categorized as being at high risk of having OSA. Snorers were more likely to be older, males and to have a higher fasting blood sugar than non-snorers.96% of snorers reported excessive daytime somnolence as predicted by the ESS score compared to 4% of non snorers. Prevalence of snoring was also higher among overweight and obese hypertensive subjects than normal body mass index hypertensive subjects.
Conclusion
Snoring is common among hypertensive subjects in South Western Nigeria. Clinically suspected OSA was similarly high in prevalence among them. Early identification and management may reduce the cardiovascular risk of hypertensive subjects.
PMCID: PMC3361213  PMID: 22655109
Snoring; sleep apnoea; hypertension; prevalence; clinical correlates; Nigeria
17.  Sleep-Disordered Breathing and Mortality: A Prospective Cohort Study 
PLoS Medicine  2009;6(8):e1000132.
In a cohort of 6,441 volunteers followed over an average of 8.2 years, Naresh Punjabi and colleagues find sleep-disordered breathing to be independently associated with mortality and identify predictive characteristics.
Background
Sleep-disordered breathing is a common condition associated with adverse health outcomes including hypertension and cardiovascular disease. The overall objective of this study was to determine whether sleep-disordered breathing and its sequelae of intermittent hypoxemia and recurrent arousals are associated with mortality in a community sample of adults aged 40 years or older.
Methods and Findings
We prospectively examined whether sleep-disordered breathing was associated with an increased risk of death from any cause in 6,441 men and women participating in the Sleep Heart Health Study. Sleep-disordered breathing was assessed with the apnea–hypopnea index (AHI) based on an in-home polysomnogram. Survival analysis and proportional hazards regression models were used to calculate hazard ratios for mortality after adjusting for age, sex, race, smoking status, body mass index, and prevalent medical conditions. The average follow-up period for the cohort was 8.2 y during which 1,047 participants (587 men and 460 women) died. Compared to those without sleep-disordered breathing (AHI: <5 events/h), the fully adjusted hazard ratios for all-cause mortality in those with mild (AHI: 5.0–14.9 events/h), moderate (AHI: 15.0–29.9 events/h), and severe (AHI: ≥30.0 events/h) sleep-disordered breathing were 0.93 (95% CI: 0.80–1.08), 1.17 (95% CI: 0.97–1.42), and 1.46 (95% CI: 1.14–1.86), respectively. Stratified analyses by sex and age showed that the increased risk of death associated with severe sleep-disordered breathing was statistically significant in men aged 40–70 y (hazard ratio: 2.09; 95% CI: 1.31–3.33). Measures of sleep-related intermittent hypoxemia, but not sleep fragmentation, were independently associated with all-cause mortality. Coronary artery disease–related mortality associated with sleep-disordered breathing showed a pattern of association similar to all-cause mortality.
Conclusions
Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40–70 y with severe sleep-disordered breathing.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 1 in 10 women and 1 in 4 men have a chronic condition called sleep-disordered breathing although most are unaware of their problem. Sleep-disordered breathing, which is commonest in middle-aged and elderly people, is characterized by numerous, brief (10 second or so) interruptions of breathing during sleep. These interruptions, which usually occur when relaxation of the upper airway muscles decreases airflow, lower the level of oxygen in the blood and, as a result, affected individuals are frequently aroused from deep sleep as they struggle to breathe. Symptoms of sleep-disordered breathing include loud snoring and daytime sleepiness. Treatments include lifestyle changes such as losing weight (excess fat around the neck increases airway collapse) and smoking cessation. Affected people can also use special devices to prevent them sleeping on their backs, but for severe sleep-disordered breathing, doctors often recommend continuous positive airway pressure (CPAP), a machine that pressurizes the upper airway through a face mask to keep it open.
Why Was This Study Done?
Sleep-disordered breathing is a serious condition. It is associated with several adverse health conditions including coronary artery disease (narrowing of the blood vessels that supply the heart, a condition that can cause a heart attack) and daytime sleepiness that can affect an individual's driving ability. In addition, several clinic- and community-based studies suggest that sleep-disordered sleeping may increase a person's risk of dying. However, because these studies have been small and have often failed to allow for other conditions and characteristics that affect an individual's risk of dying (“confounding factors”), they provide inconsistent or incomplete information about the potential association between sleep-disordered breathing and the risk of death. In this prospective cohort study (part of the Sleep Heart Health Study, which is researching the effects of sleep-disordered breathing on cardiovascular health), the researchers examine whether sleep-disordered breathing is associated with all-cause mortality (death from any cause) in a large community sample of adults. A prospective cohort study is one in which a group of participants is enrolled and then followed forward in time (in this case for several years) to see what happens to them.
What Did the Researchers Do and Find?
At enrollment, the study participants—more than 6,000 people aged 40 years or older, none of whom were being treated for sleep-disordered breathing—had a health examination. Their night-time breathing, sleep patterns, and blood oxygen levels were also assessed and these data used to calculate each participant's apnea-hypopnea index (AHI)—the number of apneas and hypopneas per hour. During the study follow-up period, 1,047 participants died. Compared to participants without sleep-disordered sleeping, participants with severe sleep-disordered breathing (an AHI of ≥30) were about one and a half times as likely to die from any cause after adjustment for potential confounding factors. People with milder sleep-disordered breathing did not have a statistically significant increased risk of dying. After dividing the participants into subgroups according to their age and sex, men aged 40–70 years with severe sleep-disordered breathing had a statistically increased risk of dying from any cause (twice the risk of men of a similar age without sleep-disordered breathing). Finally, death from coronary artery disease was also associated with sleep-disordered breathing in men but not in women.
What Do These Findings Mean?
These findings indicate that sleep-disordered breathing is associated with an increased risk of all-cause mortality, particularly in men aged 40–70 years, even after allowing for known confounding factors. They also suggest that the increased risk of death is specifically associated with coronary artery disease although further studies are needed to confirm this finding because it was based on the analysis of a small subgroup of study participants. Although this study is much larger than previous investigations into the association between sleep-disordered breathing and all-cause mortality, it has several limitations including its reliance on a single night's measurements for the diagnosis of sleep-disordered breathing. Nevertheless, these findings suggest that clinical trials should now be started to assess whether treatment can reduce the increased risk of death that seems to be associated with this common disorder.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000132.
The US National Heart Lung and Blood Institute has information (including a video) about sleep-disordered breathing (sleep apnea) (in English and Spanish)
The UK National Heath Service also provides information for patients about sleep apnea
MedlinePlus provides links to further information and advice about sleep-disordered breathing (in English and Spanish)
More information on the Sleep Heart Health Study is available
doi:10.1371/journal.pmed.1000132
PMCID: PMC2722083  PMID: 19688045
18.  Loud snoring is a risk factor for occupational injury in farmers 
BACKGROUND:
Loud snoring is a common symptom in the general population. The evidence-based literature indicates that snoring may be associated with sleep fragmentation and sleep apnea, which may affect cognitive function and predispose to occupational injury. High rates of occupational injury occur on farms and may be related to personal and health factors. Thus, loud snoring may not be a trivial symptom and should be considered as important in medical assessments.
METHODS:
A prospective cohort study was conducted in Saskatchewan. Baseline questionnaires were completed for 5502 individuals by representatives from 2390 farms. Sleep patterns at baseline were categorized as the following: no reported sleep disorders; physician-diagnosed sleep apnea (treatment unknown); and loud snoring. Survival analyses were used to relate sleep patterns with subsequent injury.
RESULTS:
A total of 6.7% (369 of 5502) of participants reported a possible sleep disorder. Of these, 69.4% (256 of 369) reported loud snoring only. Loud snoring was only associated with a consistent increase in risk (eg, HR 1.45 [95 CI 1.07 to 1.99 for work-related injury]) for five farm injury outcomes. Relationships between physician-diagnosed sleep apnea and time to first injury were not significant, presumably because a diagnosis of sleep apnea implied treatment for sleep apnea.
DISCUSSION:
Sleep disorders are an important potential risk factor for occupational injury on farms. Substantial proportions of farm residents report loud snoring and this is related to subsequent injury. Some of these cases may represent sleep fragmentation or undiagnosed obstructive sleep apnea. Identification and clinical management of sleep disorders related to snoring should be part of health assessments conducted by physicians.
PMCID: PMC3628646  PMID: 23457674
Agriculture; Farming; Injury; Occupational health; Sleep disorders; Snoring
19.  A postal survey of maternal sleep in late pregnancy 
Background
Sleep disturbances in late pregnancy are common. This study aimed to survey sleep problems in third trimester pregnant women and to compare sleep in the pre-pregnancy period with the third trimester.
Methods
Third-trimester women (n=650) were sent a postal survey containing questions relating to sleep experience, including perceived sleep quality, sleep difficulties, night waking, sleep environment, snoring, daytime tiredness and daytime napping. Time periods reported on were before pregnancy and in the last week.
Results
Respondents numbered 244 (38%). Before pregnancy, the mean reported duration of night-time sleep was 8.1 (SD 1.1) hours; in the last week this had decreased to 7.5 (SD 1.8) hours (p<.0001). Only 29% rated their sleep quality in the last week as very good or fairly good, compared with 82% rating their sleep this way before the pregnancy. The main reasons for sleeping difficulties were discomfort (67%) and pain (36%). Snoring increased significantly over the course of the pregnancy, with 37% reporting snoring often or every night in the last week. Those with a pre-pregnancy body mass index of greater than 25 were significantly more likely to snore (p=.01). Only 4% of women had an abnormal Epworth Sleepiness Scale score (i.e. >10) prior to pregnancy, whereas in the last week 33% scored in the abnormal range. Likewise, 5% had regularly napped during the daytime before pregnancy, compared with 41% in the last week.
Conclusions
Sleep problems are common in women in late pregnancy, and increase markedly compared with before pregnancy.
doi:10.1186/1471-2393-12-144
PMCID: PMC3541269  PMID: 23228137
Pregnancy; Sleep disturbances; Sleep quality; Snoring; Daytime sleepiness
20.  Gene-Environment Interaction in the Onset of Eczema in Infancy: Filaggrin Loss-of-Function Mutations Enhanced by Neonatal Cat Exposure  
PLoS Medicine  2008;5(6):e131.
Background
Loss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites) in relation to the development of eczema.
Methods and Findings
We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen (n = 379), FLG mutation increased the risk of eczema during the first year of life (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27–4.00, p = 0.005), with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79–32.60, p < 0.0001); dog exposure was moderately protective (HR 0.49, 95% CI 0.24–1.01, p = 0.05), but not related to FLG genotype. In Manchester (n = 503) an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13–3.36, p = 0.02). In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35–10.81, p = 0.01), with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16–2.20, p = 0.43). Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation.
Conclusions
We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4) and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially increases the risk of eczema within the first year of life in children with FLG loss-of-function variants, but not amongst those without. FLG-deficient individuals may need to avoid cats but not dogs in early life.
In two independent cohorts of children, Hans Bisgaard and colleagues show an association between mutations in the filaggrin gene (FLG) and ownership of cats, but not dogs, with development of eczema.
Editors' Summary
Background.
Eczema is a skin condition characterized by dry, red, and itchy patches on the skin. Eczema is associated with asthma and allergy, though allergy rarely plays a role in development or severity of eczema. Eczema usually begins during infancy, typically on the face, scalp, neck, extensor sides of the forearms, and legs. Up to one in five infants develops eczema, but in more than half of them, the condition improves or disappears completely before they are 15 years old. If eczema persists into adulthood, it usually affects the face and the skin inside the knees and elbows. There is no cure for eczema but it can be controlled by avoiding anything that makes its symptoms worse. These triggers include irritants such as wool, strong soaps, perfumes, and dry environments. A good skin-care routine and frequent moisturizing can also help to keep eczema under control, but in many cases, corticosteroid creams and ointments may be necessary to reduce inflammation.
Why Was This Study Done?
Eczema tends to run in families. This suggests that eczema is caused by genetic factors as well as by environmental factors. Recently, researchers discovered that two common “loss-of-function” variants in the gene encoding filaggrin (FLG) predispose people to eczema. People who inherit one or two defective genes make no filaggrin, a protein that normally forms a physical barrier in the skin that protects the body from potentially harmful substances in the environment. Might the weakening of this barrier in filaggrin-deficient individuals affect their responses to environmental substances to which the skin is exposed? In this study, the researchers test this potential explanation for how genetic and environmental factors (in particular, exposure to pets) might interact to determine an individual's chances of developing eczema.
What Did the Researchers Do and Find?
To test their hypothesis, the researchers studied two independent groups of infants during their first year of life—a high-risk group consisting of infants born in Copenhagen, Denmark to mothers with asthma and a group of infants born to women from the general population in Manchester, United Kingdom. The researchers determined which FLG variants each child had inherited and classified those with either one or two defective copies of FLG as having an FLG mutation. They determined pet exposure in early life by asking whether a dog or a cat was living in the parental home when the child was born (“pet ownership”) and then analyzed how these genetic and environmental factors affected the age of onset of eczema. In both groups, children with FLG mutations were twice as likely to develop eczema during the first year of life as children without FLG mutations. For children without FLG mutations, cat ownership at birth had no effect on eczema risk but for children with FLG mutations, cat ownership at birth (but not dog ownership) further increased the risk of developing eczema.
What Do These Findings Mean?
These findings show that FLG mutations and cat ownership at birth interact to determine the chances of a child developing eczema during the first year of life. They provide support, therefore, for the researchers' suggestion that the weakening of the skin's protective barrier that is caused by filaggrin deficiency increases the child's susceptibility to factors associated with cat exposure. Only a small number of children in this study carried FLG mutations and were exposed to cats from birth, so these findings need confirming in independent studies. In addition, it is still not clear how exposure to cats drives the development of eczema. Allergy was not the mechanism as the FLG-deficient children exposed to cat and who developed eczema did not develop cat-specific immunoglobin E antibodies. Nevertheless, these findings suggest that, to reduce their risk of developing eczema, filaggrin-deficient individuals should avoid cats (but not dogs) during the first few months of life.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050131.
The MedlinePlus Encyclopedia has a page on eczema (in English and Spanish); links to further information are provided by MedlinePlus
EczemaNet is a comprehensive online information resource about eczema provided by the American Academy of Dermatologists
The US National Institute of Arthritis and Musculoskeletal and Skin Diseases provides information on eczema
The UK National Health Service Direct health encyclopedia provides information for patients on eczema (in several languages)
The Copenhagen Studies on Asthma in Childhood (COPSAC) and Manchester Asthma and Allergy Study (MAAS) Web sites provide more information about the children involved in this research
doi:10.1371/journal.pmed.0050131
PMCID: PMC2504043  PMID: 18578563
21.  Atopy as a Risk Factor for Habitual Snoring at Age 1 Year 
Chest  2006;129(4):942-946.
Study objectives
To determine the prevalence of habitual snoring (HS) in 1-year-old children, and to assess the relationship between HS and atopic status in these children.
Design
Cross-sectional evaluation of a birth cohort selected from the population.
Setting
Ohio and Kentucky River Valley communities.
Participants
Children participating in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) were recruited for this study.
Measurements and results
At age 1 year, the children were evaluated for atopic status and exposure to environmental tobacco smoke (ETS). Parents were asked to complete a questionnaire pertaining to their snoring frequency and that of their child. Children with HS (snoring three or more times per week) were compared to those who either did not snore or snored less than three times per week. Data were available on 681 of the 700 children participating in CCAAPS study. Of these 681 children (377 boys and 304 girls), 542 were white (80%), 118 were African American (17%), and 21 were biracial or Asian (3%). The mean age (± SD) of our cohort at the time of assessment for snoring was 13.7 ± 2.6 months. Of the 681 children, 105 snored habitually (15%). There was a significant association between HS and the following: (1) positive atopic status (p = 0.005); (2) African-American race (p < 0.01); and (3) a history of snoring in the father (p < 0.01) or in the mother (p < 0.01). There was, however, no association between HS and ETS.
Conclusions
We found a 15% prevalence of HS in 1-year-old children born to atopic parents and a significant association with positive atopic status.
doi:10.1378/chest.129.4.942
PMCID: PMC2233942  PMID: 16608942
allergic rhinitis; children; environmental tobacco smoke; skin-prick test; obstructive sleep-disordered breathing
22.  Neuropsychological and Behavioral Functioning in Children with and without Obstructive Sleep Apnea Referred for Tonsillectomy 
Adenotonsillectomy (AT) is among the most common pediatric surgical procedures and is performed as often for obstructive sleep apnea (OSA) as for recurrent tonsillitis. This study compared behavioral, cognitive, and sleep measures in 27 healthy control children recruited from a university hospital-based pediatric general surgery clinic with 40 children who had OSA (AT/OSA+) and 27 children who did not have OSA (AT/OSA−) scheduled for AT. Parental ratings of behavior, sleep problems, and snoring, along with specific cognitive measures (i.e., short term attention, visuospatial problem solving, memory, arithmetic) reflected greater difficulties for AT children compared with controls. Differences between the AT/OSA− and control groups were larger and more consistent across test measures than were those between the AT/OSA+ and control groups. The fact that worse outcomes were not clearly demonstrated for the AT/OSA+ group compared with the other groups was not expected based on existing literature. This counterintuitive finding may reflect a combination of factors, including age, daytime sleepiness, features of sleep-disordered breathing too subtle to show on standard polysomnography, and academic or environmental factors not collected in this study. These results underscore the importance of applying more sophisticated methodologies to better understand the salient pathophysiology of childhood sleep-disordered breathing.
doi:10.1017/S1355617708080776
PMCID: PMC2561942  PMID: 18577286
Polysomnography; Neuropsychology; Sleep-Disordered Breathing; Adenotonsillectomy; Tonsillitis; Snoring
23.  Glucose intolerance and gestational diabetes risk in relation to sleep duration and snoring during pregnancy: a pilot study 
BMC Women's Health  2010;10:17.
Background
Insufficient sleep and poor sleep quality, considered endemic in modern society, are associated with obesity, impaired glucose tolerance and diabetes. Little, however, is known about the consequences of insufficient sleep and poor sleep quality during pregnancy on glucose tolerance and gestational diabetes.
Methods
A cohort of 1,290 women was interviewed during early pregnancy. We collected information about sleep duration and snoring during early pregnancy. Results from screening and diagnostic testing for gestational diabetes mellitus (GDM) were abstracted from medical records. Generalized linear models were fitted to derive relative risk (RR) and 95% confidence intervals (95% CIs) of GDM associated with sleep duration and snoring, respectively.
Results
After adjusting for maternal age and race/ethnicity, GDM risk was increased among women sleeping ≤ 4 hours compared with those sleeping 9 hours per night (RR = 5.56; 95% CI 1.31-23.69). The corresponding RR for lean women (<25 kg/m2) was 3.23 (95% CI 0.34-30.41) and 9.83 (95% CI 1.12-86.32) for overweight women (≥ 25 kg/m2). Overall, snoring was associated with a 1.86-fold increased risk of GDM (RR = 1.86; 95% CI 0.88-3.94). The risk of GDM was particularly elevated among overweight women who snored. Compared with lean women who did not snore, those who were overweight and snored had a 6.9-fold increased risk of GDM (95% CI 2.87-16.6).
Conclusions
These preliminary findings suggest associations of short sleep duration and snoring with glucose intolerance and GDM. Though consistent with studies of men and non-pregnant women, larger studies that include objective measures of sleep duration, quality and apnea are needed to obtain more precise estimates of observed associations.
doi:10.1186/1472-6874-10-17
PMCID: PMC2885310  PMID: 20470416
24.  Insomnia symptoms in older adults: associated factors and gender differences 
Objectives
The aim of this study was to examine the factors associated with insomnia in community-dwelling elderly as a function of the nature and number of insomnia symptoms (IS) e.g. difficulty with initiating sleep (DIS), difficulty with maintaining sleep (DMS) and early morning awakening (EMA).
Methods
IS were assessed in a sample of 2673 men and 3213 women aged 65 years and over. The participants were administered standardized questionnaires regarding the frequency of IS and other sleep characteristics (snoring, nightmares, sleeping medication, sleepiness) as well as various socio-demographic, behavioral and clinical variables, and measures of physical and mental health.
Results
More than 70% of men and women reported at least one IS, DMS being the most prevalent symptom in both men and women. Women reported more frequently two or three IS whereas men reported more often only one IS. Multivariate regression analyses stratified by gender showed that men and women shared numerous factors associated with IS, sleeping medication, nightmares, sleepiness, chronic diseases, and depression being independently associated with two or three IS. For both sexes, age was associated with only one IS in all age categories. Loud snoring was strongly associated with increased DMS in men only. High body mass index increased the risk for DIS in men but tended to decrease it in women. In women, hormonal replacement therapy, Mediterranean diet, caffeine and alcohol intake had a protective effect.
Conclusion
Our data suggest that women may have specific predisposition factors of multiple IS which may involve both behavioral and hormonal factors. Identification and treatment of these risk factors may form the basis of an intervention program for reduction of insomnia symptoms in the elderly..
doi:10.1097/JGP.0b013e3181e049b6
PMCID: PMC3179987  PMID: 20808113
Age Factors; Aged; Aged, 80 and over; Female; France; epidemiology; Humans; Male; Prevalence; Risk Factors; Self Report; Sex Characteristics; Sex Factors; Sleep Initiation and Maintenance Disorders; diagnosis; epidemiology
25.  Self reported snoring and daytime sleepiness in men aged 35-65 years. 
Thorax  1991;46(11):807-810.
BACKGROUND: It has been suggested that snoring alone, without conventional sleep apnoea or hypopnoea, may disrupt sleep and produce substantial daytime hypersomnolence. This study addresses this potential relationship. METHOD: Eight hundred and fifty men, aged 35-65 years, drawn from one general practice were visited at home and asked a range of questions potentially related to sleepiness, snoring, and sleep apnoea; these included inquiries about alcohol and cigarette consumption, nasal stuffiness, shift work, hypnotic or other drug use, and medical diagnoses. In addition, measurements of height, weight, and overnight arterial oxygen saturation were made. The relation between snoring and sleepiness, with allowance made for potentially confounding variables, including sleep apnoea, was assessed by multiple logistic regression. RESULTS: Positive answers to all questions about sleepiness were correlated significantly with self reported snoring. After potentially confounding variables and any sleep apnoea had been controlled for, positive answers to four questions about inappropriate drowsiness or sleepiness were independently related to snoring. For example, the odds ratio of admitting to "having almost had two or more car accidents while driving due to sleepiness" was 5.8 (95% confidence intervals: 2.7-12.5) in an "often" snorer. CONCLUSIONS: Although epidemiological associations such as this do not prove a causal relation, the study suggests that snoring (without classical sleep apnoea) may sometimes reduce sleep quality sufficiently to produce substantial daytime drowsiness.
PMCID: PMC1021034  PMID: 1771603

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