Action Against Asthma: A Strategic Plan for the Department of Health and Human Services . Priority Area 1: Determine the Causes of Asthma and Develop Interventions to Prevent Its Onset

05/01/2000

Research has not yet identified or demonstrated how to prevent the onset of asthma. Research to prevent asthma in individual patients or in high risk populations is known as "primary prevention" research. It includes both research to understand the causes of asthma and testing strategies to prevent its occurrence. This research is critical to discovering the reasons for the current epidemic of asthma.

Current DHHS Activities: Primary Prevention Research

NIH sponsors the majority of primary prevention research funded by DHHS. The Centers for Disease Control and Prevention (CDC) also undertakes work in this area. Relevant research focuses on the natural history of the disease, risk factors, genetics, and the basic mechanisms and pathogenesis of asthma. An example of the research on the natural history of asthma is exploring the hypothesis that infection with respiratory viruses in early life, such as respiratory syncytial virus, may predispose an individual to an increased risk of asthma. In contrast, certain other infections in early life may block the immune response to allergens and thereby decrease the risk of asthma (37, 38, 39). In addition, research on risk factors includes examining the potential role of environmental and occupational exposures in the onset of asthma.

A major portion of NIH asthma-related research is devoted to enhancing understanding of pathogenesis and basic mechanisms of asthma. This work covers a range of issues relating to cellular and molecular-level events in asthma that cause the lung to become injured and repaired. It will help explain why asthma persists for many years, as well as why asthma is severe in some patients and not in others. The National Heart, Lung and Blood Institute (NHLBI), the National Institute for Allergy and Infectious Diseases (NIAID), and the National Institute of Environmental Health Sciences (NIEHS) support investigations of the immune system and asthma that may lead to prevention of the allergic inflammatory process. NIEHS is also studying other strategies for primary prevention of asthma, including how exposures to environmental agents modify the immune system, which may affect the early sensitization events preceding the onset of asthma.

Genetics Research
NIH is investing significantly in research on gene-environment interactions, including a genome-wide search to identify genes that confer susceptibility to asthma.


Family clustering of asthma and allergy suggests a genetic basis for asthma. However, since the genetic background of the population changes only slowly with the succession of generations, it is most likely that the rising trend in asthma in the last 15 years relates to environmental factors interacting with genetic susceptibility. Therefore, a major focus of research at several NIH institutes is on STYLE="text-decoration: underline">gene-environment interactions, and includes a genome-wide search as part of the Environmental Genome Project to identify genes that confer susceptibility to asthma. Early findings confirm that multiple genes may be involved . Defining how genetic and environmental factors interact to predispose certain individuals to asthma holds a key to prevention strategies for the disease.

Urgent Needs: Primary Prevention Research

DHHS will increase attention to three areas that show particular promise for uncovering clues to the onset of the disease, and will expand testing of innovative prevention strategies . (Many of these topics are also relevant to two other priority areas: reducing the burden of asthma and eliminating disparities in the impact of the disease on minority populations and the poor.)

Improve understanding of early life origins of asthma. While research on various aspects of the origins of asthma is already underway, further examination is needed of the potential for early life events to cause asthma, such as pre- and post-natal exposures to viral infections, allergens, tobacco smoke, and elements of the maternal and infant diet.

High levels of airborne allergen exposure in infancy have been shown to enhance the likelihood of sensitization and the development of asthma in childhood (34, 35, 37, 67). However, the immune mechanisms associated with the effects of allergens in infancy are not known and must be investigated. Another high priority need is the development of immunologic and clinical markers of asthma in infancy and early childhood among children of distinct genetic backgrounds.

Study gene-environment interactions and links to characteristics of asthma. As genes associated with asthma are defined, it will be important to establish their function, particularly how they regulate the disease process. Since genetic factors can also interact with environmental factors, understanding these links in the development of airway inflammation is another priority need. Recent data suggest that certain characteristics of asthma (e.g., whether it is exercise-induced, nocturnal, has persistent symptoms or episodic but severe attacks) are associated with specific genetic, immunologic and environmental factors (68). Examining these further could have significant implications for the prevention and treatment of asthma in individuals and in genetically distinct populations.

Investigate adult onset of asthma. Allergens may play an important role in some adults with asthma who did not exhibit the disease in childhood . In other adults with asthma , allergies are not detected; the mechanisms of "intrinsic" asthma are not well-understood. Additional research is needed on adult-onset asthma in areas such as: asthma during pregnancy, during menopause (especially in those on hormone replacement therapy), and in the elderly who have confounding medical complications. Another need is to characterize the conditions under which occupational asthma develops, including assessment of exposure-response relationships, so that prevention strategies can be developed.

Test strategies for prevention. Intervention trials are needed to test hypotheses of how to prevent asthma, even while work on understanding the basic mechanisms is proceeding. Tests of prevention strategies for those at high risk of developing asthma could include investigating whether eliminating various exposures during early life or providing pharmacologic treatments can delay or prevent the onset of the disease. Another promising strategy is to block the allergic immune response in susceptible individuals, for example by induction of immune tolerance (6) , thus preventing asthma from ever developing. Identifying interventions to prevent asthma is the most promising approach to ending the epidemic of asthma.

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