The chronic obstructive pulmonary disease exacerbation

Chronic obstructive pulmonary disease is the only leading cause of death with a rising prevalence. The medical and economic costs arising from acute exacerbations of COPD are therefore expected to increase over the coming years. Although exacerbations may be initiated by multiple factors, the most common identifiable associations are with bacterial and viral infections. These are associated with approximately 50% to 70% and 20% to 30% of COPD exacerbations, respectively. In addition to smoking cessation, annual influenza vaccination is the most important method for preventing exacerbations. Controlled O2 is the most important intervention for patients with acute hypoxic respiratory failure. Evidence from randomized, controlled trials justifies the use of corticosteroids, bronchodilators (but not theophylline), noninvasive positive-pressure ventilation (in selected patients), and antibiotics, particularly for severe exacerbations. Antibiotics should be chosen according to the patient's risk for treatment failure and the potential for antibiotic resistance. In the acute setting, combined treatment with beta-agonist and anticholinergic bronchodilators is reasonable but not supported by randomized controlled studies. Physicians should identify and, when possible, correct malnutrition. Chest physiotherapy has no proven role in the management of acute exacerbations.     

Microbiologic determinants of exacerbation in chronic obstructive pulmonary disease

BACKGROUND: The culture of bronchial secretions from the lower airway has been reported to be positive for potentially pathogenic microorganisms (PPMs) in patients with stable chronic obstructive pulmonary disease (COPD), but the determinants and effects of this bacterial load in the airway are not established. METHODS: To determine the bronchial microbial pattern in COPD and its relationship with exacerbation, we pooled analysis of crude data from studies that used protected specimen brush sampling, with age, sex, smoking, lung function, and microbiologic features of the lower airway as independent variables and exacerbation as the outcome, using logistic regression modeling. RESULTS: Of 337 study participants, 70 were healthy, 181 had stable COPD, and 86 had exacerbated COPD. Differences in the microbial characteristics in the participating laboratories were not statistically significant. A cutoff point of 10(2) colony-forming units (CFU) per milliliter or greater for the identification of abnormal positive culture results for PPMs was defined using the 95th percentile in the pooled analysis of healthy individuals. Bronchial colonization of 10(2) CFU/mL or greater by PPMs was found in 53 patients with stable COPD (29%) and in 46 patients with exacerbated COPD (54%) (P<.001, chi(2) test), with a predominance of Haemophilus influenzae and Pseudomonas aeruginosa. Higher microbial loads were associated with exacerbation and showed a statistically significant dose-response relationship after adjustment for covariates (odds ratio, 3.62; 95% confidence interval, 1.47-8.90), but P aeruginosa persisted as a statistically significant risk factor after adjustment for microbial load (odds ratio, 11.12; 95% confidence interval, 1.17-105.82). CONCLUSIONS: One quarter of the patients with COPD are colonized by PPMs during their stable periods. Exacerbation is associated with the overgrowth of PPMs and with the appearance of P aeruginosa in the lower airway, which is associated with exacerbation symptoms independent of load.     

感染在慢性阻塞性肺疾病急性加重期的作用

慢性阻塞性肺疾病（COPD）具有很高的发病率和病死率,而慢性阻塞性肺疾病急性加重（AECOPD）则是COPD患者就诊以及住院治疗的主要原因,它不仅会加快病程的进展,使肺功能出现急剧下降,还会增加疾病相关病死率。所以,积极治疗AECOPD对于延缓COPD的病程、降低病死率非常重要。正确的治疗是建立在对病因学充分认识基础上的,感染因素是AECOPD最重要的原因,相关的研究也是COPD以及AECOPD研究的重点,目前已经充分认识到了这一因素的重要性,相关治疗措施已应用于临床。但是仍有一些尚待明确的问题,尤其是在细菌感染方面。本文结合近年来众多相关文献,对感染原因引起的AECOPD作一综述。     

Personalising exacerbation prediction strategies in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality and morbidity worldwide. One of the most important features of this disease is exacerbations where a patient’s respiratory symptoms episodically worsen. Exacerbations accounted for over 140000 hospital admissions in 2012 in the United Kingdom with considerably more exacerbations being treated in primary care. Despite significant research in this area in recent years, treatment of acute exacerbations in the community remains limited to oral glucocorticoids, antibiotics and bronchodilators. One of the issues with unpicking the complexity of exacerbations is trying to find out the exact underlying cause and mechanism that leads to symptoms and lung destruction. Currently symptoms are initially guided by symptoms alone though multiple causes of exacerbations have common presentations. This includes viral and bacterial infections and episodes relating to environmental triggers such as pollen and pollution. There is also evidence that cardiovascular factors can contribute to symptoms of breathlessness that can mimic COPD exacerbations. In this editorial we discuss recent advances in the use of precision medicine to more accurately treat exacerbations of COPD. This includes identification of phenotypes that could help rationalise treatment and more importantly identify novel drug targets. We also consider the future role of precision medicine in preventing exacerbations and identifying COPD patients that are at increased risk of developing them.     

慢性阻塞性肺疾病急性加重糖皮质激素的治疗

COPD是一种可预防和治疗的疾病,以气流受限为特征病情呈进行性发展,气流受限不完全可逆,具有较高的发病率和病死率。慢性阻塞性肺疾病急性加重（acuteexacerbationofchronicobstructivepulmonarydisease,AECOPD）作为c0PD疾病病程中的一个事件,是COPD患者就诊及住院的主要原因,对患者及社会造成了庞大经济负担。糖皮质激素在AECOPD治疗中的地位已得到肯定,但仍存在许多争议的地方,如不同途径对于治疗效果的影响、激素使用中最佳剂量及使用时间的选择、不同类型激素治疗效果的差异等,仍需要进一步研究来指导合理使用糖皮质激素。     

慢性阻塞性肺疾病急性加重的研究

慢性阻塞性肺疾病（COPD）具有很高的发病率和死亡率,而慢性阻塞性肺疾病急性加重（AECOPD）则是COPD患者就诊以及住院治疗的主要原因,也是庞大医疗费用的主要来源。本文就近年来对AECOPD的定义、病理生理、病因、治疗以及预防等的研究进展进行综述,其中一些方面已得到循证医学的证实,比如吸烟与AECOPD的关系、糖皮质激素及无创性正压通气在治疗AECOPD的作用等;但仍有一些问题尚存在争议,特别是细菌感染在AECOPD中的作用,以及抗菌治疗在AECOPD治疗中的地位,还需要更多的,设计严密的研究来证实。     

Clinical predictors of exacerbation frequency in chronic obstructive pulmonary disease

Introduction: Reduction of exacerbation frequency plays an increasingly important role in interventions in chronic obstructive pulmonary disease (COPD). To reduce this frequency efficiently, patients at risk for frequent exacerbations need to be identified. Objective: The objective of the study was to identify predictors for frequent exacerbations from multiple domains of COPD during a stable phase of the disease. Methods: Data of multiple domains of COPD were collected from 121 patients with moderate to severe COPD. Patients were divided into infrequent (<2 exacerbations per year) and frequent (≥2 exacerbations) exacerbators. Results: St. George's Respiratory Questionnaire (SGRQ) total score and a course of oral corticosteroid within 3 months prior to the study together predicted best whether patients would be infrequent or frequent exacerbators over the course of the next year. Each unit increase in total SGRQ score was associated with a 3% higher risk of being a frequent exacerbator [odds ratio (OR) = 1.03; 95% confidence interval (CI): 1.00–1.06; P = 0.047]. Patients who received a course of oral corticosteroids in the period of 3 months prior to the study had a three‐fold increased risk of being a frequent exacerbator (OR = 3.17; 95% CI: 1.20–8.34; P = 0.02). Furthermore, we observed that a sizable number of patients switched from being a frequent to an infrequent exacerbator and vice versa. Conclusions: Health‐related quality of life and a course of oral corticosteroid in the past 3 months are the best predictors of future exacerbator status. The predictive value of the model is, however, still insufficient. Furthermore, our data suggest, in contrast to previous observations, that exacerbation frequency is not a constant feature. Please cite this paper as: Brusse‐Keizer MGJ, van der Palen J, van der Valk PDLPM, Hendrix R, Kerstjens HAM. Clinical predictors of exacerbation frequency in chronic obstructive pulmonary disease. Clin Respir J 2011; 5: 227–234.     

The role of systemic corticosteroids in acute exacerbation of chronic obstructive pulmonary disease

The administration of systemic corticosteroids for patients with exacerbations of chronic obstructive pulmonary disease (COPD) has become common practice over the past 25 years. This practice remained somewhat controversial because corticosteroids can have serious adverse effects and initial clinical trials provided inconclusive evidence concerning their efficacy. Results from recent clinical trials indicate that systemic corticosteroids are modestly effective in shortening the duration of severe exacerbations of COPD. Systemic corticosteroids administered intravenously or orally to hospitalized patients with exacerbations of COPD reduced the absolute treatment failure rate by about 10%, increased the forced expiratory volume in 1 second (FEV1) by about 100 ml, and shortened the hospital stay by 1 to 2 days. Oral corticosteroids probably confer similar benefits when used for treating moderately severe COPD exacerbations in an out-patient setting. The optimal starting dose of corticosteroids is not known, but the duration of treatment should not extend longer than 2 weeks. Hyperglycemia is the most common adverse event, but secondary infections, mental disturbances, and myopathies may also occur.     

慢性阻塞性肺疾病急性加重期生物标志物的研究进展

C O PD是患病率和病死率居高不下的常见病、多发病,严重影响患者的劳动力和生活质量,也造成了巨大的社会、经济负担。而COPD急性加重（AECOPD）不仅加速疾病进展、进一步降低患者活动耐量,更增加了住院率及病死率,因而近年来开展了大量围绕 A EC O PD生物标志物的研究。本文将从外周血、痰液（包括诱导痰）、呼出气、呼出气冷凝液、BALF、支气管黏膜活检这6个方面分类对近年来A EC O PD生物标志物的研究进展作一综述。     

细菌感染在慢性阻塞性肺疾病急性加重中的作用

慢性阻塞性肺疾病(COPD)是威胁人类健康的重大疾病,据WHO统计,COPD病死率居第六位,到2025年可能升至第三位.在COPD发展过程中,反复的急性加重(AECOPD)是引起COPD发展的重要因素,严重影响患者的生活质量,是发病率和死亡率升高的主要原因之一.引起AECOPD的原因多种多样,本文就细菌感染在AECOPD中的作用作一综述.     

Risk factors for pulmonary embolism in acute exacerbation of chronic obstructive pulmonary disease

<正>Objective To study the risk factors for acute pulmonary embolism(PE)in patients with acute exacerbationof chronic obstructive pulmonary disease(AECOPD).Methods From November 2009 to May 2014,522 patients[aged 42-93 years,mean(72±9)]with AECOPD received CT pulmonary angiography(CTPA)in the     

Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease

IMPACT: This study explores the use of measuring plasma biomarkers at exacerbation of chronic obstructive pulmonary disease (COPD), providing insight into the underlying pathogenesis of these important events. RATIONALE: The use of measuring C-reactive protein (CRP) to confirm exacerbation, or to assess exacerbation severity, in COPD is unclear. Furthermore, it is not known whether there may be more useful systemic biomarkers. OBJECTIVE: To assess the use of plasma biomarkers in confirming exacerbation and predicting exacerbation severity. METHODS: We assessed 36 biomarkers in 90 paired baseline and exacerbation plasma samples from 90 patients with COPD. The diagnosis of exacerbation fulfilled both health care use and symptom-based criteria. Biomarker concentrations were related to clinical indices of exacerbation severity. Interrelationships between biomarkers were examined to gain information on mechanisms of systemic inflammation at exacerbation of COPD. MEASUREMENTS AND MAIN RESULTS: To confirm the diagnosis of exacerbation, the most selective biomarker was CRP. However, this was neither sufficiently sensitive nor specific alone (area under the receiver operating characteristic curve [AUC], 0.73; 95% confidence interval, 0.66-0.80). The combination of CRP with any one increased major exacerbation symptom recorded by the patient on that day (dyspnea, sputum volume, or sputum purulence) significantly increased the AUC to 0.88 (95% confidence interval, 0.82-0.93; p<0.0001). There were no significant relationships between biomarker concentrations and clinical indices of exacerbation severity. Interrelationships between biomarkers suggest that the acute-phase response is related, separately, to monocytic and lymphocytic-neutrophilic pathways. CONCLUSIONS: Plasma CRP concentration, in the presence of a major exacerbation symptom, is useful in the confirmation of COPD exacerbation. Systemic biomarkers were not helpful in predicting exacerbation severity. The acute-phase response at exacerbation was most strongly related to indices of monocyte function.     

病毒相关的慢性阻塞性肺疾病急性加重的研究进展

随着高敏感性检测手段应用的发展和普及,病毒在慢性阻塞性肺疾病急性加重(AECOPD)期间的检出率大大提高,这引起人们对病毒感染与AECOPD关系的重视.现就病毒与AECOPD的关系、病毒特异性生物标志物以及病毒相关AECOPD的临床预后三个方面进行综述.     

重度慢性阻塞性肺疾病急性加重期的糖皮质激素治疗

目的探讨重度慢性阻塞性肺疾病(COPD)伴有慢性呼衰、慢性心肺功能不全患者急性加重期,使用糖皮质激素治疗的疗效及意义。方法随机选择重度COPD急性加重期患者29例,比较治疗前,常规抗感染、平喘、抗心衰治疗及加用激素治疗后生活质量,呼吸困难程度变化。结果呼吸困难评分:(1)治疗前3.78±0.41,(2)抗感染、平喘、抗心衰治疗后3.63±0.49,(3)激素治疗后2.8±0.37,(3)与(1)(2)差别有统计学意义(P<0.05)。生活质量评分:(1)治疗前9.26±2.31,(2)抗感染、平喘、抗心衰治疗后8.47±1.98,(3)激素治疗后5.89±1.72,(3)与(1)(2)差别亦有统计学意义(P<0.05)。结论重度COPD伴有慢性呼吸衰竭、慢性心肺功能不全患者,可能存有肾上腺皮质功能减退,适当使用糖皮质激素治疗有一定疗效。     

Systemic antioxidant defences during acute exacerbation of chronic obstructive pulmonary disease

OBJECTIVE AND BACKGROUND: Existence of an increased oxidative stress has been confirmed in patients with acute exacerbation of COPD. This study aims to examine the extent and time-course of antioxidant defence in patients with an acute exacerbation of COPD in comparison with stable patients. METHODS: Twelve patients with acute exacerbation were studied at admission, and then 24 h and 48 h following admission and at discharge. The antioxidants assessed were the endogenous antioxidants: glutathione peroxidase, superoxide dismutase, oxidized and reduced glutathione, albumin and exogenous antioxidants: alpha-tocopherol and retinol. Trolox equivalent antioxidant capacity as a marker of antioxidant status was also measured. RESULTS: There was an increase in glutathione peroxidase and superoxide dismutase 48 h after admission (P<0.05). Alpha-tocopherol was the lowest 24 h after admission and increased significantly at discharge (P<0.05). CONCLUSIONS: There is an increase in antioxidant defence during acute exacerbation of COPD reaching a maximum at 48 h after admission. This rise in the antioxidant defence is not sufficient to prevent depletion of non-enzymatic antioxidants such as alpha-tocopherol.     

加强对慢性阻塞性肺疾病急性加重的研究

慢性阻塞性肺疾病 (ＣＯＰＤ)是近年来国内外都十分重视的一种疾病 ,不能完全可逆的气流受限是其的特征。气流受限呈进行性发展 ,有不少病人最终发展为慢性呼吸衰竭及慢性肺原性心脏病 ,使得ＣＯＰＤ成为当前病死率居高不下的一个重要疾病。在ＣＯＰＤ发展过程中 ,反复的急性加重是引起ＣＯＰＤ发展的重要因素 ,因此对ＣＯＰＤ急性加重的研究是我们面临的现实问题。Ａｎｔｈｏｎｉｓｅｎ提出的ＣＯＰＤ急性加重的标准为 :在ＣＯＰＤ发展过程中 ,患者咳嗽加重、痰量增加、脓性痰增多以及呼吸困难加重。ＭａｃＮｅｅ和Ｄｏｎａｌｄｓｏｎ等[1]…