Nocturnal hypoxaemia and quality of sleep in patients with chronic obstructive lung disease.

Fifty patients with chronic obstructive lung disease were questioned about their sleep quality and their responses were compared with those of 40 similarly aged patients without symptomatic lung disease. Patients with chronic obstructive lung disease reported more difficulty in getting to sleep and staying asleep and more daytime sleepiness than the control group. More than twice as many patients (28%) as controls (10%) reported regular use of hypnotics. In a subgroup of 16 patients with chronic obstructive lung disease (mean FEV1 0.88 (SD 0.44) sleep, breathing, and oxygenation were measured to examine the relationship between night time hypoxaemia and sleep quality. Sleep architecture was disturbed in most patients, arousals occurring from three to 46 times an hour (mean 15 (SD 14)/h). Arterial hypoxaemia during sleep was common and frequently severe. The mean (SD) arterial oxygen saturation (SaO2) at the onset of sleep was 91% (7%). Nine patients spent at least 40% of cumulative sleeping time at an SaO2 of less than 90% and six of these patients spent 90% of sleeping time below this level. Only four of 15 patients did not develop arterial desaturation during sleep. The mean minimum SaO2 during episodes of desaturation was less in rapid eye movement (REM) sleep (72% (17%)) than in non-REM sleep (78% (10%), p less than 0.05). The predominant breathing abnormality associated with desaturation was hypoventilation; only one patient had obstructive sleep apnoea. Arousals were related to oxygenation during sleep such that the poorer a patient's arterial oxygenation throughout the night the more disturbed his sleep (arousals/h v SaO2 at or below which 40% of the total sleep time was spent: r = 0.71, p less than 0.01). Hypoxaemia during sleep was related to waking values of SaO2 and PaCO2 but not to other daytime measures of lung function.     

Supplemental oxygen and exercise ability in chronic obstructive airways disease.

The influence of supplemental oxygen on exercise performance was assessed in 17 patients with severe airflow obstruction. Exercise capacity was measured by the six minute walking distance, by an endurance walking test, and by an endurance cycling test and comparison was made with performance when the patient was breathing air. In addition, the relation between the flow rate of supplemental oxygen and cycling endurance time was studied. Portable oxygen (41 min-1) carried by the patient increased the mean endurance walking time by 59% and the six minute walking distance by 17%. The endurance time for cycling at a constant work load was increased by 51% with oxygen at a flow rate of 21 min-1, by 88% at 41 min-1, and by 80% at 61 min-1. Supplemental oxygen prolonged the length of time that the patients were able to walk at a fixed speed. It also increased the mean speed achieved during a six minute walk but this was variable and did not occur in all the subjects. The benefit from supplemental oxygen was not cancelled by the effort of carrying the portable cylinder.     

Prediction of oxygenation during sleep in patients with chronic obstructive lung disease.

The accuracy of a prediction equation for assessing the lowest arterial oxygen saturation (SaO2) during sleep was determined in 24 consecutive patients with chronic obstructive lung disease referred for assessment for home oxygen therapy. Subjects had a mean (SD) FEV1 of 0.81 (0.31) litre and an FEV1/FVC of 37% (12%). There was reasonable agreement between predicted and measured values (mean difference [predicted-measured] = -2.5%) but the prediction was not precise as the 95% confidence interval for the difference was +8% to -13%. The duration of arterial oxygen desaturation, defined as the percentage of total sleep time spent below a given SaO2, was not predicted accurately. It is concluded that nocturnal arterial oxygen desaturation in individual patients with chronic obstructive lung disease cannot be predicted from "awake" measurements with sufficient accuracy to be clinically useful.     

Induction of sleep apnoea with negative pressure ventilation in patients with chronic obstructive lung disease.

BACKGROUND: Negative pressure ventilation provides intermittent non-invasive ventilatory assistance for patients with advanced chronic obstructive lung disease. Upper airway obstruction during sleep, a reported complication of the technique, may, however, limit its clinical applicability. METHODS: The effects of nocturnal negative pressure ventilation on ventilation and on indices of sleep quality were investigated in five patients with severe chronic obstructive lung disease (mean (SE) FEV1 31% (3%) predicted) who had completed three months of nightly negative pressure ventilation. Subjects underwent overnight polysomnography on consecutive nights, the first night serving as a control and negative pressure ventilation being provided on the second night. Ventilators were adjusted to result in maximum suppression of the peak phasic electromyogram signal from the diaphragm. RESULTS: Negative pressure ventilation resulted in substantial increases in episodes of obstructive apnoea and hypopnoea (mean (SE)/h 59.3 (19.8) v 3.2 (1.3) on control nights). Most obstructive events, however, were associated with under 3% oxygen desaturation, and the lowest recorded values for overnight oxygen saturation were similar on the two study nights. Negative pressure ventilation was also associated with significant increases in the frequencies of movement arousals and changes in sleep stage. CONCLUSIONS: Negative pressure ventilation applied during sleep to patients with advanced chronic obstructive lung disease may result in the development of recurrent episodes of apnoea and hypopnoea as well as altered sleep quality, which could limit its clinical applicability.     

Effects of breathing supplemental oxygen before progressive exercise in patients with chronic obstructive lung disease.

A study was carried out to determine whether supplemental oxygen before exercise would improve maximum exercise performance and relieve exertional dyspnoea in 20 patients with chronic obstructive lung disease (mean FEV1 0.79 l; forced vital capacity 2.30 l). Patients performed two progressive treadmill exercise tests to a symptom limited maximum, with at least 30 minutes rest between tests. They received compressed air or supplemental oxygen from nasal prongs for 10 minutes before exercise in a double blind randomised trial with a crossover design. Heart rate and breathlessness score on a visual analogue scale were compared between tests at 75% of the maximum distance walked in the compressed air test. The mean arterial oxygen saturation (SaO2) after oxygen (93%) was significantly higher than after compressed air (91%). There was no significant change, however, in maximum distance walked or maximum heart rate, or in the breathlessness score or heart rate at 75% of maximum distance walked. The study had a power of 93% for detecting an increase of 50 metres in maximum distance walked. There was an order effect, with better performance on the second test; but the magnitude of the difference was small. It is concluded that administration of supplemental oxygen sufficient to raise SaO2 above 90% for 10 minutes before exercise is unlikely to improve maximum exercise performance or breathlessness on exertion in patients with chronic obstructive lung disease.     

慢性阻塞性肺疾病患者睡眠质量及影响因素调查

目的了解慢性阻塞性肺疾病(COPD)患者睡眠状况及风险因素。方法便利抽取COPD患者和健康体检对照人群各100例为研究对象,采用匹兹堡睡眠质量指数量表(PSQI)、睡眠信念与态度量表(DBAS)、焦虑自评量表(SAS)、呼吸困难量表(MMRC)、圣乔治呼吸问卷(SGRQ)进行调查,采集一般资料、行肺功能等检查。结果 COPD组和对照组睡眠障碍发生率分别为72.92%和42.86%,两组比较,差异有统计学意义(P0.01)。COPD组的PSQI总分及各维度得分显著高于对照组(P0.05,P0.01)。睡眠障碍组患者与无睡眠障碍组患者在年龄、夜间治疗、第1秒用力呼气量占预计值的百分比、呼吸困难分级、SAS评分、SGRQ评分及DBAS评分方面的差异有统计学意义(P0.05,P0.01)。呼吸困难分级、DBAS、SGRQ是影响睡眠质量的主要因素(P0.05,P0.01)。结论 COPD患者睡眠质量较差。呼吸困难程度、睡眠认知、躯体症状、心理状况等是影响睡眠质量的主要因素,积极治疗原发病、改善呼吸功能和躯体症状,建立有效的睡眠认知是提高睡眠质量的关键。     

Nutritional state and exercise performance in patients with chronic obstructive lung disease.

The relation between exercise performance and certain measures of nutritional state was investigated in 83 patients with stable chronic obstructive lung disease (mean age 62 (8) years). All patients had a forced expiratory volume in one second (FEV1) less than 50% predicted, an arterial oxygen tension of more than 7.3 kPa, and no severe locomotor, cardiovascular, neurological, or endocrine disorders. Exercise performance was assessed from a 12 minute walking test; body weight (as a percentage of ideal weight), creatinine height index, and serum concentrations of albumin, transferrin, and prealbumin were assessed as measures of nutritional state. Mean values of the nutritional variables were within the normal range. The mean (SD) 12 minute walking distance was 686 (254) metres. Walking distance was positively associated with serum albumin concentration and creatinine height index but not with body weight, serum prealbumin, or serum transferrin concentrations. When patients were categorised into low, medium and high performance groups on the basis of their walking distance, a very low creatinine height index (mean (SD) 59% (19%] was found in the low performance group. Albumin explained part of the variance in walking distance independently of pulmonary function in a stepwise regression analysis. The findings suggest that in patients with chronic airflow obstruction skeletal muscle mass and serum albumin concentration are positively associated with exercise performance as measured with a 12 minute walk.     

Comparison of almitrine bismesylate and medroxyprogesterone acetate on oxygenation during wakefulness and sleep in patients with chronic obstructive lung disease.

The effects of almitrine bismesylate and medroxyprogesterone acetate on oxygenation during wakefulness and sleep were compared in six patients with chronic obstructive lung disease and carbon dioxide retention. Patients received 1.5 mg/kg almitrine (a peripheral chemoreceptor stimulant), 100 mg of medroxyprogesterone (a central respiratory stimulant), or matched placebo daily for 15 days in random order in a crossover trial. When subjects were awake almitrine increased the ventilatory response to hypoxia and increased arterial oxygen tension (PaO2) to a greater extent than medroxyprogesterone, whereas medroxyprogesterone augmented the ventilatory response to hypercapnia and decreased arterial carbon dioxide tension (PaCO2) to a greater extent than almitrine. Neither drug influenced sleep architecture significantly, except that medroxyprogesterone increased the number of arousals. Almitrine had a more favourable effect than placebo on oxygenation as estimated from arterial oxygen saturation (SaO2) during the different stages of sleep, the number of episodes of hypoxaemia, and the amount of time that SaO2 was below 80%. The only change with medroxyprogesterone by comparison with placebo was a decrease in the number of hypoxaemic episodes. It is concluded that both active drugs improved blood gases during wakefulness, but that 1.5 mg/kg of almitrine is superior to 100 mg of medroxyprogesterone in improving SaO2 during sleep.     

Comparison of arm and leg ergometry in patients with moderate chronic obstructive lung disease.

Exercise testing is traditionally performed with leg exercise on either a treadmill or a bicycle ergometer. Many of these tests are terminated before dyspnoea occurs because of leg fatigue, arthritic pain, or claudication. A study was carried out to determine whether arm ergometry testing might serve as an alternative method to leg testing in eight patients with chronic obstructive lung disease. The patients had mild to moderate dyspnoea on exertion and required bronchodilator treatment. They had smoked an average of 62 pack years and had a mean FEV1 of 1.88 l. Arm and leg ergometry yielded similar levels of maximum ventilation (arm 47.2, leg 48.6 l/min), maximum heart rates (126 v 124 beats/min), maximum tidal volume (1.5 v 1.6 l), and respiratory rate (30 v 29 breaths/min); but maximum oxygen consumption (1120 v 966 ml/min), maximum power output (62 v 26 w), and oxygen pulse (9.1 v 7.8 ml/beat) were all higher with leg than with arm ergometry. In addition, ventilation and heart rate at a given level of oxygen consumption were higher for arm than for leg work during both submaximal and maximal exercise. It is concluded that arm ergometry offers an alternative testing method to leg testing in patients with moderate chronic obstructive lung disease.     

Determinants of health-related quality of life in patients with chronic obstructive pulmonary disease.

BACKGROUND: The consequences of chronic obstructive pulmonary disease (COPD) on daily life, encapsulated by the term "health-related quality of life" (HRQL), are important in determining appropriate home care. There is a need to understand the relative contribution of respiratory impairment, physical disability, coping, age, and socioeconomic variables on HRQL. METHODS: Patients with COPD were recruited on admission to a pulmonary rehabilitation centre. Respiratory impairment was assessed by lung function tests and physical disability was evaluated by a 12 minute walking test. HRQL was assessed by means of the St George's Respiratory Questionnaire (SGRQ) measuring "symptoms", "activity", and "impact". Because the SGRQ does not include a measure of "well being", this was taken from the medical psychological questionnaire for lung diseases. The COPD coping questionnaire and a questionnaire covering basic socioeconomic variables were also used. RESULTS: One hundred and twenty six patients of mean (SD) age 65 (9) years and mean (SD) forced expiratory volume in one second (FEV1) 39 (9)% predicted were included. The scores on the SGRQ indicated severe impairment. Correlations were found between lung function parameters, 12 minute walking test, and the HRQL "activity" and "impact" components. Coping strategies were correlated with the "activity", "impact", and "well being" components. No correlations were found between age, socioeconomic variables, and HRQL. FEV1, 12 minute walking test, and the coping strategies "avoidance" and "emotional reaction" were the best predictors of HRQL. CONCLUSION: In patients with COPD methods of improving physical performance and teaching adequate coping strategies should be considered in order to improve HRQL.     

Performance, ventilation, and oxygen consumption in three different types of exercise test in patients with chronic obstructive lung disease.

Seventeen patients (six men and 11 women, mean age 66 years) with severe chronic obstructive lung disease (mean FEV1 0.8 (SD 0.3)1) performed three different types of exercise test on four occasions within one week. Three daily doses of placebo tablets were given between the third and fourth attempt at each test. The tests were the 12 minute walking test, a fixed rate and height paced step test, and a cycle ergometer test in which the work rate was increased by 10 watts each minute. Performance increased significantly (p less than 0.01) between the first and fourth attempts in each type of test (12 min walking distance 16% (SD 20%); steps climbed 96% (74%); duration of cycling 29% (41%]. There was a trend for the increase in performance between successive attempts to become progressively smaller but this was not significant. No effect of placebo on exercise performance was detected. The greatest intersubject range of performance was seen in the step test (14-126 steps) and the least in the walking test (438-1014 m). Significant correlations (p less than 0.01) were observed between performance in all three types of exercise test, but the correlations found between the results of the various tests of exercise performance and the FEV1 and the FVC were either weak (p less than 0.05) or non-significant. Ventilation (VE) and oxygen consumption (VO2) were subsequently measured and compared in eight patients during all three types of exercise test. Both the VE and the VO2 that were achieved in the step test were significantly greater than in either the cycle or the walking test. No patient was able to reach and sustain steady state values of VE and VO2 in the step test, whereas a steady state for both VE and VO2 was reached and sustained by all eight patients in the walking test. It is suggested that at least three practice attempts at any exercise test should be made before the introduction of either placebo or specific pharmacological treatment and that even then it may be necessary to allow for the effects of further repeated testing in the assessment of the results of treatment.     

Thyroid function and endocrine abnormalities in elderly patients with severe chronic obstructive lung disease.

Serum pituitary and thyroid hormones, testosterone, and the response of pituitary hormones to thyrotrophin releasing hormone were measured in 20 inpatients (mean age 68, range 42-81 years) with severe chronic obstructive lung disease and in 15 control convalescent inpatients (mean age 73, range 57-83 years) who had normal respiratory function. No significant differences were found in total and free thyroid hormone concentrations and basal concentrations of thyrotrophin, growth hormone, and prolactin; and their increments after injection of thyrotrophin releasing hormone were similar in patients with chronic obstructive lung disease, and control patients. Three patients with chronic obstructive lung disease, however, had no thyrotrophin responses to thyrotrophin releasing hormone. In men, low testosterone concentrations were found both in patients with chronic obstructive lung disease and in controls. Luteinising hormone concentrations were higher in men with chronic obstructive lung disease (p less than 0.02), whereas concentrations of follicle stimulating hormone in the two groups were not significantly different. There was no significant correlation between arterial blood gas tensions and these hormone measurements. General effects of age and illness may be more important than direct effects of hypoxia in determining hypothalamic-pituitary function in elderly patients with chronic obstructive lung disease.     

Levalbuterol in the treatment of patients with asthma and chronic obstructive lung disease

Effective asthma control requires long-term (anti-inflammatory) controller medications for patients with mild-persistent to severe-persistent disease, and quick-relief bronchodilator medication for all patients with asthma to control intermittent symptoms of cough, wheeze, and bronchoconstriction, as well as acute exacerbations. For patients with chronic obstructive pulmonary disease, quick-relief and long-acting bronchodilators are primarily used in the maintenance and treatment of associated symptoms, including shortness of breath. For many years, the most widely used bronchodilator has been racemic (R, S)-albuterol, a short-acting beta2-adrenergic agonist, commonly dispensed as an inhaled aerosol or solution. Until the introduction of levalbuterol inhalation solution (Xopenex) in 1999, all marketed forms of albuterol (including Ventolin and Proventil brands) were racemic mixtures composed of a 1:1 ratio of (R)- and (S)-stereoisomers. Administered as a proportionally equivalent nebulized dose, levalbuterol [(R)-albuterol] provides greater bronchodilation than racemic albuterol and, in the appropriate clinical setting, offers the possibility for improving clinical outcomes in patients with asthma and other obstructive airway diseases. Additionally, levalbuterol can be given at lower doses than racemic albuterol to provide comparable bronchodilation, with the potential for reduced beta-mediated adverse effects in adults and children. Only since the past decade has the technology to separate stereoisomers become available, and thus the biologic activities of the albuterol stereoisomers had not been established. Binding studies have demonstrated that (R)-albuterol binds to the beta2-adrenergic receptor with a high affinity, whereas (S)-albuterol binds with 100-fold less affinity than (R)-albuterol. Other evaluations have suggested that (R)-albuterol possesses the bronchodilatory, bronchoprotective, and ciliary-stimulatory properties of racemic albuterol, while (S)-albuterol does not contribute beneficially to the therapeutic effects of the racemate and was originally assumed to be inert. However, preclinical evaluations have shown that (S)-albuterol has effects that work in opposition to (R)-albuterol and may diminish the therapeutic effects of (R)-albuterol.     

Clinical features of polycythaemic patients with chronic obstructive non-specific lung disease

Forty-five patients with chronic hypoxic lung disease were studied to ascertain whether those with polycythaemia had specific distinguishing features. Thirty-three patients had red cell volumes less than 120% of the predicted normal values, and 12 patients had red cell volumes greater than this level and were regarded as polycythaemic. The latter were found to have a higher incidence of the features associated with obstructive bronchitis, whereas the nonpolycythaemic subjects had more emphysematous characteristics. These findings may facilitate the selection of those patients who may benefit from a therapeutic reduction of red cell volume.     

Breathlessness and portable oxygen in chronic obstructive airways disease.

Breathlessness was measured in 20 patients with severe chronic obstructive lung disease by the use of a visual-analogue scale. Severe resting arterial hypoxaemia was not a feature. The severity of breathlessness measured in this way did not correlate well with the results of spirometric tests or with walking ability. The use of portable oxygen was studied during simple walking tests for its effect on walking ability and the sensation of breathlessness. Portable oxygen improved exercise capacity but a placebo effect of the system probably accounted for some of the improvement. A clear improvement of distressing breathlessness was observed and represented a useful therapeutic response. Breathlessness and simple exercise ability were shown to respond independently to oxygen breathing. The value of short-term intermittent oxygen in patients with severe chronic obstructive lung disease needs to be evaluated in terms of both exercise ability and breathlessness.     

Changes in day and night time oxygenation with protriptyline in patients with chronic obstructive lung disease.

The effect of protriptyline, a tricyclic antidepressant, on sleep architecture, nocturnal arterial oxygen desaturation, pulmonary function, and diurnal arterial blood gases was investigated in an open study of 14 patients with stable chronic obstructive lung disease. Daytime and overnight measurements were made before and 2 and 10 weeks after they started protriptyline (20 mg daily at bedtime). Two patients had to be excluded before the second visit and one before the third visit because of changes in treatment for their chest disease. Protriptyline caused mouth dryness in all patients and dysuria in six men. With protriptyline there were no significant changes in total sleep time, sleep period time, or the percentages of total sleep time occupied by stage I-II and stage III-IV sleep. The mean (SEM) percentage of total sleep time spent in rapid eye movement (REM) sleep decreased from 11.1 (1.7) to 4.6 (0.7) at two weeks and to 4.2 (1.0) at 10 weeks. After protriptyline the time spent during sleep with an arterial oxygen saturation (SaO2) below each 5% increment above 65% was less than the baseline time; the lowest SaO2 (%) reached during sleep increased from 64.5 (1.7) to 72.7 (2.1) at 2 weeks and to 77.4 (2.1) at 10 weeks. Lung volumes and expiratory flows were unchanged during the study. Daytime arterial oxygen tension (PaO2) increased from 57 (1.4) mm Hg before treatment to 62 (1.9) mm Hg at 2 weeks and to 66 (1.9) mm Hg at 10 weeks (7.6 (0.2), 8.3 (0.3), 8.8 (0.3) kPa). Carbon dioxide tension fell from 52 (2.3) mm Hg to 49 (1.4) mm Hg at 2 weeks and to 48 (2.0) mm Hg at 10 weeks (6.9 (0.3), 6.5 (0.2), 6.4 (0.3) kPa), but these changes were not significant. These results suggest that protriptyline may benefit patients with chronic obstructive lung disease by reducing the sleep induced falls in SaO2 and improving diurnal PaO2; a controlled trial is now required.     

Effect of lung transplantation on diaphragmatic function in patients with chronic obstructive pulmonary disease.

BACKGROUND--To date there are no data on the effects of lung transplantation on diaphragmatic function in patients with end stage chronic obstructive pulmonary disease (COPD). It is not known whether the relation between the transdiaphragmatic pressure (PDI) and lung volume is altered in recipients after transplantation as a result of changes in diaphragmatic structure caused by chronic hyperinflation. The effect of lung transplantation on diaphragmatic strength was determined in patients with COPD and the relation between postoperative PDI and lung volume analysed. METHODS--Diaphragmatic strength was assessed in eight double lung transplant recipients, six single lung transplant recipients, and in 14 patients with COPD whose lung function was similar to those of the transplant recipients preoperatively. PDI obtained during unilateral and bilateral phrenic nerve stimulation at 1 Hz (twitch PDI) at functional residual capacity (FRC) and during maximal sniff manoeuvres (sniff PDI) at various levels of inspiratory vital capacity (VCin) served as parameters for diaphragmatic strength. Sniff PDI assessed at the various VCin levels were used to analyse the PDI/lung volume relation. RESULTS--Lung transplantation caused a reduction in lung volume, especially in the double lung transplant recipients. As a consequence sniff PDI was higher in the double lung transplant recipients than in the patients with COPD at all levels of VCin analysed. However, sniff PDI values analysed at comparable intrathoracic gas volumes were not reduced in the patients with COPD when compared with those who underwent lung transplantation. Bilateral twitch PDI values were similar in the patients with COPD and in the lung transplant recipients. In the single lung transplant recipients unilateral twitch PDI values were similar on the transplanted and the non-transplanted side. The relation between PDI and lung volume was similar in the patients with COPD and in the lung transplant recipients. CONCLUSIONS--In patients with COPD lung transplantation leads to an increase the maximal sniff induced PDI values by placing the diaphragm in a more favourable position for pressure generation. Since patients with COPD and postoperative lung transplant recipients showed similar PDI/lung volume relations, this suggests that chronic pulmonary hyperinflation does not cause major functional alterations of the diaphragm.