Over the past 15 years, biomedical research has produced major advances in the understanding of asthma. Prior to this period the role of inflammatory mechanisms in asthma was not understood. Asthma is now known to be a disease of airway inflammation resulting from a complex interplay between environmental exposures and genetic and other host factors. Left untreated, inflammation may lead to irreversible changes in lung structure, called airway remodeling. Together, t hese findings have changed medical treatment and environmental management of asthma.
"Through scientific advances, much of the severe morbidity and mortality from asthma can now be prevented."
- Claude Lenfant, M.D., Director, National Heart, Lung, and Blood Institute
Based on an improved understanding of asthma, inhaled anti-inflammatory medications have become the mainstay of preventive medical management for patients with persistent asthma. Development of new medications to treat and prevent the symptoms of asthma based on new insights into the cellular mechanisms of inflammation will offer options to tailor therapy to the individual patient and, minimize the possibilities of side effects.
In addition to improvements in medical therapy, better monitoring techniques now permit objective measures of lung function that are simple tools for patients and physicians to use in assessing asthma severity and monitoring changes in the disease. In a disease like asthma, which varies considerably over time, and where changes in lung function can occur before symptoms develop, objective measures provide essential information for making decisions about adjusting medications.
The Causes of Asthma and of the Asthma Epidemic Are Not Well Understood
Although the causes of the increasing rates of asthma over the past 15 years are not known, the most likely reason is an interaction between environmental and genetic factors. Atopy, the genetically inherited susceptibility to become allergic, is the most important predictor of a person developing asthma (29). A substantial research effort is underway to identify the genes responsible for susceptibility to asthma. Since the genetic make-up of the population changes slowly, genetic susceptibility alone cannot be responsible for the epidemic of asthma which has occurred in the United States over the past 15 years. Further work is needed to clarify how genetic susceptibility and environmental exposures interact to cause asthma.
Many studies have demonstrated that exposure to indoor allergens and environmental tobacco smoke are risk factors for more severe asthma (30, 31, 32, 33). Some studies suggest that indoor allergen exposure is a risk factor for the initial onset of asthma (34, 35, 36). People now spend more time indoors, thus increasing exposure to indoor allergens and pollutants. In its recent review of the current scientific literature, the Institute of Medicine (IOM) drew several conclusions about the role of numerous indoor air exposures and the initial development of asthma (37). The findings were ranked according to the level of evidence linking any of the exposures to the onset of asthma. IOM emphasized that a particular agent may be associated with the development of asthma, but that does not mean it is the sole factor determining whether an individual will develop the illness. The IOM Committee found that exposure to house dust mite allergen can STYLE="text-decoration: underline">cause the development of asthma in susceptible children. The Committee also determined that exposure to environmental tobacco smoke is ssociated with the development of asthma in younger children. Maternal smoking during pregnancy was suggested to have a stronger adverse affect than exposure after birth. In addition, limited or suggestive evidence was found by the IOM for associations between cockroach allergen exposure or respiratory syncytial virus (RSV) infection and the development of asthma in infants. Both factors have been the subject of active research during the past few years and efforts currently underway may help shed greater light on their potential role in asthma development .
Other possible, but less well studied, factors that may affect the development of asthma include exposures that stimulate the immune system. One hypothesis is that certain infections in early life may block the allergic immune response and thereby protect against asthma (38, 39, 40, 41). Other factors have been postulated to cause asthma, including the diet during the prenatal period and early infancy (42) and obesity in adolescents and adults (43, 44). Such hypotheses remain controversial, and more research is clearly needed to understand the remarkable rise in asthma and the causes of the disease.
The Environment, Indoors and Outdoors, Can Exacerbate Asthma
While much remains to be learned about the causes of asthma, many studies have identified factors that exacerbate asthma in those who already have the illness (33, 45, 46, 47, 48, 49, 50). Asthma exacerbations or "attacks" involve the onset or worsening of symptoms (e.g., some combination of shortness of breath, cough, wheezing, and chest tightness). Reducing exposure to certain allergens has been shown not only to reduce asthma symptoms and the need for medication, but also, in some studies, to improve lung function (37, 48).
The IOM report drew several conclusions about the role of specific indoor exposures in the exacerbation of asthma. The IOM committee found sufficient evidence to conclude that expo-sure to allergens produced by cats, cockroaches, and house dust mites, causes exacerbations of asthma in sensitized individuals (i.e., those who are allergic to these substances). In addition, the committee found sufficient evidence that environmental tobacco smoke causes exacerbations of asthma in pre-school-aged children (see Appendix H for executive summary of the IOM report).
People with asthma, both children and adults, can be particularly sensitive to outdoor air pollution. Common air pollutants (also known as "ambient air pollutants") such as ozone, sulfur dioxide, and particulate matter, are known to be respiratory irritants and can contribute to an exacerbation of asthma symptoms. Air pollution also might act synergistically with other environmental factors to worsen asthma (51). For example, diesel exhaust particulates, by markedly increasing the capacity to produce IgE antibodies, may enhance responsiveness to allergens (52). Also , some evidence suggests that exposure to ozone can enhance a person's responsiveness to inhaled allergens (53, 54).
Workplace Exposures Can Aggravate or Cause Asthma
In persons with asthma resulting from workplace exposure, clear relationships have been identified between the level of exposure to specific chemicals and allergens and rates of sensi-tization and symptoms (55). Over 250 agents encountered at work can cause asthma, including isocyanates, wood dusts, anhydrides, dyes, formaldehyde, metals, latex, and enzymes (56). For example, even brief exposure to more than 20 parts per billion of isocyanates is considered hazardous ; isocyanates are widely used in many countries and are responsible for the most common form of occupational asthma. Many patients suffer chronic disease even after they are removed from an occupational exposure situation. However, early diagnosis and early removal from exposure increases the likelihood of recovery (56). Since workers are exposed to a wide range of possible causative agents, often at elevated exposure levels, the occupational setting offers a significant opportunity for research on asthma causes and triggers. Such research could prove to be a useful model for understanding how environmental exposures to certain chemicals and allergens might contribute to the development of asthma.
Knowledge Exists to Successfully Manage Asthma in Most Patients
Advances in the scientific understanding of the underlying mechanisms of asthma have led to treatment that can significantly improve the health of asthma patients. The Guidelines for the Diagnosis and Management of Asthma ("Guidelines") -- developed by experts convened by the National Institutes of Health (NIH) and updated in 1997 - recommend four strategies for managing asthma that substantially reduce the frequency and severity of asthma attacks (57, 58). The Guidelines emphasize: 1) assessment and monitoring of symptoms; 2) control of environmental factors to limit exposure to allergens and other triggers; 3) use of appropriate medication; and 4) education of the patient and family in asthma care. These recommendations promote a fundamentally new understanding of asthma and its treatment by emphasizing the role of inflammation in disease development, noting the importance of objective monitoring of lung function, and stressing the need to establish partnerships between patients and health care providers through patient education (see Appendix C for a summary of the 1997 Guidelines). In 1999, the Guidelines were adapted into an easily referenced pediatric document, Pediatric Asthma: Promoting Best Practice - Guide for Managing Asthma in Children (59). The Guidelines remain the world's most comprehensive, up-to-date source of information on asthma diagnosis and management. By f ollowing the recommendations , most people with asthma should be able to lead an active life, with their asthma well-controlled.
The benchmark publication by the National Heart, Lung, and Blood Institute, Guidelines for the Diagnosis and Management of Asthma, translates advances in scientific understanding into practical strategies for asthma care.