Asthma Management — More Help Is On The Way


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Abstract

EXECUTIVE SUMMARYApproximately 19 million persons in the US have asthma, and the condition is responsible for over 5,500 deaths per year. Alarmingly, the number of persons with asthma has recently been increasing at about 5% per year in the US, and the mortality rate has increased as well. Between 1979 and 1995, the age-adjusted death rate increased from 0.9 per 100,000 in 1979 to 1.5 in 1995, a 67% increase, while the age-adjusted death rate from all causes declined 12.7%.Asthma specialists have reached a consensus on the long-term management of asthma that was published in 1997 by the National Heart, Lung and Blood Institutes in the National Asthma Education and Prevention Program (NAEPP). This program stressed the use of daily long-term anti-inflammatory medication with the goal of preventing chronic symptoms and maintaining nearly normal pulmonary function with normal activity. Pharmacologic intervention is used initially at a higher level than the patient's symptoms indicate with a “step-down” procedure to reach the minimal doses that achieve the treatment goals. Daily medications required for the moderate to severe persistent categories of asthma are the long-acting inhaled beta2-agonists as well as inhaled or systemic corticosteroids.Of all the diseases involving the respiratory system, asthma is by far the leading indication for development of new therapeutics. Many factors account for this. First, the long-term, chronic nature of the disease in many individuals indicates a need for better treatment. In a substantial number, asthma begins in childhood. Second, a significant percentage (5 to 10%) of the population is affected, and the incidence of asthma is increasing. Third, an increased understanding of the inflammatory basis for the disease has spurred the search for new treatments and combinations of drugs, not only to alleviate symptoms, but also to reverse damage to the airways.The newest drugs to enter the market for asthma treatment are the leukotriene receptor antagonists (LTRA) and the 5-lipoxygenase inhibitors. Clinicians prescribing LTRAs are beginning to come to a consensus that they will continue to grow in their utilization for asthma treatment.The enzyme 5-lipoxygenase is a crucial catalyst in the synthesis of the eicosanoids, including leukotrienes, prostaglandins, and thromboxanes. Inhibitors of this process should greatly reduce inflammatory consequences that are mediated by these substances. There is considerable development in the area of 5-LOs. Perhaps because these drugs work on an earlier part of the eicosanoid synthesis pathway, they are deemed to have a greater potential for resolving inflammatory responses than compounds involved in the later phase.Cytokines play their role in the pathogenesis of asthma by facilitating cell signaling. The cytokines signal cells to respond by binding to cell-surface receptors which, in turn, activate intracellular enzymes, such as kinases, phosphatases, and lipases. Ultimately, activation of these pathways results in the transmission of “signals” to the nucleus, where the expression of particular genes is induced or repressed. These changes in the expression program of the cells are responsible for initiating migration, the synthesis of inflammatory substances, and cellular destruction.A rational approach to the development of drugs for asthma is using the structures of the proteins involved in the inflammatory cascade to block the consequences of their interactions. Essentially all of the activity in the development of small compounds is in the preclinical stage in the United States. Many are still in the drug-discovery phase.The rate of gain for asthma therapeutics is expected to remain strong for the next several years as the leukotriene agents establish their place in the market. There should then be another growth surge around the 2007–2008 period due to strong impact of new immunotherapeutic products.Source: Asthma Alternatives — Managing Markets and Technology — Genesis 1999

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