“It was invisible, buried in the mud. I only saw it because I was looking for it.”
“What! You expected to find it?”
“I thought it not unlikely.”
C奥南Doyle[1]
我们一生的另一半 - 以及我们一生中越好的一半是夜间[2]。在许多慢性临床状况的自然史上,我们通常不将夜晚视为患者生命的另一半及其对疾病生物学和临床进展的影响。此外,与夜间相关的呼吸道疾病通常是与睡眠质量,唤醒和呼吸症相关的功能方面的代名词。我们很少将夜间视为特定症状发作的时期,例如慢性阻塞性肺疾病(COPD)患者的呼吸困难。即使是当前关于COPD慢性阻塞性肺疾病(GOLD)指南的全球全球倡议,也没有定义标准和联合方法,用于诊断和管理夜间问题,并建议对稳定疾病的患者进行随访[3]。Recently, in a meeting focussing on the night-time symptoms and sleep disturbances of COPD patients, a panel of experts reported the poor interest in clinical studies on these aspects; moreover, the possibility of exploring the potential links between symptoms occurring during the night and the long-term clinical outcomes may demonstrate the necessity highlighting some of the clinical and unexplored aspects of COPD [4]。
In this issue of theEuropean Respiratory Journal(ERJ), L安格et al.[5] respond to these scientific demands by presenting a study that recruited stable COPD patients from two national registries in Denmark (the Copenhagen City Heart Study (CCHS) and the Copenhagen General Population Study (CGPS)). Using an extensive questionnaire concerning patient lifestyle and health topics, they investigated the real prevalence of dyspnoea occurrence during the night. The authors also evaluated the implication of night symptoms on the long-term clinical outcomes and prognosis of stable COPD patients. In particular, they focused on exacerbation events (defined by an increase of rescue medication), hospital admissions due to an exacerbation, and all-cause mortality.
Although the study does not provide an objective measurement of nocturnal saturation (it has been proven that nocturnal hypoxaemia in COPD patients is associated with the development of adverse sequelae [6]) and the topic has previously been explored by Omachiet al.[7] with similar findings, the paper by L安格et al.[5]在临床上是相关的,因为他们前瞻性检查了从现实生活中招募的大量COPD患者(≥6000),并进行了很长的随访(≥8岁)。有许多关键消息。首先,夜间呼吸困难的患病率很高,约占COPD患者总数的4%,分别在严重和非常严重的患者中增加到9%和16%。正如预期的那样,该结果证实了夜间呼吸困难是稳定的COPD患者的“常见”症状,并且医生通常不会注意到患者自己[4]。因此,我们需要开发特定的测量工具,例如问卷,这些仪器可以确定COPD患者在夜间对呼吸的看法。遗憾的是,迄今为止尚无经过验证的问卷。
Secondly, night-time dyspnoea is a prevalent symptom with a very relevant impact on adverse outcomes; in comparison with non-nocturnal symptomatic COPD patients (reference), nocturnal symptomatic COPD patients have a 2.3-fold higher risk of suffering a future exacerbation. Moreover, the risks of hospital admission due to an exacerbation or of dying from any cause are 3.2-fold and 1.7-fold, respectively. In other words, it is confirmed that COPD patients waking at night due to dyspnoea have a worse long-term prognosis of frequent events occurring in later life, which certainly have an impact upon the natural history of disease [3]。
Thirdly, there are strong relationships between night-time dyspnoea and pulmonary and extrapulmonary clinical variables that commonly define the chronic severity/complexity of COPD and that influence the prognosis of patients [3,6,8–10]。In particular, the study by L安格et al.[5]表明,出现夜间呼吸困难的COPD患者的肺部障碍较大(旧金指南)[3], worse baseline perceived dyspnoea (measured using the Medical Research Council (MRC) score) [8],外周缺氧[6], an increase in events due to exacerbations [10], and the presence of current wheezing, chronic mucus hypersecretion, and some heart comorbidities like ischemic heart disease [9]和心房颤动。
This raises a question: in the future management of patients with COPD, should we consider night-time dyspnoea as a new measure of severity and disease progression? And, in relation to these considerations and the knowledge that diurnal dyspnoea is a good predictor of mortality in stable COPD patients [8](尽管在感知到的呼吸困难中,全天有很高的可变性[11]),为什么我们应该惊讶于夜间呼吸困难会改变COPD患者的预后?这个结果不太可能被发现。但是,作者之所以找到它是因为他们正在寻找它!
但是“我知道我一无所知” [12]。The study by L安格et al.[5]打开了潜在相关性的两个重要方面的两个重要方面。最近的亮点[13,14] state that in COPD, some relevant attributes (single or combined multidimensional clusters [15]) that describe the differences between patients and are related to clinically meaningful outcomes, such as disease progression or death, may allow the characterisation of clinical phenotypes. In this context, patients with a high susceptibility to exacerbations, and who actually experience frequent exacerbation episodes [10],体重低,身体成分受损的患者[16],运动能力差的患者[17]以及基线昼夜功能性呼吸困难增加的患者[8], represent specific clinical COPD phenotypes. Considering the important implications that night-time dyspnoea has on a patient’s prognosis, should we now reconsider the subpopulation of patients with night symptoms as having a new phenotype of COPD? They could be labelled “COPD symptomatic at night”? Moreover, while some COPD phenotypes related to single risk factors are susceptible to pharmacological (bronchodilators and/or inhaled steroids, nutritional support) or nonpharmacological treatment (physical exercise) and are potentially changeable, should we consider those who are “COPD symptomatic at night” to be patients in whom we can do something else? All in all, plenty of future challenges to explore!
Footnotes
Conflict of interest: None declared.
- 已收到3月ch 9, 2014.
- Accepted3月ch 10, 2014.
- ©ERS 2014