Many patients with asthma are troubled by nocturnal wheeze. The cause of this symptom is unknown, but sleep is an important factor. A study was carried out to determine whether nocturnal bronchoconstriction is related to any specific stage of sleep. Eight asthmatics with nocturnal wheeze and eight control subjects performed forced expiratory manoeuvres immediately after being woken from rapid eye movement (REM) or non-REM sleep, wakings being timed to differentiate temporal effects from those related to the stage of sleep. The control subjects showed no significant temporal bronchoconstriction or bronchoconstriction related to the stage of sleep. All patients showed bronchoconstriction overnight, the mean peak expiratory flow rate falling from 410 (SEM 50) 1/min before sleep to 186 (49)1/min after sleep. After the patients had been woken from REM sleep the forced expiratory volume in one second was on average 300 ml lower (p less than 0.02) and peak expiratory flow rate 45 1/min lower (p less than 0.03) than after they had been woken from non-REM sleep. As wakenings from REM sleep were 21(8) minutes later in the night than those from non-REM sleep multivariate analysis was performed to differentiate temporal effects from those related to the stage of sleep. This showed that the overnight decreases in forced expiratory volume in one second and peak expiratory flow rate were significantly related both to time and to REM sleep. This study suggests that asthmatics may suffer bronchoconstriction during REM sleep.
Nocturnal cough and wheeze are common in asthma. The cause of nocturnal asthma is unknown and there is conflicting evidence on whether sleep is a factor. Twelve adult asthmatic subjects with nocturnal wheeze were studied on two occasions: on one night subjects were allowed to sleep and on the other they were kept awake all night, wakefulness being confirmed by electroencephalogram. Every patient developed bronchoconstriction overnight both on the asleep night, when peak expiratory flow (PEF) fell from a mean (SE) of 418 (40) 1 min-1 at 10 pm to 270 (46) 1 min-1 in the morning, and on the awake night (PEF 10 pm 465 (43), morning 371 (43) 1 min-1). The morning values of PEF were, however, higher (p less than 0.1) after the awake night and both the absolute and the percentage overnight falls in PEF were greater when the patients slept (asleep night 38% (6%), awake night 20% (4%); p less than 0.01). This study suggests that sleep is an important factor in determining overnight bronchoconstriction in patients with nocturnal asthma.
BACKGROUND--Nocturnal airway narrowing is a common problem for patients with asthma but the role of inflammation in its pathogenesis is unclear. Overnight changes in airway inflammatory cell populations were studied in patients with nocturnal asthma and in control normal subjects. METHODS--Bronchoscopies were performed at 0400 hours and 1600 hours in eight healthy subjects and in 10 patients with nocturnal asthma (> 15% overnight fall in peak flow plus at least one awakening/week with asthma). The two bronchoscopies were separated by at least five days, and both the order of bronchoscopies and site of bronchoalveolar lavage (middle lobe or lingula with contralateral lower lobe bronchial biopsy) were randomised. RESULTS--In the normal subjects there was no difference in cell numbers and differential cell counts in bronchoalveolar lavage fluid between 0400 and 1600 hours, but in the nocturnal asthmatic subjects both eosinophil counts (median 0.11 x 10(5) cells/ml at 0400 hours, 0.05 x 10(5) cells/ml at 1600 hours) and lymphocyte numbers (0.06 x 10(5) cells/ml at 0400 hours, 0.03 x 10(5) cells/ml at 1600 hours) increased at 0400 hours, along with an increase in eosinophil cationic protein levels in bronchoalveolar lavage fluid (3.0 micrograms/ml at 0400 hours, 2.0 micrograms/l at 1600 hours). There were no changes in cell populations in the bronchial biopsies or in alveolar macrophage production of hydrogen peroxide, GM-CSF, or TNF alpha in either normal or asthmatic subjects at 0400 and 1600 hours. There was no correlation between changes in overnight airway function and changes in cell populations in the bronchoalveolar lavage fluid. CONCLUSIONS--This study confirms that there are increases in inflammatory cell populations in the airway fluid at night in asthmatic but not in normal subjects. The results have also shown a nocturnal increase in eosinophil cationic protein levels in bronchoalveolar lavage fluid, but these findings do not prove that these inflammatory changes cause nocturnal airway narrowing.
OBJECTIVE--To determine whether inhaled salmeterol, a new long acting inhaled beta adrenergic agonist, reduces nocturnal bronchoconstriction and improves sleep quality in patients with nocturnal asthma. DESIGN--Randomised, double blind, placebo controlled crossover study. SETTING--Hospital outpatient clinics in Edinburgh. SUBJECTS--Twenty clinically stable patients (13 women, seven men) with nocturnal asthma, median age 39 (range 18-60) years. INTERVENTIONS--Salmeterol 50 micrograms and 100 micrograms and placebo taken each morning and evening by metered dose inhaler. Rescue salbutamol inhalers were provided throughout the run in and study periods. MAIN OUTCOME MEASURES--Improvement in nocturnal asthma as measured by peak expiratory flow rates and change in sleep quality as measured by electroencephalography. RESULTS--Salmeterol improved the lowest overnight peak flow rate at both 50 micrograms (difference in median values (95% confidence interval for difference in medians) 69 (18 to 88) l/min) and 100 micrograms (72 (23 to 61) l/min) doses twice daily. While taking salmeterol 50 micrograms twice daily patients had an objective improvement in sleep quality, spending less time awake or in light sleep (-9 (-4 to -44) min) and more time in stage 4 sleep (26 (6-34) min). CONCLUSIONS--Salmeterol is an effective long acting inhaled bronchodilator for patients with nocturnal asthma and at a dose of 50 micrograms twice daily improves objective sleep quality.
The effects of sleep interruption and deprivation were studied in 21 patients with nocturnal asthma. Seven patients were awakened at 0200 on three consecutive night and exercised for 15 minutes. This produced no significant improvement in the overnight fall in peak expiratory flow rate (PEFR) compared with a control night of uninterrupted sleep. In a second study in five patients PEFR was measured at two-hourly intervals to estimate the time of onset of the nocturnal fall in PEFR. On three subsequent nights they were awakened and exercised one hour before this time. This also failed to prevent a fall in PEFR by 0600. Eleven patients, who had followed a similar protocol to the second study, were kept awake until after 0300 or later, and PEFR was observed hourly. Six of them (group A) sustained their usual fall in PEFR while awake, proving that sleep was not responsible for their nocturnal asthma. Five patients (group B) showed little fall in PEFR until they were allowed to sleep, when an appreciable fall was noted on waking at 0600. When sleep deprivation was repeated in two patients in group B, however, they sustained falls in PEFR while still awake. We conclude that the circadian rhythm in PEFR is often in phase with the timing of sleep but sleep does not cause nocturnal asthma. Disruption of sleep therefore has no apparent value in the treatment of nocturnal asthma.
Breathing patterns early and late in the night, at the same sleep stage, were compared in six healthy subjects and 15 adults with nocturnal asthma, to try to identify changes of overnight bronchoconstriction, and breathing patterns at different sleep stages, to see whether there were changes related to sleep stages that were indicative of bronchoconstriction. Despite an average 31% fall in FEV1 overnight in the patients with asthma, neither breathing frequency nor expiratory time, which might be expected to change during bronchoconstriction, was different early in the night from late in the night, nor did they differ between sleep stages. There was no evidence of asynchronous movement of the chest and abdomen in any patient. This study did not identify any abnormality of breathing pattern that would indicate the development of nocturnal asthma without the need to awaken the patient.
Sleep dysfunction is a common nonmotor symptom experienced by patients with Parkinson’s disease (PD). Symptoms, including excessive daytime sleepiness, sleep fragmentation, rapid eye movement (REM) sleep behavior disorder and others, can significantly affect quality of life and daytime functioning in these patients. Recent studies have evaluated the effects of deep brain stimulation (DBS) at various targets on sleep in patients with advanced PD. Several of these studies have provided evidence that subthalamic nucleus DBS improves subjective and objective measures of sleep, including sleep efficiency, nocturnal mobility, and wake after sleep onset (minutes spent awake after initial sleep onset). Although fewer studies have investigated the effects of bilateral internal globus pallidus and thalamic ventral intermedius DBS on sleep, pallidal stimulation does appear to improve subjective sleep quality. Stimulation of the pedunculopontine nucleus has recently been proposed for selected patients with advanced PD to treat severe gait and postural dysfunction. Owing to the role of the pedunculopontine nucleus in modulating behavioral state, the impact of stimulation at this target on sleep has also been evaluated in a small number of patients, showing that pedunculopontine nucleus DBS increases REM sleep. In this review, we discuss the effects of stimulation at these various targets on sleep in patients with PD. Studying the effects of DBS on sleep can enhance our understanding of the pathophysiology of sleep disorders, provide strategies for optimizing clinical benefit from DBS, and may eventually guide novel therapies for sleep dysfunction.
deep brain stimulation; globus pallidus; Parkinson’s disease; pedunculopontine nucleus; sleep; subthalamic nucleus; ventral intermediate nucleus of the thalamus
Atopic diseases, such as asthma and allergic rhinitis, are common conditions that can influence sleep and subsequent daytime functioning. Children and patients with allergic conditions from ethnic minority groups might be particularly vulnerable to poor sleep and compromised daytime functioning because of the prevalence of these illnesses in these groups and the high level of morbidity. Research over the past 10 years has shed light on the pathophysiologic mechanisms (eg, inflammatory mediators) involved in many atopic diseases that can underlie sleep disruptions as a consequence of the presence of nocturnal symptoms. Associations between nocturnal symptoms and sleep and poorer quality of life as a result of missed sleep have been demonstrated across studies. Patients with severe illness and poor control appear to bear the most burden in terms of sleep impairment. Sleep-disordered breathing is also more common in patients with allergic diseases. Upper and lower airway resistance can increase the risk for sleep-disordered breathing events. In patients with allergic rhinitis, nasal congestion is a risk factor for apnea and snoring. Finally, consistent and appropriate use of medications can minimize nocturnal asthma or allergic symptoms that might disrupt sleep. Despite these advances, there is much room for improvement in this area. A summary of the sleep and allergic disease literature is reviewed, with methodological, conceptual, and clinical suggestions presented for future research.
Sleep; allergic disease; asthma; allergic rhinitis; atopic dermatitis
Subjective and objective sleep disturbance was studied in
children with nocturnal asthma. Relations between such disturbance and
daytime psychological function were also explored, including possible
changes in learning and behaviour associated with improvements in
nocturnal asthma and sleep. Assessments included home polysomnography, parental questionnaires concerning sleep disturbance, behaviour, and
mood and cognitive testing. Compared with matched controls, children
with asthma had significantly more disturbed sleep, tended to have more
psychological problems, and they performed less well on some tests of
memory and concentration. In general, improvement of nocturnal asthma
symptoms by changes in treatment was followed by improvement in sleep
and psychological function in subsequent weeks. The effects of asthma
on sleep and the possible psychological consequences are important
aspects of overall care.
OBJECTIVE--To determine whether the nocturnal fall in plasma adrenaline is a cause of nocturnal asthma. DESIGN--Double blind placebo controlled cross-over study. In the first experiment the nocturnal fall in plasma adrenaline at 4 am was corrected in 10 asthmatic subjects with an infusion of adrenaline after parasympathetic blockade with 30 micrograms/kg intravenous atropine. In the second experiment 11 asthmatic subjects showing similar variations in peak expiratory flow rate had the nocturnal fall in plasma adrenaline corrected by infusion before atropine was given. PATIENTS--Asthmatic subjects with a diurnal variation in home peak expiratory flow rate of greater than 20% for at least 75% of the time in the two weeks before the study. MAIN OUTCOME MEASURES--Peak expiratory flow rate and plasma adrenaline. RESULTS--Correction of the nocturnal fall in plasma adrenaline at 4 am to resting 4 pm levels did not alter peak expiratory flow rate either before or after parasympathetic blockade with atropine. CONCLUSION--A nighttime fall in plasma adrenaline is not a cause of nocturnal asthma.
Objective—To determine the prevalence of sleep disordered breathing within a United Kingdom heart failure population.
Subjects—104 patients and 21 matched normal volunteers.
Methods—Overnight home pulse oximetry with simultaneous ECG recording in the patient group; daytime sleepiness was assessed using the Epworth sleepiness scale (ESS); 41 patients underwent polysomnography to assess the validity of oximetry as a screening test for Cheyne-Stokes respiration.
Results—Home oximetry was a good screening test for Cheyne-Stokes respiration (specificity 81%, sensitivity 87%). Patients with poorer New York Heart Association (NYHA) classes had higher sleepiness scores (p < 0.005). Twenty three patients had "abnormal" patterns of nocturnal desaturation suggestive of Cheyne-Stokes respiration. The mean (SEM) frequency of dips in SaO2 exceeding 4% was 10.3 (0.9) per hour in the patients and 4.8 (0.6) in normal controls (p < 0.005). Ejection fraction correlated negatively with dip frequency (r = −0.5. p < 0.005). The patient subgroup with ⩾ 15 dips/hour had a higher mean (SEM) NYHA class (3.0 (0.2) v 2.3 (0.1), p < 0.05), and experienced more ventricular ectopy (220 (76) v 78 (21) beats/hour, p < 0.05). There was no excess of serious arrhythmia.
Conclusions—Nocturnal desaturation is common in patients with treated heart failure. Low ejection fraction was related to dip frequency. Lack of correlation between dips and ESS suggests that arousal from sleep is more important than hypoxia in the aetiology of daytime sleepiness in heart failure. Overnight oximetry is a useful screening test for Cheyne-Stokes respiration in patients with known heart failure.
Keywords: Cheyne-Stokes respiration; nocturnal desaturation; heart failure
Complaints of unrefreshing sleep are a prominent component of chronic fatigue syndrome (CFS); yet, polysomnographic studies have not consistently documented sleep abnormalities in CFS patients. We conducted this study to determine whether alterations in objective sleep characteristics are associated with subjective measures of poor sleep quality in persons with CFS.
We examined the relationship between perceived sleep quality and polysomnographic measures of nighttime and daytime sleep in 35 people with CFS and 40 non-fatigued control subjects, identified from the general population of Wichita, Kansas and defined by empiric criteria. Perceived sleep quality and daytime sleepiness were assessed using clinical sleep questionnaires. Objective sleep characteristics were assessed by nocturnal polysomnography and daytime multiple sleep latency testing.
Participants with CFS reported unrefreshing sleep and problems sleeping during the preceding month significantly more often than did non-fatigued controls. Participants with CFS also rated their quality of sleep during the overnight sleep study as significantly worse than did control subjects. Control subjects reported significantly longer sleep onset latency than latency to fall asleep as measured by PSG and MSLT. There were no significant differences in sleep pathology or architecture between subjects with CFS and control subjects.
People with CFS reported sleep problems significantly more often than control subjects. Yet, when measured these parameters and sleep architecture did not differ between the two subject groups. A unique finding requiring further study is that control, but not CFS subjects, significantly over reported sleep latency suggesting CFS subjects may have an increased appreciation of sleep behaviour that may contribute to their perception of sleep problems.
Respiratory disturbances during sleep are recognized as extremely common disorders with important clinical consequences. Breathing disorders during sleep can result in broad range of clinical manifestations, the most prevalent of which are unrefreshing sleep, daytime sleepiness and fatigue, and cognitive impairmant. There is also evidence that respiratory-related sleep disturbances can contribute to several common cardiovascular and metabolic disorders, including systemic hypertension, cardiac dysfunction, and insulin-resistance. Correlations are found between asthma-related symptoms and sleep disturbances. Difficulties inducing sleep, sleep fragmentation on polysomnography, early morning awakenings and daytime sleepiness are more common in asthmatics compared with subjects without asthma. The “morning deep” in asthma is relevant for the characterization of asthma severity, and impact drugs’ choices. Sleep and night control of asthma could be relevant to evaluate disease’s control. Appropriate asthma control recovering is guarantor for better sleep quality in these patients and less clinical consequences of respiratory disturbances during sleep.
bronchial asthma; sleep disorders.
respiratory failure (CRF) is associated with nocturnal
hypoventilation. Due to the interaction of sleep and breathing, sleep quality is reduced during nocturnal hypoventilation. Non-invasive mechanical ventilation (NMV), usually performed overnight, relieves symptoms of hypoventilation and improves daytime blood gas tensions in
patients with CRF. The time course of the long term effect of NMV on
sleep and breathing during both spontaneous ventilation (withdrawing
the intervention) and NMV was investigated in patients with CRF due to
consecutive patients (13 women) of mean (SD) age 57.9 (12.0) years with
CRF due to thoracic restriction were included in the study. During the
one year observation period four polysomnographic studies were
performed: three during spontaneous breathing without NMV—before
initiation of NMV (T0) and after withdrawing NMV for one night at six
months (T6) and 12 months (T12-)—and the fourth during NMV after 12 months (T12+). Daytime blood gas tensions and lung function were also measured.
ventilation (in terms of mean oxygen saturation) progressively improved
(from T0 to T12-) during both REM sleep (24.8%, 95% CI 12.9 to 36.9)
and NREM sleep (21.5%, 95% CI 12.4to 30.6). Sleep quality during
spontaneous ventilation also improved in terms of increased total sleep
time (26.8%, 95% CI 11.6 to 42.0) and sleep efficiency (17.5%, 95%
CI 5.4 to 29.6) and decreased awakenings (54.0%, 95% CI 70.3 to
37.7). Accordingly, REM and NREM sleep stages 3 and 4 significantly
improved. However, the most significant improvements in both nocturnal
ventilation and sleep quality were seen during NMV at 12months.
term NMV both spontaneous ventilation during
sleep and sleep quality in patients with CRF due to thoracic
restriction showed evidence of progressive improvement compared with
baseline after withdrawal of NMV for a single night at six and 12 months. However, the greatest improvements in nocturnal ventilation and sleep were achieved during NMV at 12months.
Although considerable progress has been made in the treatment of chronic kidney disease, compromised quality of life continues to be a significant problem for patients receiving hemodialysis (HD). However, in spite of the high prevalence of sleep complaints and disorders in this population, the relationship between these problems and quality of life remains to be well characterized. Thus, we studied a sample of stable HD patients to explore relationships between quality of life and both subjective and objective measures of nocturnal sleep and daytime sleepiness
The sample included forty-six HD patients, 24 men and 22 women, with a mean age of 51.6 (10.8) years. Subjects underwent one night of polysomnography followed the next morning by a Multiple Sleep Latency Test (MSLT), an objective measure of daytime sleepiness. Subjects also completed: 1) a brief nocturnal sleep questionnaire; 2) the Epworth Sleepiness Scale; and, 3) the Quality of Life Index (QLI, Dialysis Version) which provides an overall QLI score and four subscale scores for Health & Functioning (H&F), Social & Economic (S&E), Psychological & Spiritual (P&S), and Family (F). (The range of scores is 0 to 30 with higher scores indicating better quality of life.)
The mean (standard deviation; SD) of the overall QLI was 22.8 (4.0). The mean (SD) of the four subscales were as follows: H&F – 21.1 (4.7); S&E – 22.0 (4.8); P&S – 24.5 (4.4); and, F – 26.8 (3.5). H&F (rs = -0.326, p = 0.013) and F (rs = -0.248, p = 0.048) subscale scores were negatively correlated with periodic limb movement index but not other polysomnographic measures. The H&F subscale score were positively correlated with nocturnal sleep latency (rs = 0.248, p = 0.048) while the H&F (rs = 0.278, p = 0.030) and total QLI (rs = 0.263, p = 0.038) scores were positively associated with MSLT scores. Both of these latter findings indicate that higher life quality is associated with lower sleepiness levels. ESS scores were unrelated to overall QLI scores or the subscale scores. Subjective reports of difficulty falling asleep and waking up too early were significantly correlated with all four subscale scores and overall QLI. Feeling rested in the morning was positively associated with S&E, P&S, and Total QLI scores.
Selected measures of both poor nocturnal sleep and increased daytime sleepiness are associated with decreased quality of life in HD patients, underscoring the importance of recognizing and treating these patients' sleep problems.
Nocturnal wheeze is common in patients with asthma, and slow release theophyllines may reduce symptoms. As theophyllines are stimulants of the central nervous system the effect of 10 days' twice daily treatment with sustained release choline theophyllinate or placebo on symptoms, overnight bronchoconstriction, nocturnal oxygen saturation, and quality of sleep were studied in a double blind crossover study in nine stable patients with nocturnal asthma (five men, four women, age range 23-64 years; forced expiratory volume in one second (FEV1) 0.85-3.8 1; vital capacity 1.95-6.1 1). When treated with the active drug all patients had plasma theophylline concentrations of at least 28 mmol/l (5 micrograms/ml) (peak plasma theophylline concentrations 50-144 mmol/l (9-26 micrograms/ml]. Morning FEV1 was higher when treated with sustained release choline theophyllinate (2.7 (SEM 0.3) 1) than placebo (2.1 (0.3) 1) (p less than 0.01). Both daytime and nocturnal symptoms were reduced when the patients were treated with sustained release choline theophyllinate and subjective quality of sleep was improved (p less than 0.002). When treated with the active drug, however, quality of sleep determined by electroencephalography deteriorated with an increase in wakefulness and drowsiness (p less than 0.05) and a reduction in non-rapid eye movement sleep (p less than 0.005). Treatment with choline theophyllinate had no effect on either the occurrence or the severity of transient nocturnal hypoxaemic episodes or apnoeas or hypopnoeas. In conclusion, sustained release choline theophyllinate prevents overnight bronchoconstriction, but impairs quality of sleep defined by electroencephalography.
Nocturnal asthma represents a unique subset of patients with asthma who experience worsening symptoms and airflow obstruction at night. The basis for this phenotype of asthma is not known, but beta 2-adrenergic receptors (beta 2AR) are known to downregulate overnight in nocturnal asthmatics but not normal subjects or nonnocturnal asthmatics. We have recently delineated three polymorphic loci within the coding block of the beta 2AR which alter amino acids at positions 16, 27, and 164 and impart specific biochemical and pharmacologic phenotypes to the receptor. In site-directed mutagenesis/recombinant expression studies we have found that glycine at position 16 (Gly16) imparts an accelerated agonist-promoted downregulation of beta 2AR as compared to arginine at this position (Arg16). We hypothesized that Gly16 might be overrepresented in nocturnal asthmatics and thus determined the beta 2AR genotypes of two well-defined asthmatic cohorts: 23 nocturnal asthmatics with 34 +/- 2% nocturnal depression of peak expiratory flow rates, and 22 nonnocturnal asthmatics with virtually no such depression (2.3 +/- 0.8%). The frequency of the Gly16 allele was 80.4% in the nocturnal group as compared to 52.2% in the nonnocturnal group, while the Arg16 allele was present in 19.6 and 47.8%, respectively. This overrepresentation of the Gly16 allele in nocturnal asthma was significant at P = 0.007 with an odds ratio of having nocturnal asthma and the Gly16 polymorphism being 3.8. Comparisons of the two cohorts as to homozygosity for Gly16, homozygosity for Arg16, or heterozygosity were also consistent with segregation of Gly16 with nocturnal asthma. There was no difference in the frequency of polymorphisms at loci 27 (Gln27 or Glu27) and 164 (Thr164 or Ile164) between the two groups. Thus the Gly16 polymorphism of the beta 2AR, which imparts an enhanced downregulation of receptor number, is overrepresented in nocturnal asthma and appears to be an important genetic factor in the expression of this asthmatic phenotype.
Nocturnal symptoms are common in young asthmatic children. Such symptoms may be caused by increased impairment of lung function when they adopt the supine posture. Thirty one children aged 2.8-8.3 years were studied, of whom 20 had asthma (10 with frequent nocturnal symptoms) and 11 had no respiratory problems (control subjects). Peak expiratory flow (PEF) was measured with a Wright's peak flow meter and functional residual capacity (FRC) by a helium gas dilution technique after 30 minutes of lying supine; the values were compared with FRC measured sitting and PEF standing. Peak flow fell significantly on adoption of the supine posture in the asthmatic children, but there was no difference in this fall between the asthmatic children with and without nocturnal symptoms. FRC also fell on adoption of the supine posture, but the decrease in FRC was significant only in the control children and the asthmatic children without nocturnal symptoms. The failure to find a greater fall in PEF or a greater change in FRC on adoption of the supine posture among asthmatic children with nocturnal symptoms suggests that mechanisms other than increased impairment of lung function are responsible for nocturnal asthma.
Asthmatics often report asthma-related nocturnal awakenings. These sleep interruptions may have a significant impact on patients' quality of life. We characterized the effect of mometasone furoate/formoterol (MF/F) administered via pressured metered-dose inhaler on incidence of nocturnal awakenings requiring short-acting β2-agonists (SABAs).
MF/F's effect on nocturnal awakenings requiring SABA was characterized across 3 phase III efficacy trials (baseline = number of nights with awakenings in week before first dose; endpoint = number of nights/wk with awakenings averaged across the 26-week treatment period). Subjects were asthmatics previously treated with low- (n=746), medium- (n=781) or high-dose (n=728) inhaled corticosteroids at various doses. Subjects in the MF/F 100/10 μg BID study were randomized to 26 weeks of twice-daily (BID) treatment with MF/F 100/10 μg, MF 100 μg, F 10 μg, or placebo; subjects in the MF/F 200/10 μg BID study to 26 weeks of BID treatment with MF/F 200/10 μg, MF 200 μg, F 10 μg, or placebo; and subjects in the MF/F 400/10 μg BID study to 12 weeks of BID treatment with MF/F 400/10 μg, MF/F 200/10 μg, or MF 400 μg. All treatments were delivered via a metered dose inhaler.
Baseline awakenings ranged from 0.84–1.05, 1.05–1.26, and 1.33–1.61 nights/wk in the MF/F 100/10 μg BID, MF/F 200/10 μg BID, and MF/F 400/10 μg BID studies, respectively. In the MF/F 100/10 μg BID study, nocturnal awakenings were reduced by MF/F = –0.42, MF = –0.21, F = –0.21, and placebo = 0.14 nights/wk; corresponding changes in the MF/F 200/10 μg BID study were –0.56, –0.35, +0.07 and 0.00 nights/wk, respectively. In each of these placebo-controlled studies, MF/F was superior to placebo (P < .001) and F (P ≤.035); MF was also superior to F and placebo. In the MF/F 400/10 μg BID study, awakenings were reduced by –0.70, –0.70 and –0.35 nights/wk by MF/F 200/10 μg, MF/F 400/10 μg, and MF 400 μg, respectively; both MF/F treatments were superior to MF (P ≤0.006).
These results provide evidence that validates the role of MF/F in reducing nocturnal asthma symptoms in patients with moderate to severe persistent asthma and supports the efficacy of MF/F compared with that of placebo and F.
The effect of an oral sustained release beta 2 agonist on symptoms, sleep quality, and peak flow rates has been studied in nine patients with nocturnal asthma. Patients received oral terbutaline 7.5 mg twice daily or placebo for seven days in a double blind crossover study and spent the last two nights of each limb in a sleep laboratory. Oral terbutaline improved morning peak flow (259 v 213 l min-1) and decreased nocturnal inhaler usage (1.3 v 1.9) with no alteration in sleep quality as assessed electroencephalographically. The study shows that oral sustained release terbutaline can be useful in the treatment of nocturnal asthma without impairment of sleep quality.
To date, no studies have evaluated for differences in subjective and objective measures of sleep disturbance in oncology outpatients with and without pain. This descriptive study recruited 182 patients from two radiation therapy (RT) departments at the time of the patient’s simulation visit. Approximately 38% of the sample reported moderate to severe pain (i.e., worst pain intensity of 6.2 ± 2.4). After controlling for age, patients with pain reported worse sleep quality and more sleep disturbance using the Pittsburgh Sleep Quality Index. With the General Sleep Disturbance Scale, patients with pain reported poorer sleep quality, increased use of sleep medications, and more daytime sleepiness. In addition using an objective measure of sleep disturbance (i.e., actigraphy), significant Gender × Pain interactions were found for sleep onset latency, percentage of time awake at night, wake duration, total sleep time, and sleep efficiency. While no differences were found in female patients, males with pain had worse scores than males without pain. Findings from this study suggest that pain and sleep disturbance are prevalent in oncology outpatients and that a patient’s age and gender need to be considered in any evaluation of the relationship between pain and sleep.
Perspective: The effects of pain on subjective and objective sleep parameters appear to be influenced by both patients’ age and gender.
pain; cancer; sleep disturbance; sleep; wakefulness; gender; insomnia; circadian rhythm; radiation therapy; actigraphy
Obstructive sleep apnea (OSA) worsens nocturnal asthma, but its potential impact on daytime asthma remains largely unassessed. We investigated whether the sleep disorder is associated with daytime, in addition to nighttime asthma symptoms.
Asthma patients at tertiary-care centers completed the Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ), and an asthma control questionnaire. SA-SDQ scores ≥36 for men and ≥32 for females defined high OSA risk. Medical records were reviewed for established diagnosis of OSA and continuous positive airway pressure (CPAP) use.
Among 752 asthma patients, high OSA risk was associated similarly with persistent daytime and nighttime asthma symptoms (p<0.0001 for each). A diagnosis of OSA was robustly associated with persistent daytime (p<0.0001), in addition to nighttime (p=0.0008) asthma symptoms. In regression models that included obesity and other known asthma aggravators, high OSA risk retained associations with persistent daytime (odds ratio =1.96 [95% confidence interval 1.31–2.94]) and nighttime asthma symptoms (1.97 [1.32–2.94]). Diagnosed OSA retained an association with persistent daytime (2.08 [1.13–3.82]) but not with nighttime (1.48 [0.82–2.69]) asthma symptoms. CPAP use was associated with lower likelihood of persistent daytime symptoms (0.46 [0.23–0.94]).
Questionnaire-defined OSA risk and historical diagnosis were each associated with persistent daytime asthma symptoms, to an extent that matched or exceeded associations with nighttime asthma symptoms. Unrecognized OSA may be a reason for persistent asthma symptoms during the day as well as the night.
asthma; asthma control; sleep; obstructive sleep apnea; obstructive sleep apnea risk
Excessive daytime sleepiness is a significant public health problem, with prevalence in the community estimated to be as high as 18%. Sleepiness is caused by abnormal sleep quantity or sleep quality. Amongst others, multiple neurological, psychological, cardiac and pulmonary disorders may contribute. Risk factors for excessive sleepiness include obesity, depression, extremes of age and insufficient sleep. In the clinical setting, two of the most commonly encountered causes are obstructive sleep apnoea and periodic limb movement disorder. There is continuing discussion of the mechanisms by which these disorders cause daytime symptoms, with intermittent nocturnal hypoxia, sleep fragmentation and autonomic dysregulation identified as important factors. The increased prevalence of obstructive sleep apnoea in obese subjects does not fully account for the increased rates of daytime sleepiness in this population and there is evidence to suggest that it is caused by metabolic factors and chronic inflammation in obese individuals. Sleepiness is also more common in those reporting symptoms of depression or anxiety disorders and significantly impacts their quality of life. Clinicians should be aware of factors which put their patients at high risk of daytime sleepiness, as it is a debilitating and potentially dangerous symptom with medico-legal implications. Treatment option should address underlying contributors and promote sleep quantity and sleep quality by ensuring good sleep hygiene. However, stimulant medication may be indicated in some cases to allow for more normal daytime functioning.
Sleep; sleep apnoea; obstructive; nocturnal myoclonus syndrome; obesity; depression
Sleep abnormalities are common in severe emphysema, and include poor sleep quality, the development of nocturnal oxygen desaturation, and the presence of coexistent obstructive sleep apnea. With lower baseline oxygenation and abnormal respiratory mechanics in patients with severe emphysema, alterations in ventilatory control and respiratory muscle function that normally occur during sleep can have profound effects, and contribute to the development of sleep abnormalities. The impact on quality of life, cardiopulmonary hemodynamics, and overall survival remains uncertain. In addition, treatment for chronic obstructive pulmonary disease and its effect on sleep abnormalities have demonstrated conflicting results. More recently, as part of the National Emphysema Treatment Trial, lung volume reduction surgery has been shown to improve both sleep quality and nocturnal oxygenation in emphysema. Although indications for performing an overnight polysomnogram in patients with emphysema have been debated, recommendations have been presented. Future studies investigating disease mechanism and response to therapy in patients with sleep abnormalities and severe emphysema are warranted.
emphysema; sleep; hypoventilation; apnea; oxygenation
Excessive daytime sleepiness is a complaint characterizing many disorders of the wakefulness—sleep cycle. This paper addresses the complaint of sleepiness objectively by an attempt to differentiate a group of control subjects from a group of patients with unambiguous narcolepsy. Fourteen control and 27 narcoleptic subjects were evaluated by one of three protocols involving nocturnal recordings, detailed interviews, and 5 or more 20-min opportunities to sleep offered at 2-h intervals beginning at 10.00 o’clock, ±30 min. Each 20-min opportunity to sleep was given to subjects lying in a darkened quiet room and asked to try to fall asleep. Polysomnographic variables were monitored and sleep was scored in 30-sec epochs by standard criteria. The interval from the start of each test to the first epoch of NREM (including stage 1 sleep) or REM sleep was called sleep latency. In two of the protocols, the subjects were awakened immediately after sleep onset. In the third protocol, the subjects were awakened after 10 min of sleep. Narcoleptics consistently fell asleep much more readily than did control subjects. We conclude that the Multiple Sleep Latency test, in addition to providing opportunities to clinically document sleep onset REM sleep periods, can demonstrate pathological sleepiness. Based on these data, we suggest that an average sleep latency less than 5 min be set as the minimum cutoff point for pathological sleepiness.