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Biomedical subjects

R R Grunstein

Publications and source records attributed to R R Grunstein.

At least 19 recordsLinked to original sources
PubMed1999

Breathing during sleep in patients with nocturnal desaturation.

The mechanisms leading to hypoxemia during sleep in patients with respiratory failure remain poorly understood, with few studies providing a measure of minute ventilation (V I) during sleep. The aim of this study was to measure ventilation during sleep in patients with nocturnal desaturation secondary to different respiratory diseases. The 26 patients studied had diagnoses of chronic obstructive pulmonary disease (COPD) (n = 9), cystic fibrosis (CF) (n = 2), neuromusculoskeletal disease (n = 4), and obesity hypoventilation syndrome (OHS) (n = 11). Also reported are the results for seven normal subjects and seven patients with effectively treated obstructive sleep apnea (OSA) without desaturation during sleep. Ventilation was measured with a pneumotachograph attached to a nasal mask. In the treated patients with OSA and in the normal subjects, only minor alterations in V I were observed during sleep. In contrast, mean V I for the group with nocturnal desaturation decreased by 21% during non-rapid-eye-movement (NREM) sleep and by 39% during rapid-eye-movement (REM) sleep as compared with wakefulness. This reduction was due mainly to a decrease in tidal volume (V T). Hypoventilation was most pronounced during REM sleep, irrespective of the underlying disease. These data indicate that hypoventilation may be the major factor leading to hypoxia during sleep, and that reversal of hypoventilation during sleep should be a major therapeutic strategy for these patients.

Adult↗
PubMed1998

Time course of pulmonary artery pressure during sleep in sleep apnoea syndrome: role of recurrent apnoeas.

Recent results in animals have suggested that repetition of hypoxaemic stimuli may result in a progressive increase in pulmonary arterial pressure (Ppa). The purpose of the present study was to investigate the effects of recurrent obstructive apnoeas on Ppa. We have, therefore, examined the nocturnal trend of Ppa in seven obstructive sleep apnoea syndrome (OSAS) patients and in five snorers. Mean Ppa was measured before, at the start, at the end and after the selected apnoeas. The analysis was performed for each 1 h period for at least 7 h throughout the night on at least 10 randomly selected apnoeas per hour. In snorers, 100 randomly chosen values were measured during every hour of the night. In the morning after the nocturnal study, the Ppa responses to acute hypoxia and hypercapnia were measured. No Ppa changes throughout the 7 h were found during sleep in snorers [Ppa slope:-0.002+/-0.10 mmHg x h(-1)]. In OSAS patients a small but significant increase in Ppa throughout the night was noted, affecting the values before [Ppa slope: 0.7+/-0.16 mmHg x h(-1)], at the start of apnoea [Ppa slope: 0.530.1 mmHg x h(-1)] as well as at the end [Ppa slope: 0.44+/-0.08 mmHg x h(-1)] and in the postapnoeic period [Ppa slope: 0.55+/-0.1 mmHg x h(-1)]. When we limited the analysis to nonrapid eye movement (NREM) sleep, a trend in progressive Ppa was also present, irrespective of changes in apnoea duration and apnoea desaturation. The Ppa rise during the night was not affected by diurnal Ppa pulmonary vascular response to hypoxia and hypercapnia or indices of sleep apnoea severity. We conclude that in obstructive sleep apnoea, pulmonary artery pressure progressively increases during the night, reflecting the cumulative effects of apnoeas and nocturnal hypoxaemia.

Adult↗
PubMed1998

The effect of octreotide on breathing and the ventilatory response to CO2 in conscious dogs.

It has been reported that injection of somatostatin into the brain-stem will lead to apnoea in animals. The aim of this study was to determine whether peripheral administration of octreotide, an analogue of somatostatin, could influence the control of breathing. We measured the tidal volume, respiratory rate and ventilatory response to CO2, before and after the intravenous injection of two dose levels of octreotide (0.1 mg and 0.5 mg) or saline in four conscious adult dogs. Injection of octreotide altered the breathing pattern with a mean decrease in the respiratory frequency of 23% (p<0.05) and an increase in the tidal volume by 16% (p<0.05), resulting in no net change in ventilation. The normal value of the ventilatory response to CO2 ranged between 1.0-3.2 L x min(-1) x mmHg(-1), with a minor variance within each dog but a significant difference amongst the four dogs (p<0.05). No significant change in the ventilatory response to CO2 was observed after octreotide. We conclude that intravenous octreotide alters the pattern of breathing but preserves minute ventilation; peripheral administration of octreotide does not influence the ventilatory response to CO2.

Animals↗
PubMed1997

Pulmonary artery pressure response to hypoxia in sleep apnea.

The pulmonary artery pressure (Ppa) responses to short runs of acute hypoxia at two different levels of end-tidal CO2 were measured in nine normal subjects and in 20 patients with moderate to severe obstructive sleep apnea (OSA). In normal subjects the mean increase in Ppa in response to eucapnic hypoxia was 8 +/- 2 mm Hg (SEM) and was not different from the response to hypercapnic hypoxia (9 +/- 2 mm Hg, p > 0.2). In patients with OSA, the mean increase of Ppa was 8 +/- 1 mm Hg to eucapnic hypoxia, and the response to hypercapnic hypoxia was higher at 10 +/- 1 mm Hg (p = 0.01). Pulmonary pressor response to hypoxia was augmented (> 10 mm Hg) by hypercapnia in four of 20 patients with OSA but in none of the normal subjects. Normoxic hypercapnia alone was a weak stimulus, increasing Ppa by > 5 mm Hg in only two of nine patients with OSA studied. In conclusion, Ppa increases in both normal subjects and patients with OSA exposed to a ramp of acute isocapnic hypoxia. There were clear interindividual differences in pulmonary artery response. Hypercapnia did not produce clinical significant changes in Ppa in either group.

Adult↗
PubMed1996

Acute withdrawal of nasal CPAP in obstructive sleep apnea does not cause a rise in stress hormones.

We hypothesized that withdrawal of nasal continuous positive airway pressure (CPAP) in patients with sleep apnea would produce a measurable stress response. To test this hypothesis, we ceased CPAP in eight patients regularly using nasal CPAP long term and measured the effect on sleep apnea as well as plasma and urinary levels of the stress hormones, noradrenaline, cortisol and adrenocorticotropic hormone (ACTH). CPAP withdrawal led to an immediate recurrence of sleep apnea with increases in apnea index, arousal index and oxygen desaturation (all p < .0001) but no change in levels of noradrenaline, cortisol or ACTH. We conclude that acute withdrawal of CPAP in patients with sleep apnea does not lead to a classic stress response.

Adrenocorticotropic Hormone↗
PubMed1996

Metabolic aspects of sleep apnea.

Sleep apnea is associated with abnormalities in metabolic function. First, there is a strong epidemiological link between central obesity and sleep apnea. Some evidence suggests that sleep apnea may promote weight gain or prevent weight loss by several mechanisms: reduction in anabolic (growth hormone and testosterone) hormone secretion, influences on energy balance and insulin sensitivity, and altered central serotonergic tone.

Energy Metabolism↗
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↗