Respiratory patterns during sleep in Down's syndrome:importance of central apnoeas

Obstructive sleep apnoea episodes have been reported repeatedly in Down's syndrome (DS) patients as a consequence of the presence of predisposing malformations or intercurrent pathology of the upper airways. There are no data on respiratory patterns of uncomplicated Down's syndrome subjects. In order to evaluate the eventual effects of central nervous system (CNS) impairment on respiration in DS, we studied the respiratory patterns during sleep of a group of 10 DS subjects, aged 8.6-32.2 y, without relevant upper airway pathology. In order to control the possible effects of sleep structure and mental retardation on the results obtained, we compared the findings in DS with those obtained from a group formed by subjects affected by fragile X syndrome (six males and one female, aged 10.0-15.42 y) another genetically determined type of mental retardation. Sleep structure was similar in both groups; however, DS subjects showed significantly higher indices of central sleep apnoea and of oxygen desaturation than fragile X patients (P < 0.005). As far as DS individuals were considered, a significant preponderance of central, as opposed to obstructive, sleep apnoeas was found (89.4% vs. 9.4%, respectively; 1.2% were mixed) which showed a significant age-related increase. Central respiratory pauses were mostly preceded by sighs, which occurred more frequently during sleep stages 1 and REM, and were often organized in long sequences of periodic-like breathing. During REM sleep, they were less frequently preceded by sighs and by body movements than during NREM sleep. Obstructive sleep apnoeas occurred more often during REM sleep and were more rarely preceded by sighs or by body movements. Both central and obstructive apnoeas induced significant oxygen desaturation in 50-69.6%. Sleep structure was not significantly modified by apnoeas and oxygen desaturation. We hypothesize that the increase in central sleep apnoeas is related to a dysfunction of the central respiratory control at a brainstem level in DS.     

Evaluation of diaphragmatic fatigue in obstructive sleep apnoeas during non-REM sleep

BACKGROUND: Resistive load applied to the airways may induce diaphragmatic fatigue, and hypoxaemia has been shown to predispose to the development of fatigue. Inspiratory muscle fatigue may occur in patients with obstructive sleep apnoea syndrome (OSAS), as these patients repetitively develop both inspiratory loading and hypoxaemia. The results of previous studies on this topic are inconclusive, probably because of the methodological approaches used. METHODS: Six obese patients with OSAS underwent a polysomnographic study. The diaphragmatic pressure time index (PTI) was evaluated as an indicator of diaphragmatic contraction, and the mean frequency of the diaphragmatic electromyogram power spectrum (Fm) and the maximum relaxation rate of transdiaphragmatic pressure (MRR) as indices of a fatiguing diaphragm. A total of 119 randomly selected apnoeas (each including 5-13 occluded efforts) were analysed throughout the night in non-REM sleep to assess possible muscle fatigue due to the high pressure generation in each apnoea. A breath-by-breath within-apnoea analysis was performed on the first three pre-apnoeic breaths, on all the occluded efforts, and on the first three unoccluded breaths following the apnoea interruption. Possible fatigue development due to the cumulative effect of apnoeas over the night was also evaluated. RESULTS: A progressive increase of Fm and MRR was found during the obstructive phase in all the subjects in the within-apnoea analysis. The overnight analysis did not show a reduction in either PTI, Fm, or MRR secondary to recurrent upper airway obstruction during the night. CONCLUSIONS: No evidence of diaphragmatic fatigue or impaired diaphragmatic contraction was found either within each apnoea or throughout the whole night, despite the generation of high PTI values during the apnoeic occluded phases. It is concluded that diaphragmatic fatigue does not occur in OSAS during non-REM sleep.     

Craniofacial abnormalities in sleep apnoea syndrome

Each year, 15 transvestibular transseptal transsphenoidal hypophysectomies are performed in Lausanne. The aim of the study was to determine the complications rate of our procedure and their influence on the life quality of patients. Questionnaires were sent to 178 patients, operated between 1984 and 1995. 125 questionnaires were returned. Out of those, 73 patients accepted to undergo a control rhinoscopy. The most frequent complains were nasal obstruction and crusting (38% each), whistling while breathing through the nose (12%), and stuffiness of the upper lip or teeth (7%). Endoscopically, we detected an anterior septal perforation in 10 cases (13.7%), 8 (80%) of which were symptomatic and a posterior septal perforation in 6 cases, all of them being asymptomatic. Finally, 36% of the patients had no complains and 19% of them had an improvement of respiration after the operation. Of the whole series of 178 patients, only 5% had complications requiring an ENT follow-up for longer than 6 months after having been operated.     

Electrophysiological brainstem investigations in obstructive sleep apnoea syndrome

In children with steroid-resistant nephrotic syndrome (SRNS) hyperlipidaemia may in the long term be associated with progressive renal insufficiency and increased risk of coronary heart disease. We have assessed the efficacy and tolerability of diet prior to and in combination with a hydroxymethylglutaryl CoA reductase inhibitor, simvastatin, in seven children with SRNS with a mean age of 8 years (range 1.8-16.3 years). Dietary advice to maintain adequate energy and protein intakes with reduced saturated fat and cholesterol intake had little impact on lipid levels pre treatment (mean reduction in cholesterol 1 mmol/l, triglyceride 1.1 mmol/l) but was maintained throughout the study duration. The mean cholesterol and triglyceride concentrations pre treatment were 12.1 +/- 2 (SEM) mmol/l and 8 +/- 2.1 (SEM) mmol/l, respectively. On a median simvastatin dose of 10 mg/day (range 5-40 mg) there was a 41% reduction in cholesterol to 6.6 +/- 0.77 (SEM) mmol/l and a 44% reduction in triglyceride to 3.9 +/- 1.38 (SEM) mmol/l at 6 months which was sustained at 12 months in five patients. The drug was well tolerated with no clinical side effects being noted. Over 6 months the mean plasma albumin concentrations increased from 18.2 +/- 1.26 (SEM) g/l to 23 +/- 2.51 (SEM) g/l, accounted for by three patients (1 complete remission, 1 partial remission, 1 end-stage renal failure). Plasma creatinine concentrations remained stable in five patients with two having progressive chronic renal failure. Growth parameters for both weight and height were maintained. Simvastatin has a beneficial effect on abnormal lipid levels in SRNS but the effectiveness of long-term therapy needs to be evaluated.     

Microarousals in patients with sleep apnoea/hypopnoea syndrome

As medical schools begin to implement their new curricula under the guidance of Tomorrow's Doctors, the authors wish to raise some discussion on the form and content of the special study module (SSM) component. In order to do this they put forward in this paper proposals for an SSM in Medicine and Literature. This course has been designed jointly and will be run concurrently in three Scottish medical schools: Glasgow, Aberdeen and Dundee. Arguments for the course's acceptability to faculties of medicine and to students are discussed and its inclusion in the curriculum in terms of its educational impact, skills training, effect on personal development and broadening of the student's perspective are justified. The course structure, content and assessment procedures are described and a reading list proposed. The General Medical Council points out that SSMs should be seen as opportunities for innovation and this course demands a different educational approach from the standard objectives-led approach of most medical education. A process-led model is more appropriate as it stresses the way that students develop while taking the course rather than the end point reached at its finish.     

New frontiers in the management of obstructive sleep apnoea syndrome

BACKGROUND: To report the dynamic magnetic resonance (MR) imaging findings of hepatolithiasis. METHODS: Dynamic MR images (fast spoiled gradient echo sequence with intravenous injection of gadopentate dimeglumine) and computed tomography, cholangiography, or angiography of nine patients with hepatolithiasis are analyzed. RESULTS: All affected hepatic segments showed atrophic changes and contained dilated intrahepatic ducts. These segments showed either iso- or hypointensity on T1-weighted imaging and hyperintensity on T2-weighted imaging. Preferential enhancement was noted throughout all phases of the dynamic study and persisted to delayed T1-weighted imaging in seven patients. In the last two patients, severe atrophic changes made evaluating signal intensity differences and enhancement patterns difficult. CONCLUSION: In addition to intrahepatic stones and biliary dilatation, segmental atrophy, signal intensity differences, and preferential and persistent enhancement are important MR findings of hepatolithiasis.     

Impairment of muscle energy metabolism in patients with sleep apnoea syndrome

Impairment of muscle energy metabolism has been demonstrated in normal subjects with chronic hypoxaemia (altitude chronic respiratory failure). The purpose of this study was to verify the hypothesis that a comparable condition could develop in patients with sleep apnoea syndrome (SAS), considering that they are exposed to prolonged and repeated hypoxaemia periods. Muscle metabolism was assessed in 11 patients with SAS performing a maximal effort on cycloergometer. In comparison with normal subjects, SAS patients reached lower maximal loads [144 +/- 7 vs. 182 +/- 10 W (P < 0.005)] and lower peak oxygen uptakes [26.4 +/- 1.2 vs 33.2 +/- 1.4 ml kg-1 min-1 (P < 0.005)]. Abnormal metabolic features were found: maximal blood lactate concentration was significantly lower than in normal subjects [0.034 +/- 0.004 vs. 0.044 +/- 0.002 mmol l-1 W-1 (P < 0.05)]; and lactate elimination rate, calculated during a 30-min recovery period, was reduced [0.127 +/- 0.017 vs, 0.175 +/- 0.014 mmol l-1 min-1 (P < 0.025)]. The extent of these anomalies correlated with the severity of SAS. The patients also showed higher maximal diastolic blood pressures than normal subjects [104 +/- 5 vs. 92 +/- 4 mmHg (P < 0.05)]. These results can be interpreted as indications of an impairment of muscle energy metabolism in patients with SAS. Decrease in maximum blood lactate concentration suggests an impairment of glycolytic metabolism, while decrease in the rate of lactate elimination indicates a defect in oxidative metabolism. Since no respiratory pathology apart from SAS was found in this group of patients, it seems legitimate to link the genesis of these impairments to repeated bouts of nocturnal hypoxaemia.     

Dentistry''s role in obstructive sleep apnoea. Review and case report

Percentage dose at the surface and at 1 mm depth for megavoltage photon beams are increased through the influence of block trays. This represents a decrease in skin sparing properties for both the epidermal and dermal layers. The increase in percentage dose varies with type and thickness of block tray material. At 6MVp, 20cm x 20cm field size, the percentage surface dose is 26%, 26.5%, 33% and 35% for open, steel honeycomb tray, 6mm perspex and 10 mm perspex block trays respectively. At 1 mm depth these values are 52%, 52.5%, 61%, 60% respectively. A similar effect is seen at higher energies. Results show that care should be taken when selecting an appropriate block tray if skin sparing is of importance.     

Screening obstructive sleep apnoea syndrome by home videotape recording in children

Overnight polysomnography (PSG) has been used to diagnose and assess the severity of obstructive sleep apnoea syndrome (OSAS) in children. The aim of this study was to determine whether home video-recording of children during sleep may be used for screening OSAS. In 58 children suspected of having OSAS, PSG results were compared with the corresponding analyses of 30 min video-recordings of each child sleeping at home. The video-recordings were evaluated by: 1) overall investigator's clinical judgement; and 2) a scoring system based on noisy breathing, movements, walking episodes, apnoea, chest retractions and mouth breathing. PSG results were highly correlated with the video test results, with agreement in 49 out of 58 (84%). In 36 of the 58 children, the PSG was abnormal compared with 41 out of 58 abnormal video tests. The sensitivity of the overall investigator judgement of video test was 94% (34 out of 36) and the specificity 68% (15 out of 22). Video scores > 10 were highly predictive of OSAS, whilst scores < 5 were associated with normality. Using a stepwise logistic regression analysis, each of the scoring variables was tested against the PSG results and an equation was formulated for predicting PSG by the video test. The equation predicted PSG results in 49 out of 58 (84%) cases. Thirty minutes of home video-recordings during sleep is a reliable screening method for obstructive sleep apnoea syndrome in children. This technique may, thus, improve patient selection for polysomnography.     

Long-term efficacy of dietary weight loss in sleep apnoea/hypopnoea syndrome

Weight loss is associated with clinical improvement in sleep apnoea/ hypopnoea syndrome (SAHS). The aim of this study was to ascertain whether the therapeutic efficacy of dietary weight loss is maintained in the long-term. From a total of 216 overweight SAHS patients treated by only a weight reduction programme, 24 cured by this method (apnoea/hypopnoea index (AHI) at diagnosis 443+/-27.8, after weight loss 3+/-3.1) were re-evaluated after a mean (+/-SD) period of 94.3+/-27.4 months post-cure. No correlation was found between changes in AHI and body mass index experienced by each patient in the two phases of the study (diagnosis to cure and cure to long-term follow-up), r=0.29, p=0.156, demonstrating a marked intra-individual variability. Six of the 13 patients who maintained their weight presented recurrence of SAHS (AHI 40.5+/-24.1) as did eight of the 11 who had regained weight (AHI 44.3+/-23.). Weight maintenance was more frequent among patients who had continued to attend periodic appointments, 10/11 versus 3/13 (p<0.001). In conclusion, weight-loss efficacy is maintained in the long-term in some sleep apnoea/hypopnoea syndrome patients. This study indicates the need for periodic follow-up of these patients as a reinforcement for weight maintenance and for early detection of the reappearance of sleep apnoea/hypopnoea syndrome.     

Nocturnal evolution of respiratory effort in obstructive sleep apnoea syndrome: influence on arousal threshold

It has been recently described that the overnight increase in maximal end-apnoeic oesophageal pressure (P(oes,max)), considered as an index of the arousal threshold to occlusion, mostly contributes to apnoea lengthening during the night. However, the rise in apnoea duration could also be caused by changes in hypoxaemia, chemosensitivity and upper airway resistance. To better define the relative contributions of each of these factors, we examined the recordings of nine patients. Before apnoea, the mean pulmonary resistance at peak inspiratory flow (RPIF) was computed. During apnoea, all swings in oesophageal pressure (P(oes)) were measured to define the P(oes,max), the increase from the minimum to the maximum (deltaP(oes)), the rate of increase in P(oes) (RP(oes)) and the P(oes) at the first occluded breath (P(oes,1)). A gradual and significant increase in apnoea duration (p=0.02), P(oes,max) (p=0.02) and deltaP(oes) (p=0.006) was present across the night without any changes in oxygen saturation, RPIF, and P(oes,1). The slope of increase in P(oes,max), apnoea duration and deltaP(oes) was correlated with the apnoea/hypopnoea index. We conclude that in obstructive sleep apnoea, the nocturnal rise in apnoea duration is attributable more to an increase in the arousal threshold related to apnoea recurrence than to changes in chemosensitivity and upper airway resistance.     

Control of breathing in obstructive sleep apnoea and in patients with the overlap syndrome

In some patients obstructive sleep apnoea (OSA) may co-exist with chronic obstructive pulmonary disease (COPD) and respiratory failure; the so-called "overlap syndrome". Obstructive, hypercapnic patients have both blunted ventilatory and mouth occlusion pressure responses during CO2 stimulation. The purpose of this study was to compare the pattern of breathing and CO2 response between OSA patients and those with the overlap syndrome. Twenty obese men with OSA and normal lung function (Group A), 11 obese men with overlap syndrome (Group B) and 13 healthy nonobese subjects (Group C) were examined. Lung function tests, breathing pattern, mouth occlusion pressure (P0.2) at rest, and respiratory responses during CO2 rebreathing were investigated. Diagnosis of OSA was established by standard polysomnography. There were no statistical differences between Groups A and B in apnoea & hypopnoea index (62 vs 54), mean arterial oxygen saturation (SaO2) during sleep (85 vs 84%) and in body mass index (BMI) 34.3 vs 36.3 kg.m-2. Minute ventilation, mean inspiratory flow and P0.2 at rest were increased in both groups of patients in comparison to controls. During CO2 rebreathing, group A had normal ventilatory and P0.2 responses, similar to controls, (2.7 +/- 1.1 vs 2.1 +/- 0.4 l.min-1.mmHg-1 and 0.7 +/- 0.3 vs 0.71 +/- 0.25 cmH2O.mmHg-1, respectively). However, Group B had significantly decreased ventilatory and P0.2 responses to CO2 (0.71 +/- 0.23 l.min-1.mmHg-1 and 0.34 +/- 0.17 cmH2O.mmHg-1, respectively). This comparison showed that patients with OSA had normal CO2 response when awake, whereas those with overlap syndrome had diminished CO2 response when awake.(ABSTRACT TRUNCATED AT 250 WORDS)     

Propensity for sleep and diurnal somnolence in the course of sleep apnea syndrome

We have compared the proliferative potential of IELs isolated from rat colon (CIEL) and small bowel (SBIEL), and compared this with that observed using spleen lymphocytes. Unless additional irradiated spleen cells were added as a source of accessory cells, both IEL populations show poor proliferation in response to Con A stimulation. The CD4/CD8 ratio in spleen, SBIEL and CIEL was markedly different (3:1, 1:3, and 1:1, respectively). Cells expressing surface markers characteristic of macrophages were not routinely found in SBIELs. Both IEL preparations inhibited spleen cell proliferation in response to Con A or immobilized anti-CD3, and produced a soluble factor(s) capable of causing similar inhibition. For CIEL this inhibition was dependent upon a proliferation-independent but cell-cell contact dependent event.     

Natural evolution of moderate sleep apnoea syndrome: significant progression over a mean of 17 months

BACKGROUND: Obstructive sleep apnoea (OSA) is associated with increased morbidity and mortality. It has remained unclear whether or not it is progressive. The evolution of OSA was examined in a retrospective case note study of 55 unselected patients of mean (SD) age 55.8 (10) years with mild to moderate disease untreated by interventional methods such as continuous positive airway pressure (CPAP) or surgery. Correlations between clinical and functional variables, upper airway anatomy, and change in disease severity were also investigated. METHODS: Patients underwent full polysomnography on two occasions (T0 and Tx) at a mean interval of 77 (50) weeks (range 17-229). In addition, upper airway imaging with computed tomographic scanning or cephalometry had been performed in 43 patients at T0. Morbidity before, during, and after the study period was assessed by questionnaire, as was smoking history and alcohol and sedative intake. RESULTS: The apnoea hypopnoea index (AHI) for the group as a whole increased from 21.8 (11.5) to 33.4 (21.3) (p = 0.0001). Using a 25% change in AHI to divide patients into worsened, stable, and improved groups showed that, although most of the patients deteriorated, 25 patients improved or remained stable. The change in AHI was not correlated with body mass index which remained stable at 29.7 (5.4) kg/m2 versus 29.7 (5.6) kg/m2. There was a trend for apnoea duration to increase. No patient reported increased alcohol consumption and only one patient reported increased use of sedatives between T0 and Tx. No correlation was found between change in AHI and age, time between recordings, anatomical measurements of the upper airway, respiratory function, oximetry, or arterial blood gas tensions. Total cardiovascular and cerebrovascular morbidity was high: hypertension (26 patients, 46%), cardiac arrhythmia (17 patients, 33%), angina (12 patients, 23%), myocardial infarction (10 patients, 19%), and stroke (10 patients, 19%). Twenty nine patients (52%) were prescribed CPAP after Tx, two of whom went on to have maxillofacial surgery. These 29 treated patients had significantly higher values of AHI at T0 and Tx and greater change in AHI than the untreated patients. CONCLUSIONS: This study shows that mild to moderate OSA has a tendency to worsen in the absence of significant weight gain and that upper airway anatomy and clinical variables do not appear to be useful in predicting progression. It follows that mild to moderate OSA justifies systematic follow up. Deterioration in AHI over a mean of 17 months led to interventional treatment in over 50% of patients in the study.     

Goitre: a cause of obstructive sleep apnoea in euthyroid patients

While hypothyroidism is considered to predispose to obstructive sleep apnoea (OSA), the presence of a goitre itself is not a recognized cause of OSA. We present the cases of two euthyroid patients with large goitres and clinical evidence of OSA, whose OSA symptoms significantly improved following partial thyroidectomy. This finding suggests that the goitre contributed to their symptoms.     

Central sleep apnoea in Arnold-Chiari malformation: evidence of pathophysiological heterogeneity

We report on the case of two young patients with type I Arnold-Chiari malformation (ACM), as revealed by a central sleep apnoea (CSA) syndrome without any other neurological defect. Case 1 was a 14-yr-old male patient, who developed severe alveolar hypoventilation and needed long-term mechanical ventilation via a tracheostomy. Case 2 was a 39-yr-old male patient, who developed features suggestive of sleep apnoea and responded to nasal continuous positive airway pressure ventilation despite the central type of apnoeas. These two cases illustrate the different pathophysiological mechanisms involved in CSA, namely a blunted chemical drive (in hypercapnic patients) and an increased chemical drive, which destabilizes the breathing pattern during sleep (in normo/hypocapnic patients). Central sleep apnoea can be the initial manifestation of Arnold-Chiari malformation and can lead to a life-threatening condition.