Effect of sustained release terbutaline on symptoms and sleep quality in patients with nocturnal asthma.

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.     

Does sleep cause nocturnal asthma?

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.     

Effect of sleep deprivation on overnight bronchoconstriction in nocturnal asthma.

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.     

Respiratory and sleep patterns during nocturnal infusions of branched chain amino acids

In the awake, normal subject, infusions of branched chain amino acids (BCAA) alter the ventilatory response to CO2. If this effect extends to the sleep state, it could contribute to our understanding of the neurophysiology of the sleep state as well as having clinical utility in ameliorating or preventing apnea syndromes. This study examined the effect of nocturnal BCAA infusion on sleep patterns (as measured by EEG, chest wall motion, Sao2 and end-tidal CO2) in five normal male subjects. Subjects were monitored with a polysomnograph from 21.00 to 7.00. Each subject was studied double-blind in random order on three occasions: a) baseline, no infusion (B); b) control, with normal saline infusion (S); and c) treatment, infusion of BCAA (BCAA). Sleep pattern analysis did not demonstrate any measurable effect of the BCAA infusion. End-tidal CO2 levels during BCAA infusion were lower than during baseline or control nights (mean +/- s.d.; BCAA: 5.8 +/- 0.7 kPa vs. B: 6.9 +/- 0.1 kPa, P less than 0.01 and S: 6.7 +/- 0.4 kPa, P less than 0.05). This study demonstrates that nocturnal BCAA infusions have effects on respiratory control during sleep; further clinical studies are required to determine whether these data have implications for disease states.     

Breathing patterns during breathing exercises in persons with tetraplegia

STUDY DESIGN: Cross-sectional, observational, controlled study. OBJECTIVES: To survey breathing patterns during breathing at rest, ordinary deep breathing (DB), positive expiratory pressure (PEP) and inspiratory resistance-positive expiratory pressure (IR-PEP) among individuals with a cervical spinal cord lesion (SCL) compared with able-bodied controls. SETTING: Sahlgrenska University Hospital, G?teborg, Sweden. METHOD: Participants consisted of 20 persons with a complete SCL at the C5-C8 level (at least 1 year postinjury) and 20 matched, able-bodied controls. Breathing patterns and static lung volumes were measured using a body plethysmograph. RESULTS: Compared to the controls, breathing patterns at rest among the people with tetraplegia were characterised by a decreased tidal volume, stable respiratory rate and total cycle duration resulting in decreased mean inspiratory and expiratory flow, and alveolar ventilation. All volume and flow parameters increased except respiratory rate, which decreased during DB and PEP. During IR-PEP, tidal volume increased less compared to PEP, and combined with a decreased respiratory rate the alveolar ventilation was lower than during breathing at rest. The functional residual capacity increased during PEP and IR-PEP in people with tetraplegia. CONCLUSION: DB exercises with or without resistance during expiration or the whole breathing cycle affect the breathing pattern in persons with tetraplegia. DB was superior in increasing volumes and flow. PEP and IR-PEP increased FRC but IR-PEP decreased volumes and flows. However, large interindividual differences in the SCL group indicate the need for caution in generalising the results. SPONSORSHIP: This work was supported in part by grants from the Memorial Foundation of the Swedish Association of registered Physiotherapists and the Association of Cancer and Road Accident Victims.     

Morbidity in nocturnal asthma: sleep quality and daytime cognitive performance.

Most patients with asthma waken with nocturnal asthma from time to time. To assess morbidity in patients with nocturnal asthma nocturnal sleep quality, daytime sleepiness, and daytime cognitive performance were measured prospectively in 12 patients with nocturnal asthma (median age 43 years) and 12 age and intellect matched normal subjects. The median (range) percentage overnight fall in peak expiratory flow rate (PEF) was 22 (15 to 50) in the patients with nocturnal asthma and 4 (-4 to 7) in the normal subjects. The patients with asthma had poorer average scores for subjective sleep quality than the normal subjects (median paired difference 1.1 (95% confidence limits 0.1, 2.3)). Objective overnight sleep quality was also worse in the asthmatic patients, who spent more time awake at night (median difference 51 (95% CL 8.1, 74) minutes), had a longer sleep onset latency (12 (10, 30) minutes), and tended to have less stage 4 (deep) sleep (-33 (-58, 4) minutes). Daytime cognitive performance was worse in the patients with nocturnal asthma, who took a longer time to complete the trail making tests (median difference 62 (22, 75) seconds) and achieved a lower score on the paced serial addition tests (-10 (-24, -3)). Mean daytime sleep latency did not differ significantly between the two groups (2 (-3, 7) minutes). It is concluded that hospital outpatients with stable nocturnal asthma have impaired sleep quality and daytime cognitive performance even when having their usual maintenance asthma treatment.     

Breathing patterns during curare-induced muscle weakness

This study examines the pattern of breathing used by normal subjects to compensate for an acute decrease in muscle strength. A continuous infusion of curare was used to reduce peak inspiratory pressure in six normal subjects from normal control levels to -45 cm H2O (moderate weakness) and to -70 cm H2O (mild weakness). Before administration of curare, inspiratory pressure exceeded -120 cm H2O. A canopy-computer-spirometer system was used for noninvasive spirometry and measurements of gas exchange. Partial curarization to a mild level of muscle weakness did not produce significant changes in the respiratory functions studied. With a moderate level of muscle weakness, there were significant increases in tidal volume from 166 to 186 ml/m2 and in inspiratory time from 1.51 to 1.71 sec (P less than 0.05). Minute ventilation and inspiratory flow did not change. However, when given 3% CO2, both normal and partially curarized subjects increased minute ventilation, from 2.3 to 5.7 L/min/m2 and from 2.5 to 6.7 L/min/m2, respectively. The increases in both conditions were secondary to increases in tidal volume. There was also a small increase in respiratory frequency from 15.4 to 18 breaths/min, P less than 0.01 in the partially curarized group given 3% CO2. Because minute ventilation was preserved while vital capacity decreased, it is proposed that respiration is maintained in the presence of muscle weakness associated with curare by diaphragmatic function which remains relatively unaffected by curarization.     

Effect of oral bronchodilators on lung mucociliary clearance during sleep in patients with asthma.

BACKGROUND: Lung mucociliary clearance rates are reduced during sleep in patients with asthma. Methylxanthines and beta 2 agonists have been shown to enhance rates of lung mucociliary clearance. This study examined whether oral slow release bronchodilators may also have an effect on this clearance mechanism during sleep in patients with asthma. METHODS: Nine patients with asthma with a mean(SE) age of 65(5) years and percentage predicted forced expiratory volume in one second (FEV1 of 61(9)% participated in a double blind, placebo controlled, within subject crossover study to assess the effect of two weeks of treatment with salbutamol (Volmax; 8 mg twice daily) or theophylline (Phyllocontin; 350 mg twice daily) on lung mucociliary clearance during sleep. Lung mucociliary clearance rates were measured by a radioaerosol technique. RESULTS: The observation period for radioaerosol clearance was approximately 0.3 hours before sleep, 6.0 hours during sleep and 0.6 hours after sleep. Mean mucociliary clearance rates for theophylline, placebo and salbutamol before sleep were: 39, 39, and 32%/hour respectively; during sleep: 11, 10, and 9%/hour respectively; and after sleep: 39, 32, and 35%/hour respectively. CONCLUSION: During sleep lung mucociliary clearance in stable asthma was reduced, which is in agreement with the group's previous findings. Treatment with controlled/slow release oral bronchodilators had no effect on this reduced rate of clearance associated with sleep.     

Sodium cromoglycate in nocturnal asthma.

To investigate whether mast cell degranulation was important in producing nocturnal asthma, the effect of a single high dose of nebulised sodium cromoglycate on overnight bronchoconstriction, oxygen saturation, and breathing patterns in eight patients with nocturnal wheeze was examined. The study took the form of a double blind placebo controlled crossover comparison. Treatment with cromoglycate did not reduce the overnight fall in FEV1 or FVC, although it was associated with improved nocturnal oxygenation. This study suggests that mast cell degranulation may not be important in the pathogenesis of nocturnal asthma.     

Platelet activation in nocturnal asthma.

Platelet activation may be a factor in the bronchial hyperresponsiveness that characterises asthma. As hyperresponsiveness is increased at night, changes in platelet activation over 24 hours were related to the diurnal changes in peak expiratory flow and plasma catecholamine concentrations in five subjects with asthma and five normal subjects. The effect of muscarinic receptor blockade with intravenous atropine at 0400 hours on these measurements was also studied. Platelet activation, assessed as the ration of beta thromboglobulin to platelet factor 4, was highest when the peak expiratory flow rate was at its lowest in the asthmatic subjects. There was no correlation between platelet activation and plasma catecholamine concentrations. Intravenous atropine did not alter the ratio of beta thromboglobulin to platelet factor 4, suggesting that parasympathetic activity is not the cause of the increased platelet activation at night.     

Ketotifen and nocturnal asthma.

Patients with asthma often wheeze at night and they also become hypoxic during sleep. To determine whether ketotifen, a drug with sedative properties, is safe for use at night in patients with asthma, we performed a double blind crossover study comparing the effects of a single 1 mg dose of ketotifen and of placebo on arterial oxygen saturation (SaO2), breathing patterns, electroencephalographic (EEG) sleep stage, and overnight change in FEV1 in 10 patients with stable asthma. After taking ketotifen, the patients slept longer and their sleep was less disturbed than after taking placebo, true sleep occupying 387 (SEM 8) minutes after ketotifen and 336 (19) minutes after placebo (p less than 0.02). On ketotifen nights the patients had less wakefulness and drowsiness (EEG sleep stages 0 and 1) and more non-rapid eye movement (non-REM) sleep than on placebo nights, but the duration of REM sleep was similar on the two occasions. Nocturnal changes in SaO2, the duration of irregular breathing, and overnight change in FEV1 were unaffected by ketotifen.     

Posture and nocturnal asthma.

To investigate whether the supine posture caused sustained bronchoconstriction and could thus contribute to the development of nocturnal asthma, nine patients with nocturnal asthma were studied on two consecutive days, lying supine for four hours on one day and sitting upright for four hours on the other, the order of the two postures being randomised. Peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) were measured immediately before and after the four hours and over the subsequent hour. There was no significant difference between the erect and supine posture for PEF (248 v 248 l/min), FEV1 (1.31 v 1.22 l), or FVC (2.34 v 2.28 l) at the end of the four hours, nor did any significant change develop subsequently. Thus the supine posture is not associated with prolonged bronchoconstriction. As each patient had previously shown an average overnight fall in PEF of more than 20%, this study strongly suggests that the supine posture is not an important cause of overnight bronchoconstriction.     

Treatment of nocturnal asthma with nedocromil sodium.

BACKGROUND--The association of nocturnal asthma symptoms with a diurnal increase in inflammatory activity suggests a role for anti-inflammatory therapy in nocturnal asthma. METHODS--Fifty patients with asthma with nocturnal symptoms entered a randomised, double blind, placebo controlled, crossover study. After a two week baseline period patients received nedocromil sodium (4 mg) or placebo four times daily. After eight weeks of treatment patients crossed to the alternative treatment for a further eight weeks. Symptom severity was recorded on a scale of 0-4 and inhaled bronchodilator use and peak flow (PEFR) were also recorded daily by the patients. Asthma severity, pulmonary function (FEV1, PEFR, FVC), and adverse events were recorded at clinic visits (baseline and after four and eight weeks of treatment). Global effectiveness was rated by clinician and patient, and treatment preference was recorded. RESULTS--Efficacy was assessed from data from 28 patients. Night-time asthma (mean (SE) difference between nedocromil sodium and placebo: -0.52 (0.13)), total nocturnal symptom severity defined as night-time asthma plus morning tightness (-0.72 (0.20)), and night-time bronchodilator use (-0.62 (0.23)) were reduced with nedocromil sodium compared with placebo treatment during the primary efficacy period (weeks 5-8) and during weeks 1-4 (-0.36 (0.12), -0.63 (0.20), and -0.55 (0.28), respectively). Morning and evening PEFR values improved slightly--but not significantly--compared with placebo. Patient and clinician opinions favoured nedocromil sodium treatment. Daytime asthma, daytime cough, and clinic assessment of asthma severity (secondary efficacy variables) were improved with nedocromil sodium treatment; day-time bronchodilator use and clinic pulmonary function were not. CONCLUSIONS--Nedocromil sodium was more effective than placebo in reducing nocturnal symptoms of asthma and bronchodilator use in this group of patients.     

Role of inflammation in 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.     

Ambulatory nocturnal oximetry and sleep questionnaire-based findings in 38 patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal diseases (ESRD) have an increased risk of sleep-disordered breathing. With regard to this disorder, controversy persists about prevalence, cost-effective assessment and socio-economical relevance. METHODS: Therefore, we performed, for the first time, overnight ambulatory oximetry in combination with a sleep questionnaire in 38 unselected patients with ESRD and 37 healthy controls. An oxygen desaturation index (ODI) >15, defined as >15 falls in oxygen saturation of > or =4% per h, was observed more frequently in ESRD patients than in healthy controls (47 vs. 3%, P<0.001). RESULTS: In general, the results derived from the assessment of the Epworth Sleepiness Scale (ESS) as well as those from the visual analogue scale (VAS) did not reflect the ODI values of the respective patient population. Interestingly, 88% of ESRD patients with the questionnaire finding 'excessively loud snoring' had an ODI of >15 as compared with 13% without this complaint (P<0.05). Furthermore, 77% of ESRD patients with a systolic blood pressure >140 mm Hg and a body mass index (BMI) >25, had an ODI of >15. The percentage of ESRD patients with a professional activity was higher in the absence of sleep-disordered breathing (63 vs. 21%, P<0.05). CONCLUSION: 'Excessively loud snoring' and a BMI >25 combined with hypertension are risk factors for sleep-disordered breathing in ESRD patients. Nocturnal oxygen desaturations are assessed efficiently by ambulatory oximetry and correlate with relevant biological and socio-economical parameters in ESRD patients.