中性粒细胞凋亡延迟与重叠综合征患者的氧化应激和系统性炎症

呼吸重叠综合征简称重叠综合征（OS）通常是指阻塞性睡眠呼吸暂停（OSA）和COPD的共患,其较单纯COPD或OSA存在更明显的低氧血症的发生,并且心血管并发症的发生率和病死率也明显增加。本文综述了OS导致氧化应激和系统性炎症的可能机制以及中性粒细胞凋亡延迟相关的调节机制。     

Bronchoalveolar lavage in COPD: fluid recovery correlates with the degree of emphysema.

Bronchoscopy with bronchoalveolar lavage (BAL) is an important research tool for assessing airway inflammation in a variety of inflammatory lung diseases. In chronic obstructive pulmonary disease (COPD), BAL recovery is often low, making analysis of the recovered fluid difficult to interpret. The present authors hypothesised that the degree of emphysema may predict BAL recovery. A total of 20 COPD patients (mean age 57 yrs, range 49-69) with a median (interquartile range) forced expiratory volume in one second (FEV1) of 51 (33-69)% predicted underwent BAL. Matched "healthy" smokers and nonsmokers served as controls. Emphysema index in COPD patients was calculated on computed tomography scan as the percentage of the right lung with pixels <-950 Hounsfield units. The carbon monoxide diffusing capacity of the lung (DL,CO) was determined by the single-breath method. COPD patients had lower BAL recovery than controls. COPD patients with an emphysema index <1 had higher BAL recovery than patients with an emphysema index >1. BAL recovery correlated negatively to emphysema index and positively to DL,CO. However, no correlation was found between recovery and FEV1. In conclusion, the extent of emphysema evaluated by computed tomography-scan index and carbon monoxide diffusing capacity of the lung may predict a low bronchoalveolar lavage recovery in chronic obstructive pulmonary disease patients. These parameters may, therefore, be useful when chronic obstructive pulmonary disease patients are selected for bronchoscopy with bronchoalveloar lavage. The present study underlines the importance of careful phenotyping of chronic obstructive pulmonary disease patients.     

Analysis of the factors related to mortality in chronic obstructive pulmonary disease: role of exercise capacity and health status

In this study, we analyzed the relationships of exercise capacity and health status to mortality in patients with chronic obstructive pulmonary disease (COPD). We recruited 150 male outpatients with stable COPD with a mean postbronchodilator FEV1 at 47.4% of predicted. Their pulmonary function, progressive cycle ergometry, and health status using the Chronic Respiratory Disease Questionnaire, the St. George's Respiratory Questionnaire (SGRQ), and the Breathing Problems Questionnaire were measured at entry. Among 144 patients who were available for the 5-year follow-up, 31 had died. Univariate Cox proportional hazards analysis revealed that the SGRQ total score and the Breathing Problems Questionnaire were significantly correlated with mortality; however, with the Chronic Respiratory Disease Questionnaire, the total score was not significantly correlated. Multivariate Cox proportional hazards analysis revealed that the peak oxygen uptake and the SGRQ total score were both predictive of mortality, independent of FEV1 and age. Stepwise Cox proportional hazards analysis revealed that the peak oxygen uptake was the most significant predictor of mortality. We found that exercise capacity and health status were significantly correlated with mortality, although different health status measures had different abilities to predict mortality. These results will have a potentially great impact on the multidimensional evaluation of disease severity in COPD.     

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.     

Chronic obstructive pulmonary disease as a risk factor for cardiovascular morbidity and mortality

Chronic obstructive pulmonary disease and other disorders, associated with reduced lung function, are strong risk factors for cardiovascular events, independent of smoking. Overall, when the lowest quintile of lung function, as measured by FEV1 is compared with the highest quintile, the risk of cardiovascular mortality increases by approximately 75% in both men and women. Having symptoms of chronic bronchitis alone increases the risk of coronary deaths by 50%. Reduced ratio of FEV1 to FVC by itself is a modest independent risk factor for coronary events, increasing the risk by 30%. However, if patients have ventricular arrhythmias, the risk of coronary events is increased twofold, suggesting that the cardiotoxic effects of obstructive airways disease are amplified in those who have underlying cardiac rhythm disturbances. In general, for every 10% decrease in FEV1, all-cause mortality increases by 14%, cardiovascular mortality increases by 28%, and nonfatal coronary event increases by almost 20%. These data indicate that chronic obstructive pulmonary disease is a powerful, independent risk factor for cardiovascular morbidity and mortality.     

Forced expiratory volume in one second: not just a lung function test but a marker of premature death from all causes.

The clinical utility of spirometric screening of asymptomatic smokers for early signs of air flow limitation has recently come under review. The current authors propose that reduced forced expiratory volume in one second (FEV(1)) is more than a measure of airflow limitation, but a marker of premature death with broad utility in assessing baseline risk of chronic obstructive pulmonary disease (COPD), lung cancer, coronary artery disease and stroke, collectively accounting for 70-80% of premature death in smokers. Reduced FEV(1) identifies undiagnosed COPD, has comparable utility to that of serum cholesterol in assessing cardiovascular risk and defines those smokers at greatest risk of lung cancer. As such, reduced FEV(1) should be considered a marker that identifies smokers at greatest need of medical intervention. Smoking cessation has been shown to attenuate FEV(1) decline and, if achieved before the age of 45-50 yrs, may not only preserve FEV(1) within normal values but substantially reduce cardiorespiratory complications of smoking. Recent findings suggest inhaled drugs (bronchodilators and corticosteroids), and possibly statins, may be effective in reducing morbidity and mortality in patients with chronic obstructive pulmonary disease. The current authors propose that spirometry has broad utility in identifying smokers who are at greatest risk of cardiorespiratory complications and greatest benefit from targeted preventive strategies, such as smoking cessation, prioritised screening and effective pharmacotherapy.     

The 'double dip' hypothesis: simultaneous prevention of cardiovascular and pulmonary morbidity and mortality using angiotensin II type 1 receptor blockers

The therapy for chronic obstructive lung disease (COPD) is largely symptomatic in nature, involving the use of bronchodilators and steroids, and the judicious use of antibiotics. None of these have been shown to have a consistent beneficial impact on outcome. Moreover, the outcome of patients with COPD is determined, to some extent, by the occurrence of cardiovascular events. The association between pulmonary disease and cardiovascular events is gaining greater recognition, and appears inexplicable solely on the basis of shared, traditional risk factors, such as smoking. There appear to be direct links between lung injury and concomitant vascular injury by virtue of a systemic inflammatory state induced by lung inflammation. The present paper raises the possibility that the outcome of patients with COPD may be improved significantly through aggressive use of therapies known to prevent cardiovascular events. Moreover, angiotensin II is also a direct mediator of lung injury; interruption of this mechanism of injury might simultaneously prevent both cardiovascular and pulmonary morbidity and mortality in patients with chronic lung disease.     

慢性阻塞性肺疾病合并症研究进展

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)表现为慢性肺部及全身炎症反应,以进行性不完全可逆性气流受限为特征.COPD患者往往合并一种或多种肺外症状(COPD合并症),这可能是COPD慢性炎症反应的伞身表现,也可能与共同的危险因素(如吸烟、年龄等)有关.这些合...     

Chronic obstructive pulmonary disease: a chronic systemic inflammatory disease

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in both the airways causing airway obstruction and the lung tissues causing emphysema. The disease is induced by inhalation of noxious gasses and particulate matter resulting in a chronic persistent inflammatory response in the lung, and the extent of the inflammatory reaction correlates with the severity of the disease. This chronic inflammatory response in the lung is also associated with a significant systemic inflammatory response with downstream adverse clinical health effects. The systemic response in COPD is associated with mortality, specifically cardiovascular mortality. This review describes the nature of the systemic inflammatory response in COPD and the clinical manifestations associated with the systemic response, with a focus on the potential mechanisms for these adverse health effects.     

Clinical course and prognosis of patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a basically benign disease, but the prognosis is so poor that the mortality rate is similar to some malignant diseases. Depending on the disease severity, the 5-year mortality rate of patients with COPD varies from 40 to 70%. The three major causes of death have been identified as COPD itself, lung cancer, and cardiovascular disease. The following factors have been reported to be related to survival: FEV1 (especially the maximal attainable lung function), age, gender, PaO2, PaCO2, body weight, and comorbidity. There have been several large-scale randomized clinical trials to examine the prophylactic effects of inhaled anti-cholinergics and inhaled corticosteroids on the annual decline in FEV1. However, unfortunately, in all of the published studies, these drugs had no effect on the annual decline in FEV1.     

Vascular Risk in Chronic Obstructive Pulmonary Disease: Role of Inflammation and Other Mediators

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition that affects 3 million adult Canadians aged 40 years or older. Most patients have mild to moderate disease and as such have only modest symptoms of cough and breathlessness. However, many will go on to experience ischemic heart disease and stroke and die of cardiovascular complications rather than from their lung disease. Indeed, nearly 50% of all hospitalizations and 25% of all deaths in patients with mild to moderate COPD are cardiovascular system related. Experimental and epidemiologic data from the past 20 years provide compelling evidence that chronic lung inflammation (related to COPD or exposure to irritants such as tobacco smoke or air pollution) contributes to atherosclerotic plaque progression and that acute inflammatory stimulus such as acute respiratory tract infections or acute exacerbations of COPD induce plaque rupture, leading to cardiovascular events. In this paper, we provide an overview of the epidemiologic and experimental data linking COPD with cardiovascular disease and highlight the clinical implications of this linkage for clinicians who evaluate and manage patients with COPD, cardiovascular diseases, or both.     

Health status measured with the CRQ does not predict mortality in COPD.

One purpose of measuring health status is to predict future outcomes. The aim of this study was to investigate the ability of health status derived from the Chronic Respiratory Disease Questionnaire (CRQ) to predict mortality in chronic obstructive pulmonary disease (COPD). One-hundred and forty-three patients with COPD were recruited. Health status, using the CRQ, and pulmonary function were measured at entry. Mortality after 7 yrs was then assessed. Univariate and multivariate Cox proportional hazards analyses were performed to predict those factors related to mortality. Of all the patients, 13 could not be followed up and 40 had died. The survival rate was 69% at 7 yrs. Univariate regression analyses revealed that the dyspnoea and emotional function domains and the total score of the CRQ were weakly but significantly correlated with mortality from all causes. However, multivariate regression analyses revealed that age and forced expiratory volume in one second were the strongest predictors of mortality, and health status was not a significant factor. Although there was a weak but significant relationship between health status and subsequent mortality in chronic obstructive pulmonary disease, it was not significant after an adjustment for age and pulmonary function. Mortality cannot be predicted from Chronic Respiratory Disease Questionnaire scores.     

慢性阻塞性肺疾病肺气肿表型急性加重期临床特征分析

目的 探讨慢性阻塞性肺疾病(COPD)肺气肿表型急性加重期的临床特征.方法 研究对象为2009年4月至2010年6月就诊于首都医科大学附属北京同仁医院呼吸科COPD急性加重期患者95例,其中男性60例,女性35例,年龄41～92岁,平均年龄(75±9)岁.根据肺部HRCT肺气肿视觉评分,分为无/轻度肺气肿组(评分≤8分...     

Respiratory syncytial virus, airway inflammation, and FEV1 decline in patients with chronic obstructive pulmonary disease

BACKGROUND: Respiratory syncytial virus (RSV) is increasingly recognized as an important pathogen in adults with cardiopulmonary disease. It has been associated with acute exacerbations of chronic obstructive pulmonary disease (COPD); however, it has also been detected in the lower airway in the stable state, but the consequences of RSV in stable disease have not previously been determined. We therefore studied the consequences of RSV persistence in adults with COPD and its effect on airway inflammation and lung function decline. METHODS: A total of 241 sputum samples from 74 patients with COPD (FEV(1)% predicted, 39.2%; interquartile range, 29.6-57.8%) were collected quarterly in the stable state over 2 yr. RSV was detected by polymerase chain reaction (PCR), quantitative microbiology was performed, and inflammatory cytokines were quantified by ELISA. RESULTS: RSV RNA was detected in 32.8% of sputum samples. Patients in whom RSV was more frequently detected (> 50% of samples RSV PCR-positive, n=18) had higher airway inflammation and faster FEV(1) decline over the study (101.4 ml/yr [95% confidence interval, 57.1-145.8]) compared with those with less frequent detection of RSV (n=56; 51.2 ml/yr [31.7-70.8]; p=0.01). The observed relationship between RSV detection and accelerated lung function decline was independent of smoking status, exacerbation frequency, and lower airway bacterial load. CONCLUSIONs: Persistent RSV detection in patients with COPD is associated with airway inflammation and accelerated decline in FEV(1). Chronic RSV infection may be a novel therapeutic target to alter the natural history of COPD.     

A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease.

Currently available inhaled bronchodilators used as therapy for chronic obstructive pulmonary disease (COPD) necessitate multiple daily dosing. The present study evaluates the long-term safety and efficacy of tiotropium, a new once-daily anticholinergic in COPD. Patients with stable COPD (age 65.2+/-8.7 yrs (mean+/-SD), n=921) were enrolled in two identical randomized double-blind placebo-controlled 1-yr studies. Patients inhaled tiotropium 18 microg or placebo (mean screening forced expiratory volume in one second (FEV1) 1.01 versus 0.99 L, 39.1 and 38.1% of the predicted value) once daily as a dry powder. The primary spirometric outcome was trough FEV1 (i.e. FEV1 prior to dosing). Changes in dyspnoea were measured using the Transition Dyspnea Index, and health status with the disease-specific St. George's Respiratory Questionnaire and the generic Short Form 36. Medication use and adverse events were recorded. Tiotropium provided significantly superior bronchodilation relative to placebo for trough FEV1 response (approximately 12% over baseline) (p<0.01) and mean response during the 3 h following dosing (approximately 22% over baseline) (p<0.001) over the 12-month period. Tiotropium recipients showed less dyspnoea (p<0.001), superior health status scores, and fewer COPD exacerbations and hospitalizations (p<0.05). Adverse events were comparable with placebo, except for dry mouth incidence (tiotropium 16.0% versus placebo 2.7%, p<0.05). Tiotropium is an effective, once-daily bronchodilator that reduces dyspnoea and chronic obstructive pulmonary disease exacerbation frequency and improves health status. This suggests that tiotropium will make an important contribution to chronic obstructive pulmonary disease therapy.     

The 6-min walk distance: change over time and value as a predictor of survival in severe COPD.

The 6-min walk distance (6MWD) is used to evaluate the functional capacity of patients with chronic obstructive pulmonary disease (COPD). The change in 6MWD over time and its correlation with changes in spirometry and survival are unclear. Patients (n=198) with severe COPD and 41 age-matched controls were followed for 2 yrs, and anthropometrics, spirometry, 6MWD and comorbidities were measured. The 6MWD decreased in the COPD group from 238 +/- 107 m to 218 +/- 112 m (-26 +/- 37 m x yr(-1)), and increased in the control group from 532 +/- 82 m to 549 +/- 86 m (12 +/- 25 m x yr(-1)). In both groups, there was a poor correlation with changes in forced expiratory volume in one second (FEV1). Nonsurvivors in the COPD group (42%) had a more pronounced change in the 6MWD (-40 versus -22 m x yr(-1)) but a similar change in FEV1 (118 versus 102 mL x yr(-1)). The 6MWD independently predicted survival, after accounting for age, body mass index, FEV1 and comorbidities. In severe chronic obstructive pulmonary disease, the 6-min walk distance predicts mortality better than other traditional markers of disease severity. Its measurement is useful in the comprehensive evaluation of patients with severe disease.     

The role of concomitant respiratory diseases on the rate of decline in FEV1 among adult asthmatics.

Several recent reports have presented evidence suggesting that adults with asthma have an accelerated rate of decline in pulmonary function compared with nonasthmatics. However, most of these studies have not taken into account the possible effect of comorbid lung disease in addition to asthma. This study was designed to determine if comorbid respiratory diseases modify or otherwise change the estimates of decline in forced expiratory volume in one second (FEV1). Study subjects were White, non-Mexican, American participants, who were > or = 20 yrs of age at the initial survey and had at least one pulmonary function testing. Respiratory disease status, based on self-reported questionnaires and pulmonary function tests, were assessed during 12 surveys spanning a period of up to 20 yrs. There were 2,926 subjects who met the inclusion criteria, 214 (7.3%) had physician-confirmed asthma, 325 (11.1%) chronic obstructive pulmonary disease (COPD), and 125 (4.3%) both physician-confirmed asthma and COPD. Longitudinal analysis revealed that among those with longstanding asthma, FEV1 values were low but did not decline at a more rapid rate than normal. Likewise, subjects with both asthma and COPD had the lowest levels of FEV1, but also a rate of decline that was not significantly increased. Only those with COPD in the absence of asthma experienced both a low initial FEV1 level and a significantly steeper rate of decline. Based on these findings, the authors conclude that forced expiratory volume in one second does not decline more rapidly in asthmatics or in those with asthma and chronic obstructive pulmonary disease, compared with nonasthmatics.     

Chronic obstructive pulmonary disease: linking outcomes and pathobiology of disease modification

Recent guidelines define chronic obstructive pulmonary disease (COPD) as a preventable and treatable disease characterized by airflow limitation and systemic consequences. Airflow limitation in COPD worsens over years as assessed by the forced expiratory volume in one second (FEV(1)). Regardless, while it is likely that cardiovascular and other systemic components also worsen as COPD progresses, there are no accepted or validated outcomes to measure such pathophysiologic changes as they relate to COPD disease progression. It is clear that health status in COPD is more closely related to levels of patients' physical functional capacity than it is to changes in FEV(1). Furthermore, the relative contributions of pathoanatomic changes such as small airways fibrosis and pulmonary emphysema to declining airflow remain unknown. These features may even progress at different rates in the same individuals. Although stopping smoking is the only intervention shown to alter the relentless progression of COPD, the resultant slowing of FEV(1) decline takes several years to evince and requires at least 1,000 subjects to demonstrate annual therapeutic benefits of as little as 20 ml. The FEV(1) cannot distinguish between peribronchiolar fibrosis and emphysema and it is feasible that, as techniques are developed and validated, lung imaging methodologies may become important and sensitive outcomes measures of time- and age-dependent lung structural changes in COPD. The development of biomarkers of lung damage, pulmonary inflammation, and systemic disease will be essential to our further understanding of the natural history of COPD and the discovery of new, effective treatments for its progression.     

Health-related quality of life in COPD: why both disease-specific and generic measures should be used.

Although research has consistently demonstrated that chronic obstructive pulmonary disease (COPD) impairs health-related quality of life (HRQL), little agreement has been evidenced regarding the factors identified as contributing to impaired HRQL. The aim was to study such factors using well established generic and specific HRQL instruments. The patients (n=68) were stratified by forced expiratory volume in one second (FEV1) to represent a wide range of disease severity. Pulmonary function, blood gases and 6-min walking distance test (6MWD) were assessed. HRQL instruments included: St George's Respiratory Questionnaire (SGRQ), Sickness Impact Profile (SIP), Hospital Anxiety and Depression Scale and Mood Adjective Check List. The strength of the impact of COPD on HRQL was represented along a continuum ranging from lung function, functional status (physical and psychosocial) to wellbeing. Although correlations between FEV1 versus SGRQ total and SIP overall scores (r=-0.42 and -0.32) were stronger than previously reported, multiple regression analyses showed that lung function contributed little to the variance when dyspnoea-related limitation, depression scores and 6MWD were included in the models. These three factors were important to varying degrees along the whole range of HRQL. Physiological, functional and psychosocial consequences of chronic obstructive pulmonary disease are only poorly to moderately related to each other. The present study concludes that a comprehensive assessment of the effects of chronic obstructive pulmonary disease requires a battery of instruments that not only tap the disease-specific effects, but also the overall burden of the disease on everyday functioning and emotional wellbeing.     

COPD und Herzerkrankung

Cardiovascular diseases are highly prevalent in patients with chronic obstructive pulmonary disease (COPD). Approximately one out of three patients with COPD dies of cardiovascular disease. Overlap syndrome (COPD and obstructive sleep apnea), pulmonary hypertension and lung hyperinflation have a further impact on cardiovascular function in patients with COPD.