Proceedings of the American Thoracic Society
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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.
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Review
Similarities and differences in asthma and chronic obstructive pulmonary disease exacerbations.
There is no generally accepted definition of an exacerbation either for asthma or for chronic obstructive pulmonary disease. There is little consistency among the symptomatic or functional criteria used in different studies. The most consistent criterion is the introduction of systemic corticosteroids for the acute worsening of the disease. ⋯ Avoidance of the causal factors decreases exacerbation rate in both diseases. Pharmacologic prevention of exacerbations in asthma has been shown for inhaled corticosteroids, combination therapy with long-acting inhaled beta(2)-agonists and inhaled corticosteroids, and monoclonal anti-IgE. Inhaled corticosteroids, long-acting inhaled beta(2)-agonists, combination therapy with both, and the long-acting inhaled anticholinergic tiotropium decrease the exacerbation rate in COPD.
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Review
Reducing the frequency and severity of exacerbations of chronic obstructive pulmonary disease.
Exacerbations contribute significantly to impaired health status in chronic obstructive pulmonary disease (COPD), but current therapy can prevent these episodes. Immunization against, for example, influenza offers specific prophylaxis for a minority of episodes. Pulmonary rehabilitation reduces hospital attendance, but its effect wanes. ⋯ In addition, the time to first exacerbation was increased compared with either drug alone. Health status changes mirrored these effects. In summary, combination therapy can effectively prevent exacerbations in patients with more advanced COPD.
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Review Comparative Study
Adeno-associated virus and lentivirus pseudotypes for lung-directed gene therapy.
The enthusiasm for cystic fibrosis gene therapy that attended the initial cloning of the gene and in vitro correction of the genetic defect eventually diminished as we learned more about the limitations of vector technologies that were available in the 1980s and 1990s. Substantial progress has been made, however, over the last 5 years in developing second- and third-generation vector constructs that should be more useful in achieving gene transfer to the lung for the treatment of pulmonary diseases such as cystic fibrosis.