The immune response to Prevotella bacteria in chronic inflammatory disease.

perspective of chronic obstructive pulmonary disease: doubt some more

Neutrophilic airway inflammation and IL-17.

Introduction. Morbidity due to reduced local immune reaction in patients affected by chronic obstructive pulmonary disease (COPD) is extremely high and continues to grow. The results of a research on changes in the local immune response in patients with COPD at the exacerbation stage are discussed in this paper. The pathogenesis of COPD during exacerbation is characterized by deterioration of the local innate and acquired immunity. The process is accompanied by pathological changes of the systemic immunity. Various cells of the immune response are involved in the inflammation process, attracting increased amounts of macrophages, neutrophils, T- and B-lymphocytes, and dendritic cells. The number of neutrophils and B-lymphocytes are observed in patients suffering from a severe disorder. Most common symptoms of COPD are irreversible narrowing of the airways, destruction of the parenchyma of the lung accompanied by emphysema, and progression of the obstructive pulmonary disease. The aim of the study – to learn the changes in functionality of bronchoalveolar lavage (BAL) cells and peripheral blood cells (PBC) in COPD patients and provide an explanation for these changes in light of pathogenetic characteristics to predict the course of the disease and justify the necessity of a local immunotherapy in comprehensive treatment of COPD patients. Research Methods. The focus of the research was on BAL cells and PBC of patients with COPD at different stages and on blood serum. CD3, CD4, CD8, CD16 and CD19 of BAL and PBC cells were identified using different specific monoclonal antibodies. Receptor expression to IL-2 (CD25) was examined, adhesive molecules were identified using CD54, proliferation levels were measured using IPO-38, as well as was measured the expression of class II antigens MHC (HLA-DR) in the blast transformation reaction that was induced by PHA and Con A mitogens. Phagocytic activity of phagocytizing neutrophils cells, alveolar macrophages (AM), and phagocytizing PBC cells was evaluated. Levels of free radical processes and antioxidant defence were studied using a chemiluminescence method. Results and Discussion. The amount of AM cells in COPD patients declined significantly, whereas the amount of neutrophils notably increased, as well as concentrations of the myeloperoxidase and the eosinophil cationic protein. Examination of phlegm and BAL cells obtained from COPD patients at the exacerbation stage of the disease indicate that 23 % of samples displayed gram-negative bacterial flora (primary pathogens being Pseudomones aeruginosa, Haemophillus influensae, Enterobacter spp.), 15 % – candidas, 61 % – pathogen type was not identified. Researching local and systemic immune response in COPD patients and functional activity changes of BAL and PBC indicated that patients showed significant changes in their local immune system, which manifested in significant reduction in the amount of neutrophils in the lavage, reduction in CD3, CD19, and increased expression of receptors to HLA-DR antigen expression. Summary. Parallel study of the local and systemic immunological responses contributes to expand our knowledge and understanding of pathogenesis of COPD. It is useful in determining methods to help decrease the number of complications and aid in COPD prophylaxis in persons of working age. It also provides information on which local immunotherapy will prove to be most effective. Exploring the subject further should provide fundamental understanding of similar and different symptoms of various disorders in patients with inflammation processes at the local immune level in different body locations, such as respiratory organs during COPD, in the peritoneal cavity during peritonitis, dermal lesions or any other changes in the local immune system of a different body location.

How Viral Infections Cause Exacerbation of Airway Diseases

Rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD) are both chronic inflammatory diseases; the prevalence of COPD in RA patients is known to be high. However, the prevalence of both RA and COPD differs according to sex; the relationship between RA and COPD may also vary according to sex. Therefore, we investigated the prevalence of COPD and its association in patients with RA in Korea by sex. We conducted a nationwide cross-sectional study using data from the Korea National Health and Nutrition Examination Survey. A total of 12417 men and 15878 women were included. In this study, RA was defined as physician diagnosed or currently under RA treatment. COPD was defined based on spirometry results, chronic symptoms, and smoking history. Multivariable logistic regression models were employed and we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for COPD prevalence in patients with RA. The prevalence of COPD was 15.5% in men with RA, 3.5% in women with RA, 7.8% in men without RA, and 2.2% in women without RA. After adjustment for potential confounding variables, including smoking status, RA was significantly associated with COPD in men (OR 2.16, 95% CI 1.06-4.40), but not in women (OR 1.58, 95% CI 0.81-3.10). In Korea, the prevalence of COPD was high in patients with RA of both sexes; RA and COPD was significantly likely to be associated in men, but not in women.

Linoleic acid supplement in cystic fibrosis: friend or foe?

Put your heart into the joint benefits of statins!

New molecular targets for the treatment of neutrophilic diseases

Genetically Programmed Biases in Th1 and Th2 Immune Responses Modulate Atherogenesis

Objective Autophagy serves a role in the pathogenesis of chronic inflammatory diseases. The aim of the present study was to compare the autophagy levels of the peripheral blood mononuclear cells (PBMCs) in patients with chronic obstructive pulmonary disease (COPD) and healthy individuals and to assess the association between autophagy and the clinical parameters of COPD. Methods Samples of peripheral blood from 20 patients with stable COPD and 20 healthy controls were collected. PBMCs were harvested using Ficoll density gradient centrifugation. Levels of the autophagy-associated proteins ubiquitin-binding protein P62 (P62), microtubule-associated proteins 1A/1B light chain 3A (LC3 Ⅰ/Ⅱ) and beclin-1 in PBMCs were detected by western blotting. Enzyme-linked immunosorbent assay kits were used to detect the serum concentrations of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α. Results Western blotting demonstrated that the protein expression of P62 decreased (P62/GAPDH = 0.212 ± 0.089 vs. 0.378 ± 0.176, P = 0.001 1), but LC3 Ⅰ/Ⅱ (4.94 ± 1.85 vs. 3.85 ± 1.06, P = 0.024 9) and beclin-1 (Beclin-1/GAPDH = 0.578 ± 0.126 vs. 0.149 ± 0.035, P < 0.01) levels increased in patients with COPD compared with healthy controls. Serum levels of IL-6 [(11.96 ± 3.46) ng/L vs. (2.70 ± 1.72) ng/L, P < 0.01], IL-8[(20.38 ± 18.44) ng/L vs. (6.00 ± 4.08) ng/L, P = 0.001 6] and TNF-α (29.50 ± 28.18 vs. 11.08 ± 12.07, P = 0.010 6) increased in patients with COPD. The extent of PBMC autophagy was negatively correlated with FEV1% predicted, but positively correlated with levels of proinflammatory cytokines. The levels of autophagy in PBMCs in patients with COPD increased and were negatively correlated with FEV1% predicted and positively correlated with circulating levels of pro-inflammatory cytokines. Conclusions Autophagy may serve a role as a biomarker of the severity of COPD or as a therapeutic target for treatment of COPD. Key words: Pulmonary disease, chronic obstructive; Peripheral vascular diseases; Monocytes; Autophagy; Tumor necrosis factor

Men are different, women too. A concept which has long been neglected in biomedical research. Except for reproductive differences women were regarded as smaller men, clinical guidelines did not differentiate between men and women. There are, however, further differences. Every cell has a sex, which might influence regulation of gene expression, disease phenotype and drug toxicity. In drug research it is important to understand the pathomechanism and clinical presentation of a disease as well as the mechanism of action of a drug. Information on drug safety and efficacy are collected in preclinical and clinical studies. Natural history of disease studies provide valuable information on the clinical presentation of a disease. It is important to provide this information gender stratified to be able to offer best care to future patients. Chronic obstructive pulmonary disease (COPD) has traditionally been regarded as a disease of white men but today almost as many women are affected by the disease as men. The burden of COPD is still projected to increase, particularly in women. Despite this there are few studies comparing the clinical manifestation and clinical course in men and women with COPD. It was the aim of this thesis to contribute new data to the natural history of COPD with a special focus on the effect of gender. The studies of this thesis were conducted with data from the General Practice Research Database (GPRD), a large population-based database in the United Kingdom. The GPRD provides anonymized medical information on a 5% representative sample of the UK population. This thesis presents six studies focussing on a population of 35,772 COPD patients, aged 40-79 years, who received their incident COPD diagnosis between 1995 and 2005 and the same number of randomly matched COPD-free patients for comparison. In a case-control analysis we compared the prevalence of co-morbidities and respiratory drug utilization in men and women with COPD. In nested case control analyses COPD and COPD-free patients were compared with respect to their risk to develop cardiovascular or gastrointestinal outcomes, depression or cancer. The first study described the COPD population with respect to co-morbidities, drug use and survival. Patients with COPD had more co-morbidities and a lower survival than COPD-free patients. In COPD patients the prevalence of diabetes, myocardial infarction, stroke / transient ischemic attack (TIA), arrhythmia and peptic ulcer were higher in men than in women while depression and osteoporosis were more prevalent in women. We observed small but significant gender differences in drug utilization and survival. The second study analysed in more detail the association between COPD and the prevalence of diabetes. The prevalence of diabetes was lower in the COPD group than in the COPD-free comparison group. This association was significant in men but not women and mainly seen in users of sulfonylurea. Studies 3-6 were follow-up and nested case control analyses evaluating the risk of the cardiovascular outcomes (arrhythmia, pulmonary embolism, deep vein thrombosis, myocardial infarction and stroke / TIA), gastro-oesophageal reflux disease, peptic ulcer, depression and cancer risk in the population of COPD patients and compared it to a COPD-free population. The incidence of most cardiovascular diseases was higher in patients with COPD. COPD had a stronger impact on the risk of MI and stroke / TIA in women than in men. Relative risks of PE, DVT and arrhythmia were similar in men and women. Severe COPD materially increased the risk of MI and PE in both men and women. The incidence rates of GORD were slightly higher in men than in women while peptic ulcer incidence rates were higher in men. COPD did not materially alter the risk of GORD or peptic ulcer. Current use of long-acting beta agonists was associated with a decreased risk of peptic ulcer. Patients with COPD had a higher risk of cancer than COPD-free patients. The increased risk was mainly driven by a high lung cancer risk among COPD patients, which was higher in women than in men. This effect was seen independent of smoking status. Many patients with COPD developed depression during follow-up, particularly patients with severe COPD. The risk of depression was higher in women than in men but COPD seemed to have a greater impact in men than in women. The studies of this thesis provide further evidence that patients with COPD are at an increased risk of depression, most cardiovascular diseases and lung cancer. They also demonstrate that gender-stratified analyses are important to adequately address the risk for a disease.

Are rhinoviral proteinases responsible for mixed TH1 and TH2 immunity in chronic obstructive pulmonary disease?

A community-based, time-matched, case-control study of respiratory viruses and exacerbations of COPD

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of lung caused predominantly by cigarette smoking,affecting lung parenchyma and airways.Th17 cells can secrete a variety of cytokines,promote the recruitment and activation of neutrophils and increase the number of CD8+T cells.Th17 cells plty an important role in COPD.In different inflammatory conditions,Th17 and CD8+ T cells participate in the pathogenesis of COPD that link innate and adaptive immune response. Key words: Th17 cells; CD8+T cells; Chronic obstructive pulmonary disease

Asthma and chronic obstructive pulmonary disease (COPD) are two distinct lung diseases with distinctive clinical and inflammatory features. A proportion of asthmatic patients experience a fixed airflow obstruction that persists despite optimal pharmacologic treatment for reasons that are still largely unknown. We found that patients with asthma and COPD sharing a similar fixed airflow obstruction have an increased lung function decline and frequency of exacerbations. Nevertheless, the decline in lung function is associated with specific features of the underlying inflammation. Airway inflammation increases during asthma exacerbation and disease severity. Less is known about the correlations between symptoms and airway inflammation in COPD patients. We found that there is no correlation between symptoms and lung function in COPD patients. Nevertheless symptoms changes are associated with specific inflammatory changes: cough is associated with an increase of sputum neutrophils in COPD, dyspnoea is associated with an increase of eosinophils. The mechanisms of this correlation remain unknown. Neutrophils inflammation is associated with bacterial colonization in stable COPD. Is not known whether inhaled corticosteroids might facilitate bacterial colonization in COPD patients. We found that the use of inhaled corticosteroids in COPD patients is associated with an increase of airway bacterial load and with an increase of airway pathogen detection. Bacterial and viral infections are the main causes of COPD and asthma exacerbations. Impaired innate immune responses to rhinovirus infections have been described in adult patients with atopic asthma. Whether this impaired immune condition is present early in life and whether is modulated by a concomitant atopic condition is currently unknown. We found that deficient innate immune responses to rhinovirus infection are already present early in life in atopic patients without asthma and in asthmatic subjects. These findings generalize the scenario of increased susceptibility to viral infections to other Th2 oriented conditions.