Chronic obstructive pulmonary disease: a novel risk factor for cardiovascular disease

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality in Canada and elsewhere. It affects 5% of all adult Canadians and is the fourth leading cause of death. Interestingly, the leading causes of hospitalizations and mortality among COPD patients are cardiovascular events. In the Lung Health Study, over 5 800 patients with mild to moderate COPD were studied. Forty-two to 48% of all hospitalizations that occurred over the study's 5-year follow-up period were related to cardiovascular complications. Various population-based studies suggest that independent of smoking, age, and gender, COPD increases the risk of cardiovascular morbidity and mortality twofold. Alarmingly, some bronchodilators, which are commonly used to treat symptoms in COPD, may increase the risk of cardiovascular morbidity and even mortality among COPD patients. In this paper, we discuss the epidemiologic evidence linking COPD and cardiovascular events as well as the potential mechanism(s) which may be responsible for this association.     

beta受体阻断药在心力衰竭合并房颤治疗中的再评价

β肾上腺素受体阻断药被认定为心力衰竭治疗领域的里程碑,在心力衰竭指南中,β肾上腺素受体阻断药为IA类推荐。但针对慢性心力衰竭的经典、大型RCT临床试验中,房颤患者所占比率不高。新近对于心力衰竭合并房颤患者应用β肾上腺素受体阻断剂的死亡率和住院率进行Meta-分析示:β肾上腺素受体拮抗剂未见有更多临床获益(即死亡率和住院率减低水平无统计学意义)。本文就心力衰竭定义、心力衰竭时交感神经系统激活、作用于交感神经系统的β肾上腺素受体阻断药药理作用及分类、β肾上腺素受体阻断药在心力衰竭并发房颤治疗中应用地位、心力衰竭并发房颤患者应用β肾上腺素受体阻断药存在的争议及其原因分析进行简要综述。     

The role of gene polymorphisms in the pathogenesis of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Irreversible airflow limitation, both progressive and associated with an inflammatory response of the lungs to noxious particles or gases, is a hallmark of the disease. Cigarette smoking is the most important environmental risk factor for COPD, nevertheless, only approximately 20–30% of smokers develop symptomatic disease. Epidemiological studies, case-control studies in relatives of patients with COPD, and twin studies suggest that COPD is a genetically complex disease with environmental factors and many involved genes interacting together. Two major strategies have been employed to identify the genes and the polymorphisms that likely contribute to the development of complex diseases: association studies and linkage analyses. Biologically plausible pathogenetic mechanisms are prerequisites to focus the search for genes of known function in association studies. Protease-antiprotease imbalance, generation of oxidative stress, and chronic inflammation are recognized as the principal mechanisms leading to irreversible airflow obstruction and parenchymal destruction in the lung. Therefore, genes which have been implicated in the pathogenesis of COPD are involved in antiproteolysis, antioxidant barrier and metabolism of xenobiotic substances, inflammatory response to cigarette smoke, airway hyperresponsiveness, and pulmonary vascular remodelling. Significant associations with COPD-related phenotypes have been reported for polymorphisms in genes coding for matrix metalloproteinases, microsomal epoxide hydrolase, glutathione-S-transferases, heme oxygenase, tumor necrosis factor, interleukines 1, 8, and 13, vitamin D-binding protein and β-2-adrenergic receptor (ADRB2), whereas adequately powered replication studies failed to confirm most of the previously observed associations. Genome-wide linkage analyses provide us with a novel tool to identify the general locations of COPD susceptibility genes, and should be followed by association analyses of positional candidate genes from COPD pathophysiology, positional candidate genes selected from gene expression studies, or dense single nucleotide polymorphism panels across regions of linkage. Haplotype analyses of genes with multiple polymorphic sites in linkage disequilibrium, such as the ADRB2 gene, provide another promising field that has yet to be explored in patients with COPD. In the present article we review the current knowledge about gene polymorphisms that have been recently linked to the risk of developing COPD and/or may account for variations in the disease course.     

Elderly heart failure patients and the role of beta-blocker therapy

In this article different aspects of chronic heart failure in old age are described. We mainly focus on the place of beta-blocker therapy in chronic heart failure. Beta-blockers are recommended for the treatment of stable chronic heart failure with left ventricular systolic dysfunction. There is additional information from recent studies that there is proven efficacy for beta-blocker therapy in patients with heart failure up to the age of 80 years. For patients with heart failure aged 80 and over the evidence to prescribe beta-blockers is limited. However, it is known that also in very elderly patients beta-blocker therapy is well tolerated. In patients with heart failure with preserved systolic ventricular function there is still no evidence that there is a beneficial effect of beta-blockers. It is still not clear if there are differences between beta-blocking agents. Of all beta-blockers, only bisoprolol, carvedilol, nebivolol and metoprolol CR are proven effective in stable chronic heart failure with impaired left ventricular systolic function and can be recommended in elderly patients on standard treatment with diuretics and ACE inhibition.     

The effects of long-acting bronchodilators on total mortality in patients with stable chronic obstructive pulmonary disease

Background

Chronic obstructive pulmonary disease (COPD) is the 4^th leading cause of mortality worldwide. Long-acting bronchodilators are considered first line therapies for patients with COPD but their effects on mortality are not well known. We performed a comprehensive systematic review and meta-analysis to evaluate the effects of long-acting bronchodilators on total mortality in stable COPD.

Methods

Using MEDLINE, EMBASE and Cochrane Systematic Review databases, we identified high quality randomized controlled trials of tiotropium, formoterol, salmeterol, formoterol/budesonide or salmeterol/fluticasone in COPD that had a follow-up of 6 months or longer and reported on total mortality. Two reviewers independently abstracted data from the original trials and disagreements were resolved by iteration and consensus.

Results

Twenty-seven trials that included 30,495 patients were included in the review. Relative risk (RR) for total mortality was calculated for each of the study and pooled together using a random-effects model. The combination of inhaled corticosteroid (ICS) and long-acting beta-2 agonist (LABA) therapy was associated with reduced total mortality compared with placebo (RR, 0.80; p = 0.005). Neither tiotropium (RR, 1.08; p = 0.61) nor LABA by itself (RR, 0.90; p = 0.21) was associated with mortality.

Conclusions

A combination of ICS and LABA reduced mortality by approximately 20%. Neither tiotropium nor LABA by itself modifies all-cause mortality in COPD.     

Beta-blocker usage and prostate cancer survival: A nested case–control study in the UK Clinical Practice Research Datalink cohort

BackgroundRecent laboratory and epidemiological evidence suggests that beta-blockers could inhibit prostate cancer progression. Methods: We investigated the effect of beta-blockers on prostate cancer-specific mortality in a cohort of prostate cancer patients. Prostate cancer patients diagnosed between 1998 and 2006 were identified from the UK Clinical Practice Research Database and confirmed by cancer registries. Patients were followed up to 2011 with deaths identified by the Office of National Statistics. A nested case–control analysis compared patients dying from prostate cancer (cases) with up to three controls alive at the time of their death, matched by age and year of diagnosis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression. Results: Post-diagnostic beta-blocker use was identified in 25% of 1184 prostate cancer-specific deaths and 26% of 3531 matched controls. There was little evidence (P = 0.40) of a reduction in the risk of cancer-specific death in beta-blocker users compared with non-users (OR = 0.94 95% CI 0.81, 1.09). Similar results were observed after adjustments for confounders, in analyses by beta-blocker frequency, duration, type and for all-cause mortality. Conclusions: Beta-blocker usage after diagnosis was not associated with cancer-specific or all-cause mortality in prostate cancer patients in this large UK study.     

TNF-308 gene polymorphism is associated with COPD risk among Asians: meta-analysis of data for 6,118 subjects

Chronic obstructive pulmonary disease (COPD) is a complex polygenic disease in which gene–environment interactions play a critical role in disease onset and progression. The gene encoding tumor necrosis factor (TNF) is one of several candidate loci for the pathogenesis of COPD and is highly polymorphic. A number of studies have investigated the association between the TNF-308 polymorphisms and COPD risk in different populations, and resulted in inconsistent results. A systematic review and meta-analysis of the published studies were performed to gain a clearer understanding of this association. The PubMed, Embase, Web of Science, and CNKI databases were searched for case–control studies published from 1966 to April 2009. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Twenty-four eligible studies, comprising 2,380 COPD cases and 3,738 controls, were included in the meta-analysis. The pooled result showed that the TNF-308 polymorphisms were significantly associated with an increased risk of COPD (OR = 1.335, 95% CI: 1.172–1.522, for allele A carriers versus G/G; OR = 1.330, 95% CI = 1.174–1.505, for allele A versus allele G). Subgroup analysis supported the results in the Asian populations, but not in the Caucasian populations. When the analysis was limited to only those studies in which the COPD cases and controls were smokers/ex-smokers, the pooled results supported the conclusion. This meta-analysis suggested that the TNF-308 A allele is a more significant risk factor for developing COPD among Asian populations, but not among Caucasians.     

Bronchiectasis as a Comorbidity of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Background

Bronchiectasis revealed by chest computed tomography in COPD patients and its comorbid effect on prognosis have not been addressed by large-sized studies. Understanding the presence of bronchiectasis in COPD is important for future intervention and preventing disease progression.

Methods

Observational studies were identified from electronic literature searches in Cochrane library, PubMed, ScienceDirect databases, American Thoracic Society and European Respiratory Society meeting abstracts. A systematic review and meta-analysis of studies was performed to summarize the factors associated with bronchiectasis in COPD patients. Primary outcomes included the risks for exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality. Odds ratios (ORs) were pooled by random effects models.

Results

Fourteen observational studies were eligible for the study. Compared with COPD without bronchiectasis, comorbid bronchiectasis in COPD increased the risk of exacerbation (1.97, 95% CI, 1.29–3.00), isolation of a potentially pathogenic microorganism (4.11, 95%CI, 2.16–7.82), severe airway obstruction (1.31, 95% CI, 1.09–1.58) and mortality (1.96, 95% CI, 1.04–3.70).

Conclusions

The presence of bronchiectasis in patients with COPD was associated with exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality.     

Prevalence and risk of viral infection in patients with acute exacerbation of chronic obstructive pulmonary disease: a meta-analysis

Exacerbations of chronic obstructive pulmonary disease (COPD) lead to substantial morbidity and mortality. Viral infections could be an important cause of acute exacerbations of COPD (AECOPD) and only a few studies report the prevalence of respiratory viruses on this disease. We aimed to update the review on the prevalence of respiratory viral infection in patients with AECOPD with a meta-analysis. We reviewed the prevalence of respiratory viruses on this disease by searching PubMed systematically to identify primary studies published from Jan 1990 to March 2012. Studies met with seven criteria were extracted for meta-analysis. A total of 17 studies were eligible for the meta-analysis. Weighted overall prevalence of respiratory viruses in patients with AECOPD was 39.3 % (95 % CI 36.9–41.6) with a high degree of a heterogeneity (I ² > 75 %). In contrast, the rate in stable COPD patients from four studies was 13.6 % (95 % CI 9.0–18.2) without any apparent heterogeneity. Pooled risk ratio for respiratory viral infection was 4.1 (95 % CI 2.0–8.5) for AECOPD as compared with stable COPD. Rhinovirus was the most common virus and with a weighted prevalence of 14.8 % (95 % CI 13.3–16.5). Respiratory viruses probably are important etiological agents in patients with AECOPD as compared with the stable COPD patients. This result would help to provide better strategies for management of AECOPD and health-care planning.     

Human albumin administration in critically ill patients: systematic review of randomised controlled trials

Objective: To quantify effect on mortality of administering human albumin or plasma protein fraction during management of critically ill patients. Design: Systematic review of randomised controlled trials comparing administration of albumin or plasma protein fraction with no administration or with administration of crystalloid solution in critically ill patients with hypovolaemia, burns, or hypoalbuminaemia. Subjects: 30 randomised controlled trials including 1419 randomised patients. Main outcome measure: Mortality from all causes at end of follow up for each trial. Results: For each patient category the risk of death in the albumin treated group was higher than in the comparison group. For hypovolaemia the relative risk of death after albumin administration was 1.46 (95% confidence interval 0.97 to 2.22), for burns the relative risk was 2.40 (1.11 to 5.19), and for hypoalbuminaemia it was 1.69 (1.07 to 2.67). Pooled relative risk of death with albumin administration was 1.68 (1.26 to 2.23). Pooled difference in the risk of death with albumin was 6% (95% confidence interval 3% to 9%) with a fixed effects model. These data suggest that for every 17 critically ill patients treated with albumin there is one additional death. Conclusions: There is no evidence that albumin administration reduces mortality in critically ill patients with hypovolaemia, burns, or hypoalbuminaemia and a strong suggestion that it may increase mortality. These data suggest that use of human albumin in critically ill patients should be urgently reviewed and that it should not be used outside the context of rigorously conducted, randomised controlled trials.

Key messages

• Human albumin solution has been used in the treatment of critically ill patients for over 50 years
• Currently, the licensed indications for use of albumin are emergency treatment of shock, acute management of burns, and clinical situations associated with hypoproteinaemia
• Our systematic review of randomised controlled trials showed that, for each of these patient categories, the risk of death in the albumin treated group was higher than in the comparison group
• The pooled relative risk of death with albumin was 1.68 (95% confidence interval 1.26 to 2.23) and the pooled difference in the risk of death was 6% (3% to 9%) or six additional deaths for every 100 patients treated
• We consider that use of human albumin solution in critically ill patients should be urgently reviewed

     

Respiratory rehabilitation after acute exacerbation of COPD may reduce risk for readmission and mortality – a systematic review

Background

Acute exacerbations of chronic obstructive pulmonary disease (COPD) represent a major burden for patients and health care systems. Respiratory rehabilitation may improve prognosis in these patients by addressing relevant risk factors for exacerbations such as low exercise capacity. To study whether respiratory rehabilitation after acute exacerbation improves prognosis and health status compared to usual care, we quantified its effects using meta-analyses.

Methods

Systematic review of randomized controlled trials identified by searches in six electronic databases, contacts with experts, hand-searches of bibliographies of included studies and conference proceedings. We included randomized trials comparing the effect of respiratory rehabilitation and usual care on hospital admissions, health-related quality of life (HRQL), exercise capacity and mortality in COPD patients after acute exacerbation. Two reviewers independently selected relevant studies, extracted the data and evaluated the study quality. We pooled the results using fixed effects models where statistically significant heterogeneity (p ≤ 0.1) was absent.

Results

We identified six trials including 230 patients. Respiratory rehabilitation reduced the risk for hospital admissions (pooled relative risk 0.26 [0.12–0.54]) and mortality (0.45 [0.22–0.91]). Weighted mean differences on the Chronic Respiratory Questionnaire were 1.37 (95% CI 1.13–1.61) for the fatigue domain, 1.36 (0.94–1.77) for emotional function and 1.88 (1.67–2.09) for mastery. Weighted mean differences for the St. Georges Respiratory Questionnaire total score, impacts and activities domains were -11.1 (95% CI -17.1 to -5.2), -17.1 (95% CI -23.6 to -10.7) and -9.9 (95% CI -18.0 to -1.7). In all trials, rehabilitation improved exercise capacity (64–215 meters in six-minute walk tests and weighted mean difference for shuttle walk test 81 meter, 95% CI 48–115).

Conclusion

Evidence from six trials suggests that respiratory rehabilitation is effective in COPD patients after acute exacerbation. Larger trials, however, are needed to further investigate the role of respiratory rehabilitation after acute exacerbation and its potential to reduce costs caused by COPD.     

Use of beta-blocker therapy in older patients after acute myocardial infarction in Ontario.

BACKGROUND: Despite its proven efficacy, beta-blocker therapy remains underused in elderly patients after myocardial infarction (MI). The objectives of this study were to identify undertreated groups of seniors and to determine whether older and frailer patients are being selectively dispensed low-dose beta-blocker therapy. METHODS: From a comprehensive hospital discharge database, all people aged 66 years or more in Ontario who survived an acute MI between April 1993 and March 1995 were identified and classified into those who did not receive beta-blocker therapy and those dispensed low, standard or high doses of this agent. Logistic regression models were used to study the effect of age, sex, comorbidity, potential contraindications to beta-blocker therapy and residence in a long-term-care facility on the odds of not being dispensed a beta-blocker. Among beta-blocker users, the odds of being dispensed low relative to standard or high doses of this agent were evaluated. RESULTS: Of the 15,542 patients, 7549 (48.6%) were not dispensed a beta-blocker. Patients 85 years of age or more were at greater risk of not receiving beta-blocker therapy (adjusted odds ratio [OR] 2.8, 95% confidence interval [CI] 2.5-3.2) than were those 66 to 74 years. Having a Charlson comorbidity index of 3 or greater was associated with an increased risk of not receiving beta-blocker therapy (adjusted OR 1.5, 95% CI 1.3-1.8) compared with having lower comorbidity scores. Patients who resided in a long-term-care facility were at increased risk of not being prescribed beta-blocker therapy (adjusted OR 2.6, 95% CI 2.0-3.4). Among the 5453 patients with no identifiable contraindication to beta-blocker therapy, women were significantly less likely than men to receive this agent (p = 0.005). Of the 6074 patients who received beta-blockers, 2248 (37.0%) were dispensed low-dose therapy. Patients aged 85 years or more had an increased risk of being dispensed low-dose therapy (adjusted OR 1.6, 95% CI 1.3-2.0) compared with those aged 66 to 74 years. Compared with those who had the lowest comorbidity scores, patients with the highest comorbidity scores were more likely to be dispensed low-dose beta-blocker therapy (adjusted OR 1.3, 95% CI 1.0-1.8). INTERPRETATION: Almost half of Ontario patients aged 66 or more who survived an MI, particularly those who were older or frailer, did not receive beta-blocker therapy. Among those dispensed beta-blocker therapy, older and frailer patients were more frequently dispensed low-dose therapy.     

Effects of beta-blockers on fracture risk

Laboratory studies make clear that the sympathetic nervous system does impact on bone cell and tissue function. However, these effects are inconsistent between models, possibly reflecting sympathetic effects at different levels, from the central nervous system through to the bone cells. Observational studies of the use of beta-blockers are confounded by the indications for which these drugs are prescribed, and by other medications that are commonly co-prescribed with them. These data are inconsistent, although a recent meta-analysis did conclude that beta-blocker use was associated with a significant decrease in fracture risk. However, the more recent studies cast doubt on this finding, and the limited data regarding fractures in randomized controlled trials certainly do not support this conclusion. Therefore, there is not an adequate evidence base to support using beta-blockers as a treatment for osteoporosis, nor can they be regarded as a discriminating risk factor for fracture assessment. Until there are definitive randomized, controlled trials of beta-blockers, which include fracture as an endpoint, it is unlikely that the current confusing situation will be resolved.     

Lifetime Smoking History and Cause-Specific Mortality in a Cohort Study with 43 Years of Follow-Up

BackgroundIn general, smoking increases the risk of mortality. However, it is less clear how the relative risk varies by cause of death. The exact impact of changes in smoking habits throughout life on different mortality risks is less studied.MethodsWe studied the impact of baseline and lifetime smoking habits, and duration of smoking on the risk of all-cause mortality, mortality of cardiovascular diseases (CVD), chronic obstructive pulmonary disease (COPD), any cancer and of the four most common types of cancer (lung, colorectal, prostate, and breast cancer) in a cohort study (Vlagtwedde-Vlaardingen 1965–1990, with a follow-up on mortality status until 2009, n = 8,645). We used Cox regression models adjusted for age, BMI, sex, and place of residence. Since previous studies suggested a potential effect modification of sex, we additionally stratified by sex and tested for interactions. In addition, to determine which cause of death carried the highest risk we performed competing-risk analyses on mortality due to CVD, cancer, COPD and other causes.ResultsCurrent smoking (light, moderate, and heavy cigarette smoking) and lifetime persistent smoking were associated with an increased risk of all-cause, CVD, COPD, any cancer, and lung cancer mortality. Higher numbers of pack years at baseline were associated with an increased risk of all-cause, CVD, COPD, any cancer, lung, colorectal, and prostate cancer mortality. Males who were lifetime persistent pipe/cigar smokers had a higher risk of lung cancer [HR (95% CI) = 7.72 (1.72–34.75)] as well as all-cause and any cancer mortality. A longer duration of smoking was associated with a higher risk of COPD, any and lung cancer [HR (95% CI) = 1.06 (1.00–1.12), 1.03 (1.00–1.06) and 1.10 (1.03–1.17) respectively], but not with other mortality causes. The competing risk analyses showed that ex- and current smokers had a higher risk of cancer, CVD, and COPD mortality compared to all other mortality causes. In addition, heavy smokers had a higher risk for COPD mortality compared to cancer, and CVD mortality.ConclusionOur study indicates that lifetime numbers of cigarettes smoked and the duration of smoking have different impacts for different causes of mortality. Moreover, our findings emphasize the importance of smoking-related competing risks when studying the smoking-related cancer mortality in a general population and that smoking cessation immediately effectively reduces the risk of all-cause and any cancer mortality.     

Effect of Beta-Blocker Therapy on the Risk of Infections and Death after Acute Stroke – A Historical Cohort Study

BackgroundInfections are a frequent cause for prolonged hospitalization and increased mortality after stroke. Recent studies revealed a stroke-induced depression of the peripheral immune system associated with an increased susceptibility for infections. In a mice model for stroke, this immunosuppressive effect was reversible after beta-blocker administration. The aim of our study was to investigate the effect of beta-blocker therapy on the risk of infections and death after stroke in humans.Methods625 consecutive patients with ischemic or hemorrhagic stroke, admitted to a university hospital stroke unit, were included in this historical cohort study. The effect of beta-blocker therapy on post-stroke pneumonia, urinary tract infections and death was investigated using multivariable Poisson and Cox regression models.Results553 (88.3%) patients were admitted with ischemic stroke, the remaining 72 (11.7%) had a hemorrhagic stroke. Median baseline NIHSS was 8 (IQR 5–16) points. 301 (48.2%) patients received beta-blocker therapy. There was no difference in the risk of post-stroke pneumonia between patients with and without beta-blocker therapy (Rate Ratio = 1.00, 95%CI 0.77–1.30, p = 0.995). Patients with beta-blocker therapy showed a decreased risk for urinary tract infections (RR = 0.65, 95%CI 0.43–0.98, p = 0.040). 7-days mortality did not differ between groups (Hazard Ratio = 1.36, 95%CI 0.65–2.77, p = 0.425), while patients with beta-blocker therapy showed a higher 30-days mortality (HR = 1.93, 95%CI 1.20–3.10, p = 0.006).ConclusionsBeta-blocker therapy did not reduce the risk for post-stroke pneumonia, but significantly reduced the risk for urinary tract infections. Different immune mechanisms underlying both diseases might explain these findings that need to be confirmed in future studies.     

Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer,wine, or spirits.

OBJECTIVES: To review the effect of specific types of alcoholic drink on coronary risk. DESIGN: Systematic review of ecological, case-control, and cohort studies in which specific associations were available for consumption of beer, wine, and spirits and risk of coronary heart disease. SUBJECTS: 12 ecological, three case-control, and 10 separate prospective cohort studies. MAIN OUTCOME MEASURES: Alcohol consumption and relative risk of morbidity and mortality from coronary heart disease. RESULTS: Most ecological studies suggested that wine was more effective in reducing risk of mortality from heart disease than beer or spirits. Taken together, the three case-control studies did not suggest that one type of drink was more cardioprotective than the others. Of the 10 prospective cohort studies, four found a significant inverse association between risk of heart disease and moderate wine drinking, four found an association for beer, and four for spirits. CONCLUSIONS: Results from observational studies, where alcohol consumption can be linked directly to an individual''s risk of coronary heart disease, provide strong evidence that all alcoholic drinks are linked with lower risk. Thus, a substantial portion of the benefit is from alcohol rather than other components of each type of drink.     

Systemic inflammation and mortality in chronic obstructive pulmonary disease

Cardiovascular diseases and cancer (especially lung cancer) are leading causes of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Some have implicated systemic inflammation, which is commonly observed in COPD, as the potential mechanistic bridge between COPD and these disorders. This concept has been supported by animal studies especially in rabbits, which have clearly demonstrated the effect of local lung inflammation on systemic inflammation and on the progression of atherosclerosis and by cross-sectional population-based studies, which have shown a significant relationship between systemic inflammation, as measured by circulating C-reactive protein (CRP) and the risk of cardiovascular diseases in COPD patients. These data have been further extended by a recent study that has elucidated the temporal nature of the relationship between systemic inflammation and the risk of cardiovascular events and cancer in COPD patients. This study showed that baseline CRP levels predicted the incidence of cardiovascular events and cancer-specific mortality over 7 to 8 years of follow-up. CRP levels also predicted all-cause mortality. Collectively, these data indicate that systemic inflammation may play an important role in mediating the extra-pulmonary complications of COPD. Systemic inflammation may contribute substantially to the overall morbidity and mortality of COPD patients.     

The genetics of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a significant cause of global morbidity and mortality. Previous studies have shown that COPD aggregates in families, suggesting a genetic predisposition to airflow obstruction. Many candidate genes have been assessed, but the data are often conflicting. We review the genetic factors that predispose smokers to COPD and highlight the future role of genomic scans in identifying novel susceptibility genes.