Proceedings of the American Thoracic Society
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In adults and children with asthma, viral infections (rhinovirus [RV] infection being the most prevalent) will often trigger an increase in symptomatology. The mechanisms responsible for viral-induced exacerbations remain uncertain. Proposed mechanisms include direct infection of the lower respiratory tract, the inflammatory response to viruses, increases in bronchial responsiveness and up-regulation of intercellular adhesion molecule-1 expression in bronchial epithelium. ⋯ In recent years studies have suggested that viruses and allergens may have a synergistic effect on individuals with asthma, thus having a greater influence on exacerbation rate together than either factor alone. Models of experimentally induced RV infection in both allergic and nonallergic individuals using bronchoalveolar lavage and segmental allergen challenge have helped researchers to investigate the possibility of an interaction between allergen sensitization, exposure, and virus infection and their role in the induction of an asthma exacerbation. This review aims to summarize the evidence supporting the role of viruses (in particular RV) as well as the role of, and interaction with, allergen sensitization and exposure on exacerbations of asthma.
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Exacerbations are an important cause of the morbidity and mortality associated with asthma and chronic obstructive pulmonary disease. Newer therapies include long-acting beta(2)-agonists, which are more effective than short-acting bronchodilators. ⋯ In the future, combinations of long-acting beta(2)-agonists and anticholinergic bronchodilators may offer additive clinical benefits. However, although the treatment and prevention of exacerbations of chronic obstructive pulmonary disease and asthma have been improved by using combinations of known therapies, further research addressing the underlying etiology as well as molecular and pathophysiologic mechanisms of exacerbation is needed to better target novel therapies to the appropriate patient populations and to develop new therapeutic strategies.
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Review Comparative Study
Use of nonviral vectors for cystic fibrosis gene therapy.
Over the last decade, three groups within the United Kingdom (Edinburgh, Oxford, and Imperial College, London) have undertaken key studies in the development of clinical gene therapy for cystic fibrosis. In 2001, catalyzed by the Cystic Fibrosis Trust, these groups came together to form the United Kingdom Cystic Fibrosis Gene Therapy Consortium. ⋯ This is driven by a clinical trial program, with a product pipeline and the necessary development of novel preclinical and human assays. The program is milestone-related, has a structure that lies between the pharmaceutical industry and academia, and has as its endpoint negotiations with industry to undertake a phase III clinical trial of the identified product.
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Review
Exacerbations and progression of disease in asthma and chronic obstructive pulmonary disease.
Exacerbations, characterized by an increase in patients' symptoms above baseline, are characteristic of both chronic obstructive pulmonary disease (COPD) and asthma. Prevention of exacerbations and their expedient treatment are major goals for reducing the morbidity and cost of both conditions. Exacerbations, however, may also adversely affect the natural history of these disorders, perhaps by contributing to increased rates of lung function decline, systemic effects, and premature mortality. ⋯ Second, health status is adversely affected by exacerbations, and although the mechanisms are unclear, the effects are long lasting and may be irreversible. Less is known in asthma about the effect of exacerbations on natural history, but many of the same pathogenetic processes involved in COPD exacerbations likely play a role in some subjects with asthma as well. Future studies of how exacerbation affects the "natural history" of asthma and COPD will require a better understanding of the heterogeneity of exacerbations but promises to identify new therapeutic strategies to treat these disorders.