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Biomedical subjects

Ronald R Grunstein

Publications and source records attributed to Ronald R Grunstein.

At least 19 recordsLinked to original sources
PubMed2026

Safety, tolerability, and efficacy of alixorexton, a selective orexin 2 receptor agonist for narcolepsy type 1 (Vibrance-1): a randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: The clinical potential of orexin 2 receptor (OX2R) agonism for improving measures of wakefulness and cataplexy in patients with narcolepsy type 1 has been described in a phase 2 study. Here, we aimed to evaluate the safety, tolerability, and efficacy of alixorexton, another oral OX2R agonist, in narcolepsy type 1. METHODS: In this randomised, double-blind, placebo-controlled, phase 2 trial, adult participants (aged 18-70 years) with narcolepsy type 1 were recruited from 46 hospitals and private research centres across the USA, Europe, and Australia. Participants were centrally randomly assigned (1:1:1:1) in blocks of four via an interactive response technology system stratified by region and baseline weekly cataplexy rate (WCR) to receive 4 mg, 6 mg, or 8 mg tablets of alixorexton or placebo once daily for 6 weeks, followed by an optional 7-week open-label extension. Participants had narcolepsy type 1, diagnosed per the International Classification of Sleep Disorders, Third Edition, and confirmed by overnight polysomnography and the Multiple Sleep Latency Test or cerebrospinal hypocretin-1 concentrations. The sponsor, assessors, investigators, and participants were masked during the randomised double-blind treatment period. Efficacy and safety assessments were conducted in participants who received at least one dose of study drug. The primary endpoint was change from baseline to week 6 in mean sleep latency (MSL) on the Maintenance of Wakefulness Test (MWT). Safety endpoints included treatment-emergent adverse events. This trial was registered with ClinicalTrials.gov (NCT06358950) and is completed. FINDINGS: Between May 24, 2024, and May 5, 2025, 153 individuals were screened and 92 participants were randomly assigned to receive alixorexton 4 mg (n=23), 6 mg (n=22), 8 mg (n=24), or placebo (n=23). Mean age was 33&#xb7;5 years (SD 12&#xb7;1), 57 (62%) were women, and 35 (38%) were men. At week 6, the observed MSL on the MWT was 2&#xb7;3 min (SD 2&#xb7;7) for placebo, 24&#xb7;0 min (8&#xb7;7) for alixorexton 4 mg, 25&#xb7;9 min (9&#xb7;4) for 6 mg, and 28&#xb7;2 min (11&#xb7;4) for 8 mg. Alixorexton improved MSL on the MWT, with a least-squares mean placebo-corrected change from baseline of 22&#xb7;2 min (95% CI 17&#xb7;2-27&#xb7;2) for alixorexton 4 mg, 24&#xb7;1 min (19&#xb7;0-29&#xb7;1) for 6 mg, and 26&#xb7;0 min (21&#xb7;0-31&#xb7;0) for 8 mg (adjusted p=0&#xb7;0099 for 4 mg, adjusted p<0&#xb7;0001 for 6 mg and 8 mg). Treatment-emergent adverse events occurring in at least 5% of participants given alixorexton and more frequently than those given placebo up to week 6 were pollakiuria (38 [55%]), insomnia (19 [28%]), salivary hypersecretion (17 [25%]), micturition urgency (ten [14%]), blurred vision (ten [14%]), and hyperhidrosis (five [7%]). INTERPRETATION: In this phase 2 trial, once-daily oral alixorexton provided clinically meaningful improvements at 6 weeks for participants with narcolepsy type 1, including in wakefulness, excessive daytime sleepiness, and cataplexy. The treatment was generally well tolerated, with adverse events consistent with the known on-target effects of OX2R agonists. Together, these findings support the further phase 3 evaluation of alixorexton as a potential therapeutic option for people with narcolepsy type 1. FUNDING: Alkermes.

Humans↗
PubMed2007

Association between ventilatory response to hypercapnia and obstructive sleep apnea-hypopnea index in asymptomatic subjects.

The majority of awake ventilatory control studies have shown normal or decreased ventilatory response to hypercapnia (HCVR) in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients. These findings are contrary to experimental studies suggesting increased loop gain and greater breathing instability in OSAHS patients. We have investigated the relationship between central chemoreflex sensitivity tested by HCVR and obstructive sleep apnea/hypopnea index (OSAHI) in asymptomatic subjects. Twenty normal volunteers (10 men and 10 women) from the general population without physical complaints including sleep-related symptoms were included. The subjects were studied for awake ventilatory responses to hypoxia (HVR) and hypercapnia. Overnight polysomnography (PSG) was performed in two consecutive nights with the first night used as acclimatization. The subjects have an average body mass index (BMI) of 27 +/- 5 SD kg/m(2), ages of 35 +/- 9 SD years and Epworth sleepiness scale of 2.1 +/- 1.8 SD. A positive linear relationship was found between HCVR and logarithmically transformed OSAHI (r = 0.67, p = 0.001). BMI and age were not significantly correlated to HCVR or Log OSAHI. No relationship was found between HVR and Log OSAHI (r = 0.25, p = 0.29). Percentage oxygen saturation nadir during sleep was found to significantly correlate to both daytime HCVR (r = -0.60, p = 0.005) and Log OSAHI (r = -0.65, p = 0.002) and tended to correlate to HVR (r = -0.41, p = 0.07). Arousal index during sleep was not associated with either HCVR (p = 0.93) or HVR (p = 0.26). In conclusion, heightened central chemosensitivity was positively related to OSAHI in asymptomatic volunteers. We believe these findings are in keeping with the evolving theory of loop gain being a significant factor for respiratory control instability and obstructive apnea genesis. The mechanism can be applied to asymptomatic subjects with even minimal sleep-disordered breathing.

Adult↗
PubMed2006

Effects of short-term CPAP withdrawal on neurobehavioral performance in patients with obstructive sleep apnea.

STUDY OBJECTIVE: Changes in sleep parameters and neurobehavioral functioning were systematically investigated after an acute (1 night) and short-term (7 nights) period of withdrawal from continuous positive airway pressure (CPAP) treatment and 1 subsequent night of CPAP reintroduction in patients with obstructive sleep apnea. DESIGN: Repeated-measurement within-subject design. SETTING: Sleep laboratory, university teaching hospital. PARTICIPANTS: Twenty participants receiving optimal CPAP therapy for > or = 12 months. INTERVENTIONS: CPAP withdrawal. MEASUREMENTS AND RESULTS: Polysomnograms were performed on Night 0 (with CPAP), Night 1 and Night 7 (without CPAP) and Night 8_R (with CPAP). Acute CPAP withdrawal resulted in the recurrence of sleep-disordered breathing with sleep disruption, hypoxemia, and increased subjective sleepiness. Short-term CPAP withdrawal exacerbated hypoxemia, increased subjective and objective sleepiness and poor mood ratings. Neurobehavioral functioning assessed using the Psychomotor Vigilance Task was impaired following Night 7 and associated with hypoxemia and changes in morning levels of tumor necrosis factor-alpha. However, other neurobehavioral measures were not affected. Autonomic arousals measured via respiratory-related reductions in finger blood volume by peripheral arterial tonometry decreased from Night 1 to Night 7. On Night 8_R, reintroduction of CPAP treatment eliminated most airway obstruction, maintained oxygenation, and reversed daytime sleepiness and some vigilance decrements. CONCLUSION: Despite recurrence of sleep-disordered breathing with increased sleepiness and impaired vigilance, most neurobehavioral variables were unaffected by CPAP withdrawal. The reduction in vigilance appeared to be associated with worsened hypoxemia and changed levels of tumor necrosis factor-alpha. Resumption of CPAP treatment had immediate benefits on sleep consolidation and subjective sleepiness.

Body Mass Index↗
PubMed2006

Brain function in obstructive sleep apnea: results from the Brain Resource International Database.

Obstructive sleep apnea (OSA) is expected to impair vigilance and executive functioning, owing to the sensitivity of the prefrontal cortex to the effects of sleep fragmentation and intermittent hypoxia. Studies examining the pattern of cognitive dysfunction show variable results, with the heterogeneity in part due to small sample sizes in current studies and little consistency of the tests used. We examined a group of fifty subjects from the Brain Resource International Database (BRID), predicted to have OSA on the basis of the Multivariable Apnea Prediction Index, and compared them with 200 matched controls. On electrophysiological tests, the OSA group showed reduced eyes closed alpha power, increased auditory oddball N100 and P200 amplitude, but reduced N200 and P300 amplitude. The latency to P300 was not significantly different between groups, but latencies to N200 and P200 were prolonged in the OSA group. Performance testing of the executive function found that verbal interference and the switching of attention were impaired in the OSA group. We have demonstrated that a diagnostic algorithm based on apnea symptoms and demographic factors can be used to select a group with likely OSA manifesting deficits in information processing and executive function.

Acoustic Stimulation↗
PubMed2005

Ethnicity and obstructive sleep apnoea.

There is a scarcity of adult prevalence studies of OSA outside the Caucasian populations of North America, Europe and Australia, and comparisons have been complicated by methodological differences in sleep study settings, respiratory events definition, measured risk factors and clinical outcomes, and the lack of objective parameters for the measurement of ethnicity itself. Comparing studies with the same methodological design and respiratory events definition, recent large-scale prevalence studies from Hong Kong, Korea and India show similar OSA rates to populations of mainly Caucasian composition. OSA is a very complex disorder determined by several phenotypes such as obesity, craniofacial structure and abnormalities in neuromuscular and ventilatory control. Genetics may partially explain some of the ethnic clustering of these phenotypes, modulated by cultural and environmental factors. The exact contribution of these component phenotypes to overall OSA risk will be determined by their varying prevalence and relative risk conferred across ethnic groups. For lesser degrees of obesity, Asians are at risk for a more severe degree of illness compared with Caucasians. Inter-ethnic studies suggests that African-American ethnicity may also be a significant risk factor for OSA. The increased prevalences of OSA among American Indians and Hispanic adults, and increased severity among Pacific Islanders and Maoris, were mainly explained by increased obesity parameters. Most cephalometric studies have largely been conducted without specific regard to ethnicity and comparisons of findings across studies have been mainly limited by differences in sampling methods and the varying selection and definition of measured cephalometric variables. The limited number of studies with inter-ethnic comparative data suggest cephalometric variables and their degree of contribution to OSA vary across ethnic groups.

Adult↗
PubMed2005

Treatment of obesity hypoventilation syndrome and serum leptin.

BACKGROUND: Leptin is a protein produced by adipose tissue that circulates to the brain and interacts with receptors in the hypothalamus to inhibit eating. In obese humans, serum leptin is up to four times higher than in lean subjects, indicating that human obesity is associated with a central resistance to the weight-lowering effects of leptin. Although the leptin-deficient mouse (ob/ob) develops obesity hypoventilation syndrome (OHS), in humans with OHS, serum leptin is a better predictor of awake hypercapnia in obesity than the body mass index (BMI). This suggests that central leptin resistance may promote the development of OHS in humans. We speculated that the reversal of OHS by regular non-invasive ventilation (NIV) therapy decreases leptin levels. OBJECTIVES: The aim of this study was to investigate whether ventilatory treatment of OHS would alter circulating leptin concentrations. METHOD: We measured fasting serum leptin levels, BMI, spirometry and arterial blood gases in 14 obese hypercapnic subjects undergoing a diagnostic sleep study. RESULTS: The average age of the subjects was (mean +/- SE) 62 +/- 13 years, BMI 40.9 +/- 2.2 kg/m(2), PaCO(2) 6.7 +/- 0.2 kPa, PaO(2 )8.9 +/- 0.4 kPa and total respiratory disturbance index 44 +/- 35 events/hour. Subjects were clinically reviewed after a median of 2.3 years (range 1.6-3) with repeat investigations. Nine patients were regular NIV users and 5 were non-users. NIV users had a significant reduction in serum leptin levels (p = 0.001), without a change in BMI. In these patients, there was a trend towards an improved daytime hypercapnia and hypoxemia, while in the 5 non-users, no changes in serum leptin, BMI or arterial blood gases occurred. CONCLUSION: Regular NIV use reduces serum leptin in OHS. Leptin may be a modulator of respiratory drive in patients with OHS.

Body Mass Index↗
PubMed2005

The effect of infective exacerbations on sleep and neurobehavioral function in cystic fibrosis.

RATIONALE: Adults with cystic fibrosis (CF) are susceptible to hypoxemia, hypercapnia, arousal from sleep, and neurobehavioral impairment. OBJECTIVES: We hypothesized that pulmonary exacerbations would adversely affect sleep and neurobehavioral performance. METHODS: Patients with exacerbations (cases) had sleep studies and neurobehavioral testing before and after inpatient intravenous therapy. Adults with stable CF underwent the same testing procedures (control subjects). MEASUREMENTS AND MAIN RESULTS: When clinically stable, cases and control subjects had similar lung function, intelligence, and body mass index. Among cases, treatment of an exacerbation improved lung function, quality of life, mood, sleepiness, and activation. Cases spent more time awake after sleep onset (p = 0.02), less time in REM sleep (p = 0.03), and were more hypoxemic than control subjects when unwell. The severity of hypoxemia correlated with lung function. On admission, cases had slower throughput than control subjects in the serial addition and subtraction task (cases, 16 +/- 4, vs. control subjects, 17 +/- 3; F[1, 36] = 5.15, p = 0.03) and a slower response time on the digit symbol substitution task (F[1, 36] = 11.91, p = 0.001), which persisted after treatment (F[1, 36] = 8.48, p = 0.006). Cases experienced significant improvements in sleep efficiency, amount of REM sleep, and hypoxia with treatment. Their performance in the serial addition and subtraction task, psychomotor vigilance task, and simulated driving task also improved with treatment. Sex modified the effect of an exacerbation on some aspects of performance. CONCLUSIONS: Exacerbations of lung disease in adults with CF adversely affect sleep and tests of neurobehavioral performance regardless of underlying disease severity. The implications for performance in daily life need further evaluation because patients often delay admission to hospital to fulfill study or work commitments.

Adolescent↗
PubMed2005

Medical devices for the diagnosis and treatment of obstructive sleep apnea.

Obstructive sleep apnea is increasingly being recognized as a serious public health problem, and is characterized by repetitive, complete or partial closure of the upper airway during sleep, resulting in sleep fragmentation and oxygen desaturation. The key symptoms of obstructive sleep apnea are snoring, witnessed apneas, excessive daytime sleepiness and deficits in neurocognitive function, adversely impacting on quality of life. The last 10 years have seen a steady increase in evidence linking obstructive sleep apnea to long-term cardiovascular morbidity, including hypertension, myocardial infarction and stroke, and an increased risk of motor vehicle accidents. The discovery of continuous positive airway pressure treatment, and the resultant recognition of the high prevalence of snoring and obstructive sleep apnea, and their impact on health, has spawned a new and rapidly growing global industry. Whilst diagnostic technologic advancements have evolved relatively rapidly, many questions relating to the use of such devices in clinical practice remain unresolved. Similarly, on the therapeutic front, advances in continuous positive airway pressure technology have broadened the use of such treatment, although compliance remains an important impediment to widespread treatment of this common disorder. This has prompted a search for simpler treatment alternatives, ranging from surgical, medical and dental therapies, although none have matched the efficacy of continuous positive airway pressure. Advances in our understanding of the neurobiology of sleep and respiration herald the prospect of pharmacologic treatment in the longer term.

Continuous Positive Airway Pressure↗
PubMed2004

Sleepiness, sleep-disordered breathing, and accident risk factors in commercial vehicle drivers.

Sleep-disordered breathing and excessive sleepiness may be more common in commercial vehicle drivers than in the general population. The relative importance of factors causing excessive sleepiness and accidents in this population remains unclear. We measured the prevalence of excessive sleepiness and sleep-disordered breathing and assessed accident risk factors in 2,342 respondents to a questionnaire distributed to a random sample of 3,268 Australian commercial vehicle drivers and another 161 drivers among 244 invited to undergo polysomnography. More than half (59.6%) of drivers had sleep-disordered breathing and 15.8% had obstructive sleep apnea syndrome. Twenty-four percent of drivers had excessive sleepiness. Increasing sleepiness was related to an increased accident risk. The sleepiest 5% of drivers on the Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire had an increased risk of an accident (odds ratio [OR] 1.91, p = 0.02 and OR 2.23, p < 0.01, respectively) and multiple accidents (OR 2.67, p < 0.01 and OR 2.39, p = 0.01), adjusted for established risk factors. There was an increased accident risk with narcotic analgesic use (OR 2.40, p < 0.01) and antihistamine use (OR 3.44, p = 0.04). Chronic excessive sleepiness and sleep-disordered breathing are common in Australian commercial vehicle drivers. Accident risk was related to increasing chronic sleepiness and antihistamine and narcotic analgesic use.

Accident Prevention↗
PubMed2004

Sequential use of oxygen and bi-level ventilation for respiratory failure in cystic fibrosis.

BACKGROUND: Supplemental nocturnal oxygen is widely used for hypoxaemic respiratory failure in adults with CF. METHODS: In order to determine the factors that predict the development of progressive hypercapnia on oxygen ("failure of oxygen therapy") and the subsequent role of bi-level pressure support ventilation (BVS), we reviewed the outcomes of 39 adults with CF who were treated for hypoxaemic respiratory failure between 1991 and 2002 using strict physiological criteria for the commencement of oxygen and the subsequent commencement of BVS. RESULTS: Twenty of the 39 failed oxygen therapy, 13 of these within 12 months. Baseline PaCO2, rather than age, BMI or FEV1, predicted failure of oxygen therapy within 12 months. A PaCO2>6.5 kPa (49 mm Hg) was significantly associated with failure within 12 months (p=0.04). Twenty patients with mean PaCO2 7.9+/-1.3 kPa (59+/-10 mm Hg) and mean pH 7.38+/-0.05 had a significant reduction in their mean PaCO2 after 1 month of BVS (p=0.007). CONCLUSIONS: Both oxygen and BVS can successfully stabilise patients to transplant. In patients commencing oxygen, baseline PaCO2 is predictive of the development of progressive hypercapnia within 12 months. BVS can successfully attenuate the rise in PaCO2 in the short term.

Adult↗
PubMed2004

Pharmacotherapy for excessive daytime sleepiness.

Excessive daytime sleepiness (EDS) has recognized detrimental consequences such as road traffic accidents, impaired psychological functioning and reduced work performance. EDS can result from multiple causes such as sleep deprivation, sleep fragmentation, neurological, psychiatric and circadian rhythm disorders. Treating the underlying cause of EDS remains the mainstay of therapy but in those who continue to be excessively sleepy, further treatment may be warranted. Traditionally, the amphetamine derivatives, methylphenidate and pemoline (collectively sympathomimetic) psychostimulants were the commonest form of therapy for EDS, particularly in conditions such as narcolepsy. More recently, the advent of modafinil has broadened the range of therapeutic options. Modafinil has a safer side-effect profile and as a result, interest in this drug for the management of EDS in other disorders, as well as narcolepsy, has increased considerably. There is a growing school of thought that modafinil may have a role to play in other indications such as obstructive sleep apnea/hypopnea syndrome already treated by nasal continuous positive airway pressure but persisting EDS, shift work sleep disorders, neurological causes of sleepiness, and healthy adults performing sustained operations, particularly those in the military. However, until adequately powered randomised-controlled trials confirm long-term efficacy and safety, the recommendation of wakefulness promoters in healthy adults cannot be justified.

Amphetamines↗
PubMed2004

Sleep disordered breathing in cystic fibrosis.

Cough, sleep fragmentation and oxyhaemoglobin desaturation have all been documented during sleep in patients with cystic fibrosis (CF). It has been proposed that repeated episodes of nocturnal hypoxia act as a stimulus for the development of pulmonary hypertension and right ventricular failure, a complication that is associated with a poor prognosis. In addition, sleep disturbance from these events could lead to poor daytime function and quality of life. This review provides a detailed description of the mechanisms underlying sleep disordered breathing in this population, what is known regarding its effects upon daytime function and current treatment options. Most importantly, we review what is needed from future research in this challenging area of care in patients with CF.

Acute Disease↗
PubMed2004

Predictive value of Kushida index and acoustic pharyngometry for the evaluation of upper airway in subjects with or without obstructive sleep apnea.

Acoustic pharyngometry is a relatively new noninvasive method that quantifies geometrically complexed pharyngeal dimensions. Our study aimed to investigate the predictability and usefulness of acoustic pharyngometry in diagnosis of obstructive sleep apnea (OSA), and we developed a prospective clinical trial in 16 subjects without apnea and 54 subjects with apnea. All seventy subjects received polysomnography (PSG) to assess the sleep architecture, including breathing and the degree of apnea hypopnea index. Acoustic pharyngometry was performed in four body positions (sitting, supine, right and left lateral) while awake with tidal breathing in addition to morphometric measurements (Kushida index) of oral cavity. This study shows that the cross-sectional area and volume of the upper airway is smaller in the supine position than any other positions. As well, the oropharyngeal junction area of the supine position is the most predictive parameter to discriminate between subjects with or without OSA. Acoustic pharyngometry can be a clinically useful tool for localizing the narrowed portion of the upper airway and predicting obstructive sleep apnea.

Acoustics↗
PubMed2003

Fatal distraction: a case series of fatal fall-asleep road accidents and their medicolegal outcomes.

Obstructive sleep apnoea is associated with an increased risk of sleep-related motor vehicle accidents. Seven recent legal cases of fatal motor vehicle accidents on NSW roads are presented, where the driver who caused the accident was suffering from an unrecognised or under-treated sleep disorder. The legal outcomes in these cases were variable: some of the drivers have been acquitted and others have been jailed. All remained licensed to drive immediately after their accidents. In some of the cases, the driver was cleared of any culpable driving offence because of a defence of sleepiness or a sleep attack without warning ("Jiminez defence"). This appears at odds with current medical research and legal opinion in other countries. More research is needed to understand the relation between sleep disorders and awareness of sleepiness. Medical practitioners need to be aware of current advice and guidelines with respect to obstructive sleep apnoea and driving.

Accidents, Traffic↗
PubMed2003

The short-term effects of high-dose testosterone on sleep, breathing, and function in older men.

Androgen therapy may precipitate obstructive sleep apnea in men. Despite increasing androgen use in older men, few studies have examined sleep and breathing. Randomized, double-blind, placebo-controlled studies examining effects of testosterone simultaneously on sleep, breathing, and function in older men are not available. Seventeen community-dwelling healthy men over the age of 60 yr were randomized to receive three injections of im testosterone esters at weekly intervals (500 mg, 250 mg, and 250 mg) or matching oil-based placebo and then crossed over to the other treatment after 8 wk of washout. Polysomnography, anthropometry, and physical, mental, and metabolic function were assessed at baseline and after each treatment period. Testosterone treatment reduced total time slept ( approximately 1 h), increased the duration of hypoxemia ( approximately 5 min/night), and disrupted breathing during sleep (total and non-rapid eye movement respiratory disturbance indices both increased by approximately seven events per hour) (all P < 0.05). Despite expected effects on body composition (increase in total and lean mass, reduction in fat mass, P < 0.05, bioimpedance method), upper airway dimensions did not change (acoustic reflectometry). Driving ability (computer simulation), physical activity (accelerometry, Physical Activity Scale in the Elderly), quality of life (SF36, Functional Outcomes of Sleep Questionnaire), mood (Profile of Mood States Questionnaire), sleepiness (Epworth, Stanford scales), and insulin resistance (homeostasis model) also were not changed by treatment. Short-term administration of high-dose testosterone shortens sleep and worsens sleep apnea in older men but did not alter physical, mental, or metabolic function. These changes did not appear to be due to upper airway narrowing. Further study of longer-term lower-dose androgen therapy on sleep and breathing is needed to evaluate its safety in older men.

Aged↗
PubMed2002

Subjective sleep quality in cystic fibrosis.

OBJECTIVES: To evaluate sleep quality in patients with cystic fibrosis (CF). METHODS: The Pittsburgh Sleep Quality Index (PSQI) questionnaire was administered to 37 CF patients with moderate to severe lung disease in a clinically stable state. Sleep studies were performed concurrently. PSQI scores were correlated with results of anthropometric variables, arterial blood gas tensions, lung function variables, and polysomnographic variables. Potential differences in objective measurements between patients with high and low scores on the PSQI were assessed. RESULTS: Thirty-seven patients with CF were studied, aged 27+/-8 (mean+/-1 SD) years and forced expiratory volume in 1 s (FEV(1)) 36+/-12% predicted. The mean PSQI was 5.7+/-4.0. Fourteen of the 37 patients had a high PSQI, i.e. >5. Significant correlations between objective variables and both component scores and total PSQI were as follows: age and 'subjective sleep quality' (r=0.4, P<0.05), age and 'sleep duration' (r=0.3, P<0.05), FEV(1) % predicted and 'subjective sleep quality' (r=-0.4, P<0.05), carbon monoxide transferred per litre of lung volume (KCO) % predicted and 'daytime dysfunction' (r=-0.4, P<0.01), PaCO(2) and 'sleep latency' (r=0.4, P<0.01), arterial carbon dioxide tension (PaCO(2)) and 'habitual sleep efficiency' (r=0.3, P<0.05), PaCO(2) and total PSQI (r=0.4, P<0.05), absolute minimum sleep oxyhemoglobin saturation by pulse oximetry (SpO(2) %) and 'sleep latency' (r=-0.4, P<0.05), absolute minimum sleep SpO(2) % and 'sleep duration' (r=-0.4, P<0.05), absolute minimum sleep SpO(2) % and total PSQI (r=-0.4, P<0.05) and awake transcutaneous CO(2) and 'sleep duration' (r=0.45, P<0.05). Better sleep efficiency (P<0.05) and a greater % of rapid eye movement (REM) sleep (P<0.05) were found in those patients with a PSQI of < or =5. CONCLUSIONS: A number of CF patients reported poor sleep quality. A relationship was shown between subjective sleep quality and physiological variables describing disease severity. Better sleep efficiency and % REM sleep were seen in patients with low PSQI scores. These results suggest a useful role for the PSQI in assessing sleep quality in patients with CF.

Journal Article↗
PubMed2002

Night-to-night variability in sleep in cystic fibrosis.

OBJECTIVES: The impact of night-to-night variability (NNV) on polysomnography (PSG) has been reported mainly in normal subjects, the elderly and patients with obstructive sleep apnea with focus on changes in the apnea/hypopnea index, rather than measures of nocturnal oxygenation. There is very limited data on NNV in patients with cystic fibrosis (CF). The goal of this study was to assess for first-night effect and reliability of PSG measurements on nocturnal oxygenation and respiratory disturbance in CF. METHODS: A prospective observational study was performed in patients with CF who consented to PSG on two consecutive nights. Paired t-tests and intra-class correlation coefficients (ICCs) were calculated for repeated measures of sleep stage time, sleep efficiency, arousal indices, measures of nocturnal oxygenation, and respiratory events in all sleep stages. RESULTS: Thirty-one patients with CF were studied, aged 27+/-8 (mean+/-1 SD) years and forced expiratory volume in 1 s (FEV(1)) of 37+/-11% of predicted. Relative to the first-night PSG, on the second PSG, we observed the following: shorter latency to rapid eye movement (REM) sleep (P<0.001), increased sleep efficiency (P<0.01), decreased wake after sleep onset (WASO) time (P<0.01), decreased percentage of non-REM time with oxyhemoglobin saturation by pulse oximetry (SpO(2))< or =90% (P<0.05), decreased number of central apneas per hour (P<0.05) and reduced respiratory rate in stage 2 sleep on night 2 (P<0.05). Despite these changes, the ICCs between night 1 and night 2 showed good repeatability/reliability for measures of nocturnal oxygenation and indices of respiratory disturbance, including the percentage of total sleep time with SpO(2)< or =90% (ICC=0.85) and apnea-hypopnea index (ICC=0.75). Likewise, the ICCs were extremely high for respiratory rate in stage 2 (ICC=0.94), slow wave sleep (ICC=0.97), and REM sleep (ICC=0.96). CONCLUSION: Although a first-night effect is seen with sleep efficiency, REM latency, and WASO, a single-night PSG in patients with CF yields reliable information on nocturnal oxygenation and respiratory disturbance.

Journal Article↗