Caffeine levels following treatment of obstructive sleep apnoea

BACKGROUND: Randomised trials show that treatment of obstructive sleep apnoea (OSA) with nasal continuous positive airway pressure (CPAP) greatly improves sleepiness and also lowers diurnal systemic blood pressures (BP). Such patients consume more coffee than controls (presumably to combat their sleepiness) and might reduce their consumption following effective treatment, thus lowering BP by this mechanism rather than via a direct effect of alleviating OSA. METHODS: Plasma caffeine levels before and after treatment with either therapeutic (n=52) or subtherapeutic (control, n=49) CPAP were measured in stored blood samples from a previous randomised controlled trial of CPAP for 4 weeks in patients with OSA. RESULTS: There was a small significant rise in caffeine levels when the two groups were analysed as a whole (p=0.02), but not individually. Despite the fall in sleepiness measured objectively in the therapeutic CPAP group, there was no difference in absolute (or change in) caffeine levels between the two groups (mean (SE) micro mol/l; therapeutic CPAP 9.2 (1.2), 10.2 (1.0), subtherapeutic 6.7 (0.9), 8.6 (0.9) before and after treatment, respectively). CONCLUSION: Reduced coffee consumption is unlikely to be the explanation for the falls in BP following treatment of OSA.     

Effect of increased lung volume on sleep disordered breathing in patients with sleep apnoea

BACKGROUND: Previous studies have shown that changes in lung volume influence upper airway size and resistance, particularly in patients with obstructive sleep apnoea (OSA), and that continuous positive airway pressure (CPAP) requirements decrease when the lung volume is increased. We sought to determine the effect of a constant lung volume increase on sleep disordered breathing during non-REM sleep. METHODS: Twelve subjects with OSA were studied during non-REM sleep in a rigid head-out shell equipped with a positive/negative pressure attachment for manipulation of extrathoracic pressure. The increase in lung volume due to CPAP (at a therapeutic level) was determined with four magnetometer coils placed on the chest wall and abdomen. CPAP was then stopped and the subjects were studied for 1 hour in three conditions (in random order): (1) no treatment (baseline); (2) at "CPAP lung volume", with the increased lung volume being reproduced by negative extrathoracic pressure alone (lung volume 1, LV1); and (3) 500 ml above the CPAP lung volume(lung volume 2, LV2). RESULTS: The mean (SE) apnoea/hypopnoea index (AHI) for baseline, LV1, and LV2, respectively, was 62.3 (10.2), 37.2 (5.0), and 31.2 (6.7) events per hour (p = 0.009); the 3% oxygen desaturation index was 43.0 (10.1), 16.1 (5.4), and 12.3 (5.3) events per hour (p = 0.002); and the mean oxygen saturation was 95.4 (0.3)%, 96.0 (0.2)%, 96.3 (0.3)%, respectively (p = 0.001). CONCLUSION: An increase in lung volume causes a substantial decrease in sleep disordered breathing in patients with OSA during non-REM sleep.     

Case-control study of 24 hour ambulatory blood pressure in patients with obstructive sleep apnoea and normal matched control subjects

BACKGROUND: There is considerable debate regarding the relationship between obstructive sleep apnoea (OSA) and hypertension. It is unclear whether OSA is an independent vascular risk factor as studies attempting to assess this association have produced conflicting results because of confounding variables such as upper body obesity, alcohol, and smoking. A case-control study of 24 hour ambulatory blood pressure was undertaken in patients with OSA and matched controls to assess whether OSA is an independent correlate of diurnal hypertension. METHODS: Forty five patients with moderate to severe OSA and excessive daytime sleepiness were matched with 45 controls without OSA in a sleep study. Matched variables included age, body mass index (BMI), alcohol, cigarette usage, treated hypertension, and ischaemic heart disease. Upper body obesity was compared by waist:hip and waist:height ratios; 24 hour ambulatory blood pressure recordings were performed (before treatment for OSA) in all subjects. RESULTS: Patients with OSA had significantly increased mean (SD) diastolic blood pressure (mm Hg) during both daytime (87.4 (10.2) versus 82.8 (9.1); p=0.03, mean difference 4.6 (95% CI 0.7 to 8.6) and night time (78.6 (9.3) versus 71.4 (8.0); p<0.001, mean difference 7.2 (95% CI 3.7 to 10.6)), and higher systolic blood pressure at night (119.4 (20.7) versus 110.2 (13.9); p=0.01, mean difference 9.2 (95% CI 2.3 to 16.1)). The nocturnal reduction in blood pressure ("dipping") was smaller in patients with OSA than in control subjects. CONCLUSIONS: Compared with closely matched control subjects, patients with OSA have increased ambulatory diastolic blood pressure during both day and night, and increased systolic blood pressure at night. The magnitude of these differences is sufficient to carry an increased risk of cardiovascular morbidity. The slight excess of upper body fat deposition in the controls may make these results conservative.     

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/min(1000)), 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 microg/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.     

Comparison of three ways to determine and deliver pressure during nasal CPAP therapy for obstructive sleep apnoea

BACKGROUND: The simplest method of initiating and maintaining therapeutic continuous positive airways pressure (CPAP) therapy for obstructive sleep apnoea (OSA) has not been established. METHODS: Ninety eight subjects with OSA requiring CPAP treatment (more than 10 dips in oxygen desaturation of >4% per hour of sleep study and Epworth Sleepiness Score (ESS) >9) were randomised prospectively to three different methods of CPAP delivery for 6 months: (1) autotitration pressure throughout; (2) autotitration pressure for 1 week followed by fixed pressure (95th centile) thereafter; and (3) fixed pressure determined by algorithm (based on neck size and dip rate). Patients and investigators were blind to group allocation. One week after initiation the patients were routinely reviewed by sleep nurses. Study assessments took place before starting CPAP treatment and 1 and 6 months after to assess ESS, maintenance of wakefulness test, 24 hour blood pressure, general health (SF-36), and sleep apnoea related quality of life. CPAP internal monitoring data were also collected. RESULTS: There were no significant differences in any of the outcome measures or CPAP monitoring data between the three groups. The 95th centile CPAP pressures delivered in the 6 month and 1 week autotitration groups were higher than in the algorithm group, but the median pressures were lowest in the 6 month autotitration group. CONCLUSIONS: The method of determining CPAP pressure for treatment of moderate to severe OSA makes no significant difference to clinical outcome measures. The autotitration CPAP machine used has no advantage in this setting over simpler methods of pressure determination.     

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.     

Effect of continuous positive airway pressure on ventricular ectopy in heart failure patients with obstructive sleep apnoea

BACKGROUND: Obstructive sleep apnoea (OSA) elicits a number of cardiovascular perturbations that could lead acutely or chronically to increased ventricular ectopy in patients with heart failure (HF). We tested the hypothesis that treatment of OSA with continuous positive airway pressure (CPAP) in patients with HF would reduce the frequency of ventricular premature beats (VPBs) during sleep in association with reduced sympathetic nervous system activity. METHODS: Following optimisation of medical treatment, 18 HF patients with OSA and >10 VPBs per hour of sleep were randomised to a control group (n = 8) or a treatment group who received CPAP (n = 10). The frequency of VPBs and urinary norepinephrine (noradrenaline) concentrations during total sleep time were determined at baseline and after 1 month. RESULTS: Control patients did not experience any significant changes in apnoea-hypopnoea index (AHI), mean nocturnal O(2) saturation, or the frequency of VPBs. In contrast, there was a significant reduction in AHI (p<0.001), an increase in minimum O(2) saturation (p = 0.05), a reduction in urinary norepinephrine concentrations (p = 0.009), and a 58% reduction in the frequency of VPBs during total sleep (from mean (SE) 170 (65) to 70 (28) per hour, p = 0.011) after 1 month of CPAP treatment. CONCLUSIONS: In patients with HF, treatment of co-existing OSA by CPAP reduces the frequency of VPBs during sleep. These data suggest that reductions in VPBs and other ventricular arrhythmias through treatment of OSA might improve the prognosis in patients with HF.     

Ventilatory responses to hypercapnia and hypoxia in relatives of patients with the obesity hypoventilation syndrome

BACKGROUND: It is unclear why some morbidly obese individuals have waking alveolar hypoventilation while others with similar obesity do not. Some evidence suggests that patients with the obesity hypoventilation syndrome (OHS) may have a measurable premorbid impairment of ventilatory chemoresponsiveness. Such an impairment of ventilatory chemoresponsiveness in OHS, however, may be an acquired and reversible consequence of severe obstructive sleep apnoea (OSA). We hypothesised that, in patients with OHS who do not have coincident severe OSA, there may be a familial impairment in ventilatory responses to hypoxia and hypercapnia. METHODS: Sixteen first degree relatives of seven patients with OHS without severe OSA (mean (SD) age 40 (16) years, body mass index (BMI) 30 (6) kg/m(2)) and 16 subjects matched for age and BMI without OHS or OSA were studied. Selection criteria included normal arterial blood gas tensions and lung function tests and absence of sleep apnoea on overnight polysomnography. Ventilatory responses to isocapnic hypoxia and to hyperoxic hypercapnia were compared between the two groups. RESULTS: The slope of the ventilatory response to hypercapnia was similar in the relatives (mean 2.33 l/min/mm Hg) and in the control subjects (2.12 l/min/mm Hg), mean difference 0.2 l/min/mm Hg, 95% confidence interval (CI) for the difference -0.5 to 0.9 l/min/mm Hg, p=0.5. The hypoxic ventilatory response was also similar between the two groups (slope factor A: 379.1 l/min * mm Hg for relatives and 373.4 l/min * mm Hg for controls; mean difference 5.7 l/min * mm Hg; 95% CI -282 to 293 l/min * mm Hg, p=0.7; slope of the linear regression line of the fall in oxygen saturation and increase in minute ventilation: 2.01 l/min/% desaturation in relatives, 1.15 l/min/% desaturation in controls; mean difference 0. 5 l/min/% desaturation; 95% CI -1.7 to 0.7 l/min/% desaturation, p=0. 8). CONCLUSION: There is no evidence of impaired ventilatory chemoresponsiveness in first degree relatives of patients with OHS compared with age and BMI matched control subjects.     

Effects of nasal CPAP on simulated driving performance in patients with obstructive sleep apnoea

BACKGROUND: Many patients with obstructive sleep apnoea (OSA) have difficulty in driving and experience increased automobile accidents. It has previously been shown that patients with OSA perform poorly on a laboratory based divided attention driving test (DADT). METHODS: Seventeen men with OSA of mean (SD) age 49.7 (11.2) years and an initial apnoea/hypopnoea index (AHI) of 73.0 (28.9) were restudied from one to 12 (mean (SD) 9.2 (4.2)) months after initiating treatment with nasal continuous positive airway pressure (CPAP) to examine the effects of treatment on DADT performance. Eighteen age and sex matched controls were also retested 8.4 (3.4) months after their initial tests. Following a practice session, all subjects were given the DADT for 20 minutes before each daytime nap of the standard multiple sleep latency test (MSLT). RESULTS: Untreated patients with OSA, who performed much worse than controls in all measures, improved significantly on all measures of performance, particularly in tracking error which returned to the level of controls in all but one patient. Changes in performance were much greater for patients with OSA than for controls in tracking error (mean difference 106 (95% CI 75 to 135) cm), sleep latency/ MSLT (5.3 (95% CI 2.7 to 8.0) min), number of correct responses (1.2 (95% CI 0.4 to 1.9)), number of missed responses (1.7 (95% CI 0.9 to 2.3)), and number out of bounds (10.0 (95% CI 7.9 to 13.6)), but not for response time (0.1 (95% CI -0.3 to 0.2) s). Improvement in tracking error was highly correlated with improvement in sleepiness (r = 0.65). CONCLUSIONS: Impairment in laboratory driving performance skills in patients with OSA is reversed by successful treatment with nasal CPAP. Changes in daytime sleepiness account for some but not all of the improvement.


     

Randomised controlled crossover trial of humidified continuous positive airway pressure in mild obstructive sleep apnoea

BACKGROUND: It is unclear whether continuous positive airway pressure (CPAP), the treatment of choice for severe obstructive sleep apnoea (OSA), is effective at improving outcomes in mild OSA. METHODS: To help define the role of humidified CPAP in mild OSA, a randomised crossover study was undertaken of patients with an apnoea hypopnoea index (AHI) of 5-30/hour. Subjective sleepiness, objective wakefulness, mood, reaction time, and quality of life were measured at baseline, after 3 weeks treatment with humidified CPAP and 3 weeks sham CPAP (2 week washout). RESULTS: Twenty nine of 31 enrolled patients (age 25-67 years, seven women, mean (SD) body mass index 31.5 (6) kg/m2) completed the protocol. Humidified CPAP improved polysomnographic indices of OSA and Epworth Sleepiness Scale (2.4 points (95% CI 0.6 to 4.2)). Objective wakefulness (modified maintenance of wakefulness test) showed a trend towards improvement (5.2 minutes (95% CI -0.6 to 11)). Mood (Hospital Anxiety and Depression Scale), quality of life (SF 36, Functional Outcomes of Sleep Questionnaire), and reaction times (Psychomotor Vigilance Task) were not improved more than sham CPAP. Compliance with humidified and sham CPAP both averaged 4.9 hours/night. Placebo effects were evident in many outcomes and there was no clear treatment preference. CONCLUSIONS: Humidified CPAP improves subjective sleepiness and possibly objective wakefulness but not reaction times, quality of life, or mood. These results do not support the routine use of CPAP in all patients with mild OSA, but offers some support for the trialling of CPAP in those with severe sleepiness.     

Continuous positive airway pressure reduces daytime sleepiness in mild to moderate obstructive sleep apnoea: a meta-analysis

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) affects an estimated 2-4% of the middle aged population. Meta-analyses of randomised controlled trials have shown that the severe presentation of the syndrome (apnoea hypopnoea index (AHI) >30/hour) is effectively treated with continuous positive airway pressure (CPAP). Until recently there have been insufficient data to determine whether CPAP improves sleepiness in the larger subgroup with mild to moderate OSAS (AHI 5-30/hour). METHODS: A systematic search of Medline and a hand search identified seven randomised controlled trials where CPAP was compared with either a placebo or with conservative management in the treatment of mild to moderate OSAS (AHI 5-30/hour). All trials used the Epworth Sleepiness Scale (ESS), four used the Multiple Sleep Latency Test (MSLT), and three used the Maintenance of Wakefulness Test (MWT) to measure sleepiness. RESULTS: Meta-analyses indicated that CPAP significantly reduced subjective daytime sleepiness (ESS) by 1.2 points (95% CI 0.5 to 1.9, p = 0.001), improved objective daytime wakefulness (MWT) by 2.1 minutes (95% CI 0.5 to 3.7, p = 0.011), but did not affect objective daytime sleepiness (MSLT, mean benefit -0.2 minutes, 95% CI -1.0 to 0.6, p = 0.6). The two significant effects were small (effect size <0.30). CONCLUSIONS: CPAP elicits small improvements in subjective sleepiness and objective wakefulness in people with mild to moderate OSAS. However, the effects on sleepiness are of limited clinical significance.     

Ambulatory pulmonary artery pressure monitoring during sleep and exercise in normal individuals and patients with COPD

BACKGROUND: Pulmonary hypertension is a common complication of chronic obstructive airways disease (COPD) and its presence implies a poor prognosis. However, it is difficult to measure and its specific contribution to symptoms is difficult to quantify. A micromanometer tipped pulmonary artery catheter was used to measure pulmonary artery pressure (PAP) during sleep and on exercise. METHODS: Ten patients (five with COPD receiving long term oxygen therapy and five normal individuals) were studied. Pulmonary artery pressure was recorded continuously during two periods of sleep (breathing oxygen followed by air for the COPD group) and during exercise. RESULTS: In the COPD group PAP during sleep on oxygen was significantly lower than PAP during sleep breathing air (mean (SD) difference 9.6 (5.3) mm Hg, 95% CI 4.9 to 14.3, p= 0.016). PAP during exercise was not significantly different from PAP during sleep breathing air (mean (SD) difference 0.8 (8.9) mm Hg, 95% CI -7.0 to 8.6, p= 0.851). In normal individuals the group mean (SD) PAP was 15 (5.9) mm Hg for the first nocturnal period and 15 (5.7) mm Hg for the second nocturnal period. PAP during exercise was not significantly different from PAP during sleep breathing air (mean (SD) difference 3.3 (2.2) mm Hg, 95% CI 1.1 to 5.5, p= 0.061). CONCLUSION: In patients with COPD, PAP rose significantly during sleep to levels similar to those measured during exercise, but this could be reversed with oxygen.     

Blood pressure after cardiac transplantation in childhood.

BACKGROUND: There has been little formal study of blood pressure in children after cardiac transplantation. METHODS: Twenty-four-hour and clinical blood pressure (BP) were measured in 28 children (>6 months after transplantation) and compared with a large amount of normal data. RESULTS: Conventional (clinical) systolic BP (SBP) was elevated in 9 (32.1%) of 28 (95% confidence interval [CI] 15.8 to 52.3), and conventional diastolic BP (DBP) was elevated in 5 (17.8%) of 28 (95% CI 6.0 to 36.8). Mean 24-hour BP was >97.5 percentile in 2 (7.7%) of 26 (95% CI 0.9 to 25.1) for SBP and in 7 (28.0%) of 25 (95% CI 12.1 to 49.4) for DBP. In comparison with the control population, mean nighttime SBP was 8.9 mm Hg higher in the transplanted group (95% CI 4.8 to 13.1), but daytime and mean 24-hour SBP were similar. Mean day, night, and 24-hour DBP was significantly higher in the transplanted patients. The nighttime decrease in BP was significantly less than controls for SBP, but not for DBP. Conventional BP measurement was poorly predictive of 24-hour BP. There was a significant association between mean 24-hour SBP and interventricular septal thickness (r(2)=0.35; p=0.01). DBP was not associated with interventricular septal thickness (r(2)=0.07; p=0.20) but was significantly correlated with the time since transplantation (r=0.42; p=0.03 for conventional DBP and r=0.43; p=0.04 for 24-hour DBP). CONCLUSIONS: The elevation of DBP in children after cardiac transplantation is unexplained. The elevation in nighttime SBP has possible important therapeutic implications and is not predicted by conventional (clinical) BP measurement.     

Nasal CPAP and weight loss in hypertensive patients with obstructive sleep apnoea.

BACKGROUND--The high prevalence of obstructive sleep apnoea (OSA) in patients with systemic hypertension and of hypertension in patients with OSA suggests a causal link between the two disorders. This study was carried out to determine whether nasal continuous positive airway pressure (CPAP) and weight loss affect daytime hypertension in OSA. METHODS--Sixty hypertensive patients with OSA took part in the study; 33 accepted nasal CPAP and used their machine for 5.7 (0.2) hours per night, and the remaining 27 patients refused nasal CPAP and upper airway surgery so the only therapeutic intervention was a recommendation of weight loss. A significant change in hypertension during follow up was defined as either a change in mean blood pressure of at least 10 mm Hg (or more than 8%) without a change in drug treatment, or a reduction in drug dosage with mean blood pressure within these limits. Weight loss was defined as a body mass index of at least 5% below the baseline value. RESULTS--After 512 (41) days, hypertension had become less severe in seven of 12 patients (58%) treated with weight loss only, in eight of 28 patients (29%) with nasal CPAP only, in two of five patients with nasal CPAP and weight loss, and in one of 15 patients without nasal CPAP or weight loss. Multivariate analysis of variance with the outcome of hypertension at follow up as the dependent variable revealed that only the percentage change in body mass index significantly contributed to the course of hypertension. CONCLUSION--The course of hypertension in OSA is more closely linked to weight loss than to elimination of sleep apnoea by nasal CPAP.     

Randomised prospective parallel trial of therapeutic versus subtherapeutic nasal continuous positive airway pressure on simulated steering performance in patients with obstructive sleep apnoea

BACKGROUND: Obstructive sleep apnoea (OSA) impairs vigilance and may lead to an increased rate of driving accidents. In uncontrolled studies accident rates and simulated steering performance improve following treatment with nasal continuous positive airway pressure (NCPAP). This study seeks to confirm the improvement in steering performance in a randomised controlled trial using subtherapeutic NCPAP as a control treatment. METHODS: Fifty nine men with OSA (Epworth Sleepiness Score (ESS) of > or =10, and > or =10/h dips in SaO(2) of >4% due to OSA) received therapeutic or subtherapeutic NCPAP ( approximately 1 cm H(2)O) for one month. Simulated steering performance over three 30-minute "drives" was quantified as: standard deviation (SD) of road position, deterioration in SD across the drive, length of drive before "crashing", and number of off-road events. The reaction times to peripheral target stimuli during the drive were also measured. RESULTS: Subtherapeutic NCPAP did not improve overnight >4% SaO(2) dips/h compared with baseline values, thus acting as a control. The SD of the steering position improved from 0.36 to 0.21 on therapeutic NCPAP, and from 0.35 to 0.30 on subtherapeutic NCPAP (p = 0.03). Deterioration in SD of the steering position improved from 0.18 to 0.06 SD/h with therapeutic NCPAP and worsened from 0.18 to 0.24 with subtherapeutic NCPAP (p = 0.04). The reaction time to target stimuli was quicker after therapeutic than after subtherapeutic NCPAP (2.3 versus 2.7 seconds, p = 0.04). CONCLUSIONS: Therapeutic NCPAP improves steering performance and reaction time to target stimuli in patients with OSA, lending further support to the hypothesis that OSA impairs driving, increases driving accident rates, and that these improve following treatment with NCPAP.     

Systemic activity of inhaled corticosteroid treatment in asthmatic children: corticotrophin releasing hormone test

BACKGROUND: A study was undertaken to assess the function of the hypothalamic-pituitary-adrenal axis (HPA) in a group of asthmatic children before and after treatment with inhaled corticosteroids. METHODS: Thirty prepubertal patients of mean (SD) age 6.7 (1.8) years were treated with inhaled corticosteroids. All children underwent a corticotrophin releasing hormone (CRH) test with evaluation of serum cortisol and adrenocorticotrophin hormone (ACTH) levels before and after 3 months of treatment. Twenty four hour urine samples were also collected to measure free cortisol (UFC) excretion. RESULTS: Subjects showed no difference between basal serum cortisol levels (mean change -18; 95% CI -41 to 5; p=0.118) and delta (peak minus basal) levels (mean change -13; 95% CI -38 to 12; p=0.308) before and after treatment, whereas the peak cortisol level (mean change -31; 95% CI -55 to -7; p=0.013) and area under the curve (AUC) (mean change -175; 95% CI -288 to -63; p=0.003) after CRH were significantly lower following treatment. Basal, peak and AUC ACTH were significantly lower after treatment (p<0.05, p=0.004 and p=0.003, respectively), while delta ACTH was similar before and after treatment ((mean change -12; 95% CI - 31 to -7; p=0.199). No significant reduction in 24 hour UFC was observed after the treatment period (before 14.9 (7.1), after 15.0 (11.6); mean change 0.1, 95% CI -5.2 to 5.4; p=0.967). No correlation was found between UFC and any of the parameters of cortisol excretion following the CRH test, either before or after treatment. CONCLUSIONS: These data suggest that, at the dosage and for the treatment period used, inhaled steroids do not seem to suppress the HPA axis in the majority of patients. The CRH test may be more sensitive than 24 hour UFC and morning plasma cortisol levels in evaluating systemic activity of inhaled corticosteroid treatment.     

Mechanisms used to restore ventilation after partial upper airway collapse during sleep in humans

BACKGROUND: Most patients with obstructive sleep apnoea (OSA) can restore airflow after an obstructive respiratory event without arousal at least some of the time. The mechanisms that enable this ventilatory recovery are unclear but probably include increased upper airway dilator muscle activity and/or changes in respiratory timing. The aims of this study were to compare the ability to recover ventilation and the mechanisms of compensation following a sudden reduction of continuous positive airway pressure (CPAP) in subjects with and without OSA. METHODS: Ten obese patients with OSA (mean (SD) apnoea-hypopnoea index 62.6 (12.4) events/h) and 15 healthy non-obese non-snorers were instrumented with intramuscular genioglossus electrodes and a mask/pneumotachograph which was connected to a modified CPAP device that could deliver either continuous positive or negative pressure. During stable non-rapid eye movement sleep the CPAP was repeatedly reduced 2-10 cm H2O below the level required to eliminate flow limitation and was held at this level for 5 min or until arousal from sleep occurred. RESULTS: During reduced CPAP the increases in genioglossus activity (311.5 (49.4)% of baseline in subjects with OSA and 315.4 (76.2)% of baseline in non-snorers, p = 0.9) and duty cycle (123.8 (3.9)% of baseline in subjects with OSA and 118.2 (2.8)% of baseline in non-snorers, p = 0.4) were similar in both groups, yet patients with OSA could restore ventilation without cortical arousal less often than non-snorers (54.1% vs 65.7% of pressure drops, p = 0.04). When ventilatory recovery did not occur, genioglossus muscle and respiratory timing changes still occurred but these did not yield adequate pharyngeal patency/ventilation. CONCLUSIONS: Compensatory mechanisms (increased genioglossus muscle activity and/or duty cycle) often restore ventilation during sleep but may be less effective in obese patients with OSA than in non-snorers.     

Peripheral airway obstruction in primary pulmonary hypertension

BACKGROUND: As there is controversy about changes in lung function in primary pulmonary hypertension (PPH), lung mechanics were assessed with a focus on expiratory airflow in relation to pulmonary haemodynamics. METHODS: A cross sectional study was performed in 64 controls and 171 patients with PPH (117 women) of mean (SD) age 45 (13) years, pulmonary artery pressure (PAPmean) 57 (15) mm Hg, and pulmonary vascular resistance 1371 (644) dyne.s/cm(5). RESULTS: Mean (SD) total lung capacity was similar in patients with PPH and controls (98 (12)% predicted v 102 (17)% predicted, mean difference -4 (95% confidence interval (CI) -7.89 to -0.11); residual volume (RV) was increased (118 (24)% predicted v 109 (27)% predicted, mean difference 9 (95% CI 1.86 to 16.14); and vital capacity (VC) was decreased (91 (16)% predicted v 102 (10)% predicted, mean difference -11 (95% CI 15.19 to -6.80). RV/TLC was increased (117 (27)% predicted v 97 (29)% predicted, mean difference 20 (95% CI 12.3 to 27.8)) and correlated with PAPmean (r=0.31, p<0.001). In patients with PAPmean above the median of 56 mm Hg, RV/TLC was further increased (125 (32)% predicted v 111 (22)% predicted, mean difference -14 (95% CI -22.2 to -5.8)). Expiratory flow-volume curves were reduced and curvilinear in patients with PPH. CONCLUSIONS: Peripheral airway obstruction is common in PPH and is more pronounced in severe disease. This may contribute to symptoms. Reversibility of bronchodilation and relation to exercise capacity need further evaluation.     

Prognostic importance of ambulatory blood pressure recordings in patients with chronic kidney disease

Ambulatory systolic blood pressure (BP) correlates better with risk factors for progression of chronic kidney disease (CKD) compared to clinic measured BP, but its role in predicting end-stage renal disease (ESRD) and death in patients with CKD is unknown. In a cohort study of 217 Veterans with CKD BP was measured by ambulatory monitoring and in the clinic. Twenty-four hour ambulatory BP was 133.5 +/- 16.6/73.1 +/- 11.1 mm Hg and clinic BP was 155.2 +/- 25.6/84.7 +/- 14.2 mm Hg. The composite renal end point of ESRD or death over a median follow-up of 3.5 years occurred in 75 patients (34.5%), death occurred in 52 patients (24.0%), and ESRD in 36/178 patients (20.2%). Thirty-nine patients died before reaching ESRD. One standard deviation (s.d.) increase in systolic BP increased the risk of composite outcome to 1.69 (95% confidence interval (CI) 1.32-2.17) for standard clinic measurement and to 1.88 (95% CI 1.48-2.39) for 24 h ambulatory BP recording. One s.d. increase in 24 h ambulatory systolic BP increased the risk of ESRD to 3.04 (95% CI 2.13-4.35) and to 2.20 (95% CI 1.43-3.39) when adjusted for standard clinic systolic BP. Non-dipping was associated with increased risk of total mortality and composite end point. In patients with CKD, BPs obtained by ambulatory monitoring are a stronger predictor of ESRD or death compared to BPs obtained in the clinic. Systolic ambulatory BP and nondipping are independent predictors for ESRD after adjusting for clinic BP. However, adjustment for other risk factors for CKD progression removes the independent prognostic value of ambulatory BP.     

Treatment of obstructive sleep apnoea leads to improved microvascular endothelial function in the systemic circulation

BACKGROUND: Obstructive sleep apnoea (OSA) is a common and potentially reversible cause of systemic hypertension. The mechanisms whereby OSA leads to hypertension and the effects of treatment on arterial function, however, are not well established. Microvascular arterial endothelial and smooth muscle function was assessed in subjects with OSA before and after treatment with continuous positive airways pressure (CPAP). METHODS: Ten subjects of mean (SE) age 49 (8) years with at least moderately severe OSA had detailed forearm vascular reactivity studies before and after 3 months of CPAP treatment. The systemic circulation was assessed by measuring brachial artery pressure, flow and resistance responses to intra-arterial infusions of acetylcholine (ACh; an endothelium dependent vasodilator), sodium nitroprusside (SNP; an endothelium independent vasodilator), L-NMMA (a nitric oxide (NO) antagonist), and L-arginine (the substrate for NO). RESULTS: Before CPAP, ACh and SNP infusions increased forearm blood flow in a dose dependent manner (p<0.01). After CPAP, endothelium dependent dilation to ACh was significantly increased (434 (23)% of baseline after CPAP v 278 (20)% before CPAP, p<0.001), whereas SNP induced dilation was unchanged. Resting NO production was higher after CPAP, evidenced by a significantly greater reduction in basal flow by L-NMMA (p=0.05). L-Arginine reversed the effect of L-NMMA in all cases. CONCLUSION: In patients with OSA, treatment with CPAP improves baseline endothelial NO release and stimulates endothelium dependent vasorelaxation in the systemic circulation. This is a potential mechanism for improving systemic and vascular function in patients with OSA treated with CPAP.