慢性阻塞性肺疾病患者继发肺部真菌感染的临床分析

目的探讨慢性阻塞性肺疾病(COPD)患者继发肺部真菌感染的临床特点。方法回顾性分析2008年1月到2010年12月安徽医科大学第一附属医院收治的COPD继发肺部真菌感染患者病例,并对其耐药情况进行比较。结果本组199例COPD患者检出白色念珠菌137例(68.84%),光滑念珠菌32例(16.08%),热带念珠菌17例(8.54%),克柔念珠菌9例(4.52%),毛霉菌3例(1.51%),清酒假丝酵母菌1例(0.50%);白色念珠菌检出率有下降趋势,热带念珠菌有上升趋势;196例真菌对伏立康唑、氟康唑、两性霉素B、伊曲康唑、氟胞嘧啶的耐药率分别为3.6%、5.1%、1.0%、8.7%和0;2008年至2010年白色念珠菌和光滑念珠菌耐药率变化差异无统计学意义。结论 COPD患者继发肺部真菌感染病原菌仍以白色念珠菌为主,其次为光滑念珠菌和热带念珠菌;白色念珠菌和光滑念珠菌耐药率无明显改变。     

Proteinases in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a major health problem worldwide, and we have little specific therapy to offer these patients. One potential strategy to limit loss of lung function in COPD would be to inhibit matrix-degrading proteinases. Several serine proteinases and matrix metalloproteinases are expressed in association with COPD in humans. Application of gene-targeted macrophage elastase and neutrophil elastase to a mouse model of cigarette-smoke-induced emphysema has uncovered roles for these proteinases in airspace enlargement, and has identified many interactions between these proteolytic systems.     

Relationship between periodontitis-related antibody and frequent exacerbations in chronic obstructive pulmonary disease

Background

To identify patients with chronic obstructive pulmonary disease (COPD) who are susceptible to frequent exacerbations is important. Although periodontitis aggravated by poor oral hygiene might increase the risk of lower respiratory tract infection, the relationship between periodontitis and COPD exacerbations remains unknown. This prospective cohort study investigates the relationship between periodontitis-related antibody and exacerbation frequency over a one-year period.

Methods

We assessed an IgG antibody titer against Porphyromonas gingivalis, which is a major pathogen of periodontitis, and then prospectively followed up 93 individuals over one year to detect exacerbations.

Results

The numbers of exacerbations and the rate of individuals with frequent exacerbations (at least two per year) were significantly lower in patients with higher IgG titer than those with normal IgG titer (0.8 vs. 1.2 per year, p  = 0.045 and 14.3 vs. 38.6%, p  = 0.009, respectively). Multivariate logistic regression analysis showed that being normal-IgG titer for periodontitis-related antibody significantly increased the risk of frequent exacerbations (relative risk, 5.27, 95% confidence interval, 1.30–25.7; p  = 0.019) after adjusting for other possible confounders, such as a history of exacerbations in the past year, disease severity, COPD medication and smoking status.

Conclusions

Normal-IgG titer for periodontitis-related antibody can be an independent predictor of frequent exacerbations. Measuring periodontitis-related antibody titers might be useful to identify patients with susceptibility to frequent exacerbations so that an aggressive prevention strategy can be designed.     

Immunology of asthma and chronic obstructive pulmonary disease

Asthma and chronic obstructive pulmonary disease (COPD) are both obstructive airway diseases that involve chronic inflammation of the respiratory tract, but the type of inflammation is markedly different between these diseases, with different patterns of inflammatory cells and mediators being involved. As described in this Review, these inflammatory profiles are largely determined by the involvement of different immune cells, which orchestrate the recruitment and activation of inflammatory cells that drive the distinct patterns of structural changes in these diseases. However, it is now becoming clear that the distinction between these diseases becomes blurred in patients with severe asthma, in asthmatic subjects who smoke and during acute exacerbations. This has important implications for the development of new therapies.     

Animal models of chronic obstructive pulmonary disease

The mechanisms involved in the genesis of chronic obstructive pulmonary disease (COPD) are poorly defined. This area is complicated and difficult to model because COPD consists of four separate anatomic lesions (emphysema, small airway remodeling, pulmonary hypertension, and chronic bronchitis) and a functional lesion, acute exacerbation; moreover, the disease in humans develops over decades. This review discusses the various animal models that have been used to attempt to recreate human COPD and the advantages and disadvantages of each. None of the models reproduces the exact changes seen in humans, but cigarette smoke-induced disease appears to come the closest, and genetically modified animals also, in some instances, shed light on processes that appear to play a role.     

Plasma lipoproteins in chronic obstructive pulmonary disease

Plasma lipoprotein fractions have been assessed in 29 patients with chronic obstructive pulmonary disease (COPD), and compared with non-COPD subjects. Triglycerides were significantly lower in COPD females only, the other parameters being almost identical. Thus, the atherosclerosis index of plasma lipoproteins in COPD did not differ almost at all from that of non-COPD subjects, demonstrating that the low prevalence of angina and/or myocardial infarction in COPD patients is not only a consequence of reduced coronary atherosclerosis.     

Integrative genomics of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a complex disease with both environmental and genetic determinants, the most important of which is cigarette smoking. There is marked heterogeneity in the development of COPD among persons with similar cigarette smoking histories, which is likely partially explained by genetic variation. Genomic approaches such as genomewide association studies and gene expression studies have been used to discover genes and molecular pathways involved in COPD pathogenesis; however, these “first generation” omics studies have limitations. Integrative genomic studies are emerging which can combine genomic datasets to further examine the molecular underpinnings of COPD. Future research in COPD genetics will likely use network-based approaches to integrate multiple genomic data types in order to model the complex molecular interactions involved in COPD pathogenesis. This article reviews the genomic research to date and offers a vision for the future of integrative genomic research in COPD.     

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.     

Molecular mechanisms in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with progressive airflow obstruction. Tobacco smoking is the main risk factor worldwide. In contrast to asthma, anti-inflammatory therapies are rather ineffective in improving chronic symptoms and reducing inflammation, lung function decline, and airway remodeling. Specific drugs that are directed against the remodeling and chronic inflammation, thereby preventing lung tissue damage and progressive lung function decline, must be developed. Experimental models and expression studies suggest that anti-vascular endothelial growth factor (VEGF) receptor strategies may be of use in patients with emphysema, whereas anti-HER1-directed strategies may be more useful in patients with pulmonary mucus hypersecretion, as seen in chronic bronchitis and asthma. Growth factors and cytokines including VEGF, fibroblast growth factors, transforming growth factor-β, tumor necrosis factor-α, CXCL1, CXCL8, and CCL2, and signal transduction proteins such as mitogen-activated protein kinase p38 and nuclear factor-⦊B, seem to be important pathogenetic molecules in COPD. Specific antagonists for these proteins may be effective for different inflammatory diseases. However, their efficacy for COPD therapy has not yet been demonstrated. Finally, other drugs such as retinoic acids may provide restoration of lung tissue structure. Such approaches, however, must await the first results of growth factor or cytokine antagonist therapy in chronic lung diseases.     

慢性阻塞性肺疾病患者继发真菌性医院肺炎的病原菌分布及耐药性分析

目的探讨慢性阻塞性肺疾病（Chronic obstructive pulmonary diseases,COPD）患者继发真菌性医院肺炎的病原菌分布及耐药情况。方法回顾性分析2011年1月至2012年12月间31例COPD患者继发肺部真菌感染的情况。结果 31例COPD继发肺部真菌感染的患者送检标本中共检到34株真菌,以曲霉菌属居首位,占29.41%,其次为白色假丝酵母菌,占26.41%。7种常用抗真菌药物对真菌显示有不同的抗菌活性,尤以伊曲康唑、氟康唑、5-氟胞嘧啶为佳。结论 COPD患者继发肺部真菌感染多为曲霉菌属和白色假丝酵母菌。临床疑为COPD患者继发肺部真菌感染病例须及时采集标本培养,以早期发现病原性真菌和选择有效药物治疗。     

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.     

Skeletal muscle dysfunction in chronic obstructive pulmonary disease

It has become increasingly recognized that skeletal muscle dysfunction is common in patients with chronic obstructive pulmonary disease (COPD). Muscle strength and endurance are decreased, whereas muscle fatigability is increased. There is a reduced proportion of type I fibers and an increase in type II fibers. Muscle atrophy occurs with a reduction in fiber cross-sectional area. Oxidative enzyme activity is decreased, and measurement of muscle bioenergetics during exercise reveals a reduced aerobic capacity. Deconditioning is probably very important mechanistically. Other mechanisms that may be of varying importance in individual patients include chronic hypercapnia and/or hypoxia, nutritional depletion, steroid usage, and oxidative stress. Potential therapies include exercise training, oxygen supplementation, nutritional repletion, and administration of anabolic hormones.     

Circadian rest-activity rhythm in chronic obstructive pulmonary disease

To characterize circadian rest-activity rhythm in COPD, 26 cases (66.9 ± 8.5y) and 15 controls (63.0 ± 10.7y) were assessed by actimetry. Rhythm fragmentation was measured by intradaily variability (IV), while synchronization to the 24-h light-dark cycle was measured by interdaily stability (IS). The average activity during the least active 5-h period (L5) and the average activity during the most active 10-h period (M10) were used to calculate the relative amplitude mean [RAm = (M10-L5)/(M10+L5)]. COPD patients presented higher IVm (0.242 ± 0.097 vs 0.182 ± 0.063) and L5 (36.849 ± 18.239 vs 19.888 ± 12.268) and lower RAm (0.696 ± 0.134 vs 0.833 ± 0.093) than controls. Future studies on the effects of chronotherapy measures in COPD are warranted.