Shift in sleep apnoea type in heart failure patients in the CANPAP trial.

In patients with heart failure (HF), the predominant type of sleep apnoea can change over time in association with alterations in circulation time. The aim of this study was to determine whether, in some patients with HF, a spontaneous shift from mainly central (>50% central events) to mainly obstructive (>50% obstructive events) sleep apnoea (CSA and OSA, respectively) over time coincides with improvement in left ventricular ejection fraction (LVEF). Therefore, sleep studies and LVEFs of HF patients with CSA from the control arm of the Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure (CANPAP) trial were examined to determine whether some converted to mainly OSA and, if so, whether this was associated with an increase in LVEF. Of 98 patients with follow-up sleep studies and LVEFs, 18 converted spontaneously to predominantly OSA. Compared with those in the nonconversion group, those in the conversion group had a significantly greater increase in the LVEF (2.8% versus -0.07%) and a significantly greater fall in the lung-to-ear circulation time (-7.6 s versus 0.6 s). In patients with HF, spontaneous conversion from predominantly CSA to OSA is associated with an improvement in left ventricular systolic function. Future studies will be necessary to further examine this relationship.

Sibutramine versus continuous positive airway pressure in obese obstructive sleep apnoea patients.

The aim of the present study was to compare the efficacy of 1 yr of sibutramine-induced weight loss versus continuous positive airway pressure (CPAP) treatment on sleep-disordered breathing, cardiac autonomic function and systemic blood pressure in obese patients with obstructive sleep apnoea. Subjects with a body mass index of > or =30 kg.m(-2) without previous treatment for obstructive sleep apnoea underwent either sibutramine (n = 22) or CPAP (n = 18) treatment for 1 yr. Sibutramine induced a 5.4+/-1.4 kg decrease in body weight compared to the CPAP group, in which no changes in anthropometric variables were observed. The CPAP treatment improved all sleep and respiratory variables, whereas sibutramine-induced weight loss improved only nocturnal arterial oxygen saturation profile. Only CPAP treatment improved night-time systolic and diastolic blood pressure and 24-h and daytime ambulatory diastolic blood pressure. Sibutramine-induced weight loss had no impact on indices of heart rate variability, whereas CPAP treatment increased daytime time domain indices. CPAP treatment for 1 yr had beneficial impacts on nocturnal breathing disturbances, and improved nocturnal oxygenation, night-time systolic and diastolic blood pressure, and daytime cardiac parasympathetic modulation. Sibutramine did not improve sleep-disordered breathing, systemic blood pressure or heart rate variability. There were no adverse effects, such as increment in blood pressure or arrhythmias, associated with this treatment regimen.

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.

Relationship between severity of nocturnal desaturation and adaptive thermogenesis: preliminary data of apneic patients tested in a whole-body indirect calorimetry chamber.

The purpose of this study was to investigate the possibility of a relationship between the severity of obstructive sleep apnea syndrome (OSAS) and adaptive thermogenesis. Daily energy expenditure (DEE) and sleeping metabolic rate (SMR) were measured in apneic and a priori nonapneic subjects who were tested in a whole-body indirect calorimetry chamber for 24 h. The apneic patients were diagnosed by nocturnal home oximetry to determine the percentage of total recording time spent below 90% arterial oxygen saturation (% TRT <90% SaO(2)). Reference equations established from body weight and age in nonapneic subjects were used to predict DEE and SMR in apneic patients. The predicted values of the apneic patients were then compared to their measured values. No significant difference was found between predicted and measured values in SMR nor in DEE. We observed a significant relationship between the severity of nocturnal desaturation and the difference between predicted and measured DEE in apneic patients (r = -0.74, P < 0.05) and a similar negative trend with SMR (r = -0.65, P = 0.08). These preliminary data suggest that a nocturnal hypoxia may influence adaptive thermogenesis in apneic patients and complicate their body weight regulation.

Impediment in upper airway stabilizing forces assessed by phrenic nerve stimulation in sleep apnea patients.

BACKGROUND: The forces developed during inspiration play a key role in determining upper airway stability and the occurrence of nocturnal breathing disorders. Phrenic nerve stimulation applied during wakefulness is a unique tool to assess Upper airway dynamic properties and to measure the overall mechanical effects of the inspiratory process on UA stability. OBJECTIVES: To compare the flow/pressure responses to inspiratory and expiratory twitches between sleep apnea subjects and normal subjects. METHODS: Inspiratory and expiratory twitches using magnetic nerve stimulation completed in eleven untreated sleep apnea subjects and ten normal subjects. RESULTS: In both groups, higher flow and pressure were reached during inspiratory twitches. The two groups showed no differences in expiratory twitch parameters. During inspiration, the pressure at which flow-limitation occurred was more negative in normals than in apneic subjects, but not reaching significance (p = 0.07). The relationship between pharyngeal pressure and flow adequately fitted with a polynomial regression model providing a measurement of upper airway critical pressure during twitch. This pressure significantly decreased in normals from expiratory to inspiratory twitches (-11.1 +/- 1.6 and -15.7 +/- 1.0 cm H2O respectively, 95% CI 1.6-7.6, p < 0.01), with no significant difference between the two measurements in apneic subjects. The inspiratory/expiratory difference in critical pressure was significantly correlated with the frequency of nocturnal breathing disorders. CONCLUSION: Inspiratory-related upper airway dilating forces are impeded in sleep apnea patients.

A new standardised and self-administered quality of life questionnaire specific to obstructive sleep apnoea.

BACKGROUND: A short, standardised, self-administered quality of life questionnaire would be a useful addition to the outcome measures in obstructive sleep apnoea (OSA) research. A study was therefore undertaken to validate a new OSA specific self-administered questionnaire (the Quebec Sleep Questionnaire, QSQ) for use in clinical trials. METHODS: This study followed a description of health related quality of life in patients with OSA. Construct validity and responsiveness were tested by comparing the baseline and changes in domain scores (daytime sleepiness, diurnal symptoms, nocturnal symptoms, emotions, social interactions) with those of questionnaires measuring related constructs (SF-36, Epworth Sleepiness Scale, Beck Depression Inventory, SCL-90, and Functional Outcomes in Sleep Questionnaire). RESULTS: Sixty patients (48 men) of mean (SD) age 55 (10) years participated in the study. In the analysis of the discriminative function of the questionnaire, moderate to high correlations were found between the scores in each domain of the QSQ and the corresponding questionnaires. In the analysis of its evaluative function significant differences were found in score changes between patients who were treated and those who were not, and moderate to high correlations were seen between changes in scores in the QSQ and changes in the corresponding questionnaires. Most of these correlations met the a priori predictions made regarding their magnitude. CONCLUSION: The QSQ is a valid measure of health related quality of life in patients with OSA and is sensitive to treatment induced changes.

[Health-related quality of life measurement: a critical reading guide]. / Qualité de vie liée à la santé: un guide de lecture.

INTRODUCTION: Quality of life is rarely assessed in the pulmonary function laboratory. Quality of life, or at least some of its domains, should be directly measured. STATE OF ART: Quality-of-life questionnaires developed according to established protocols can be very useful in clinical practice. In clinical studies, the choice of a questionnaire depends on its function (evaluative or discriminative) which should be supported by its measurement properties (validity, reliability, responsiveness). PERSPECTIVES AND CONCLUSIONS: The methodology of critical appraisal of an article about quality of life proposed in this reading guide are in keeping with the principles of evidence-based medicine.

Effects of continuous positive airway pressure on upper airway inspiratory dynamics in awake patients with sleep-disordered breathing.

Continuous positive airway pressure (CPAP) is the main treatment of the obstructive sleep apnoea syndrome (OSAS). We assessed its effects on the upper airway (UA) dynamics in response to bilateral anterior magnetic phrenic nerve stimulation (BAMPS) in 17 awake untreated OSAS patients (15 males; 52 +/- 7 years) whose effective CPAP (P(eff)) had been determined beforehand by a conventional titration sleep study. All twitch-related inspirations were flow-limited, flow first rising to a maximum (V(Imax)), then decreasing to a minimum (V(Imin)), and then increasing again (M-shaped pattern). Up to V(Imin), the relationship between driving pressure (P(d)) and flow (V) could adequately be fitted to a polynomial regression model (V = k(1)P(d) + k(2)P(d)(2); r(2) = 0.71-0.98, P < 0.0001). At atmospheric pressure V(Imax) was 700 +/- 377 ml s(-1), V(Imin) was 458 +/- 306 ml s(-1), k(1) was 154.5 +/- 63.9 ml s(-1) (cmH(2)O)(-1), and k(2) was 10.7 +/- 7.3 ml s(-1) (cmH(2)O)(-1). CPAP significantly increased V(Imax) and V(Imin) (peak values 1007 +/- 332 ml and 837 +/- 264 ml s(-1), respectively) as well as k(1) and k(2) (peak values 300.9 +/- 178.2 ml s(-1) (cmH(2)O)(-1) and 55.2 +/- 65.3 ml s(-1) (cmH(2)O)(-1), respectively). With increasing CPAP, k(1)/k(2) increased up to a peak value before decreasing. We defined as P(eff,stim) the CPAP value corresponding to the highest k(1)/k(2) value. P(eff,stim) was correlated with P(eff) (P(eff) = 7.0 +/- 2.0; P(eff,stim) = 6.4 +/- 2.6 cmH(2)O; r = 0.886; 95 % CI 0.696-0.960, P < 0.001). We conclude that CPAP improves UA dynamics in OSAS and that the therapeutic CPAP to apply can be predicted during wakefulness using BAMPS.

Usefulness of phrenic nerve stimulation to measure upper airway collapsibility in normal awake subjects.

Upper airway (UA) collapsibility can be characterized during sleep by looking at the changes in inspiratory flow limitation (IFL) with changing nasal pressure. IFL can be induced during wakefulness using phrenic nerve stimulation (PNS) applied during exclusive nasal breathing. The aim of the study was to evaluate the possibility of measuring UA critical pressure (Pcrit) in normal awaked subjects using electrical PNS (EPNS) or bilateral anterior magnetic phrenic stimulation (BAMPS). Instantaneous flow, esophageal (Peso) and mask pressures (Pmask), and genioglossal (GG) end-expiratory EMG activity were recorded in 13 normal subjects (4F, 9M) with randomly changing Pmask (0 to -20 cmH2O). For each trial, we examined the relationship between maximal inspiratory flow (Vtmax) of IFL twitches and the corresponding Pmask. Pcrit could be determined in 12 subjects (mean -33.5 +/- 16.3 cmH2O). No difference in Pcrit values was found between the EPNS and BAMPS methods but the strength of the Vtmax/Pmask relationship was higher with BAMPS. GG end-expiratory EMG activity increased with decreasing Pmask but no significant relationship was found between the slope of the GG end-expiratory EMG activity/Pmask relationship and Pcrit. We conclude that: (1) Pcrit can be measured during wakefulness in normal using PNS: (2) Pcrit measurements may be easier and more reliable with BAMPS than EPNS: and (3) Pcrit does not seem to be influenced by the pressure-related changes in GG end-expiratory EMG.

Independent validation of the Sleep Apnoea Quality of Life Index.

BACKGROUND: Obstructive sleep apnoea (OSA) affects important domains of quality of life which remain unexplored by conventional sleep recordings. The objective of this study was to examine the measurement properties (both discriminative and evaluative) of the Sleep Apnoea Quality of Life Index (SAQLI), a new OSA specific quality of life questionnaire. METHODS: Consecutive patients recently diagnosed with OSA completed a French version of the SAQLI twice over a 3 month period. Its construct validity and responsiveness were tested by comparing baseline and change scores obtained in each domain (symptoms, activities, emotions, social interactions) with those of questionnaires measuring related constructs (SF-36, Epworth Scale, Beck Depression Inventory, and Symptom Checklist 90). The symptoms scores were also correlated with physiological measures obtained at baseline polysomnographic recording. RESULTS: Forty seven patients (40 men) of mean (SD) age 53 (10) years and mean (SD) apnoea/hypopnoea index 38 (21) participated in the study. During the study period 33 of the 47 patients were treated for OSA (31 with nasal CPAP, one with uvulopalatopharyngoplasty, and one with an oral appliance). Moderate to high correlations were found between the scores in each domain of the SAQLI and the corresponding instruments. There were significant differences in change scores between patients who were treated and those who were not, moderate correlations between SAQLI change scores and changes in the corresponding instruments, and no correlation between the symptoms scores and the baseline nocturnal features. Most of these correlations met the a priori predictions made regarding their magnitude. CONCLUSION: The SAQLI has strong construct validity and is responsive to change in quality of life but has the disadvantage of having to be administered by an interviewer.

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".

Site of phrenic nerve stimulation-induced upper airway collapse: influence of expiratory time.

Electrical phrenic nerve stimulation (EPNS) applied at end expiration during exclusive nasal breathing can be used to characterize upper airway (UA) dynamics during wakefulness by dissociating phasic activation of UA and respiratory muscles. The UA level responsible for the EPNS-induced increase in UA resistance is unknown. The influence of the twitch expiratory timing (200 ms and 2 s) on UA resistance was studied in nine normal awake subjects by looking at instantaneous flow, esophageal and pharyngeal pressures, and genioglossal electromyogram (EMG) activity during EPNS at baseline and at -10 cmH(2)O. The majority of twitches had a flow-limited pattern. Twitches realized at 200 ms and 2 s did not differ in their maximum inspiratory flows, but esophageal pressure measured at maximum inspiratory flow was significantly less negative with late twitches (-6.6 +/- 2.7 and -5.0 +/- 3.0 cmH(2)O respectively, P = 0.04). Pharyngeal resistance was higher when twitches were realized at 2 s than at 200 ms (6.4 +/- 2.4 and 2.7 +/- 1.1 cmH(2)O x l(-1). s, respectively). EMG activity significant rose at peak esophageal pressure with a greater increase for late twitches. We conclude that twitch-induced UA collapse predominantly occurs at the pharyngeal level and that UA stability assessed by EPNS depends on the expiratory time at which twitches are performed.

Influence of genioglossus tonic activity on upper airway dynamics assessed by phrenic nerve stimulation.

Upper airway (UA) dynamics can be evaluated during wakefulness by using electrical phrenic nerve stimulation (EPNS) applied at end-expiration during exclusive nasal breathing by dissociating twitch flow and phasic activation of UA muscles. This technique can be used to quantify the influence of nonphasic electromyographic (EMG) activity on UA dynamics. UA dynamics was characterized by using EPNS when increasing tonic EMG activity with CO(2) stimulation in six normal awake subjects. Instantaneous flow, esophageal and nasopharyngeal pressures, and genioglossal EMG activity were recorded during EPNS at baseline and during CO(2) ventilatory stimulation. The proportion of twitches presenting an inspiratory-flow limitation pattern decreased from 100% at baseline to 78.7 +/- 21.4% (P = 10(-4)) during CO(2) rebreathing. During CO(2) stimuli, maximal inspiratory twitch flow (VI(max)) of flow-limited twitches significantly rose, with the driving pressure at which flow limitation occurred being more negative. For the group as a whole, the increase in VI(max) and the decrease in pressure were significantly correlated with the rise in end-expiratory EMG activity. UA stability assessed by EPNS is dramatically modified during CO(2) ventilatory stimulation. Changes in tonic genioglossus EMG activity significantly contribute to the improvement in UA stability.

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.

Assessment of upper airway dynamics in awake patients with sleep apnea using phrenic nerve stimulation.

Phrenic nerve stimulation can reproduce during wakefulness the dissociation between upper airway and inspiratory muscles that is associated with obstructive sleep-related breathing disorders. This could provide a useful management tool in the study of passive upper airway (UA) dynamics during wakefulness in patients with the obstructive sleep apnea-hypopnea syndrome (OSAHS). To assess the feasibility of the technique in this setting, we studied the dynamics of diaphragm twitch-associated inspiratory flow in eight patients with OSAHS. Cervical magnetic stimulation (CMS) and bilateral anterior magnetic phrenic stimulation (BAMPS) were applied at end-expiration during exclusive nasal breathing. Electrical phrenic nerve stimulation (ES) proved not feasible. The driving pressure and the respiratory resistance at peak twitch esophageal pressure obtained at maximal stimulation intensity were significantly higher with BAMPS than with CMS. A twitch-flow limitation pattern was observed in seven of eight subjects; VI(max) values of flow-limited twitches obtained at 100% stimulation intensity was 0.81 +/- 0.5 L/s with BAMPS and 0.87 +/- 0.5 L/s with CMS (p = 0.4). The number of flow-limited BAMPS twitches dropped from an average 77.5% to 18.4% with nasal continuous positive airway pressure (CPAP) levels corresponding to the patient's home treatment. We conclude that (1) BAMPS is potentially a useful tool to evaluate the dynamics of flow through the passive UA in awake OSAHS patients, (2) BAMPS may be superior to CMS in evaluating UA properties in OSAHS.

[Physiopathology of sleep respiratory obstruction anomalies. Experimental methods and practical applications]. / Physiopathologie des anomalies respiratoires obstructives du sommeil. Méthodes expérimentales et applications pratiques.

Recent progress in the physiology of the upper airways has led to significant advances in evaluating the dynamics of upper airway occlusion during sleep. Measuring the collapsibility of the upper airways and localizing the site of obstruction should theoretically lead to efficacious non-mechanical treatment and enable selection of patients susceptible of benefiting from surgical procedures. From a diagnostic point of view, fluctuations in the nasal pressure curve appear to give more precise information on ventilatory changes and their association with disrupted sleep pattern than conventional parameters such as thermistance signals or induction plethysmography. Again, from a pathophysiological point of view, little is known about the role or tissue inflammation and repeated upper airway trauma in the transition from simple snoring to sleep apnea syndrome. Current studies lead to the conclusion that the dilatroy muscles of the upper airways in the apneic subject are the target for adaptive trophic, immunohistochemical and metabolic phenomena in response to stimulation comparable to training against resistance. Although there is no evidence that sleep affects neuromuscular activity in apneic subjects, the disappearance of compensatory hyperactivity on awakening and the reduction of muscle contraction efficacy (transmission of the dilatory force to soft tissues) observed in patients may explain the greater instability of the upper airways characteristic of sleep apnea syndrome.