John Stradling

Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial.

BACKGROUND Obstructive sleep apnoea is associated with raised blood pressure. If blood pressure can be reduced by nasal continuous positive airway pressure (nCPAP), such treatment could reduce risk of cardiovascular disease in patients with obstructive sleep apnoea. Our aim was to see whether nCPAP for sleep apnoea reduces blood pressure compared with the most robust control intervention subtherapeutic nCPAP. METHODS We did a randomised parallel trial to compare change in blood pressure in 118 men with obstructive sleep apnoea (Epworth score > 9, and a > 4% oxygen desaturation index of > 10 per h) who were assigned to either therapeutic (n=59) or subtherapeutic (59) nCPAP (about 1 cm H(2)O pressure) for 1 month. The primary outcome was the change in 24-h mean blood pressure. Secondary outcomes were changes in systolic, diastolic, sleep, and wake blood pressure, and relations between blood pressure changes, baseline blood pressure, and severity of sleep apnoea. FINDINGS Therapeutic nCPAP reduced mean arterial ambulatory blood pressure by 2.5 mm Hg (SE 0.8), whereas subtherapeutic nCPAP increased blood pressure by 0.8 mm Hg (0.7) (difference -3.3 [95% CI -5.3 to -1.3]; p=0.0013, unpaired t test). This benefit was seen in both systolic and diastolic blood pressure, and during both sleep and wake. The benefit was larger in patients with more severe sleep apnoea than those who had less severe apnoea, but was independent of the baseline blood pressure. The benefit was especially large in patients taking drug treatment for blood pressure. INTERPRETATION In patients with most severe sleep apnoea, nCPAP reduces blood pressure, providing significant vascular risk benefits, and substantially improving excessive daytime sleepiness and quality of life.

Snoring, sleep disturbance, and behaviour in 4-5 year olds.

Parents of 996 children aged 4-5 years identified consecutively from the Oxford health visitor register were asked to complete a questionnaire about breathing disorders during sleep. A total of 782 (78.5%) was returned. Ninety five (12.1%) children were reported to snore on most nights. Habitual snoring was significantly associated with daytime sleepiness, restless sleep, and hyperactivity. The questionnaire responses were used to select two subgroups, one at high risk of a sleep and breathing disorder and a control group. These children (132 in total) were monitored at home with overnight video recording and oximetry, and had formal behavioural assessment using the Conners scale. Seven (7/66) children from the high risk group and none from the control group had obvious sleep disturbance consequent on snoring and upper airway obstruction. Thus our estimate of the prevalence of sleep and breathing disorders in this age group is 7/996 or 0.7%. The high risk group had significantly higher nocturnal movement, oxygen saturation dip rates, and overnight pulse rates than the controls. Maternal but not paternal smoking was associated with the high risk group. Parents and teachers thought those in the high risk group were more hyperactive and inattentive than the controls, but only their parents thought them more aggressive. Significant sleep and breathing disorders occur in about 0.7% of 4-5 year olds. Children whose parents report snoring and sleep disturbance have objective evidence of sleep disruption and show more behaviour problems than controls.

Comparison of therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised prospective parallel trial

BACKGROUND Nasal continuous positive airway pressure (NCPAP) is widely used as a treatment for obstructive sleep apnoea. However, to date there are no randomised controlled trials of this therapy against a well-matched control. We undertook a randomised prospective parallel trial of therapeutic NCPAP for obstructive sleep apnoea compared with a control group on subtherapeutic NCPAP. METHODS Men with obstructive sleep apnoea, defined as an Epworth sleepiness score of 10 or more and ten or more dips per h of more than 4% SaO2 caused by obstructive sleep apnoea on overnight sleep study, were randomly assigned therapeutic NCPAP or subtherapeutic NCPAP (about 1 cm H2O) for 1 month. Primary outcomes were subjective sleepiness (Epworth sleepiness score), objective sleepiness (maintenance of wakefulness test), and SF-36 questionnaire measurements of self-reported functioning and well-being. FINDINGS 107 men entered the study: 53 received subtherapeutic NCPAP and 54 therapeutic NCPAP. Use of NCPAP by the two treatment groups was similar: 5.4 h (therapeutic) and 4.6 h (subtherapeutic) per night. Subtherapeutic NCPAP did not alter the overnight number of SaO2 dips per h compared with baseline, and thus acted as a control. Therapeutic NCPAP was superior to subtherapeutic NCPAP in all primary outcome measures. The Epworth score was decreased from a median of 15.5 to 7.0 on therapeutic NCPAP, and from 15.0 to 13.0 on subtherapeutic NCPAP (between treatments, p<0.0001). Mean maintenance-of-wakefulness time increased from 22.5 to 32.9 min on therapeutic NCPAP and, not significantly, from 20.0 to 23.5 min on subtherapeutic NCPAP (between treatments p<0.005). Effect sizes for SF-36 measures of energy and vitality were 1.68 (therapeutic) and 0.97 (subtherapeutic) NCPAP (between treatments p<0.0001). For mental summary score, the corresponding values were 1.02 and 0.4 (between treatments p=0.002). INTERPRETATION Therapeutic NCPAP reduces excessive daytime sleepiness and improves self-reported health status compared with a subtherapeutic control. Compared with controls, the effects of therapeutic NCPAP are large and confirm previous uncontrolled clinical observations and the results of controlled trials that used an oral placebo.

Sleep disordered breathing: Effects of adenotonsillectomy on behaviour and psychological functioning

Children on the adenotonsillectomy waiting list aged 6 years or more were screened by questionnaire and overnight sleep monitoring to identify 12 with a moderate sleep and breathing disorder (SBD) group. They were matched by age and sex with 11 children who had a similar history of snoring and sleep disturbance but without an obvious sleep and breathing problem when monitored (snorer group) and also with a group of ten children most of whom were refered for an unrelated surgical procedure (control group). All children were studied before and 3–6 months after surgery. Pre-operatively the SBD and snorer groups both had significantly more restless sleep than the control group. The SBD group also had significantly more (>4%) dips in oxygen saturation than the other two groups. After surgery there were no longer any significant differences between the three groups. After adenotonsillectomy the SBD group showed a significant reduction in aggression, inattention and hyperactivity on the parent Conners scale, and an improvement in vigilance on the Continuous Performance Test. The snorer group also improved showing less hyperactive behaviour than pre-operatively and better vigilance. The control groupss behaviour and performance did not change significantly. There were no significant changes in the performance of the Matching Familiar Figures Test in any of the groups.

Effect of adenotonsillectomy on nocturnal hypoxaemia, sleep disturbance, and symptoms in snoring children

61 snoring children selected for adenotonsillectomy, mainly for recurrent tonsillitis, were compared with a matched group of 31 healthy children for symptoms of sleep apnoea, extent of sleep hypoxaemia, and amount of sleep disturbance. The studies were repeated six months postoperatively, and after six months in the healthy children. Preoperatively, 61% of the children had degrees of sleep hypoxaemia above normal and 65% had abnormally disturbed sleep. A questionnaire administered to the parents about their children showed abnormal patterns of answers about sleep problems daytime sleepiness, hyperactivity, aggression, learning difficulties, restless sleep, and odd sleeping positions. After adenotonsillectomy, the abnormal hypoxaemia, excessive sleep disturbance, and multiple symptoms almost resolved; a growth spurt also occurred.

Effect of CPAP on insulin resistance and HbA1c in men with obstructive sleep apnoea and type 2 diabetes

Background: The effects of continuous positive airway pressure (CPAP) for obstructive sleep apnoea (OSA) on insulin resistance are not clear. Trials have found conflicting results and no appropriate control groups have been used. Methods: Forty-two men with known type 2 diabetes and newly diagnosed OSA (>10 dips/h in oxygen saturation of >4%) were randomised to receive therapeutic (n = 20) or placebo CPAP (n = 22) for 3 months. Baseline tests were performed and repeated after 3 months. The study was double blind. Results: Results are expressed as mean (SD). CPAP improved the Epworth sleepiness score significantly more in the therapeutic group than in the placebo group (−6.6 (4.5) vs −2.6 (4.9), p = 0.01). The maintenance of wakefulness test improved significantly in the therapeutic group but not in the placebo group (+10.6 (13.9) vs −4.7 (11.8) min, p = 0.001). Glycaemic control and insulin resistance did not significantly change in either the therapeutic or placebo groups: HbA1c (−0.02 (1.5) vs +0.1 (0.7), p = 0.7, 95% CI −0.6% to +0.9%), euglycaemic clamp (M/I: +1.7 (14.1) vs −5.7 (14.8), p = 0.2, 95% CI −1.8 to +0.3 l/kg/min1000), HOMA-%S (−1.5 (2.3) vs −1.1 (1.8), p = 0.2, 95% CI −0.3% to +0.08%) and adiponectin (−1.1 (1.2) vs −1.1 (1.3), p = 0.2, 95% CI −0.7 to +0.6 &mgr;g/ml). Body mass index, bioimpedance and anthropometric measurements were unchanged. Hours of CPAP use per night were 3.6 (2.8) in the treatment group and 3.3 (3.0) in the placebo group (p = 0.8). There was no correlation between CPAP use and the measures of glycaemic control or insulin resistance. Conclusion: Therapeutic CPAP does not significantly improve measures of glycaemic control or insulin resistance in men with type 2 diabetes and OSA.

Prevalence of obstructive sleep apnoea in men with type 2 diabetes

Background: A study was undertaken to establish the prevalence of obstructive sleep apnoea (OSA) in men with type 2 diabetes. Methods: Men with type 2 diabetes from local hospital and selected primary care practitioner databases received questionnaires about snoring, apnoeas, and daytime sleepiness based on the Berlin questionnaire. Selected respondents had overnight oximetry to establish whether they had OSA. Comparisons of oximetry were made with those from a previous general population study. HbA1c results were collected. Results: 1682 men were sent questionnaires, 56% of whom replied. 57% scored as “high” and 39% as “low” risk for OSA; 4% were already known to have OSA. Oximetry was performed in 240 respondents from both risk groups: 31% of the “high” and 13% of the “low” risk group had significant OSA (more than 10 >4% Sao2 dips/hour or Sao2 tracing consistent with OSA). These results were verified by detailed sleep studies. Extrapolation of the oximetry data to the questionnaire respondent population suggests that 23% had OSA. Comparison of the oximetry results with men from a previous general population study (using only more than 10 >4% Sao2 dips/hour to define OSA) showed the prevalence of OSA is significantly higher in this diabetes population (17% v 6%, p<0.001). Multiple linear regression revealed BMI and diabetes as significant independent predictors of OSA. Following correction for BMI (which explained 13% of the variance in OSA), diabetes explained a further 8% of the variance (p<0.001). There was a low correlation between OSA severity and HbA1c in the subgroup recruited from the hospital database (r = 0.2, p = 0.006) which remained significant after allowing for obesity (p = 0.03). Conclusions: OSA is highly prevalent in men with type 2 diabetes; most are undiagnosed. Diabetes itself may be a significant independent contributor to the risk of OSA.

Mechanisms of vascular damage in obstructive sleep apnea

Obstructive sleep apnea (OSA) is characterized by repetitive apnea–hypopnea cycles during sleep, which are associated with oxygen desaturation and sleep disruption. Up to 30% of the adult population in Western countries are thought to be affected by asymptomatic OSA and approximately 2–4% by symptomatic OSA (also known as obstructive sleep apnea syndrome, or OSAS). Controlled trials have demonstrated that OSAS causes hypertension and prospective epidemiological studies have indicated that OSAS might be an independent risk factor for stroke and myocardial ischemia. Three biological mechanisms are thought to underpin the association of OSA with endothelial dysfunction and arterial disease: intermittent hypoxia leading to increased oxidative stress, systemic inflammation, and sympathetic activity; intrathoracic pressure changes leading to excessive mechanical stress on the heart and large artery walls; and arousal-induced reflex sympathetic activation with resultant repetitive blood-pressure rises. More clinical interventional trials are needed to determine the magnitude of the effect OSA has on cardiovascular damage and to enable a comparison with conventional vascular risk factors.

Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials

Background: Obstructive sleep apnoea (OSA) is associated with high cardiovascular morbidity and mortality and is an independent risk factor for hypertension. Novel circulating cardiovascular risk markers enabling a more accurate prediction of cardiovascular risk have been identified. Examination of these markers may clarify the increased risk in OSA and contribute to an analysis of the benefits of treatment. Methods: Plasma levels of total cholesterol and triglyceride and activated coagulation factors XIIa and VIIa, factors VII, VIII, XII, fibrinogen, thrombin-antithrombin (TAT), von Willebrand factor antigen (vWFAg), soluble P-selectin (sP-sel), and homocysteine were measured before and after treatment for 1 month with therapeutic or subtherapeutic (control) continuous positive airways pressure (CPAP) in 220 patients with OSA. Results: Levels of activated coagulation factors XIIa, VIIa, TAT and sP-sel were higher in OSA patients at baseline than in unmatched controls, but did not fall with 1 month of therapeutic CPAP treatment. The raised sP-sel levels correlated only with body mass index (p = 0.002). There was a trend towards a significant fall in total cholesterol with therapeutic CPAP (p = 0.06) compared with the control group. In the therapeutic group there was a clinically significant mean fall in total cholesterol of 0.28 mmol/l (95% confidence interval 0.11 to 0.45, p = 0.001) which may reduce cardiovascular risk by about 15%. Conclusion: A number of activated coagulation factors are increased in untreated OSA patients, potentially contributing to vascular risk, but they do not fall with 1 month of CPAP treatment. Nasal CPAP may produce a clinically relevant fall in total cholesterol level, potentially reducing cardiovascular risk, but this needs to be verified in a larger prospective study.

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.