噻托溴铵对稳定期COPD患者夜间睡眠低氧的临床疗效

目的观察噻托溴铵对慢性阻塞性肺疾病(COPD)患者夜间睡眠低氧和睡眠质量的疗效。方法 40例存在夜间睡眠低氧的稳定期COPD患者随机分为两组,治疗组吸入噻托溴铵,对照组吸入安慰剂,治疗前后检测夜间血氧饱和度、血气分析、肺功能和匹兹堡睡眠质量指数(PSQI)评分。结果治疗后治疗组夜间平均血氧饱和度、夜间最低血氧饱和度、动脉血氧分压和动脉血氧饱和度较对照组明显升高(均P<0.05),夜间血氧饱和度小于90%的时间占总睡眠时间的百分比和PSQI总分较对照组显著降低(均P<0.01),第1秒用力呼气容积、用力肺活量和深吸气量较对照组显著增加(均P<0.01)。结论噻托溴铵能改善COPD患者夜间睡眠低氧和睡眠质量。     

Oxygen desaturation during a 6 min walk test is a sign of nocturnal hypoxemia

BACKGROUND/OBJECTIVES:

Patients with chronic obstructive pulmonary disease (COPD) may experience sleep disordered breathing with nocturnal desaturation. An exploratory study was performed to determine whether any commonly measured clinical parameters were useful in predicting nocturnal desaturation in patients with COPD. A validation study was subsequently performed to confirm the utility of the parameter identified in the exploratory study as most useful in this regard.

METHODS:

A total of 103 (exploratory cohort) and 200 (validation cohort) consecutive patients with COPD admitted for pulmonary rehabilitation were evaluated. Standard outcome measures including nocturnal oximetry and the 6 min walk test (6MWT) on room air with continuous pulse oximetry were assessed. Patients with sleep apnea or those undergoing long-term oxygen therapy were excluded.

RESULTS:

In the exploratory study, the mean (± SD) patient age was 70±9.9 years, with forced expiratory volume in 1 s of 0.76±0.34 L, which was 36±16% of predicted. Body mass index, arterial oxygen tension, oxygen saturation by pulse oximetry at rest and during the 6MWT all demonstrated significant correlations with percentage of time spent with a saturation <90%. When the lowest pulse oximetry during the 6MWT was ≤88%, 10 of 21 patients demonstrated a saturation <90% for at least 30% of sleep time. This measure yielded a positive likelihood ratio of 3.77 (95% CI 1.87 to 7.62) compared with those who did not reach this threshold value. The validation study confirmed similar detection characteristics.

CONCLUSIONS:

Results from the present study suggest that monitoring oxygen saturation changes during a 6MWT is useful in helping to identify COPD patients who may experience significant nocturnal desaturation.     

慢性阻塞性肺疾病孤立夜间低氧血症的研究进展

COPD患者易出现夜间低氧血症,尤其是在快动眼睡眠时期。夜间低氧血症（nocturnaloxygendesaturation,NOD）不仅可发生于日间明显的低氧血症患者中（日间PaO2≤55mmHg）,亦可发生于日间无或轻度低氧血症（日间PaO2〉55mmHg或SaO2〉90％）患者。在我国通常将后者称为孤立NOD患者,本文就孤立NOD国内外研究现状作一综述。     

Drug therapy of sleep-related hypoxaemia

In patients with chronic obstructive pulmonary disease (COPD) exhibiting daytime hypoxaemia, a worsening of the latter occurs during sleep, particularly during REM sleep. The most efficient therapy of this sleep-related hypoxaemia is the nocturnal administration of O₂ at a flow rate of 1.5–3 l/min. An alternative therapy, when daytime hypoxaemia is not too severe (PaO₂>55 mmHg), is the use of almitrine (100 mg/day), a drug which improves daytime hypoxaemia in most COPD patients. The improvement of sleep hypoxaemia with almitrine is related to the increased daytime PaO₂ and cannot be considered as a specific effect of almitrine on sleep-related respiratory events. It must be emphasized that almitrine is ineffective in about 25% of COPD patients (“nonresponders”) and that almitrine can be used with conventional O₂ therapy in patients with severe hypoxemia (day-time PaO₂<55mmHg).     

重叠综合征

慢性阻塞性肺疾病（COPD）是一种以气流受限不完全可逆为特征的常见的慢性呼吸系统疾病。睡眠呼吸暂停低通气综合征（SAHS）也是一种具有潜在危险的常见病。故COPD与SAHS合并存在者即重叠综合征患者的概率相当高。COPD患者睡眠时显著的低氧血症和高碳酸血症发生于快动眼睡眠期。重叠综合征患者较单纯SAHS或COPD患者有更为严重的睡眠有关的低氧血症,表现出更为严重的肺功能损害和肺动脉高压。因此,重叠综合征患者的及时诊断和合理治疗具有重要临床意义。     

伴与不伴睡眠呼吸暂停综合征的COPD患者肺功能与低氧血症的关系

目的探讨慢性阻塞性肺疾病（COPD）伴与不伴睡眠呼吸暂停综合征（SAHS）患者夜间低氧与肺功能的关系。方法对140例稳定期COPD患者进行肺通气功能测定和家庭夜间血氧饱和度监测。用Spearman相关系数来对肺功能与最低血氧饱和度（LSaO2）,平均血氧饱和度（MSaO2）、SaO2低于90％时间占总睡眠时间百分比（SIT 90％）进行相关分析。结果相关分析表明夜间最低血氧饱和度与体重指数（BMI）呈负相关（r=-0．25,P〈0．05）、与FVC占预计值％（FVC％）、残气容积（RV）（r值分别为0．26、0．25,P均〈0．05）呈正相关,夜间平均血氧饱和度（MSaO2）与峰流量（PEF）、FVC％、FEV1占预计值％（FEV1％）、最大呼气中段流量（MMEF）呈正相关（r值分别为0．21、0．27、0．25、0．22,P均〈0．01）,与RV呈负相关（r=-0．32,P〈0．01）,SIT90％与RV呈正相关（r=0．22,P〈0．05）、与PEF、FVC、FVC％、FEV1、FEV1％呈负相关（r值分别为-0．29、-0．21,P均〈0．05）。阻塞程度相同的重叠综合征与单纯COPD患者在FEV1％,PEF％,RV％,TLC％,BMI,SIT90％,LSaO2等方面比较差异有统计学意义。结论COPD患者夜间低氧与COPD肺功能分级相关。伴SAHS的COPD患者（重叠综合征）夜间低氧比单纯COPD患者更严重。     

24-hour bronchodilation following a single dose of the novel β(2)-agonist olodaterol in COPD

Background

Current guidelines recommend long-acting bronchodilators as maintenance therapy in COPD when symptoms are not adequately controlled with short-acting agents. Olodaterol is a novel long-acting β₂-adrenoceptor agonist with a pre-clinical profile that suggests 24-h bronchodilation may be achieved with once-daily administration.

Objective

To assess dose- and time-response in terms of bronchodilator efficacy, and to evaluate pharmacokinetics, safety and tolerability of single doses of olodaterol administered via Respimat^® Soft Mist™ Inhaler in COPD patients.

Methods

A single-center, double-blind, placebo-controlled, 5-way crossover study including 24-h spirometry (FEV₁, FVC), safety, tolerability and pharmacokinetics (in a subset of patients) following dosing of olodaterol 2 μg, 5 μg, 10 μg and 20 μg; the washout period between test-days was at least 14 days. Primary endpoint of the study was the 24-h post-dosing FEV₁. Patients participating in the pharmacokinetic assessments continued in an open-label extension phase to establish pharmacokinetics of olodaterol 40 μg.

Results

36 patients were assigned to treatment; mean baseline prebronchodilator FEV₁ was 1.01 L (37% predicted normal). All doses of olodaterol provided significantly greater bronchodilation compared to placebo in 24-h FEV₁ post-dose (p < 0.001); a clear dose–response relationship was observed, with values ranging from 0.070 L for olodaterol 2 μg to 0.119 L for olodaterol 20 μg. Similarly, olodaterol was superior to placebo (p < 0.001) in peak FEV₁ (0.121 L to 0.213 L) and average FEV₁ both during the daytime (0–12 h; ranging from 0.099 L to 0.184 L) and night-time (12–24 h; ranging from 0.074 L to 0.141 L). FVC results were consistent with those observed for FEV₁. Pharmacokinetic evaluation of the peak plasma concentrations and renal excretion suggested no obvious deviation from dose-proportionality over the investigated dose range of 2 μg–40 μg; in most patients, no plasma levels could be detected following the 2 μg dose. All treatments were well tolerated with no apparent dose relation in terms of adverse events.

Conclusions

Olodaterol appears to be a promising long-acting β₂-adrenoceptor agonist,with bronchodilation maintained over 24 h that offers an opportunity for once-daily dosing in patients who require maintenance bronchodilator therapy for the management of COPD symptoms.     

睡眠片段对慢性阻塞性肺疾病和阻塞型睡眠呼吸暂停低通气患者日间嗜睡的意义

睡眠片段与白天嗜睡间的关系一直是研究的热点，也取得了较大的进展。本文将近年来慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）和阻塞型睡眠呼吸暂停低通气综合征（obstructive sleep apnea-hypopnea syndrome,OSAHS）的研究进展中关于睡眠片段的文献做一综述。     

慢性阻塞性肺疾病昼夜血氧变化及其临床意义

已有研究表明慢性阻塞性肺疾病(COPD)患者血氧的波动在氧化应激、炎症反应中均起重要作用[1]。由于COPD患者白天可能已有低氧血症,因此单纯夜间血氧饱和度水平不能真正反映昼夜血氧变化情况,而目前关于血氧的昼夜变化幅度对病情影响的研究较少。因此,本研究将从COPD患者昼夜血氧变化幅度的角度探讨其临床意义。     

慢性阻塞性肺疾病评估测试评分对预后的评估意义

目的探讨慢性阻塞性肺疾病评估测试(CAT)评分与慢性阻塞性肺疾病(COPD)患者预后因素之间的相关性,明确CAT评分对COPD患者预后评估的应用价值。方法选取2013年1月至2015年1月我院呼吸内科住院及门诊就诊的106例COPD患者为研究对象。对106例患者治疗前后进行CAT评分、6 min步行实验(6MWD)、改良英国MRC呼吸困难指数(m MRC)、BODE(B为体质量指数,O为气道阻塞程度,D为呼吸困难分数,E为运动耐力)指数、圣乔治呼吸问卷(SGRQ)评分及肺功能的测定。采用单因素线性相关分析CAT评分与患者各临床特征之间的相关性。结果随着CAT评分的升高,患者6MWD、用力呼气容积(FVC)实测值、FVC实测/预测值、一秒用力呼气容积(FEV1)实测值、FEV1实测/预测值、FEV1/FVC、呼气峰流速(PEF)实测值、PEF实测/预测值均明显降低(P0.05),而m MRC评分、BODE指数及SGRQ总评分明显升高(P0.05);患者经短期治疗后,CAT评分、BODE指数及SGRQ总评分均显著低于治疗前(P0.05),而6MWD、FEV1实测值、FEV1实测/预测值、FEV1/FVC则均显著高于治疗前(P0.05);单因素相关分析发现,治疗前CAT评分与m MRC评分(r=0.254,P=0.018)、BODE指数(r=0.426,P=0.009)及SGRQ总评分(r=0.563,P=0.007)呈显著正相关,与6MWD(r=-0.387,P=0.008)、FVC实测值(r=-0.181,P=0.023)、FVC实测/预测值(r=-0.192,P=0.021)、FEV1实测值(r=-0.201,P=0.016)、FEV1实测/预测值(r=-0.214,P=0.013)及FEV1/FVC(r=-0.223,P=0.012)呈显著负相关;治疗后CAT评分与m MRC评分(r=0.304,P=0.011)、BODE指数(r=0.382,P=0.010)及SGRQ总评分(r=0.621,P=0.004)呈显著正相关,与6MWD(r=-0.407,P=0.007)、FEV1实测值(r=-0.211,P=0.014)、FEV1实测/预测值(r=-0.228,P=0.012)及FEV1/FVC(r=-0.231,P=0.011)呈显著负相关。结论 CAT评分与COPD患者m MRC评分、BODE指数、SGRQ总评分、6MWD及肺功能指标均有较好的相关性,具有较好的预测COPD患者预后的应用价值。