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Background: Patients with the sleep apnoea/hypopnoea syndrome have increased salt and water excretion at night which has been reported to be associated with an increase in plasma levels of atrial natriuretic peptide (ANP). A study was performed to determine whether any rise in plasma ANP levels was related to nocturnal hypoxaemia., Methods: Nine patients with sleep apnoea/hypopnoea syndrome were studied on two nights, one breathing air and the other 28% oxygen, the order being randomised. Venous levels of ANP, aldosterone, and renin activity were measured., Results: No decrease in plasma ANP levels on oxygen was seen, and, indeed, there was no evidence of an overnight increase in ANP levels., Conclusion: Oxygen therapy does not diminish nocturnal plasma ANP levels in patients with sleep apnoea/hypopnoea syndrome.

Background: Continuous positive airway pressure (CPAP) therapy is the treatment of choice for the sleep apnoea/hypopnoea syndrome. Compliance with this relatively obtrusive therapy has not been well studied., Methods: Usage of CPAP was investigated in 54 patients with sleep apnoea/hypopnoea syndrome (median 36 (range 7-129) apnoeas + hypopnoeas/hour slept) over the first 1-3 months after starting CPAP therapy. In all cases CPAP usage was monitored by hidden time clocks that indicated for how long the machines were switched on--that is, the CPAP run time. In 32 patients the time at which the CPAP mask pressure was at the therapeutic level of CPAP pressure set for that patient--that is, the mask time--was also monitored. In all patients objective daytime sleepiness was assessed by multiple sleep latency before and after CPAP therapy., Results: The mean (SE) nightly CPAP run time was 4.7 (0.4) hours. There was no correlation between run time and severity of the sleep apnoea/hypopnoea syndrome as assessed by apnoea + hypopnoea frequency or multiple sleep latency, and no correlation between CPAP usage and improvement in multiple sleep latency. Thirty two patients in whom mask time was recorded had therapeutic CPAP pressures for 89% (3%) of their CPAP run times. Patients who experienced side effects from CPAP used their CPAP machines significantly less than those who did not., Conclusions: Patients with sleep apnoea/hypopnoea syndrome used CPAP for less than five hours/night on average with no correlation between severity of sleep apnoea/hypopnoea syndrome and CPAP usage. Patients who complained of side effects used their CPAP therapy less. It is recommended that, as a minimum, CPAP run time should be regularly recorded in all patients receiving CPAP therapy.

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.

Posture has a major effect on breathing during sleep. Snoring, hypopneas, and apneas are all more common lying than sitting and more common supine than in a lateral lying position. Because the effect of the lateral lying position on upper airway caliber has not previously been studied, we examined this in 20 normal awake subjects and also determined the effect of neck position. The acoustic reflection technique was used. Pharyngeal cross-sectional areas (CSA) fell significantly from the sitting to supine position (oropharyngeal junction, from 1.65 +/- [SEM] 0.6 cm to 1.31 +/- 0.07 cm), but there was no difference in CSA between the supine and lateral positions for oropharyngeal junction (1.36 +/- 0.06 cm), mean pharyngeal area, maximal pharyngeal area, or pharyngeal volume. Neck hyper-extension significantly increased pharyngeal CSA (e.g., oropharyngeal junction null position 1.51 +/- 0.08, hyper-extension 1.94 +/- 0.11 cm), but there was no significant effect of neck flexion on airway CSA. These results confirm that in normal awake subjects, pharyngeal areas are smaller lying than sitting but also showed no significant difference between CSA in the supine and lateral lying positions. The study also demonstrates that the upper airway caliber increases with neck extension in conscious adults.

Patients with the sleep apnea/hypopnea syndrome (SAHS) often have more apneas supine that sitting. We have shown radiologically that although the retropalatal airway narrows on lying down, the retroglossal airway widens. We have thus investigated the effect of posture on genioglossal EMG activity in 10 normal subjects and 10 patients with SAHS (58 +/- 29 SD apneas + hypopneas/h) using peroral intramuscular EMG electrodes. Data were analyzed by three-way analysis of variance, with diagnosis, posture, and route as factors. Peak inspiratory and tonic expiratory genioglossal EMG were both than sitting, with no significant difference between normal subjects and SAHS higher (p < 0.001) supine patients, although there was a trend (p < 0.09) toward the supine posture having a greater effect on peak inspiratory EMG in the SAHS patients. There was no significant effect of breathing route on either peak inspiratory (p > 0.9) or tonic expiratory (p > 0.8) genioglossal EMG, but there were significant differences between the groups (p < 0.01), the SAHS patients having higher and the normal subjects lower EMG tone with nasal in comparison with oral breathing on both inspiration and expiration. This study therefore shows that both body posture and breathing route are important determinants of genioglossal EMG tone.

Background: Patients with the sleep apnoea/hypopnoea syndrome often receive continuous positive airway pressure to improve their symptoms and daytime performance, yet objective evidence of the effect of this treatment on cognitive performance is lacking., Methods: A prospective parallel group study was performed comparing the change in objective daytime sleepiness as assessed by multiple sleep latency, cognitive function, and mood in 21 patients (mean (SE) number of apnoeas and hypopnoeas/hour 57 (6)) who received continuous positive airway pressure for three months and 16 patients (49(6) apnoeas and hypopnoeas/hour) who received conservative treatment for a similar period., Results: Both groups showed significant within group changes in cognitive function between baseline and three months, but when comparisons were made between groups the only significant difference was a greater improvement in multiple sleep latency with continuous positive airway pressure. However, the improvement in sleep latency with continuous positive airway pressure was relatively small (3.5 (0.5) to 5.6 (0.7) min). The group treated with continuous positive airway pressure was divided into those who complied well with treatment (> 4.5 hours/night) and those who did not. Those who complied well (n = 14) showed significant improvement in mean sleep latency and also in depression score compared with the controls but no greater improvement in cognitive function., Conclusion: This study confirms significant improvements in objective sleepiness and mood with continuous positive airway pressure, but shows no evidence of major improvements in cognitive function.

BACKGROUND--The aetiology of the sleep apnoea/hypopnoea syndrome (SAHS) is unclear in many patients. Snoring, a prerequisite for SAHS, runs in families. A study was carried out to determine whether there is an increased frequency of irregular breathing during sleep in relatives of patients with SAHS. METHODS--A prospective study was performed of first degree relatives of 20 consecutive non-obese (BMI < 30 kg/m2) patients with SAHS. Questionnaires on SAHS symptoms were sent to all first order relatives and those living within 150 miles of Edinburgh were invited for overnight monitoring of their breathing, sleep, and oxygenation patterns in the sleep laboratory. RESULTS--Ten of the 40 relatives had more than 15 apnoeas + hypopnoeas/hour of sleep, and eight had more than five 4% desaturations/hour. These frequencies of irregular breathing and desaturation are significantly higher than in the British population. Cephalometric studies showed no skeletal abnormality but an increased uvular width was found in the affected relatives. CONCLUSIONS--There is an increased frequency of abnormal breathing during sleep in relatives of non-obese patients with SAHS.

A practical implementation of acoustic reflectometry for determining airway areas in routine clinical use is described. Advances over previous systems include portability, free breathing during measurements, no need to equilibrate with helium/oxygen, and real-time display of airway areas. Validation of the reflectometer with an airway model gave accuracies and reproducibilities (coefficient of variation (CV)) in the range 5-10%. With human volunteers, the within-run CV was typically 10%, and the day-to-day CV was 20%. The effect of breathing pattern on airway areas is demonstrated. In ten normal volunteers, acoustic and magnetic resonance imaging (MRI) methods of assessing pharyngeal and glottal areas were compared. The results (mean +/- SD) for the oropharynx were 1.0 +/- 0.3 cm2 acoustically and 0.9 +/- 0.5 cm2 by MRI (p = 0.77). The corresponding figures for glottal areas were 1.3 +/- 0.3 cm2 and 1.1 +/- 0.4 cm2 (p = 0.09).

Background: Manual analysis of sleep, breathing, and oxygenation records is the "gold standard" for diagnosing sleep abnormalities but is time consuming and cumbersome. The accuracy and cost of a computerised sleep analysis system have therefore been investigated., Methods: Manual and computerised (CNS Sleep Lab) scores from 43 consecutive clinical sleep studies were prospectively compared for accuracy and the time and costs were recorded., Results: There were good correlations and no systematic differences between manual and computer scoring for total sleep time, sleep onset latency, and duration of REM sleep. There was a small but clinically insignificant systematic difference in breathing pattern analysis, the number of hypopnoeas/hour being lower with manual than with computer scoring (13 (SE 3) v 15 (SE 3)/hour). There was no difference between computer and manual scoring of the frequency of apnoeas, so the frequency of apnoeas + hypopnoeas was clinically insignificantly higher with computer scoring with a highly significant correlation between the two techniques. The time taken to perform the analyses was not different between the two methods (manual 83 (SE 8) v computer 86 (SE 8) minutes). The computer system was six times more expensive than the manual system and annual running costs, including full maintenance contract and 15% depreciation, were twice as great., Conclusion: The CNS Sleep Lab is sufficiently accurate for use in clinical sleep studies but is significantly more expensive and does not save technician time.

1. To clarify the relationship between nocturnal oxygen desaturation and erythropoietin production in patients with chronic obstructive pulmonary disease, we determined arterial oxygen saturation and serum immunoreactive erythropoietin levels over 24 h in eight patients with chronic obstructive pulmonary disease and in nine normal subjects. 2. In the normal subjects, there was a significant circadian variation in serum erythropoietin levels with the highest mean deviation from the geometric mean at 22.00 hours and the nadir at 05.00 hours. 3. The three patients with chronic obstructive pulmonary disease with the most marked nocturnal desaturation (lowest arterial oxygen saturation < 57%) and most marked daytime hypoxaemia (daytime arterial partial pressure of oxygen < 6 kPa) had raised nocturnal serum erythropoietin levels. In two of these patients, the serum erythropoietin level was raised throughout the 24 h and erythrocyte mass was also raised. In the other patient, the serum erythropoietin level was not raised in five daytime samples and erythrocyte mass was normal. 4. The other five patients with chronic obstructive pulmonary disease with less severe nocturnal hypoxaemia (lowest arterial oxygen saturation range 78-86%) had serum erythropoietin levels (range 14-36 m-i.u./ml) which were indistinguishable from normal (range 12-44 m-i.u./ml) and showed circadian changes which were not significantly different (P = 0.35) from those in the normal subjects. 5. Thus, mild nocturnal oxygen desaturation is not associated with elevation of serum erythropoietin levels, whereas daytime hypoxaemia with associated severe nocturnal desaturation is associated with increased serum erythropoietin levels both by day and by night.

Cough, wheeze and breathlessness at night are common problems for many asthmatics and result from airway narrowing. Therapy should consist of improving management of their asthma over the full 24 h day by use of inhaled steroids and conventional inhaled bronchodilators. Such therapy should be introduced before treatment specifically improving nocturnal airway calibre is introduced. Inhaled long acting beta 2-agonists are the current long acting bronchodilator of choice in such patients.

Marked hypoxemia occurs during REM sleep in patients with chronic obstructive pulmonary disorder. This article deals with the mechanisms, pathophysiologic consequences, and treatment of REM hypoxemia.

1. To investigate the role of mast cells and eosinophils in the pathogenesis of nocturnal asthma, the plasma methylhistamine concentration, serum eosinophil cationic protein level and peak expiratory flow rate were measured 2-hourly for 24 h in 10 patients with nocturnal asthma and in 10 healthy control subjects. Nocturnal asthma was defined as at least one nocturnal awakening per week due to cough, wheeze or breathlessness with an average overnight fall in peak expiratory flow rate of at least 15% during a 2-week run-in period. 2. The lowest peak expiratory flow rate occurred at 02.00-04.00 hours in the group with nocturnal asthma, whose overnight fall in peak expiratory flow rate was 29 +/- 5% in comparison with 5 +/- 1% (means +/- SEM) in the normal subjects. 3. Plasma methylhistamine levels at night (0.200-04.00 hours) were lower than during the day (10.00-20.00 hours) in both asthmatic patients and normal subjects (asthmatic patients: day, median 0.22 ng/ml, 95% confidence intervals 0.18-0.34 ng/ml; night, 0.17 ng/ml, 0.13-0.24 ng/ml; P < 0.01; normal subjects: day, 0.31 ng/ml, 0.24-0.41 ng/ml; night, 0.24 ng/ml, 0.21-0.33 ng/ml; P < 0.01). 4. The serum eosinophil cationic protein level was higher by day (30 ng/ml, 8-47 ng/ml) than by night (21 ng/ml, 5-34 ng/ml; P < 0.04) in the group with nocturnal asthma, but did not change significantly with the time of day in the normal subjects (day: 8 ng/ml, 4-14 ng/ml; night: 8 ng/ml, 5-21 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

As alcohol ingestion may worsen the sleep apnea/hypopnea syndrome, we have investigated the alcohol consumption of patients with the sleep apnea/hypopnea syndrome in comparison to control subjects to determine whether patients with the sleep apnea/hypopnea syndrome drink excessively. A lifetime alcohol history was taken from each. There was no significant difference between the 50 patients with the sleep apnea/hypopnea syndrome and 95 age-matched controls in either the lifetime (patients 27, SEM 5 x 10(3); controls 26, SEM 4 x 10(3) units) or current (12, SEM 2; 12, SEM 2 units per week) alcohol consumption. There was no evidence that alcohol consumption was related to the development of arterial carbon dioxide retention or peripheral edema in such individuals.

We previously reported that the best definition of hypopneas in the sleep apnea/hypopnea syndrome (SAHS) is based on reduction in thoracoabdominal movement. However, the repeatability of scoring hypopneas from thoracoabdominal movement has not been assessed, nor has the need to record flow as well as thoracoabdominal movement. Thus, two polysomnographers independently scored both apneas and hypopneas on all-night polysomnograms of patients with SAHS. There was close agreement between the polysomnographers for the number of hypopneas (r = 0.98; mean difference 11%) and for the number of apneas (r = 0.99; mean difference 8%). The agreement was similar for the durations of both hypopneas (r = 0.99; mean difference 13%) and apneas (r = 0.99; mean difference 11%). There was also close agreement between the total number of respiratory events scored with and without reference to the flow signal (r = 0.99; mean difference 1.4%) with a maximum under-recognition of 18 events per night in a subject with 237 apneas per night. Thus, hypopneas can be scored reproducibly. In addition, the value of always recording and scoring flow as well as thoracoabdominal signals is questioned.

The effect of theophylline on sleep quality and cognitive performance in patients with obstructive lung disease has been the subject of controversy. To examine the direct effects of theophylline on sleep quality and cognitive performance, without confounding effects from bronchodilatation, we have undertaken a study of the drug in healthy subjects. A double-blind, placebo-controlled crossover protocol was used to study the effect of oral sustained-release theophylline (Theodur) on subjective sleep quality, objective sleep quality, and cognitive performance. Overnight sleep studies were carried out on Nights 13 and 14 of each 2-wk study limb, and cognitive performance tests administered on Days 1 and 13 of each limb. A total of 18 subjects satisfactorily completed the study (8 males, median age 37, range 24 to 67 yr). Theophylline levels were median 10.2, range 2.3 to 13.3 micrograms/ml on Day 1 and 14.7, range 9.6 to 17.5 micrograms/ml on Day 13. No significant difference was observed between theophylline and placebo on subjective or objective sleep quality or on acute or medium-term cognitive performance. We conclude that theophylline does not affect sleep quality or cognitive performance in normal adults.

Background: The use of computed tomography in mediastinal staging of lung cancer relies on the premiss that malignant lymph nodes are larger than benign ones. This hypothesis was tested by linking node size and presence or absence of malignancy and looking at factors possibly influencing the size of benign nodes., Methods: All accessible mediastinal lymph nodes were taken from 56 consecutive patients with lung cancer who underwent thoracotomy. Nodes were measured and histologically examined. Resected cancer bearing lung from 44 of these patients was assessed for degree of acute and chronic inflammation., Results: Lymph node size was not significantly related to the presence of metastatic disease, 58% of malignant and 43% of benign lymph nodes measuring over 15 mm. Similarly, there was no statistically significant relation between size of lymph nodes and the likelihood of malignancy, 20% of lymph nodes of 10 mm or more but also 15% of those less than 10 mm being malignant. Thresholds of 15 and 20 mm showed similar results. The maximum size of benign lymph nodes was significantly greater in those patients with histological evidence of acute pulmonary inflammation than in those without., Conclusions: The study shows that in patients with lung cancer (1) malignant mediastinal lymph nodes are not larger than benign nodes; (2) small mediastinal lymph nodes are not infrequently malignant; and (3) benign adenopathy is more common in patients with acute pulmonary inflammation.

Patients with sleep apnea/hypopnea syndrome commonly demonstrate impaired daytime performance. In a prospective study, 29 patients with sleep apnea/hypopnea syndrome were assessed polysomnographically to determine the relationship of cognitive performance and daytime sleepiness with sleep disruption, hypoxemia, and mood. Deterioration of cognitive performance correlated significantly with increasing severity of nocturnal breathing irregularity, magnitude of nocturnal hypoxemia, and extent of sleep disruption. Multiple regression analysis identified frequency of apneas plus hypopneas and of arousal and the extent of nocturnal hypoxemia as the variables most strongly associated with cognitive deficits. Anxiety and depression also contributed to this impairment. Objective daytime sleepiness was not significantly associated with nocturnal variables. This study showed that the frequency of breathing irregularities and the extent of both sleep disruption and nocturnal hypoxemia are important in determining daytime function in patients with sleep apnea/hypopnea syndrome. All of these factors should be considered when deciding which patients require treatment.

Polysomnography is used increasingly to investigate patients with possible sleep apnoea/hypopnoea syndrome (SAHS), but it has not been assessed critically. We thus examined prospectively the value of electrophysiological and respiratory monitoring in 200 consecutive adults (163 men, 37 women; mean [SD] age 50 [13] years) having polysomnography. At polysomnography, 91 patients had SAHS (greater than 15 apnoeas + hypopnoeas [A + H] per h asleep) and 11 had periodic limb-movement disorder. Recording sleep electrophysiologically was of no diagnostic value and SAHS could be as accurately defined by A + H per time in bed as by A + H per time asleep. 66% of patients with SAHS could be diagnosed with oximetry alone, but many of the undiagnosed patients had moderately severe SAHS and benefited from treatment. Neurophysiological sleep recording is unnecessary and oximetry alone is of limited value in the overnight investigation of patients suspected of having SAHS.

Increased parasympathetic tone does not fully explain the night-time bronchoconstriction responsible for nocturnal cough and wheezing in asthmatic subjects. The overnight variation in function of the other neural pathway innervating bronchial smooth muscle--the non-adrenergic, non-cholinergic (NANC) system--was thus examined. NANC function was tested after parasympathetic and beta-adrenergic blockade in 12 normal subjects and 12 patients with mild asthma by comparing the bronchodilator effect (measured as oscillatory resistance, Ros) of capsaicin (an NANC stimulant) at 0400 h with that at 1600 h. The order in which capsaicin or diluent was given was randomised, and observers were blind as to which substance had been inhaled. Bronchodilatation was greater at 1600 h than at 0400 h in both the normal subjects (mean decrease in Ros 1-3 min after capsaicin at 1600 h 9% [SEM 1], at 0400 h -2% [1]; p less than 0.001) and the asthmatic group (1% [1], -7% [2]; p = 0.001). The results suggest that inhibition of NANC function in the early morning may contribute to overnight bronchoconstriction.

Respiratory inductance plethysmography (RIP) has been widely used to measure ventilation during sleep, but its accuracy in this role has not been adequately tested. We have thus examined the accuracy of the RIP by comparing tidal volume measured with RIP with that measured by a pneumotachograph in eight unrestrained normal subjects during sleep. We have also studied the effect of posture on the accuracy of the RIP. In all sleep stages the correlation between RIP tidal volume measurements and expired volume showed relatively poor correlations (mean r = 0.49-0.60), and the bias of the measurements varied widely. Changes in posture altered the correlations between the two measurements, with no systematic differences between positions. When the subjects resumed a position, the 95% confidence intervals of tidal volume measurement did not overlap the original confidence limits in that posture on 13 of 25 occasions. This study shows that the RIP does not accurately measure tidal volume during sleep in unrestrained subjects and should only be used for semiquantitative assessment of ventilation during sleep.

The aim of the study was to determine the maximum effective dose of nebulized ipratropium bromide, 0.5 or 1.0 mg, in the treatment of acute severe attacks of asthma. Thirty-two patients (ten males, 19-53 years) who were admitted with acute severe asthma were, in a double-blind trial, randomized to receive either 0.5 or 1.0 mg of isotonic, preservative-free ipratropium bromide nebulized in saline. Ear oxygen saturation, peak flow and heart rate were measured on admission and regularly following nebulization. Two hours after nebulization of the ipratropium, terbutaline (5 mg) was administered by nebulizer and further measurements taken 30 min later. Twenty-six patients completed the study, 13 in each group. Peak expiratory flow (PEF) increased by 51% [1211 min-1 increasing to 1831 min-1 (mean)] in the 0.5-mg ipratropium group, and by 37% (1551 min-1 to 2071 min-1) in the 1.0-mg group. There were no significant differences in heart rate or ear oxygen saturation changes between the groups. Nebulized terbutaline led to a small further rise in peak flow in both groups (341 min-1 in the 0.5-mg group; 411 min-1 in the 1.0-mg group). No side-effects were noticed in either group. We conclude that 0.5 mg of nebulized ipratropium is as effective as 1.0 mg in the treatment of acute severe asthma.

The effect of posture on upper airway dimensions was assessed for two reasons. First, some patients with untreated sleep apnea/hypopnea syndrome (SAHS) report they sleep better sitting upright. Second, to allow comparison of the differing techniques used to determine the site of maximal airway narrowing in awake patients with SAHS, as some are carried out in the erect and others in the supine posture. Lateral cephalometry was therefore carried out in 33 nonsnoring normal subjects and in 29 patients with obstructive SAHS (mean apneas plus hypopneas, 46 per hour; range, 17 to 103). In both normal subjects and patients, uvular width was increased (p less than 0.05) in the supine posture, and this was associated with significant narrowing of the retropalatal airway in the patients with SAHS (erect, 5.0 +/- SD 2.6 mm; supine, 3.6 +/- 2.8 mm; p less than 0.01). In both normal subjects and patients, the retroglossal hypopharynx widened (p less than 0.05) in the supine posture (e.g., in patients with SAHS, posterior airway space was: erect, 11.5 +/- 4.5 mm; supine, 13.4 +/- 4.8 mm; p = 0.003). In the supine posture there was anterior movement of the hyoid and neck flexion in both groups. However, a study of the effect of neck flexion in the erect posture showed that neck flexion produced no changes in airway caliber. Thus, posture is an important determinant of upper airway dimensions.

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.

To clarify the roles of lung function, nocturnal hypoxemia and obesity in the development of peripheral edema in patients with the sleep apnea/hypopnea syndrome (SAHS), 65 consecutive SAHS patients had diagnostic sleep studies and respiratory function testing. Eighteen patients (27%) had peripheral edema without other explanation. Their sleep apnea/hypopnea index was similar to those without edema, but they were more obese (p less than 0.01) and had worse lung function (p less than 0.01) and lower oxygen saturation (SaO2) awake (p less than 0.01). These 18 became more hypoxemic during sleep than predicted from their awake SaO2 (p less than 0.005). Eleven patients with edema had evidence of pulmonary hypertension on cardiac catheterization, chest radiograph, or electrocardiograph and could be weight matched to 11 SAHS patients without edema. Those with right heart failure were more hypoxic (p less than 0.01) when awake, desaturated more frequently during sleep (p less than 0.01), and had lower FEV1% predicted (p less than 0.01). Thus, extent of both daytime and nighttime hypoxemia are important in the development of right heart failure in patients with SAHS.

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.

Sixty patients with histologically proven lung cancer who had been accepted for mediastinoscopy or thoracotomy were prospectively entered into a study to evaluate computed tomographic (CT) scanning, 57Co-bleomycin scanning, and barium swallow in preoperative assessment of mediastinal lymph node metastasis. Fifty-six patients had thoracotomy at which all accessible lymph nodes were sampled. Twenty-four patients were found to have mediastinal tumor on histologic analysis of the resected mediastinal lymph nodes. Neither 57Co-bleomycin scanning nor barium swallow were clinically useful, with sensitivities of 21 percent and 11 percent respectively, whereas CT scanning was helpful. However, there was no clear cutoff point of node size to optimize sensitivity and specificity for CT scanning. When nodes greater than or equal to 15 mm were taken to indicate likely malignancy, the sensitivity was 58 percent and the specificity was 87 percent and when greater than or equal to 10 mm was used the sensitivity was 80 percent but the specificity was only 55 percent. There was no clear relationship between the size of the largest resected lymph node in each patient and the presence of malignant lymph nodes. Only 42 percent of patients with resected nodes greater than or equal to 2 cm had histologic evidence of metastases. We conclude that CT scanning should be used to indicate the presence and site of mediastinal lymph nodes, which, when visualized, should always be sampled and histologically examined prior to resection of primary tumor.

While there are many research questions still requiring performance of research sleep studies in patients with COPD, their use is not advocated in routine clinical practice, except in patients who have symptoms of the sleep apnoea/hypopnoea syndrome or possibly in those without daytime hypoxaemia (PaO2 greater than 60 mmHg) who have marked polycythaemia or marked cor pulmonale.

Sleep apnoea syndrome, consisting of daytime sleepiness and loud snoring, is caused by obstruction of the upper airways. This paper reviews the techniques which could be used for localising and quantifying the degree of obstruction while the patient is sleeping. Each has specific limitations and it is concluded that while none is ideal, magnetic resonance imaging and ultrasound show the greatest promise.

A computer program was developed to calculate the frequency dependence of dynamic compliance (Cdyn) using continuous data analysis. Cdyn was measured repeatedly in eight normal human subjects over a 2-yr period. Comparison with Cdyn results measured manually showed that the computer program improved 10-fold the ratio of variance within subjects to between subjects of the compliance at specific frequencies, but there was only slight improvement in indices of the slope of the frequency dependence of compliance. We suggest that the absolute compliance at specific frequencies merits further consideration as a pathophysiological measurement and that, if the frequency dependence of compliance continues to be used, standardization of its calculation should be applied and the wide normal range should be more widely appreciated. Measurements of Cdyn in subjects breathing 80% helium-20% oxygen confirm that inertia is insignificant when breathing with tidal volumes of less than 500 ml and frequency of less than 1.5 Hz.

The role of drug therapy in the treatment of the sleep apnea/hypopnea syndrome is unclear. In a randomised, double-blind, placebo-controlled study, we investigated the value of 14-day therapy with protriptyline (20 mg daily) or acetazolamide (250 mg 4 times per day) on symptoms and on the frequency of apneas, hypopneas, arousals, and 4% desaturations in 10 patients with obstructive sleep apnea/hypopnea syndrome. Overall, protriptyline did not have a significant effect either on symptoms or on any of the above polysomnographic criteria. Acetazolamide reduced the apnea/hypopnea frequency [placebo 50 +/- 26 (SD); acetazolamide 26 +/- 20/h of sleep, p less than 0.03] and tended to decrease the frequency of 4% desaturations (placebo 29 +/- 20; acetazolamide 19 +/- 16/h of sleep, p = 0.06). Despite these physiological improvements, acetazolamide did not significantly improve symptoms and paraesthesiae were common. Contrary to earlier studies, we conclude that protriptyline may have a limited role in the treatment of the sleep apnea syndrome. The reason why acetazolamide produced a physiological, but not a symptomatic, response requires further investigation.

The changes in maximum expiratory flow rates after washing out lung air with a helium/oxygen mixture (He/O2, 80 : 20) were measured in 24 patients with chronic irreversible airflow obstruction (FEV1 1.77 +/- SD 0.39 litres; FVC 3.62 +/- 0.59 litres), and in six normal subjects. The percentage increase in flow breathing He/O2 was variable; however, it was similar in normal subjects and in patients with airflow obstruction, and in both groups decreased at low lung volumes. Contrary to previous studies, only three patients with chronic airflow obstruction failed consistently to increase flow rates by greater than or equal to 20% when breathing He/O2 at all lung volumes measured. In six normal subjects and 12 patients with chronic airflow obstruction airway gas viscosity was increased by breathing a neon/oxygen mixture (Ne/O2, 80 : 20). The response to Ne/O2 was again variable (normal subjects delta Vmax.40 4 +/- SD 14%; patients delta Vmax.40 18 +/- 8%). Only two normal subjects and one patient with airflow obstruction consistently reduced their flow rates when breathing Ne/O2. These results indicate either that there is no difference in the distribution of airflow resistance in normal subjects and in patients with chronic airflow obstruction, or that density as well as viscosity is an important determinant of flow in very small airways. In either case, He/O2 breathing is not a good discriminator of the site of airflow obstruction.

Sleep apnea syndromes and nonapneic arterial oxygen desaturation during sleep are reported more commonly in men than in women. Because men have recently been shown to have a considerably reduced hypoxic ventilatory response (HVR) during sleep, we questioned if this finding would apply to women as well. Accordingly, we measured isocapnic hypoxic responsiveness in 6 normal women during wakefulness and all stages of sleep during both follicular and luteal phases of the menstrual cycle. During non-REM sleep, women were found to maintain their waking levels of HVR, measured as the slope of the relationship between ventilation and decreasing hemoglobin saturation. Hypoxic ventilatory response fell to 70% of the awake value during REM sleep, which was a significant change (p less than 0.05). Although HVR tended to be greater in the luteal than in the follicular phase of the menstrual cycle, both awake and asleep, this was significant only in Stage 2 sleep (p less than 0.05). When compared with recently reported men studied in this laboratory, these women demonstrated significantly less awake HVR even when corrected for body surface area (p less than 0.05). During sleep men and women had similar hypoxic responses, although this represents a considerable decrement in the awake response in the men and little change in the women. How these findings relate to the observed sexual differences in "sleep disordered breathing" is speculative.

Sixty consecutive patients with central bronchial carcinomas were studied by fibreoptic bronchoscopy. In all forceps biopsy and bronchial needle aspiration were performed, and in 54 bronchial brushings were obtained. The combination of bronchial brushings and forceps biopsy diagnosed bronchial carcinoma of a defined cell type in 80% of patients. Bronchial needle aspiration was the most effective single technique giving a cytological diagnosis in 80% of patients, and when all three techniques were combined the positive rate increased to 92%. No major complications occurred using bronchial needle aspiration. Needle aspiration was particularly helpful when sampling from lesions in the upper lobes where forceps biopsies were technically difficult, from tumours lying submucosally, and from abnormalities caused by extrinsic compression. We conclude that bronchial needle aspiration should be used routinely, together with other sampling techniques, in the diagnosis of central bronchial carcinoma with the fibreoptic bronchoscope.

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.

We found that respiratory measurements in Chinese visitors to Colorado differed from those in height- and weight-matched Western residents of Denver, Colo., in the following ways (p less than 0.05): The Chinese had higher respiratory frequencies (15.5 +/- 0.93 vs. 11.4 +/- 0.85 breaths/min), lower tidal volumes (530 +/- 35.9 vs. 693 +/- 477.7 ml), lower alveolar ventilation (4.0 +/- 0.15 vs. 4.7 +/- 0.21 liters), lower forced vital capacities (4.53 +/- 0.16 vs. 5.43 +/- 0.12 liters), lower total lung capacities (6.25 +/- 0.26 vs. 7.16 +/- 0.17 liters), higher resting PaCO2 (36.3 +/- 0.94 vs. 33.6 +/- 0.74 Torr) and lower pHa (7.406 +/- 0.004 vs. 7.419 +/- 0.004). The Chinese also had lower ventilatory responses to CO2 (1.40 +/- 0.10 vs. 2.00 +/- 0.201/min/mm Hg) than did the Caucasians. The measurements made in the Chinese in Denver were similar to those reported for Chinese in China. Thus there may be differences in respiratory function between normal Chinese and normal Western subjects.

The sleep apnoea/hypopnoea syndrome has been reported to be rare in Britain. We have offered a clinical service for the diagnosis and treatment of this condition in Scotland for four years during which there has been an increase in referral rate from 19 patients in year 1 to 61 in year 4. We report the clinical features of the 80 patients. Seventy-eight snored and 70 were somnolent, each falling asleep at least once each day when not in bed. Ten reported falling asleep whilst driving or flying. Twenty-nine slept restlessly, 28 were not refreshed by sleep and 21 had nocturnal choking attacks. Ankle swelling was reported by 26 and 25 were hypertensive (diastolic BP greater than 95 mmHg). Two had hyperthyroidism and one acromegaly. Nineteen have been successfully treated by continuous positive airway pressure therapy at home. The data suggest that regional centres should be established in Britain to diagnose and treat this condition.

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.

We have observed patients who clinically have the obstructive sleep apnea syndrome but have no apneas, instead having recurrent nocturnal hypoventilation. There is disagreement about the definition and significance of such sleep-related hypopneas. We have thus analyzed breathing patterns, oxygenation and sleep records of 50 consecutive patients referred with the clinical features of the sleep apnea syndrome and found to have abnormal breathing during sleep to determine: (1) the best definition of hypopnea, and (2) how frequently patients have the clinical features of the sleep apnea syndrome without recurrent apneas. Hypopnea definitions based on decreases in thoracoabdominal movement yielded hypopnea frequencies that were significantly closer to desaturation and arousal frequencies than hypopnea definitions based on flow reduction. The best hypopnea definition was that of a 50% reduction in thoracoabdominal movement lasting for 10 s. This was validated in 33 normal subjects, all of whom had fewer than 11 hypopneas/h, and fewer than 14 apneas plus hypopneas/h of sleep. Thirty-two of the 50 patients had 10 or more apneas/h, the remaining 18 having 9 to 98 hypopneas/h such that all patients had more than 16 apneas plus hypopneas/h. Patients with recurrent hypopneas were clinically indistinguishable from and had a similar frequency of 4% desaturations (zero to 104/h) and arousals (7 to 98/h) to the patients with frequent apneas. This study confirms that hypopneas are clinically important and that the "sleep apnea syndrome" may occur in the absence of recurrent apneas.

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.