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R R Grunstein

Publications and source records attributed to R R Grunstein.

At least 19 recordsLinked to original sources
PubMed1995

Impact of self-reported sleep-breathing disturbances on psychosocial performance in the Swedish Obese Subjects (SOS) Study.

Patients with severe obesity commonly have obstructive sleep apnea (OSA). In order to determine the impact of OSA on psychosocial morbidity in severe obesity, subjects enrolled in the Swedish Obese Subjects (SOS) Study were classified into two subgroups based on questionnaire data: one group with a high likelihood and one with a low likelihood of OSA. These groups were contrasted and multivariable analysis was used to examine whether OSA had independent effects on divorce rate, sick leave, work performance, income and self-estimated general health after adjustment for obesity, fat distribution, alcohol, smoking, medications and coexisting medical conditions. A high likelihood of OSA was identified in 338 men and 155 women, compared with 216 men and 481 women who had a low likelihood of OSA. Men with OSA were identical in age to men without OSA and had slightly higher levels of visceral fat (p = 0.01), but were similar in most psychosocial variables except self-perceived general health. Women with OSA were identical in age and visceral fat mass to women without OSA, but were characterized by a higher rate of impaired work performance, sick leave and divorce. When frequent sleepiness was used as an additional discriminator between OSA and non-OSA groups, marked differences in psychosocial morbidity were observed. Multivariable analysis revealed either OSA or frequent sleepiness or both to be independent predictors of amount of sick leave, worse self-rated general health, impaired work performance and divorce rate. Therefore OSA, measured by self report, is an important independent predictor of psychosocial morbidity in subjects with severe obesity.

Body Mass Index↗
PubMed1995

Sleep-related breathing disorders. 5. Nasal continuous positive airway pressure treatment for obstructive sleep apnoea.

CPAP should be considered the first line of treatment in patients with moderate to severe obstructive sleep apnoea. In our centre in Sydney this generally means patients with more than 20 apnoea/hypopnoeas per hour with repeated dips in oxyhaemoglobin saturation and usually some symptomatology. Despite this first line role of nasal CPAP, recent objective studies question whether earlier enthusiastic reports on adherence to CPAP are correct. The role of technical innovations in new CPAP machines in improving usage remains to be tested. The "drop out" rate from physician selection for a CPAP trial to highly compliant user is certainly more than 50% of patients. What happens to these patients? Data from some studies suggest that surgical treatments are used, at least in the USA, but in all probability many of these patients remain untreated. The challenge in the next decade is either to improve CPAP devices to increase usage in this group or to develop other treatment options. The role of intensive inhospital "acclimatisation" to CPAP also has yet to be objectively tested. It is unclear whether "intelligent" CPAP will make huge inroads in increasing the number of patients who accept CPAP trials, prescriptions, or compliance. It will have minimal impact on patients with mask problems or claustrophobia or those who feel that CPAP is inconvenient. There is a high likelihood that it will reduce technologist workload during CPAP titration studies. "Intelligent" CPAP may help to reduce total overnight mouth leakage and therefore reduce nasal side effects. The current expense of developing such devices will mean that they are unlikely to supersede much cheaper standard "one pressure" CPAP machines in the next few years.

Female↗
PubMed1995

Impact of obstructive sleep apnea and sleepiness on metabolic and cardiovascular risk factors in the Swedish Obese Subjects (SOS) Study.

OBJECTIVE: To determine if obstructive sleep apnea (OSA) is independently associated with cardiovascular risk factors and health status in subjects with severe obesity. DESIGN: Cross-sectional analysis of epidemiological data. SUBJECTS: 3034 participants in the Swedish Obese Subjects (SOS) Cohort. Two sub-groups with a high and low likelihood for OSA based on questionnaire data were analysed in detail. MEASUREMENTS: General health questionnaires, anthropometric data including CT calibrated values for body fat distribution and lean body mass, blood pressure, fasting insulin, triglycerides, cholesterol, uric acid, glucose. RESULTS: Self-reported loud snoring and observed breathing pauses (high likelihood of OSA) was associated with increased frequency of WHO Grade 4 dyspnea, admissions to hospital with chest pain, myocardial infarction, blood pressure, fasting insulin, fasting triglyceride (women only), uric acid (women only) after adjustment for body fat distribution and other potential confounders. CONCLUSION: OSA may be another medical disorder which contributes to morbidity in severe obesity and is associated with some of the components of the metabolic syndrome observed in the centrally obese.

Adult↗
PubMed1995

Large lungs and growth hormone: an increased alveolar number?

Previous physiological studies suggest that increased lung growth in patients with acromegaly is associated with either a normal or above normal pulmonary transfer factor. These findings can be interpreted to suggest either alveolar hypertrophy or hyperplasia as the mechanism for lung growth in this condition. Since the ventilated airspaces retain normal elastic properties, we wanted to determine whether the mechanism for lung growth in acromegaly is the result of an increased alveolar number rather than size. Measurements of pulmonary distensibility (K) (an index of alveolar size), elastic recoil, single-breath carbon monoxide transfer factor and carbon monoxide transfer coefficient (KCO), pulmonary capillary blood volume and alveolar membrane diffusing capacity, together with chest width, were compared in nonsmoking, acromegalic and normal men and women, with and without an increased lung size. Pulmonary transfer factor was normal for all groups studied, regardless of lung size. However, KCO was inversely related to total lung capacity (% predicted) for all subjects and KCO (% predicted) was inversely related to chest width in men. Pulmonary capillary blood volume (% predicted) was inversely related to total lung capacity (% predicted) for subjects with large lungs. Pulmonary distensibility (K), membrane diffusing capacity and elastic recoil were within the normal range. These findings suggest normal alveolar size, alveolar membrane surface area and mechanical function in subjects with large lungs. They also suggest that KCO may not be a reliable guide to the interpretation of the mechanism of lung growth in individuals with disproportionately large lungs, and may be reduced because not all the alveoli are perfused. The normal values for pulmonary distensibility found in all our individuals with large lungs, including acromegalics, suggest that lung growth has been achieved by an increased alveolar number rather than size. However, morphometric studies of the lungs of nonsmoking, acromegalic subjects without lung disease, are required to substantiate this finding.

Acromegaly↗
PubMed1995

Pulmonary hypertension in obstructive sleep apnoea.

To determine the frequency and correlates of pulmonary hypertension in sleep-disordered breathing, pulmonary artery pressure, lung function and arterial blood gases were measured in 100 consecutive patients with obstructive sleep apnoea (OSA) (respiratory disturbance index (RDI) of > 20 episodes.h-1). Twenty six of the patients had significant chronic airflow limitation (CAL). Overall, 42% of patients had awake pulmonary artery pressure > 20 mmHg. Patients with pulmonary hypertension were older, had higher arterial carbon dioxide tension (PaCO2), lower arterial oxygen tension (PaO2) and lower forced expiratory volume in one second (FEV1) values compared with normotensive patients. Pao2, PaCO2 and FEV1 were correlated with the levels of pulmonary artery pressure (correlation coefficient (r2) 0.50, 0.46 and 0.49, respectively). These three factors combined could explain 33% of the variability in pulmonary artery pressure. Six patients had pulmonary hypertension despite a PaO2 in excess of 10.7 kPa (80 mmHg). We conclude that pulmonary hypertension is common in patients with moderate and severe sleep apnoea, especially those with coexisting chronic airflow limitation. The presence of daytime hypoxaemia is not a prerequisite in the development of pulmonary hypertension in these patients.

Case-Control Studies↗
PubMed1994

Effect of octreotide, a somatostatin analog, on sleep apnea in patients with acromegaly.

OBJECTIVE: To determine the effects of octreotide, a somatostatin analog, on the severity of sleep apnea and on growth hormone levels in patients with acromegaly. DESIGN: Open-label, prospective study. SETTING: Tertiary referral hospital. PATIENTS: 19 patients with active acromegaly. INTERVENTION: Octreotide in a 6-month, stepwise incremental dosage. MEASUREMENTS: Sleep studies and indices of hormonal activity (levels of insulin-like growth factor 1 [IGF-1] and growth hormone). RESULTS: A 50% decrease occurred in the respiratory disturbance index (baseline compared with 6 months, 39 events/h compared with 19 events/h; P = 0.0002), and a 40% decrease occurred in total apnea time (27.6% of total sleep time compared with 15.1%; P = 0.001). Indices of oxygen desaturation, sleep quality, and subjective sleepiness improved after 6 months of octreotide. A parallel decrease was noted in mean levels of growth hormone (40.0 micrograms/L compared with 9.1 micrograms/L; P = 0.003) and IGF-1 (107 nmol/L compared with 47 nmol/L; P = 0.0001). However, no correlation was noted between the decrease in the total amount of sleep time spent in apnea and the decrease in growth hormone levels (rho = -0.35; P > 0.2). The residual respiratory disturbance index after 6 months of treatment was similar in patients who improved, regardless of whether or not biochemical remission (IGF-1 < 35 nmol/L) occurred. CONCLUSIONS: Improvement in indices of sleep apnea severity occurs in association with octreotide treatment in patients with sleep apnea and acromegaly. However, sleep apnea may either persist despite normalization of growth hormone levels or may improve markedly even if there is only partial biochemical remission.

Acromegaly↗
PubMed1994

Sleep-disordered breathing and obesity.

Recent epidemiological data indicate that obstructive sleep apnoea (OSA) and related conditions are extremely common in the middle-aged population. Obesity is an important aetiological factor in sleep-disordered breathing with a multifactorial role in the pathogenesis of upper airway occlusion. One extreme of the spectrum of sleep-disordered breathing is obesity-hypoventilation syndrome (one type of OSA with awake respiratory failure). Sleep-disordered breathing has a number of clinical consequences, including excess cardiovascular morbidity. Obesity is an important confounder of this association. Treatment of these disorders has been revolutionized by the use of nasal continuous positive airway pressure (CPAP). Weight reduction reduces apnoea severity but is not curative in most obese patients with sleep apnoea.

Body Weight↗
PubMed1994

Effect of short-term hormone replacement in the treatment of obstructive sleep apnoea in postmenopausal women.

BACKGROUND: Women appear to be increasingly susceptible to snoring and sleep disordered breathing after the menopause. This observation, coupled with the considerable sex difference in sleep apnoea, may be explained on the basis of a protective effect of female hormones. This study was carried out to determine whether hormone replacement therapy has a role in the management of obstructive sleep apnoea in postmenopausal women. METHODS: The effect of short-term (mean (SE) 50 (3) days) hormone replacement therapy with either oestrogen alone or in combination with progesterone on sleep disordered breathing was investigated in 15 postmenopausal women with moderate obstructive sleep apnoea. The effect of treatment on the ventilatory response to hypoxia and hypercapnia was assessed in 10 patients. RESULTS: There was no reduction in the clinical severity of obstructive sleep apnoea after hormone treatment despite an increase in the serum oestrogen level from 172 (23) to 322 (33) pmol/l. There was a small but clinically insignificant reduction in the apnoea/hypopnoea index during REM sleep from 58 (6) to 47 (7). There was no difference in response between the oestrogen only group and the oestrogen plus progesterone group. Hypercapnic ventilatory responsiveness did not change with hormone treatment, but an change with hormone treatment, but an increase in hypoxic ventilatory responsiveness was observed. CONCLUSIONS: These data indicate that short-term hormone replacement is unlikely to have an effective role in the clinical management of postmenopausal women with obstructive sleep apnoea. The observed reduction in the apnoea/hypopnoea index during REM sleep, however, suggests that longer term treatment, or the use of higher doses, may have an effect.

Drug Therapy, Combination↗
PubMed1994

Effect of testosterone administration on upper airway collapsibility during sleep.

Testosterone is thought to play a role in the pathogenesis of obstructive sleep apnea (OSA), but the mechanism is unclear. We present a case in which testosterone administration induced or exacerbated OSA in a 13-year-old male. We demonstrated that exacerbation of OSA by testosterone was associated with an increase in upper airway collapsibility during sleep, and that this improved after cessation of hormone administration. Our data strongly suggest that the mechanism by which testosterone administration may induce or exacerbate OSA is through an influence on neuromuscular control of upper airway patency during sleep.

Adolescent↗
PubMed1994

Central sleep apnea is associated with increased ventilatory response to carbon dioxide and hypersecretion of growth hormone in patients with acromegaly.

Although obstructive sleep apnea (OSA) occurs commonly in acromegaly, we have recently reported an unexpectedly high prevalence of central sleep apnea (CSA) in these patients. Acromegalic patients with CSA have increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels compared with their counterparts with OSA. Studies in animals, normal humans, and patients with sleep apnea have suggested that CSA is associated with increased gain of the respiratory control system. To examine the relationship between sleep apnea, respiratory control, and hormonal activity in acromegaly, we performed sleep studies and examined ventilatory responses to hypoxia at resting CO2 (HVR) and 8 mm Hg above resting CO2 (HHVR) and hypercapnia (HCVR) in 54 patients with acromegaly who also underwent detailed endocrine evaluation. Patients with CSA (n = 11) had higher HCVR (3.47 +/- 0.57 L/min/mm Hg) than did patients with obstructive sleep apnea (OSA) (1.86 +/- 0.19, n = 33) and patients without sleep apnea (1.77 +/- 0.21, n = 10). Measures of ventilatory control were all correlated with the mean of 12 hourly GH concentrations, but only HCVR was correlated with IGF-1 levels. Multiple linear regression analysis revealed that HCVR, HHVR, and IGF-1 could explain 39% of the variability in the degree of CSA in acromegalic patients with sleep apnea. We conclude that increased ventilatory responsiveness and elevated hormonal parameters of disease activity both contribute to the pathogenesis of central sleep apnea in acromegaly.

Acromegaly↗
PubMed1994

Obstructive sleep apnea in obese noninsulin-dependent diabetic patients: effect of continuous positive airway pressure treatment on insulin responsiveness.

Patients with noninsulin-dependent diabetes mellitus (NIDDM) are often obese and frequently complain of tiredness. These features are also characteristically seen in patients with obstructive sleep apnea (OSA). Therefore, it was the aim of this study to assess the prevalence of OSA among a group of obese NIDDM patients who have some clinical features of OSA. The effect of reversal of OSA by nasal continuous positive airway pressure (CPAP) treatment on insulin responsiveness was also investigated. From a population of 179 NIDDM patients with a body mass index (BMI) greater than 35 kg/m2, we performed ambulatory sleep monitoring on 31 (15 males and 16 females) who admitted to either heavy snoring or excessive sleepiness. Results were reviewed by a sleep physician blinded to the clinical status of the patients, and 22 (70%) were found to have moderate or severe OSA, with mean oxygen desaturation indexes of 10.3 +/- 5.3 and 30.7 +/- 13.2 episodes/h, respectively. A subgroup of 10 patients (seven males and three females) with a mean BMI of 42.7 +/- 4.3 kg/m2 was treated with nightly CPAP for 4 months. These subjects all had significant OSA, with frequent obstructive apneas (mean, 47 +/- 31.6 episodes/h) and oxygen desaturation (mean minimum O2 saturation, 74 +/- 9.5%), as determined by polysomnography. One patient was excluded from analysis because of infrequent use of CPAP. Insulin responsiveness in terms of glucose disposal measured by hyperinsulinemic euglycemic clamps improved from 11.4 +/- 6.2 to 15.1 +/- 4.6 mumol/kg.min (P < 0.05) during CPAP treatment. These results indicate that OSA occurs commonly in obese NIDDM patients with excessive sleepiness or heavy snoring. Treatment of their OSA may improve insulin responsiveness.

Adult↗
PubMed1994

Relationship between chemosensitivity, obesity and blood pressure in obstructive sleep apnoea.

It has previously been documented that patients with obstructive sleep apnoea (OSA) have an abnormal blood pressure (pressor) response to acute hypoxia when awake. The relationship between hypoxic chemosensitivity and 24 h blood pressure in OSA is not known. Twenty-four hour ambulatory BP (ABP) was measured at 15 min intervals for 24 h using a non-invasive device (Oxford Medilog ABP or Spacelabs 90207 recorder) in 49 men (mean age 51 +/- 9 years), with OSA. The BP response to acute hypoxia was measured either directly (radial arterial line) or indirectly (Finapress) during wakefulness. The pressor response to hypoxia (expressed as the slope of the regression line of mean BP on % fall in arterial oxygen saturation) was compared with the results of the ABP recording, sleep study data and clinical variables. A pressor response to acute hypoxia was present in all patients (mean 1.4 +/- 1.1 mmHg/% delta SaO2, range 0.1-4.5). There was a relationship between the magnitude of the pressor response to hypoxia, severity of sleep apnoea (RDI and minimum SaO2) and central obesity (waist measurement). In contrast, there was no relationship between BP response to hypoxia during wakefulness and 24-h BP. However, increasing obesity and severity of OSA were associated with loss of the normal fall in BP at night. We conclude that enhanced chemosensitivity is common in OSA but there is no demonstrable link between chemosensitivity and mean daytime or night-time ABP.

Acute Disease↗
PubMed1993

Effect of nasal continuous positive airway pressure during sleep on 24-hour blood pressure in obstructive sleep apnea.

Ambulatory blood pressure (BP) was measured noninvasively (Oxford Medilog ABP) at 15-minute intervals for 24 hours before and after 8 weeks of treatment with nasal continuous positive airway pressure (nCPAP) in 19 men with obstructive sleep apnea (OSA). We included both normotensive and hypertensive patients, but hypertensives were studied after withdrawal of antihypertensive drugs. Ambulatory BP before and after treatment was compared using patients as their own controls. Treatment with nCPAP was successfully established in 14 of the 19 patients (74%). Blood pressure fell significantly in patients who were successfully treated: 24-hour mean BP (systolic/diastolic) decreased from 141 +/- 18/89 +/- 11 mm Hg to 134 +/- 19/85 +/- 13 mm Hg (p < 0.05). The reduction in 24-hour mean systolic BP occurred during both day and night, but a significant fall in mean diastolic BP was only observed during the day. The mean blood pressure fell in both normotensive and hypertensive patients. Patients who were inadequately treated with nCPAP had no reduction in mean 24-hour BP. Effective treatment of sleep apnea with nCPAP was associated with a significant fall in both systolic and diastolic BP independent of changes in body weight or alcohol consumption, suggesting that sleep apnea was an independent factor contributing to elevated nighttime and daytime BP in these patients.

Blood Pressure↗