1,721,207 research outputs found
Gene-environment interactions in the development of chronic obstructive pulmonary disease
No full textThe completion of the Human Genome Project, the HapMap project, technological advances in single-nucleotide-polymorphism genotyping and the potential of genome-wide association analysis will allow the identification of susceptibility genes for chronic obstructive pulmonary disease. The challenge is to understand the influence of multiple genetic factors and multiple environmental factors as well as gene-gene and gene-environment interactions. Careful clinical characterization of phenotypes for chronic obstructive pulmonary disease is essential and this will include comparison of biomarkers of distinct pathologies including radiological assessment to separate the components of pulmonary emphysema and small-airway disease
Chemokine receptor inhibitors as a novel option in treatment of asthma
No full textThe migration of cells towards and into the site of an inflammatory insult is critical for maintenance of the inflammatory response and its resolution. This is particularly so in the case of asthma where recruitment of key effector cells may control disease severity, responsiveness to current therapies and the airway remodelling associated with the disease. Chemokine receptor antagonists have the hope of preventing inflammatory cell recruitment to the airway and perhaps as a consequence affect the resolution of airway remodelling. A number of selective antagonists directed at various CC and CXC receptors thought to be important in asthma are currently at various stages of clinical development. Results from these studies will determine whether chemokine receptor antagonists will prove beneficial in severe glucocorticoid-dependent and -resistant asthmatic subjects. Furthermore, it is possible that early treatment with these agents may prevent the disease from becoming established. © 2004 Bentham Science Publishers Ltd
Clinical definition of COPD exacerbations and classification of their severity
No full textA standardized definition of chronic obstructive pulmonary disease (COPD) exacerbation still represents an unmet need in respiratory medicine; definitions currently rely oil clinical empiricism with little evidence-based scientific support. Exacerbations of COPD are certainly clear events in the mind of practicing physicians. However, when one tries to provide simple concepts such as their definition and classification of severity, one realizes how little we know. Current symptom- and event-based definitions of a COPD exacerbation, as well as the classifications of the severity of COPD exacerbations, all have their own limitations. Efforts to assess the efficacy of new therapies in the treatment and prevention of COPD exacerbations have been hampered by the lack of a widely agreed upon and consistently used definition. There is a need for greater investment in research oil COPD exacerbations in order to promote a better understanding of COPD exacerbation
Transcription factors in asthma and COPD
No full textThis chapter reviews the physiological function of the transcription factors in the normal cells and the role of some transcription factors that may be relevant in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). Asthma and COPD are characterized by an increased expression of components of the inflammatory cascade. The increased expression of these proteins seen in asthma and COPD is the result of enhanced gene transcription. Transcription factors regulate the expression of many genes, including inflammatory genes, and play a key role in the pathogenesis of asthma and COPD since they regulate the increased gene expression that may underlie the acute and chronic inflammatory mechanisms that characterize these diseases. Transcription factors may amplify and perpetuate the inflammatory process, so it is possible that abnormal functioning of transcription factors may determine disease severity and response to treatment. Several new compounds based on interacting with specific transcription factors or their activation pathways are now in development for the treatment of asthma and COPD, and some drugs already in clinical use are thought to work via transcription factors. In the future the role of transcription factors and the genetic regulation of their expression in asthma and COPD may be an increasingly important aspect of research, as this may be one of the critical mechanisms regulating the expression of clinical phenotypes and their responsiveness to therapy
Interactions between long-acting ß2-agonists and glucocorticoids
No full textLong acting ß2-agonists and glucocorticoids together control asthma in ~95% of affected individuals, although symptoms return after treatment is stopped. Treatment of chronic obstructive pulmonary disease (COPD) scarcely influences the natural course of the disease. Neither long-acting ß2-agonists (LABAs) nor glucocorticoids alone significantly influence the course of COPD. Recent evidence suggests that a combination of the two therapies is more promising. It can decrease the exacerbation rates in severe COPD and may also decrease mortality
Chronic obstructive pulmonary disease and lung cancer: new molecular insights
No full textBoth chronic obstructive pulmonary disease (COPD) and lung cancer are major causes of death worldwide. In most cases this reflects cigarette smoke exposure which is able to induce an inflammatory response in the airways of smokers. Indeed, COPD is characterized by lower airway inflammation, and importantly, the presence of COPD is by far the greatest risk factor for lung cancer amongst smokers. Cigarette smoke induces the release of many inflammatory mediators and growth factors including TGF-β, EGFR, IL-1, IL-8 and G-CSF through oxidative stress pathways and this inflammation may persist for decades after smoking cessation. Mucus production is also increased by these inflammatory mediators, further linking airway inflammation to an important mechanism of lung cancer. A greater understanding of the molecular and cellular pathobiology that distinguishes smokers with lung cancer from smokers with and without COPD is needed to unravel the complex molecular interactions between COPD and lung cancer. By understanding the common signalling pathways involved in COPD and lung cancer the hope is that treatments will be developed that not only treat the underlying disease process in COPD, but also reduce the currently high risk of developing lung cancer in these patients
Role of transcription factors in the pathogenesis of asthma and COPD
No full textInflammation is a central feature of asthma and chronic obstructive pulmonary disease (COPD). Despite recent advances in the knowledge of the pathogenesis of asthma and COPD, much more research on the molecular mechanisms of asthma and COPD are needed to aid the logical development of new therapies for these common and important diseases, particularly in COPD where no effective treatments currently exist. In the future the role of the activation/repression of different transcription factors and the genetic regulation of their expression in asthma and COPD may be an increasingly important aspect of research, as this may be one of the critical mechanisms regulating the expression of different clinical phenotypes and their responsiveness to therapy, particularly to anti-inflammatory drugs
Anti-inflammatory mechanisms of glucocorticoids targeting granulocytes
No full textAsthmatic inflammation involves the recruitment and activation of inflammatory cells, and changes in the structural cells of the lung and asthma are characterized by an increased expression of components of the inflammatory cascade including cytokines, chemokines, growth factors, enzymes, receptors and adhesion molecules. The increased expression of these proteins seen in asthma is generally the result of enhanced gene transcription, since many of the genes are not expressed in normal cells but are induced in a cell-specific manner during the inflammatory process. There is clear evidence that neutrophils, long thought of as being transcriptionally inert, can respond to stimuli to induce inflammatory genes. Glucocorticoids are very effective in controlling the inflammation seen in asthmatic airways. Beyond their recognized actions on eosinophil and neutrophil apoptosis, glucocorticoids have profound effects on the chemotaxis, activation and release of mediators from granulocytes (eosinophils, neutrophils and basophils). Few mechanistic studies are available in these cells, but it appears that in granulocytes, glucocorticoids target the same signaling pathways, such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), that are important in other cells. We summarize these known mechanisms at the end of this review
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