Biochemical markers of cardiac dysfunction in children with obstructive sleep apnoea (OSA)

Objectives

We explored relationships between biochemical markers and cardiac responses of children with and without obstructive sleep apnoea (OSA) during exercise. We hypothesised that serum markers of sympathetic nervous system activity and low-grade inflammation would correlate with cardiac responses to exercise in children with or without OSA.

Methodology

The study included 40 of 71 children with previously characterised responses to cardiopulmonary exercise testing. Measures included serum cytokine levels using a multiplex bead-based assay (interleukins IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α and IFN-γ). Serum amyloid A (SAA) was quantified by nephelometry, and metanephrine/normetanephrine levels were measured by liquid chromatography, mass-spectroscopy. Comparisons were made between children with and without OSA, and with and without obesity. Relationships between biomarkers and various cardiac parameters were explored by linear regression.

Results

Amongst the 40 children in this study, OSA was present in 23. Compared to the 17 children without OSA, those with OSA had higher resting serum IL-6 levels compared to those without (median 3.22 pg/ml vs. 2.31, p?<?0.05). Regarding correlations with cardiac function after adjusting for OSA, IL-8 negatively correlated to heart rate (HR) response following exercise (p?=?0.03) and IFN-γ negatively correlated with Stroke Volume Index (SVI) (p?=?0.03). Both metanephrine and normetanephrine levels positively correlated with SVI (p?=?0.04, p?=?0.047; respectively) and QI (p?=?0.04, p?=?0.04; respectively) during exercise when adjusting for OSA.

Conclusions

Children with OSA have raised morning levels of serum IL-6. Separately, higher levels of IFN-γ and IL-8 and lower levels of metanephrine and normetanephrine related to poorer cardiac function during exercise.

     

Effect of moderate alcohol upon obstructive sleep apnoea.

Moderate-to-large quantities of alcohol are known to aggravate severe obstructive sleep apnoea (OSA), however, the reported effects of moderate alcohol consumption upon mild-to-moderate OSA are inconsistent. Given the reported benefits of moderate alcohol consumption on cardiovascular mortality, recommendations regarding the management of patients with OSA are difficult to formulate. The aim of this study was to evaluate the effects of moderate alcohol on sleep and breathing in subjects with mild-to-moderate OSA. Twenty-one male volunteers, who snored habitually, underwent polysomnography with and without 0.5 g alcohol x kg body weight (BW)(-1) consumed 90 min prior to sleep time, in random order. The mean blood alcohol concentration (BAC) following alcohol at the time of lights out was 0.07 g x dL(-1). The distribution amongst the various sleep stages was not significantly altered by alcohol. The mean apnoea/hypopnoea index rose from 7.1+/-1.9 to 9.7+/-2.1 events x h(-1) (mean+/-SEM, p=0.017); however, there was no significant change in the minimum arterial oxygen saturation measured by pulse oximetry Sp,O2, apnoea length or snoring intensity. Mean sleep cardiac frequency rose significantly from 53.9+/-1.4 to 59.9+/-1.9 beats x min(-1) (P<0.001) and overnight urinary noradrenalin increased from 14.9+/-2.3 to 18.8+/-2.3 nmol x mmol creatinine(-1) (p=0.061) on the alcohol night compared to the nonalcohol night. To conclude, modest alcohol consumption, giving a mean blood alcohol concentration of 0.07 g x dL(-1), significantly increases both obstructive sleep apnoea frequency and mean sleep cardiac frequency.     

Predicting uptake of continuous positive airway pressure (CPAP) therapy in obstructive sleep apnoea (OSA): a belief-based theoretical approach

Purpose

Obstructive sleep apnoea (OSA) is a common disorder, for which continuous positive airway pressure (CPAP) therapy is a standard treatment. Despite its well-established efficacy, many patients choose not to initiate CPAP treatment. The present study investigated the degree to which biological measures (e.g. Apnoea–Hypopnoea Index [AHI]), symptom experiences (e.g. fatigue) and illness representations (e.g. perceived consequences) predict the decision of individuals newly diagnosed with OSA to undergo a trial of CPAP therapy.

Methods

Four hundred forty-nine individuals (316 males) newly diagnosed with OSA. Epworth sleepiness scale (ESS), Fatigue Severity Scale, Depression Anxiety Stress Scale and Illness Perception Questionnaire-Revised (IPQ-R) were administered at time of sleep study. These, patient demographics and sleep study variables were used to determine factors predicting patient decision to proceed with a trial of CPAP.

Results

The participants were most likely to attribute their OSA to unchangeable and psychological factors. For those with moderate OSA (AHI, 15 to 30) IPQ-R illness consequence was predictive of decision to initiate CPAP (p = 0.002). For severe OSA (AHI >30) age, ESS and IPQ illness causal beliefs were predictive of decision to initiate CPAP (p < 0.001).

Conclusions

Illness beliefs are important determinants of the choice of recently diagnosed OSA patients whether or not to undertake a trial of CPAP therapy. Concerns about illness consequences were important in those with moderate OSA. In severe OSA, sleepiness symptoms are more prominent and a more significant determinant of CPAP uptake along with age and causal beliefs.     

Resistant hypertension, obstructive sleep apnoea and aldosterone

Obstructive sleep apnoea (OSA) and hypertension commonly coexist. Observational studies indicate that untreated OSA is strongly associated with an increased risk of prevalent hypertension, whereas prospective studies of normotensive cohorts suggest that OSA may increase the risk of incident hypertension. Randomized evaluations of continuous positive airway pressure (CPAP) indicate an overall modest effect on blood pressure (BP). Determining why OSA is so strongly linked to having hypertension in cross-sectional studies, but yet CPAP therapy has limited BP benefit needs further exploration. The CPAP studies do, however, indicate a wide variation in the BP effects of CPAP, with some patients manifesting a large antihypertensive benefit such that a meaningful BP effect can be anticipated in some individuals. OSA is particularly common in patients with resistant hypertension (RHTN). The reason for this high prevalence of OSA is not fully explained, but data suggest that it may be related to the high occurrence of hyperaldosteronism in patients with RHTN. In patients with RHTN, it has been shown that aldosterone levels correlate with severity of OSA and that blockade of aldosterone reduces the severity of OSA. Overall, these findings are consistent with aldosterone excess contributing to worsening of underlying OSA. We hypothesize that aldosterone excess worsens OSA by promoting accumulation of fluid within the neck, which then contributes to increased upper airway resistance.     

Obesity, obstructive sleep apnoea and metabolic syndrome

OSA is increasingly recognized as a major health problem in developed countries. Obesity is the most common risk factor in OSA and hence, the prevalence of OSA is undoubtedly rising given the epidemic of obesity. Recent data also suggest that OSA is highly associated with the metabolic syndrome, and it is postulated that OSA contributes to cardiometabolic dysfunction, and subsequently vasculopathy. Current evidence regarding the magnitude of impact on ultimate cardiovascular morbidity or mortality attributable to OSA-induced metabolic dysregulation is scarce. Given the known pathophysiological triggers of intermittent hypoxia and sleep fragmentation in OSA, the potential mechanisms of OSA-obesity-metabolic syndrome interaction involve sympathetic activation, oxidative stress, inflammation and neurohumoral changes. There is accumulating evidence from human and animal/cell models of intermittent hypoxia to map out these mechanistic pathways. In spite of support for an independent role of OSA in the contribution towards metabolic dysfunction, a healthy diet and appropriate lifestyle modifications towards better control of metabolic function are equally important as CPAP treatment in the holistic management of OSA.     

Steering simulation performance in patients with obstructive sleep apnoea and matched control subjects.

Patients with obstructive pulmonary disease (OSA) have an increased rate of driving accidents, perhaps due to poor vigilance or impaired cognitive skills that influence their driving ability. The authors have assessed whether patients with OSA perform differently to control subjects on a steering simulator which allows the separate assessment of the two visual tasks required for steering a car, immediate positioning on road with reference to the road edges, and assessment of the curve of the oncoming road which allows faster driving. Twelve patients with OSA and 12 control subjects, matched for age, sex and driving experience, performed three 30-min drives with either all the oncoming road visible, only the near part of the road visible, or only the distant part of the road visible. Steering was assessed by measuring the SD around the theoretical perfect path (steering error) and the number of times the driver went "off road". Subjects identified the appearance of target numbers at the four corners of the screen as quickly as possible, thus making the test a divided attention task. Patients with OSA performed significantly less well on the three different road fields as measured by steering error (p<0.001), time to detect the target number (p<0.03), and off road events (p<0.03). The patients appeared to be particularly impaired on the two drives when only part of the road ahead was available to guide steering. This steering simulator, with its more realistic view of the road ahead, identifies impaired performance in patients with obstructive sleep apnoea. In addition it suggests that patients with obstructive sleep apnoea may be more disadvantaged compared to normal subjects when the view of the road ahead is limited (such as in fog).     

Effect of simulated altitude during sleep on moderate-severity OSA

Objective:   These studies were conducted to test the hypothesis that isobaric hypoxia would switch OSA to central sleep apnoea (CSA).
Methods:   Five adult men (mean age 54.2 ± 5.5 years, mean BMI 29.9 ± 6.7 kg/m²) with moderate OSA underwent overnight polysomnography at three altitudes. The highest altitude was simulated in a normobaric hypoxic chamber.
Results:   The obstructive respiratory disturbance index fell from 25.5 ± 14.4/h at 60 m to 17.3 ± 9.2/h at 610 m and 0.5 ± 0.7/h at 2750 m ( P  = 0.004 compared with 60 m). The central respiratory disturbance index rose from 0.4 ± 0.5/h at 60 m to 8.1 ± 5.8/h at 610 m and 78.8 ± 29.7/h at 2750 m ( P  < 0.001 compared with 60 m). Mean sleep SaO₂ fell from 94 ± 1% at 60 m to 93 ± 1% at 610 m to 85 ± 4% at 2750 m ( P  < 0.001 compared with 60 m).
Conclusion:   Moderate severity OSA at sea level (60 m) was completely replaced by severe CSA at a simulated altitude of 2750 m. The authors believe that the OSA resolved because of an increased respiratory rate and an increase in upper airway tone, whereas CSA developed because of hypocapnia in non-rapid eye movement sleep.     

Cognition, sleep and respiration in at-risk children treated for obstructive sleep apnoea.

Sleep-disordered breathing in children has been associated with cognitive impairment. The purpose of this study was to examine the impact of tonsillectomy and adenoidectomy (T&A) on sleep, respiration and cognitive function in children of pre-school age with obstructive sleep apnoea (OSA) from a low-income community population. Altogether, 19 children attending state-funded pre-school programmes underwent overnight polysomnography and cognitive assessment before and following surgical treatment for OSA; 19 matched controls were also assessed. Following T&A, OSA subjects' delta sleep increased, rapid eye movement sleep decreased, and respiratory and arousal indices improved. There were no significant differences in OSA subjects' post-operative sleep or respiratory measures compared to controls. Prior to T&A, cognitive scores were significantly lower in OSA subjects versus controls; following T&A, OSA subjects' scores improved compared to pre-operative scores and did not differ from those of matched controls. Following tonsillectomy and adenoidectomy, at-risk pre-schoolers recruited directly from the community showed normalised sleep and respiratory patterns and improved cognitive scores. These findings, in this uniquely vulnerable population, which is unlikely to seek evaluation and treatment for obstructive sleep apnoea, underscore the potential value of outreach screening programmes for sleep-disordered breathing, particularly among low-income groups of pre-school age.     

Overview and implications of obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is a leading public health problem both in the developed and developing nations. However, awareness regarding diagnostic options, management and consequences of untreated OSA remains inadequate. In developing nations, the resources for adequate sleep medicine facilities are scarce. Therefore, there is a need for low cost, simple and accurate diagnostic and therapeutic modalities exists. Untreated OSA leads to excessive daytime sleepiness, diminished performance and an overall poor quality of life. The role of OSA in promoting insulin resistance, atherosclerosis, hypertension and a procoagulant state has now been established. Newer insights into the biochemical and genetic mediators of OSA have raised hopes regarding the development of a "cure". However, as of now, continuous positive airway pressure (CPAP) therapy remains the first-line treatment. Though its use improves the quality of life as well as metabolic derangements observed in OSA, patients' acceptance remains low. Its high cost and long-term use are also cumbersome. Newer modes of delivering CPAP, oral appliances and upper airway surgery are the other options available. It is hoped that their appropriate use to increase patients' compliance may improve the quality of life as well as provide a survival benefit.     

Gender difference in sleep profile of severely obese patients with obstructive sleep apnea (OSA)

OBJECTIVES: Few papers addressed the gender difference in the polisomnographic features of obstructive sleep apnea (OSA). In this paper we investigated the sleep architecture and the nocturnal respiratory pattern in a group of severely obese women with OSA compared with a group of men with OSA matched by age and weight. DESIGN: A cross-sectional study. SETTING: Primary-care setting. SUBJECTS, MAIN OUTCOME MEASURES: Anthropometric parameters, respiratory function data and a full night polisomnography were evaluated in a group of 45 obese subjects, 20 females and 25 males, with a previous diagnosis of OSA. RESULTS: The group of the severely obese women with OSA presented greater disturbances of the sleep architecture than the group of the men does (wake time after sleep onset 92.6+/-52.4 vs 58.2+/-45.2 min, P<0.05; total wake time 104.8+/-51.4 vs 67.8+/-47.4, P<0.05; number of awakenings 15.5+/-3.6 vs 10.2+/-6.215, P<0.001; OSA that occurred almost exclusively during REM sleep (REM OSA) 35% vs 4%, P<0.05) and a reduced sleep efficiency (69.6+/-15.9 vs 80.3+/-14.0%, P<0.05). CONCLUSIONS: Severely obese women with OSA, even with milder OSA, present greater disturbances of the sleep architecture with a more severe sleep disruption and more frequently REM OSA in comparison with men matched by age and weight.     

Peer attitudes, sex, and the effects of alcohol on simulated driving performance

This study presents an investigation of the effects of peer attitude, gender, and blood alcohol level on driving performance using a driving simulator. The subjects were 18 male and 18 female social drinkers from the general population, aged 18-25, and holding a current drivers' licence. Subjects were randomly assigned to pro or against drinking driving conditions and tested at different blood alcohol levels. The results revealed that subjects in the for drinking driving condition perceived themselves to be more capable than they actually were and drove increasingly faster and made more mistakes than subjects in the against drinking driving condition when under the influence of alcohol. Significant sex differences were observed only for performance on the driving simulator. Males, in the main, engaged in more dangerous driving and risk taking in simulated driving conditions than females.     

Right ventricle structure and function in patients with obstructive sleep apnea (OSA)

The structure and function of right ventricle was echocardiographically assessed in patients (pts) with OSA and analyzed taking into account the presence of obesity and/or systemic hypertension (SH). Therefore, 118 pts (98 M, 20 F, aged 48,5 8,4 yr) were divided into OH = obese with z OSA and SH (n = 22), ON = obese with OSA, and no SH (n = 20), OC = OSA without either obesity and SH (n = 21), GH = obese without OSA but with SH (n = 18), GN = obese without either OSA or SH (n =17). Control group (ZZ) comprised 20 healthy subjects (14M,6F). Right ventricular diameter (RVD), diastolic (DRVW), and systolic right ventricle free wall thickness (SRVW) were measured and its systolic thickening (ST-RVW) was calculated. Acceleration time of ejection into pulmonary artery (AcT) was measured with Doppler echocardiography. RESULTS: St. sign. p < 0.05 between: 1: all groups except OH and ON, GH and GN, GH and OC, GN and OC; 2--like 1 except ZZ and OC; 3--OH and all subgroup except ON, ON and GH, ON and ZZ, OC and GN; 4-- ON and all subgroups except OH, OH and OC, OH and GH, OH and GN. CONCLUSIONS: Enlargement and functionally compromised RV is found in OBS mostly with concomitant obesity. Pulmonary hypertension at rest in patients with isolated OSA is rare and also requires additional contributing factors.     

Health-related quality of life in obstructive sleep apnoea.

The identification of the areas of quality of life (QoL) most likely to be affected by obstructive sleep apnoea (OSA) would be an important step in the evaluation of the impact of the disease and its treatment modalities. The objective of this study was to describe the impact of OSA on patients' QoL. A list of 186 items potentially related to QoL of patients with OSA was constructed. From this list, consecutive patients were asked, at the time of the diagnosis, to identify the most significant items and to grade their importance on a 5-point scale. The item impact was determined from the proportion of patients who identified it as important, and the mean importance score attributed to this item (impact score=frequency x importance). One hundred patients (82 male; mean age: 51 yrs) were interviewed. The items having the most important impact on QoL clustered into five domains: 1) daytime symptoms; 2) nocturnal symptoms; 3) limitation of activities; 4) emotions; and 5) interpersonal relationships. The impact of obstructive sleep apnoea on quality of life is not limited to excessive daytime sleepiness. Obstructive sleep apnoea significantly contributes to the impairment of all domains of what is usually referred to as "health-related quality of life".     

Impact of CPAP on asthmatic patients with obstructive sleep apnoea.

The impact of continuous positive airway pressure (CPAP) treatment on the airway responsiveness of asthmatic subjects with obstructive sleep apnoea (OSA) has scarcely been studied. A prospective study was performed comparing the changes in airway responsiveness and quality of life in stable asthmatic OSA patients, before and 6 weeks after their nocturnal CPAP treatment. A total of 20 subjects (11 males and nine females) participated in the study. With the nocturnal CPAP treatment, the apnoea/hypopnoea index dropped from 48.1 +/- 23.6 x h(-1) to 2.6 +/- 2.5 x h(-1). There were no significant changes in airway responsiveness after CPAP treatment (provocative concentration causing a 20% fall in forced expiratory volume in one second (FEV(1); PC(20) 2.5 mg x mL(-1) (1.4-4.5)) compared with baseline (PC(20) 2.2 mg x mL(-1) (1.3-3.5)). There was no significant change in FEV(1) either. However, the asthma quality of life of the subjects improved from 5.0 +/- 1.2 at baseline to 5.8 +/- 0.9 at the end of the study. In conclusion, nocturnal continuous positive airway pressure treatment did not alter airway responsiveness or forced expiratory volume in one second in subjects with stable mild-to-moderate asthma and newly diagnosed obstructive sleep apnoea. However, nocturnal continuous positive airway pressure treatment did improve asthma quality of life.