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.     

慢性阻塞性肺疾病急性加重期细菌感染和气道炎症关系研究

目的研究慢性阻塞性肺疾病（COPD）患者在急性加重期是否存在下呼吸道细菌感染，其气道炎症程度较稳定期的变化以及两者之间的关系。方法入选确诊的COPD稳定期患者，在急性加重期对其痰液进行细菌学定量、定性分析，并在稳定期和急性加重期用酶联免疫吸附试验（ELISA）法对痰液和支气管肺泡灌洗液（BALF）进行白介素6（IL-6）、IL-8、以及肿瘤坏死因子α（TNF-α）水平检测。结果46例中、重度COPD患者在急性加重期时，痰标本菌落计数〉10^6cfu／ml和BALF菌落计数〉10^3 cfu／m1分别为45．65％（21／46）和54．5％（6／11），其中流感嗜血杆菌占首位，IL-8、IL-6及TNF-α在急性加重期的浓度分别为（1420．0±938．56）pg／ml、（370．43±300．40）pg／ml及（260．85±234．43）pg／ml，较稳定期显著增高（Pd0．01），各细胞因子水平之间呈显著正相关。细菌培养阳性组的IL-8、IL-6及TNF-α的浓度显著高于痰菌阴性组（P〈0．05）。结论细菌感染为导致COPD急性加重的重要原因，并可能是引起气道炎症因子水平上升的主要因素。     

Systemic and upper and lower airway inflammation at exacerbation of chronic obstructive pulmonary disease

RATIONALE: In addition to pulmonary involvement, stable chronic obstructive pulmonary disease (COPD) is associated with nasal and systemic inflammation. Although exacerbations of COPD are associated with increased pulmonary and systemic inflammation, determinants of the systemic response remain obscure, and nor is it known whether there is nasal involvement. OBJECTIVES: To investigate upper airway, lower airway, and systemic inflammation at exacerbation of COPD. METHODS: We sampled sputum, nasal wash, and serum from 41 exacerbations (East London cohort) for analysis of pathogenic microorganisms and inflammatory indices (sputum/nasal wash leukocytes, interleukin [IL]-6, IL-8, and myeloperoxidase; serum IL-6 and C-reactive protein). Values were compared with stable COPD. MEASUREMENTS AND MAIN RESULTS: Exacerbation of COPD is associated with greater nasal, sputum, and serum inflammation than the stable state. At exacerbation, inflammatory markers were highly correlated within nasal wash and serum (all r >/= 0.62, p < 0.001), but not sputum. The degree of upper airway inflammation correlated with the degree of lower airway inflammation (e.g., nasal wash/sputum myeloperoxidase; r = 0.50, p = 0.001). The degree of systemic inflammation correlated with the degree of lower airway inflammation (e.g., serum IL-6/sputum IL-8; r = 0.35, p = 0.026), and was greater in the presence of a sputum bacterial pathogen (29.0 g/dl C-reactive protein difference, p = 0.002). We did not find relationships between the upper airway and systemic compartments. CONCLUSIONS: Exacerbation of COPD is associated with pan-airway inflammation; the systemic inflammatory response is proportional to that occurring in the lower airway and greater in the presence of a bacterial pathogen.     

慢性阻塞性肺疾病与慢性炎症

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患病率高、病程长、病死率高,已成为严重的社会负担.小气道炎症是COPD的主要病变及导致肺功能进行性损害的主要原因,同时大量研究证明COPD患者存在系统性炎症,但目前对于COPD气道炎症与系统性炎症的关系尚不十分明确.     

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.     

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.     

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。     

慢性阻塞性肺疾病道炎症变化其与肺功能相关性研究

目的 观察慢性阻塞性肺疾病急性加重期(acute exacerbation of chronic obstructive pulmonary disease,AECOPD)患者气道炎症细胞及细胞因子的变化,探讨其与肺功能恶化的相关性.方法 取AECOPD患者及健康志愿者诱导痰作细胞学计数和分类;测定肺功能,检测诱导痰上清液的肿瘤坏死因子á(tumor necrosis factor-á,TNF-á)、白介素5(interleukin-5,IL-5)等细胞因子.结果 AECOPD组的诱导痰嗜酸粒细胞百分比、中性粒细胞百分比与正常对照组比较,差异有统计学意(P<0.01);与正常对照组比较,AECOPD诱导痰上清液TNF-á浓度差异有统计学意义(P相似文献   

Local and systemic inflammation in chronic obstructive pulmonary disease

There is growing evidence for systemic inflammation in chronic obstructive pulmonary disease (COPD). Increased circulating levels of inflammatory cytokines and acute phase proteins occur in stable disease, and COPD exacerbations are notably associated with pulmonary and systemic inflammation. Although the course of inflammation is determined by the balance between pro- and antiinflammatory mediators, in COPD most attention has focused on the former. During exacerbation, however, upregulation of antiinflammatory markers occurs. The main causes of systemic inflammation in COPD remain to be elucidated, although systemic hypoxia is a candidate factor. Although a relationship between lung and systemic inflammation has been suggested, experimental evidence indicates no direct correlations in the regulation of inflammation in the pulmonary and systemic compartments. Longitudinal studies are needed to unravel the role of systemic inflammation in the course of COPD, to analyze the role of acute exacerbations on the chronicity of inflammation, and to evaluate the response of systemic inflammation to different interventions. Emphasis should be placed on the identification of signaling pathways induced and/or altered in skeletal muscle by inflammation, as muscle wasting is a prominent feature of chronic inflammatory disease conditions and contributes significantly to impaired physical functioning and health status in COPD.     

Haemophilus influenzae from patients with chronic obstructive pulmonary disease exacerbation induce more inflammation than colonizers

RATIONALE: Airway infection with Haemophilus influenzae causes airway inflammation, and isolation of new strains of this bacteria is associated with increased risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To determine whether strains of H. influenzae associated with exacerbations cause more inflammation than strains that colonize the airways of patients with COPD. METHODS: Exacerbation strains of H. influenzae were isolated from patients during exacerbation of clinical symptoms with subsequent development of a homologous serum antibody response and were compared with colonization strains that were not associated with symptom worsening or an antibody response. Bacterial strains were compared using an in vivo mouse model of airway infection and in vitro cell culture model of bacterial adherence and defense gene and signaling pathway activation in primary human airway epithelial cells. RESULTS: H. influenzae associated with exacerbations caused more airway neutrophil recruitment compared with colonization strains in the mouse model of airway bacterial infection. Furthermore, exacerbation strains adhered to epithelial cells in significantly higher numbers and induced more interleukin-8 release after interaction with airway epithelial cells. This effect was likely mediated by increased activation of the nuclear factor-kappaB and p38 mitogen-activated protein kinase signaling pathways. CONCLUSIONS: The results indicate that H. influenzae strains isolated from patients during COPD exacerbations often induce more airway inflammation and likely have differences in virulence compared with colonizing strains. These findings support the concept that bacteria infecting the airway during COPD exacerbations mediate increased airway inflammation and contribute to decreased airway function.     

Systemic inflammation and comorbidities in chronic obstructive pulmonary disease

The relationship between systemic inflammation and comorbidities in patients with chronic obstructive pulmonary disease (COPD) is unclear. This article discusses (1) the prevalence and clinical impact of comorbidities in COPD; (2) the current knowledge on definition, prevalence, consequences, and treatment of systemic inflammation in COPD; and (3) the relationship of systemic inflammation and lung cancer in COPD.     

The biology of a chronic obstructive pulmonary disease exacerbation

Much of the morbidity and mortality in chronic obstructive pulmonary disease relates to symptomatic deteriorations in respiratory health termed exacerbations. Exacerbations also are associated with changes in lung function and both airway and systemic inflammation. The most common causes of exacerbation are micro-organisms: respiratory viruses such as rhinovirus, and various bacterial species. This article reviews and discusses current understanding of the biology of exacerbations, considering the definition, epidemiology, etiology, and the nature and evolution of the changes in symptoms, lung function, and inflammation that characterize these important events.     

Nasal and sinus inflammation in chronic obstructive pulmonary disease

Epidemiologic studies suggest that as many as 75% of patients with COPD have concomitant nasal symptoms and more than 1/3 of patients with sinusitis also have lower airway symptoms of asthma or COPD. Because the inflammatory response of the upper and lower airways are similar, and both sites have a similar exposure to allergens and irritants, it is not surprising that rhinitis or sinusitis would coexist with COPD. Possible mechanisms of combined upper and lower airway dysfunction include the so-called nasal-bronchial reflex, inflammation caused by smoking, mouth breathing caused by nasal obstruction, and pulmonary aspiration of nasal contents. Patients with chronic sinusitis commonly have nonspecific bronchial hyperresponsiveness, suggesting a neural reflex. Postnasal drainage of nasal inflammatory mediators during sleep also may increase lower airway responsiveness. Therapy of nasal and sinus disease is associated with improved pulmonary function in patients with COPD.     

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.     

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。     

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。     

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。     

慢性阻塞性肺疾病肺血管炎症的研究进展

COPD是累及气道、肺实质和肺血管的慢性炎症,气道炎症在COPD的发展中起着重要作用,但目前对于肺血管炎症(尤其是小动脉炎症)的研究及关注较少.有研究结果 表明,肺功能正常的长期吸烟者以及未发生缺氧的轻度COPD患者已经存在肺血管明显的炎症反应[1],并出现肺血管内皮结构异常和肺血管重塑[2],吸烟和肺血管炎症可能是COPD肺血管重塑的始动因素.为此,我们对COPD肺血管炎症的特征、相关因素和机制的研究进展进行综述.