Effects of continuous positive airway pressure on lung function in patients with chronic obstructive pulmonary disease and sleep disordered breathing

OBJECTIVE: Sleep disordered breathing (SDB), namely hypoventilation and obstructive sleep apnoea, occur in about 50% of patients with severe chronic obstructive pulmonary disease (COPD). Previous studies that have investigated the reversal of SDB in such patients with nasally applied intermittent positive airway pressure have reported a fall in PaCO2 but little change in airflow obstruction. We reasoned that the lack of improvement in airflow obstruction may be due to insufficient expiratory pressure. Accordingly, we sought to determine the effects of chronic nasal continuous positive airway pressure (CPAP), at highest tolerable levels, upon blood gases and airflow obstruction in patients with severe COPD and SDB. METHODOLOGY: Fourteen patients were studied, ten of whom were able to tolerate CPAP (10.2 +/- 0.9 cmH2O) for at least 3 months. RESULTS: Within the CPAP compliant group, there was a fall in PaCO2 (58.0 +/- 3.5 to 48.0 +/- 0.9 mmHg, P = 0.015) associated with a rise in PaO2 (54.8 +/- 3.8 to 63.2 +/- 1.8 mmHg, P = 0.015) and forced expiratory volume in 1 s (0.95 +/- 0.13 to 1.10 +/- 0.13 L, P < 0.005). Concurrent with these improvements was a substantial fall in hospitalization rates (from 3.85 to 0.73 admissions per annum). CONCLUSION: Improvements in gas exchange, airflow obstruction and hospitalization rates were observed in patients with COPD and SDB treated with nasal CPAP during sleep.     

Comparison of three auto-adjusting positive pressure devices in patients with sleep apnoea.

Auto-adjustable continuous positive airway pressure (APAP) devices are an emerging treatment alternative to fixed-pressure continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea syndrome. They have been engineered to automatically adjust the pressure to the optimal level on a continuous basis. However, not all APAP technologies use the same algorithm. Three different APAP devices (Autoset Spirit, Breas PV 10i and RemStar Auto) were compared in a randomised crossover trial in patients already established on fixed-pressure CPAP therapy. The outcome measures were compliance, quality of life and side-effects. Twenty-seven middle-aged patients (25 male) previously diagnosed with severe obstructive sleep apnoea syndrome (median (interquartile range) apnoea/hypopnoea index 48 (29-76)), established on CPAP therapy for >3 yrs, were randomised to each APAP device for 4 weeks. Mean pressure and patient compliance were significantly lower on the Breas PV 10i than on the other APAP devices. The devices were similar in terms of quality of life, daytime sleepiness and upper airway side-effects, but patients evaluated them significantly differently in terms of device features, sleep quality and pressure comfort, with the Breas PV 10i being the least popular. Auto-adjustable positive airway pressure devices differ in pressure delivery and patient compliance in obstructive sleep apnoea syndrome patients.     

Effects of nasal continuous positive airway pressure on pulmonary haemodynamics and tissue oxygenation in patients with obstructive sleep apnoea

We investigated the acute effects of nasal continuous positive airway pressure (CPAP) on pulmonary haemodynamics and tissue oxygenation in eight men with obstructive sleep apnoea (OSA) by means of right heart catheterization. They were tested at four dosage levels of nasal CPAP: 0, 5, 10, and 15 cmH2O. Nasal CPAP significantly reduced the cardiac index at the 10 and 15 cmH2O doses. The mean pulmonary artery pressure was significantly elevated with 10 and 15 cmH2O, and pulmonary capillary wedge pressure was significantly increased with 15 cmH2O of nasal CPAP. Pulmonary vascular resistance was significantly increased with 10 cmH2O of nasal CPAP. The 5 cmH2O dose of nasal CPAP did not affect significantly these parameters. Mixed venous oxygen tension was unchanged at any pressure. We conclude that tissue oxygenation was maintained in the OSA patients during administration of nasal CPAP, even though a high CPAP clearly affected pulmonary haemodynamics.     

Effects of obesity upon genioglossus structure and function in obstructive sleep apnoea.

Obesity is a common feature of the obstructive sleep apnoea syndrome. It can influence the structure and function of skeletal muscles. However, its effects upon the upper airway muscles have not been explored directly. This study assessed the structure and function of the genioglossus in patients with obstructive sleep apnoea syndrome and in healthy subjects (with and without obesity, defined by a body mass index > 30 kg x m(-2)). Further, to investigate the effects of continuous positive airway pressure (CPAP) treatment, patients with obstructive sleep apnoea syndrome after at least 1 yr under CPAP were also studied. The study found that obese and nonobese patients showed different in vitro geniglossus endurance properties. In obese patients, geniglossus endurance was indistinguishable from normal while, nonobese patients, at diagnosis, showed increased genioglossus fatigability; this was not observed in patients treated with CPAP. By contrast, patients with obstructive sleep apnoea syndrome showed at diagnosis a higher percentage of type II fibres than controls and patients under CPAP treatment independently of obesity. This difference is mainly due to a predominance of subtype IIb fibre. This difference was not observed in the group of patients treated with CPAP. Genioglossus twitch force was normal in all patients. These results suggest that different pathogenic mechanisms may underlie the development of obstructive sleep apnoea syndrome in obese and nonobese patients. This observation may have potential clinical implications.     

Nocturnal asthma: snoring, small pharynx and nasal CPAP

We studied two populations of patients who snored and had frequent nocturnal asthma attacks: ten overweight men presenting with typical obstructive sleep apnoea syndrome, and a group of five adolescents with regular snoring and an increase in negative inspiratory oesophageal pressure during stage II non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. All subjects presented cranio-mandibular abnormalities at cephalometric evaluation, with a narrow space behind the base of the tongue. Both populations were treated with nasal continuous positive airway pressure (CPAP) during sleep. Snoring and partial or complete airway obstruction were eliminated, as were the nocturnal asthma attacks. Two adolescents treated with upper airway surgery after nasal CPAP showed no nocturnal asthma at short-term follow-up. Nasal CPAP had no effect on daytime asthma. One hypothesis is that a subgroup of asthmatic patients with small pharynxes may have enhanced vagal stimulation during sleep compared with other asthmatic patients. This enhancement would be related to the repetitive Müller manoeuvres noted with airway obstruction during sleep. Combined with the local effects of snoring, this extra vagal stimulation would be a precipitating factor in nocturnal asthma attacks.     

Mortality of sleep apnoea patients treated by nasal continuous positive airway pressure registered in the ANTADIR observatory. Association Nationale pour le Traitement A Domicile de l'Insuffisance Respiratoire chronique.

The aim of this study was to examine risk factors for and causes of mortality in patients with obstructive sleep apnoea syndrome (OSAS) treated by nasal continuous positive airway pressure (CPAP). Univariate and multivariate analyses of the data on patients registered in the Association Nationale pour le Traitement A Domicile de l'Insuffisance Respiratoire chronique (ANTADIR) Observatory between January 1, 1985 and December 31, 1993 and followed to January 1, 1996. Survival ratios were compared to those of the French population. A case control study compared patients who died with patients of the same age and sex, in the same Regional Association, who were equipped with CPAP at the same time. Five-thousand-six-hundred-and-sixty-nine patients had CPAP treatment. Two-hundred-and-seventy-six had died. One-hundred-and-twenty-four deaths were examined and compared to 123 control subjects. Overall mortality was the same as the general French population. Independent risk factors for death were age, oxygen tension in arterial blood (Pa,O2) and forced expiratory volume in one second (FEV1) (per cent predicted). In the case-control study independent risk factors for death in the past history were cardiac arrhythmia with an odds ratio (OR) of 2.8 (95% confidence interval (CI) 1.1-7.2), respiratory disorders (OR 2.8; CI 1.6-4.9) ischaemic events (OR 2.2; CI 1.2-4.2), neurological and psychiatric disorders (OR 2.4; CI 1.1-5.4). A significant excess of cardiovascular deaths and an excess of deaths from accidents and poisonings was found. In conclusion, patients die on therapy predominantly from cardiovascular causes but many have a past history of cardiovascular conditions. Compliance with treatment may be important for survival. Continuous positive airway pressure is an effective therapy for obstructive sleep apnoea syndrome but older patients with reduced spirometry and hypoxaemia may need more attention paid to these aspects of their condition.     

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.     

Platelet function in patients with obstructive sleep apnoea syndrome.

Patients with obstructive sleep apnoea syndrome (OSAS) are subject to an increased cardiovascular morbidity including myocardial infarction and stroke. Platelets play an important role in the pathogenesis and triggering of acute cardiovascular syndromes. So far, the influence of OSAS on platelet function is not fully understood. Platelet aggregability to epinephrine, collagen, arachidonic acid, and adenosine diphosphate in vitro was measured in 17 consecutive male patients (53.0+/-2.1 yrs) with polysomnographically verified OSAS and compared with that of 15 male controls (50.1+/-3.6 yrs) at 20:00 h, 24:00 h, and 06:00 h. In addition, the long-term effects of continuous positive airway pressure (CPAP) therapy on platelet aggregability was assessed after 6 months. Platelet aggregation in vitro induced by epinephrine showed a slight increase overnight in the untreated OSAS patients (NS) whereas it decreased slightly (NS) in the controls and in the treated OSAS patients. Pretherapeutic platelet aggregability was significantly lowered by CPAP therapy both at 24:00 h (64.0+/-6.5 versus 55.3+/-6.7%, p<0.05) and at 06:00 h (64.1+/-6.5 versus 45.8+/-7.6%; p=0.01). Platelet aggregability during sleep in the controls resembled that found in patients with OSAS during CPAP therapy. The results suggest that obstructive sleep apnoea syndrome contributes, at least in part, to platelet dysfunction and that long-term continuous positive airway pressure treatment may reduce platelet aggregability.     

Endothelin-1 plasma levels are not elevated in patients with obstructive sleep apnoea.

Endothelin-1 (ET-1), a potent vasoconstrictor, is released mainly by vascular endothelial cells under the influence of hypoxia and other stimuli. ET-1 is related to endothelial dysfunction, as well as arterial and pulmonary hypertension, all of which are thought to be associated with obstructive sleep apnoea (OSA). This study evaluated venous plasma concentrations of ET-1 and noradrenaline and 24-h systemic blood pressure in 29 patients with OSA (age=56.9+/-1.6 yrs; body mass index=29.5+/-0.7 kg x m2 (mean+/-SEM)). Blood samples were taken in the morning, evening and during sleep. In the same way, the patients were assessed during a night of continuous positive airway pressure (CPAP) and after 13.9+/-1.4 months while still on CPAP. ET-1 levels were compared to those of control subjects, who were selected from in- and outpatients and were matched to patients for age, sex, presence of arterial hypertension and coronary artery disease. ET-1 plasma levels were not elevated in the patients compared to the controls (41.6+/-2.2 and 44.9+/-1.3 pg x mL(-1), respectively, p=0.20). The ET-1 concentration did not change significantly, neither during sleep nor in the first night on CPAP therapy, nor under long-term treatment with CPAP. ET-1 neither correlated to the severity of OSA nor to that of systemic hypertension. The results suggest that endothelin-1 does not play a crucial role in the pathophysiology of obstructive sleep apnoea.     

Importance of sleep stage- and body position-dependence of sleep apnoea in determining benefits to auto-CPAP therapy.

The influence of sleep stage- and body position-dependence of sleep apnoea on treatment efficacy and compliance between conventional continuous positive airway pressure (CPAP) and auto CPAP therapy was evaluated. Thirty-three newly treated sleep apnoea hypopnoea syndrome (SAHS) patients were randomly allocated to conventional or auto-CPAP therapy. Six patients of each treatment group were classified as having sleep stage- and body position-dependent obstructive breathing abnormalities according to the results of the baseline sleep study. After 3 weeks of treatment, the Epworth sleepiness score tended to be higher (p = 0.08) and the ability to stay awake lower (p = 0.02) in patients with dependent breathing abnormalities treated with fixed CPAP, than in the other patients. The effective pressure/time index was significantly lower in sleep stage- and body position-dependent patients treated with fixed CPAP, than in the other patients (p = 0.02). The number of hours the machine was turned on and a positive pressure applied, tended to be smaller in dependent patients treated with fixed CPAP than in independent patients of this treatment group and in patients treated with auto-CPAP. A night-to-night variability index (VI) of positive pressure changes was obtained in the auto-CPAP group. This index significantly decreased with time in the dependent patients while it remained unchanged in the independent group. It is concluded that auto-continuous positive airway pressure may have specific indications in a subset of obstructive sleep apnoea patients with sleep stage- and body position dependent nocturnal breathing abnormalities.     

Effect of treating severe nasal obstruction on the severity of obstructive sleep apnoea.

An association between mouth breathing during sleep and increased propensity for upper airway collapse is well documented, but the effect of treatment for nasal obstruction on mouth breathing during sleep and simultaneous obstructive sleep apnoea (OSA) severity has not been described previously. A randomised single blind placebo- and sham-controlled crossover study of treatment (topical decongestant and external dilator strip) for nasal obstruction was carried out in 10 patients (nine males; mean+/-SEM 46+/-5 yrs) with nasal obstruction and OSA. All patients had normal acoustic pharyngometry. The effect of treatment on nasal resistance, mouth breathing during sleep and OSA severity was quantified. Treatment of nasal obstruction was associated with a dramatic and sustained reduction in nasal resistance and the oral fraction of ventilation during sleep (mean (95% confidence interval) absolute reduction in oral fraction 30% (12-49)). Improvements in sleep architecture were observed during active treatment, and there was a modest reduction in OSA severity (change in apnoea-hypopnoea index 12 (3-22)). In conclusion, treating nasal obstruction reduced mouth breathing during sleep and obstructive sleep apnoea severity, but did not effectively alleviate obstructive sleep apnoea.     

Assisted ventilation for heart failure patients with Cheyne-Stokes respiration.

Patients with chronic congestive cardiac failure (CCF) frequently suffer from central sleep apnoea syndrome (CSAS). Continuous positive airway pressure (CPAP) has been suggested as a treatment. The authors hypothesised that bilevel ventilation might be easier to initiate and superior to CPAP at correcting the sleep-related abnormality of breathing in patients with CCF. After excluding those with a history suggestive of obstructive sleep apnoea, 35 patients with CCF (left ventricular ejection fraction <35%) were screened with overnight oximetry and the diagnosis of CSAS was established with polysomnography in 18. Two 14-day cycles of CPAP (0.85 kPa (8.5 mbar)) or bilevel ventilation (0.85/0.3 kPa (8.5/3 mbar)) in random order, were compared in a crossover study. Sixteen patients (13 males), mean age 62.0+/-7.4 yrs completed the study. The pretreatment apnoea/hypopnoea index of 26.7+/-10.7 was significantly reduced by CPAP and bilevel ventilation to 7.7+/-5.6 and 6.5+/-6.6, respectively. The arousal index fell from 31.1+/-10.0 per hour of sleep to 15.7+/-5.4 and 16.4+/-6.9, respectively. Significant and equal improvements with CPAP and bilevel ventilation were found for sleep quality, daytime fatigue, circulation time and New York Heart Association class. The authors conclude that continuous positive airway pressure and bilevel ventilation equally and effectively improve Cheyne-Stokes respiration in patients with congestive cardiac failure.     

Automatic CPAP titration with different self-setting devices in patients with obstructive sleep apnoea.

Autotitrating continuous positive airway pressure (CPAP) devices automatically adjust the pressure according to upper airway obstructions. The aim of this study was to compare the treatment effects of different automatic CPAP devices (AutoSet, Horizon and Virtuoso) with conventional CPAP in patients with obstructive sleep apnoea independently of financial manufacturer support. Twelve male patients with obstructive sleep apnoea were submitted to a crossover study protocol with overnight polysomnography for 6 consecutive nights. After diagnostic polysomnography, the CPAP pressure was manually titrated. Over the next 4 nights, the patients were treated with any one of the three automatic CPAP devices or fixed CPAP in random order. The apnoea/hypopnoea index on the diagnostic night was 67.3+/-21.7 events h(-1), and was significantly reduced to 0.7+/-1.2, 3.0+/-2.9, 2.3+/-2.5 and 12.0+/-13.6 events x h(-1) with the fixed CPAP, AutoSet, Horizon and Virtuoso devices respectively. An apnoea/ hypopnoea index of <5 events h(-1), an indicator of optimal treatment, was achieved in all patients with fixed CPAP and in 10 patients using the Autoset and Horizon devices, but in only six of the 12 using the Virtuoso. The mean pressure was significantly lower with the AutoSet and Virtuoso devices, but not with the Horizon as compared to fixed CPAP. The maximum pressure was significantly higher with the Horizon. It is concluded that automatic continuous positive airway pressure devices produce a significant reduction in apnoea/hypopnoea index; however, there is considerable difference in the efficacy of the various devices.     

Objective measurement of compliance with nasal CPAP treatment for obstructive sleep apnoea syndrome

Compliance with nasal continuous positive airway pressure (CPAP) has become a major concern, since this treatment is efficacious, but constraining. In 46 consecutive obstructive sleep apnoea (OSA) patients, we measured compliance with nasal CPAP by establishing a mean rate of use, with a built-in time counter read at three-month intervals, over a mean follow-up period of 232 +/- 27 days. The mean rate of use in the whole group was 5.14 +/- 0.31 hours per day. The acceptance rate was 90.9-93.2%, showing that patient acceptance is not a limitation in the use of nasal CPAP.     

Optimal continuous positive airway pressure in patients with obstructive sleep apnoea: role of craniofacial structure

Although nasal continuous positive airway pressure (CPAP) is effective in improving nocturnal obstructive apnoea, daytime sleepiness and well-being in patients with obstructive sleep apnoea syndrome (OSAS), not all patients tolerate this treatment. Since optimal CPAP titration is essential to maintain compliance, it is important to elucidate the factors that help to determine the optimal pressure. However, the determinants of the optimal CPAP level are controversial. The subjects comprised 27 Japanese male patients with OSAS who underwent standard polysomnography (PSG), pulmonary function tests, arterial blood gas analysis, cephalometry and CPAP titration. Twenty normal controls also underwent cephalometric analysis. The apnoea-hypopnoea index (AHI), mean oxygen saturation (mean SaO2) and the lowest SaO2 during sleep were found to be 54.7+/-22.6, 89.0+/-5.6%, and 69.7+/-9.0%, respectively by PSG. The mean optimal CPAP was 9.6+/-1.8 cmH2O. The cephalometric angles (SNA, SNB and NSBa) were similar to those found in the control subjects. but MP-H, and PNS-P were significantly longer than those in the control subjects as shown by cephalometry. The optimal CPAP was correlated with the mean SaO2 (P<0.0001), neck circumference (P<0.05) and three cephalometric variables (NSBa: P<0.01, MP-H: P<0.05, PNS-P: P<0.05). Multiple, step-wise, regression analysis showed that the mean SaO2 and NSBa were independent variables that best predicted the optimal CPAP. These variables accounted for 57.5% of the total variance (R2=0.575, P<0.001). Optimal CPAP was closely correlated with oxygen desaturation during sleep. However, the craniofacial structure had additional effects such as an independent factor in determining the optimal CPAP level.     

Proportional positive airway pressure: a new concept to treat obstructive sleep apnoea.

Proportional positive airway pressure (PPAP) was designed to optimize airway pressure for the therapy of obstructive sleep apnoea (OSA). In a randomized crossover prospective study, the clinical feasibility of PPAP and its immediate effects on the breathing disorder and sleep in comparison with continuous positive airway pressure (CPAP) was evaluated. Twelve patients requiring CPAP therapy underwent CPAP and PPAP titration in a random order. Obstructive and mixed respiratory events could be completely abolished with both forms of treatment. This efficacy could be achieved at a significantly lower mean mask pressure during PPAP titration (8.45+/-2.42 cmH2O) compared to CPAP (9.96+/-2.7 cmH2O) (p=0.002). The mean minimal arterial oxygen saturation (Sa,O2) (82.8+/-6.5%) on the diagnostic night increased significantly (p<0.001) to an average Sa,O2 of 93.35+/-1.71% and 93.19+/-2.9% during CPAP and PPAP titration. Total sleep time, slow wave sleep and rapid eye movement (REM) sleep increased significantly by the same amount during both CPAP and PPAP titration (p<0.001), while sleep stage nonrapid eye movement (NREM) 1 and 2 decreased. Six patients preferred the PPAP titration night, four patients did not have a preference, and two patients preferred CPAP. The present data show that proportional positive airway pressure is as effective as continuous positive airway pressure in eliminating obstructive events and has the same immediate effect on sleep. The lower average mask pressure during proportional positive airway pressure implies potential advantages compared to continuous positive airway pressure. Proportional positive airway pressure presents a new effective therapeutic approach to obstructive sleep apnoea.     

Prevalence and treatment of central sleep apnoea emerging after initiation of continuous positive airway pressure in patients with obstructive sleep apnoea without evidence of heart failure

Background  

This study aimed to assess the prevalence of complex sleep apnoea (CompSA), defined as central sleep apnoea (CSA) emerging after the initiation of continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA), in patients with normal brain natriuretic peptide (BNP) levels, along with assessing the prevalence of CSA persisting in such patients after the onset of CPAP therapy. We hypothesised that the prevalence of CompSA and persistent CSA after CPAP initiation would be low in patients with OSA and normal BNP levels.     

Sleep apnoea and Turner's syndrome.

A 32-yr-old female with Turner's syndrome and anatomical craniofacial abnormalities, presented with obstructive sleep apnoea syndrome. This was initially treated by nasal continuous positive airway pressure and secondarily cured by maxillomandibullar advancement osteotomy. Anatomical upper airway abnormalities and hormonal factors, which predispose Turner patients to develop obstructive sleep apnoea syndrome, are discussed. A systematic assessment and treatment of sleep-disordered breathing is probably of interest in these patients.     

Continuous positive airway pressure does not reduce blood pressure in nonsleepy hypertensive OSA patients.

Obstructive sleep apnoea (OSA) is associated with high cardiovascular morbidity and mortality. Several randomised controlled trials have shown that continuous positive airway pressure (CPAP) treatment of OSA reduces blood pressure (BP). This randomised, sham-placebo controlled crossover trial assesses whether CPAP produces a similar clinically significant fall in BP in hypertensive OSA patients, but without hypersomnolence. Thirty-five, nonsleepy, hypertensive patients with OSA were treated with CPAP for 1 month, randomised first to either therapeutic or sham-placebo (subtherapeutic CPAP, about 1 cmH(2)O pressure). The second months' alternative treatment followed a 2-week washout period. BP was measured over 24 h, before and at the end of the two treatment periods: mean 24-h BP was the primary outcome variable. There was no overall significant difference in mean 24-h BP: the change in mean 24-h BP on therapeutic CPAP was -2.1 mmHg (sd 8.1), and -1.1 mmHg (sd 8.1) on subtherapeutic CPAP, with a difference of 0.7 mmHg (95% confidence interval (CI) +2.9- -4.4). There was a small significant fall in Epworth Sleepiness Score, therapeutic (-1.4) versus sham (-0.3), and difference -1.2 (95% CI -2.0- -0.4), but no change in objective sleepiness. In nonhypersomnolent hypertensive patients with obstructive sleep apnoea, there is no significant fall in mean 24-h blood pressure with continuous positive airway pressure, in contrast to the fall seen in hypersomnolent patients with obstructive sleep apnoea.