Asthma therapy: Changing perspectives

Asthma is one of the most common chronic diseases worldwide, and its prevalence--particularly among children--is increasing in many countries.^1,2 In 1997, an estimated 9.6% of persons in the United States had asthma (Table 1).³

There are many reasons physicians should continue to be concerned about asthma, the most obvious being the potential for life-threatening exacerbations. In 1998, the death rates for asthma averaged 4.7 and 4 per 100,000 persons for black women and men, respectively, and 1.6 and 1.2 for white women and men, respectively.³ In addition, asthma is a leading cause of absence from work or school.³

Overview

Asthma involves chronic inflammation of the airways and associated hyperresponsiveness that lead to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. Symptoms are associated with widespread but variable airflow obstruction that usually reverses spontaneously or in response to medications.

There are a number of risk factors for asthma, including genetic predisposition, atopy, and airway hyperresponsiveness. Environmental factors also play a role. Exposure to allergens, pollutants, tobacco smoke, and occupational sensitizers can predispose a person to asthma. Bacterial, viral, and parasitic respiratory infections can trigger airway inflammation.

Socioeconomic factors also contribute--the incidence of asthma is particularly high in poor persons who live in overcrowded inner-city environments.⁴ In some cases, host and environmental factors may interact to contribute to chronic asthma.

Patients are classified according to the severity of their asthma before treatment. The category is determined by the single most severe feature, whether this involves daytime or nighttime symptoms or pulmonary function parameters. The 4 asthma categories are mild intermittent, mild persistent, moderate persistent, and severe persistent (Table 2).⁵

This classification system for asthma serves as the basis for a stepwise approach to management that is recommended by the National Asthma Education and Prevention Program (Table 3).⁶ In this protocol, patients who have mild intermittent asthma need no daily medication, unless they have severe exacerbations. For patients who have mild persistent asthma, the preferred treatment is low-dose inhaled corticosteroids, with other medications--leukotriene modifiers, cromolyn, nedocromil, or sustained-release theophylline--as alternative choices.

For patients who have moderate persistent asthma, low-dose inhaled corticosteroids are also preferred, but in conjunction with a long-acting ß₂-agonist. Alternative treatments for this patient group are to increase inhaled corticosteroids to the medium-dose range or give low- to medium-dose inhaled corticosteroids and either a leukotriene modifier or theophylline. Persons who have severe persistent asthma are treated with inhaled high-dose corticosteroids and long-acting ß₂-agonists. If necessary, this can be supplemented with oral corticosteroids.

Current issues

While the current treatment guidelines are helpful, the best outcomes are achieved when treatment is individualized. This is hardly surprising given the host of factors, such as allergy and environmental exposures, that contribute to asthma. Furthermore, patients tend to respond variably to asthma medications, and their classification often changes depending on patients' symptoms and response to therapy.

This focus on individualized care is part of a trend that has emerged over the past decade. Asthma specialists now focus more on achieving long-term asthma control rather than primarily on preventing and managing acute exacerbations. This broader goal of long-term asthma control requires that physicians pay adequate attention to the patient's overall quality of life. How often do symptoms awaken the patient? How many days of work or school is the patient missing because of asthma? Does asthma interfere with the patient's ability to pursue hobbies or participate in sports or other physical activities?

With long-term asthma control moving to center stage, clinical trials will have to measure therapeutic response in terms of patient-centric outcomes. Pulmonary function tests will probably always be useful for providing a standardized, quantifiable method of outcomes assessment, but they are not the only answer and are not without limitations.

Dr Stephen Peters, professor of medicine and pediatrics in the section on pulmonary, critical care, allergy, and clinical immunology at the Center for Human Genomics at Wake Forest University School of Medicine in Winston-Salem, North Carolina, offers valuable insight into outcomes assessments in his article on the assessment of asthma severity and control on page S8. Dr Peters also discusses how patient-oriented scales, such as the Asth-ma Control Questionnaire and the Asthma Control Test, have already proved useful as a means of gaining a more global assessment of patient status, and why such scales are likely to have an expanding role in the future.

No discussion of asthma management and quality of life would be complete without addressing the current controversy over the universal need for controller therapy. Physicians in favor of the routine use of controller therapy, even for patients with the mildest form of asthma, argue that inhaled corticosteroids and leukotriene receptor antagonists clearly reduce the incidence of asthma exacerbations and improve quality of life and other clinical outcomes. Dr Anne Fuhlbrigge concludes that because persistent asthma may be more common than previously thought, and because response to treatment tends to be quite variable, a trial of controller therapy is worthwhile for all persons with asthma. Dr Fuhlbrigge, who is an instructor in medicine at Harvard Medical School and is affiliated with the division of pulmonary and critical care medicine at Brigham and Women's Hospital in Boston, presents these and other points in her article on page S17.

Physicians who do not recommend controller therapy for all persons with asthma note the variable efficacy of these treatments. Furthermore, corticosteroids are not without adverse effects, and the risk and costs of exposure to controller medications may outweigh the benefits in persons with mild asthma. Dr Aaron Deykin presents this side of the debate in his article on page S23. Dr Deykin is assistant professor of medicine at Harvard Medical School; medical director, pulmonary function laboratory and lung transplantation program; and associate director, asthma research center, Brigham and Women's Hospital in Boston.

We hope these discussions provide you with a broader understanding of the issues to consider when choosing therapy for your patients with asthma. If we can improve patient outcomes not just in terms of pulmonary function test results but in terms of tangible "real-life" benefits, then we will have served our patients well.

References:

REFERENCES

1. International Study of Asthma and Allergies in Children (ISAAC) Steering Committee. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC.

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2. Global Initiative for Asthma. Global burden of asthma, May 2004. Available at: www. ginasthma.com. Accessed August 1, 2005.
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4. Pappas G, Hadden WC, Kozak LJ, Fisher GF. Potentially avoidable hospitalizations: inequalities in rates between US socioeconomic groups.

Am J Public Health.

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5. National Institutes of Health/National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program Expert Panel. Clinical practice guidelines: expert panel report 2--guidelines for the diagnosis and management of asthma. Bethesda, Md: National Institutes of Health/National Heart, Lung, and Blood Institute; 1997. Publication 97-4051.
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