Disease Management: Asthma
By Irene Fried
Provocative headlines about the “hygiene hypothesis” warn us once again that trying too hard to rid our environment of germs may be harmful to our health. Tongue-in-cheek admonitions to ‘eat dirt’ aside, there is growing evidence that early childhood exposure to viral infections or endotoxins helps to develop the immune system and protect against allergy and asthma. Side by side with this developing understanding and the hope that it may lead to preventive measures and perhaps a vaccine, researchers are also exploring the linkage of genetic variations and drug response to enable earlier targeting of effective therapies once the interaction of predisposition and environmental factors has resulted in onset of the disease.
There is good reason for the growing concern with asthma, a chronic disease that affects both children and adults. According the American Academy of Allergy Asthma and Immunology (AAAAI), about 17 million Americans have asthma, which led to 4,657 deaths in 1999. Five million children are affected, making asthma the most common serious chronic disease of childhood. The National Heart, Lung, and Blood Institute (NHLBI) of the NIH estimates the prevalence of asthma to have increased over the past two decades by nearly half in children and one-third in adults, with 5.5 percent of the population age 17 and under, and 4 percent of the population over age 18 affected. The cost of asthma in 2000 was estimated to be $12.7 billion, with direct costs amounting to $8.1 billion and lost earnings due to illness and death totaling $4.6 billion. Rates of emergency department visits are on the rise, with the highest rates in children under five, but the greatest increase in children ages 10-17.
The word asthma derives from the Greek, and means “laborious breathing.” The NHLBI and World Health Organization (WHO) define asthma as a “chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T lymphocyctes, macrophages, neutrophils and epithelial cells.” Asthma is generally defined symptomatically by swelling of the bronchial tubules, and constriction of the airway, leading to reduced pulmonary function.
According to Kathleen Sheerin, M.D. of the Atlanta Allergy and Asthma Clinic, diagnosis of asthma is generally accomplished through a combination of taking a good patient history and pulmonary function testing, rather than blood work or imaging. Allergy testing is also key. “Many people diagnosed before age 40 have allergy as an underlying cause of their asthma, and the position of the AAAAI is that skin testing is still the most sensitive way of testing for allergy,” she explains. Measurement of IgE antibodies through blood testing has, however, been gaining momentum with the introduction of the ImmunoCap allergy test system from Pharmacia Diagnostics of Uppsala, Sweden.
A blood test offers the advantage of being able to be performed by a primary care physician, which makes it more accessible than skin tests that require a specialist’s care. In addition, the potential for serious reaction means that skin tests are not recommended in small children and seniors. It is also difficult to obtain a pulmonary function test from small children, which complicates the ability to make an early diagnosis of asthma. For all of these reasons, blood testing presents a major advantage in early, accurate diagnosis, to identify or to eliminate allergy as a cause or precursor to asthma. However, standardization of blood test results from lab to lab has been an issue in gaining the confidence of allergy specialists. Calibrated to WHO reference standards, on the other hand, in vitro tests can offer the advantage of standardized allergen extracts, including dust mites, grass pollens, tree pollens and dander, that are identified triggers for asthma.
In the late 1990s, studies on the Early Treatment of the Atopic Child (ETAC) demonstrated that children with a specific allergy (atopic dermatitis) who were treated early with antihistamines were less likely to go on to develop asthma. And reports published earlier this year from a large epidemiological investigation of patients with allergic rhinitis show that it predisposes to development of asthma later in life. To be able to forestall that development, early diagnosis by a primary care provider would be important.
Currently, prescription for asthma treatment is made by clinical criteria based on frequency and severity of symptoms. “Asthma and allergy have good diagnostic tools,” says Sheerin, “but treatment is still the art of medicine.” But art benefits from science, and the paints we have for the palette may soon become more sophisticated with the blending of diagnostic and treatment elements.
The ability to predetermine whether or not an individual would respond to a particular therapy would enable physicians to prescribe effective treatment sooner. This type of diagnostic test is on the horizon for Roche Diagnostics, which is working in research and development with decode Genetics of Reykjavik, Iceland. “Using a pharmacogenetic approach, decode and others have shown that significant numbers of people respond in different ways to standard therapies,” said Thomas Metcalfe, senior vice president, responsible for business development in molecular diagnostics for Roche. “We believe that it would be valuable in asthma testing to be able to distinguish between people who have a good chance or a very low chance of responding to those standard therapies, so that an informed treatment choice can be made.”
At what points in the development or progression of asthma would gene-based testing be beneficial? Predisposition screening, according to Metcalfe, would probably not be appropriate because even if an individual were determined to be at relatively high risk for asthma, there are no current measures that could be prescribed to prevent the onset of disease. A predisposition test may be useful for differential diagnosis when young children present with wheezing symptoms because young kids find it difficult to do functional tests. And physicians could follow up the diagnosis of asthma with a test to see which therapy may elicit the optimal response from an individual patient. Or, for a patient in whom a therapy has already been initiated but appears ineffective, a diagnostic test could help to determine what the next therapeutic option should be.
This type of testing holds promise both because of the prevalence of asthma and because early identification of the right therapy can make an important difference in patient outcome. “One could ask the question of how many people suffer serious deterioration because they are not on the right therapy at the earliest possible time. In childhood asthma in particular, airways can undergo irreversible remodeling the longer the disease isn’t properly treated. This is a promising line of research because it can lead to a more rational approach to therapy choice, allowing physicians to prescribe the best treatment in a more timely and cost-effective fashion,” adds Metcalfe.
Irene Fried is a freelance writer in Raleigh, North Carolina.
