Background
What Are the Facts about Asthma?
What do Theodore Roosevelt, Tom Dolan, Antonio Vivaldi, Nancy Hoghead, Ludvig van Beethoven, and Jackie Joyner-Kersee have in common? They are all famous asthmatics. Asthma has now reached epidemic proportions in the United States and it affects millions of people regardless of race and age. Both the environment and genes are factors in the severity of asthma. With the increase of students with asthma and allergies over the years, it is apparent that we have become a society that relies heavily on medication to be a "cure-all" or "quick-fix" for whatever ails us without thinking of the after-effects such as where do these medications end up after they leave our bodies!?, and are these remedies doing more harm than good when we consider how we are to naturally respond to an invading entity that enters our bodies. Is it better to "treat" allergy and asthma symptoms through medication, or is it better to be well-educated on what causes allergic reactions and avoid these known allergens? Still, we need to realize and ask the question, how do we relieve the symptoms?
Asthma is a chronic respiratory disease that causes inflammation of the airways. This results in difficult breathing, wheezing, and coughing. An allergic reaction is a defense against an invading body. Does this mean that every allergic reaction is useful? Or does it mean that some people are more sensitive than others to different allergens? The reason why asthma and allergies will be used interchangeably in this unit is because most asthma sufferers are allergic to some offending agent which acts as a "trigger" to start the inflammatory asthmatic process.
Asthma is primarily a childhood disease. Over the last two decades, epidemiologists have called this increase of asthma sufferers, particularly in children, the "asthma paradox" because, although, there have been great improvements in medicines and therapy to treat asthma, there have been increases in morbidity and mortality as a result of asthma. In contrast to this being a paradoxical phenomenon, evolutionary theorists believe in the timing of biological events as the explanation for the rise in asthma. The natural history of our species is a fundamental beginning point for new analyses of human disorders and degenerative disease, as well as the effects of culture on human environments. This sets the stage for exploring the notion of mismatches or discordances between more evolutionarily stable or "expected" human physical, social, and psychological environments and the "actual" environments encountered by modern humans 3.
What Are the Causes of Asthma?
What is causing this increase in allergies and asthma? Could it be because of poor nutrition, our polluted environment, predisposition to allergies, or a family history to asthma? One topic that has had many debates is "nature versus nurture." It is quite clear that with asthma, both entities play a role in this disease. Some scientists believe it may be due to modern people living in super clean environments, which causes our immune system to function improperly because it is not properly stimulated. Thus, a sterile environment may prevent infants from developing a strong immune system. Also, it has been hypothesized that certain medical and technological advances in the Western world play important roles in the increase of asthma. In particular, vaccines, purified drinking water, and antibiotics have prevented many typical early childhood infections and as a result may tilt the immune system towards an "allergic pathway." 4 Therefore, because our immune systems have fewer germs to fight, they may attack other things such as milk, peanuts, pollen, etc., normally harmless substances that cause an abnormal reaction.
Others believe the rise in asthma may be due to global warming. Warmer temperatures lead to a longer growing season for plants, therefore a longer time to produce pollen. This relates to the discussion of air pollution as being a cause. Smog in the air does cause some people to have difficulty breathing. Other airborne chemicals can compromise an asthmatic's health. Not only are there pollutants in the outdoor air, but indoors as well due to cigarette smoke; allergies to pet dander, dust mite feces, cockroach feces, rodent feces; use of aerosols; molds; and carpets that act as a natural trap of allergens. Allergens are factors that "set off" an allergic reaction. Almost all asthmatics exacerbate their condition with exercise whether it's running, jogging, cycling, rowing, and swimming. The major cause of exercise-induced asthma is due to hyperventilation. There are also three medical conditions that can aggravate asthma. They are sinusitis, rhinicitus, and gastroesophageal reflux. Still other scientists believe that asthma and allergies have always existed but nowadays physicians are better able to diagnose these symptoms and report these findings.
What Role Do Our Genes Play in Relation to Asthma and Allergies?
Most experts do believe that genes play a role in childhood development of allergies. Children are more likely to have allergies if their parents have allergies. Looking into the history of asthma, we can discuss atopy of asthma. As mentioned earlier, when a person has an abnormal reaction to a normally harmless substance, the term "atopy" comes into play. Atopy means a condition in which people with genetic predispositions to allergy upon exposure to ubiquitous biological or chemical substances that are inhaled or ingested produce significantly greater quantities of the immunoglobulin E (IgE) than the average individual 5. Atopy refers to a group of inherited diseases that are brought about by a type of altered reactivity. With new advances in immunology, asthma phenotype is better understood. Phenotype is an observable trait or characteristic of an organism due to its genotype and the environment. The genotype of an organism is the instructions carried in its genetic code. Therefore genes along with environmental factors are both key in how asthma fits in human populations.
What Happens Inside Our Bodies When We Are Exposed to an Allergen?
An allergen is a substance that produces an allergic reaction. These substances share two characteristics. One, they are always organic meaning they are alive or were once alive. Two, these substances are harmless to a nonallergic person. An allergic reaction has two phases, a sensitization phase and an effector phase and it requires three components: the allergen, the allergic antibody (IgE), and the mast cell. In the sensitization phase, a person comes in contact with the allergen, which then initiates the production of allergic antibody (IgE) by the immune system. The IgE travels through the bloodstream and attaches to the mast cells which line the respiratory tract. Upon reexposure to the allergen, the IgE that is attached to the mast cell will also bind to the allergen resulting in a process known as degranulation. At this point the cell releases a series of chemicals of histamines and other mediators resulting in an allergic reaction.
Why do we produce this antibody? Is it there to simply be a nuisance to cause these debilitating symptoms? The answer is that it is believed that this antibody, IgE, was first created to fight against parasitic worms because antibodies fight foreign invaders. Antibodies are proteins called immunoglobulins. Recent studies have shown that people that have been exposed to parasitic worms have reduced allergies and they have high levels of IgE in their system. Going back to our super-clean environments, without being exposed to these parasites will lead our bodies to fight against pollen and other allergens and be the casualties of this war. Interestingly, these same parasites that might have caused the evolution of the antibody may be used as a cure to fight asthma and allergies. Scientists are not one-hundred percent sure about why the evolution of IgE occurred; they do know that consideration should be given to the patients' care, but at what expense? What are long-range effects of treating the conditions with pharmaceuticals? Can they push for a change in one's environment? This may only be solved by those who can afford to change.
What is the History of Asthma?
We know that asthma existed since at least ancient Egypt, and there is evidence that asthma has been around long before that. The Georg Ebers Papyrus - found in Egypt in the 1870s - contains prescriptions written in hieroglyphics for more than 700 remedies. One of the ancient Egyptian remedies against asthma was to heat a mixture of herbs on bricks and inhale their fumes. Asthma has evolved over time. It has been discovered that the immunological pathway to asthma is shared by other animals in the class Mammalia. In human history these pathways rid the body of parasites such as helminth worms (e.g., Schistosoma mansoni). To attack these parasites, production of the antibody IgE increases. Worms such as schistosomes, which cause liver and kidney failure, and filaria, which cause blindness, were all substantially greater problems before the introduction of modern sanitation and vector control. 6 This idea is still considered to be a hypothesis to explain the relationship between parasitic worms and increased levels of IgE.
What is the Relationship between the Environment and Asthma?
Environmental factors may account for the disproportionate number of low-income people and minorities developing asthma and allergies due to poor living conditions. As discussed earlier, research has revealed that there is an alarmingly high rate of asthma sufferers living in inner-cities. Housing for poor people is usually near factories that put out pollutants. There is substantial epidemiological evidence that asthma sufferers are more susceptible to air pollutants and these main pollutants are ozone, sulfur dioxide, nitrogen dioxide, and particulate matter. It is believed that these contaminants cause bronchial reflexes. Another problem is these contaminants cause airway inflammation. Since most poor communities are usually riddled with crime, most people tend to spend a lot more time indoors which leads to indoor air pollution problems.
On average, people spend over 90% of their time indoors and at least 50% of that time in the home 7. Living in tight quarters, as in the projects, there is a greater risk of living with cockroaches. Studies have shown that not only are children affected by cockroach allergies, but adults are affected, as well. Not only is living in areas that may have increased levels of air pollution problematic, but poverty usually comes along with inadequate health care. While genetic predisposition contributes to asthma morbidity, it probably does not play a predominant role in the recent epidemic rise in asthma morbidity. Socioeconomic status and access to medical care, on the other hand, appear to be important correlates to asthma 8. Many asthmatics in the inner cities are uninsured. Also, there could be language and cultural issues that may prevent people getting the medical attention needed.
What Can Be Done to Reduce the Incidences of Asthmatic Attacks?
In order to reduce the incidences of asthmatic attacks one must reduce exposure to known allergens. In the case of dust mites you should encase pillows and mattresses, launder bedding in hot water, remove carpets or treat carpets with an acaricide, vacuum using a HEPA filter and double-thick bags, and remove stuffed animals. To reduce animal allergens, you should remove the animal from the home. If this cannot be done then keep animal out of the bedroom, bathe a pet dog or cat once a week and vacuum carpets as outlined above. To reduce fungal allergens, you should clean washable surfaces with 5% bleach, remove contaminated carpets, keep windows closed in warm months and use air conditioning, avoid exposure to moldy vegetation, wear dust masks, and use air-conditioned vehicles. For cockroach allergens, you should remove wastes, fix leaky pipes, seal cracks in walls and floors, and bait traps with hydramethylanon or abermictin. Therefore, parents must adhere to stringent behaviors in the home in order to reduce the incidences of asthmatic outbreaks.
Another way asthma can be reduced is to acknowledge the socioeconomic status and psychological factors of asthma. Many studies have been conducted on the association between poverty, low educational levels and asthma. Families with the added burden of poverty may not prioritize good asthma management protocols. Low educational levels will also lead to a lack of knowledge about asthma programs, thus limiting sufferers from getting the support they need. With these inadequacies, the increased stress on the asthma sufferer will heighten asthma prevalence and morbidity. Long-term solutions to the rising rates of asthma morbidity in these communities will therefore require significant social environmental changes as well as effective medical and behavioral interventions. 9
What Are the Treatments for Asthma?
Besides avoiding particular known allergens as a means to control asthma, there are other treatments that can suppress the effects of asthma. There are two categories of medications used for the treatment of asthma. They are in the class of short-term control or quick-relief medications. The second class of medications is long-term control. All asthma patients must have short-acting relief such as albuterol metered dose inhaler (MDI) on an "as-needed" basis. Those patients that have persistent asthma should be using long-term medication, as well. There are drugs that have little anti-inflammatory activity, known as "bronchodilating" agents. These are "symptom treaters." These drugs relax the smooth muscle surrounding the bronchioles and this helps to enlarge the airway. There are three categories of agents: beta-adrenergic agents, theophylline, and anticholinergic agents. Then there are drugs that affect inflammation and have modest broncodilating activity. These drugs are potentially disease modifiers. These include corticosteroids, cromolyn sodium, and nedocromil. A new set of drugs, antileukotrienes, have modest-to moderate brochodilating activity and are anti-inflammatory as well.
Glucocorticoids (GCs) are the most effective treatment of asthma for the past 50 years. Oral glucocorticoids had short-term benefits, but long-term adverse side effects. These side-effects were reduced when GC was delivered directly into the airways by metered-dose inhalers (MDIs). The effects of glucocorticoids on the molecular level are that it binds to a specific cytoplasmic receptor called the glucocorticoid receptor (GCR) which is translocated to the nucleus and eventually binds to specific DNA sites called glucocorticoid response elements (GRE). There are between 10 and 100 genes that have GRE sites and are directly influenced by GCs. Many of the genes encoded for proinflammatory cytokines lack GREs Therefore, GC must also act to suppress inflammation, by interfering with nuclear transcription factors which are involved in the transcription of proinflammatory cytokine genes. GCs, on the cellular level, inhibit the effects on the inflammatory response associated with asthma, by inhibiting the transcription of multiple cytokines, thus, inhibiting inflammatory cell activation.
Theophylline is a second- or third-line defense in the treatment of asthma. It's considered a second defense because of its adverse affects. For severe asthma, theophylline can be used in conjunction with inhaled corticosteroid. It is an effective medication, but it must be used with limitation. There are many other short- and long-term medications that have been studied to treat asthma.
Another treatment for asthma is immunotherapy: the injection of allergens of which the patient is sensitive causing symptoms. The injections are given over a three-to-five year period gradually increasing the doses over time. It helps to produce a "blocking antibody." This therapy is most useful in controlling symptoms due to the inhalation of grass, tree, and weed pollen, certain mold spores and dust mite feces. This treatment has been recently developed and is termed as nonanaphylactogenic anti IgE monoclonal antibodies. What this does is to reduce IgE levels. The therapeutic anti IgE antibodies block the binding of IgE to IgE receptors. This particular binding affinity has two distinct advantages. First, the antibody will inhibit IgE effector functions by blocking IgE binding to high affinity receptors on IgE effector cells such as mast cells or basophils. Second, the antibody will not cause mast-cell or basophil activation because it cannot bind IgE on mast cells or basophils 10.
What Are the Downsides to the Treatments?
The most common side-effect of inhaled GCs is local which could lead to thrush and vocal cord muscle myopathy. Myopathy is a disorder of the muscles affecting the muscle's range of motion. Other side-effects could lead to toxicity resulting in suppression of the hypothalamic-pituitary-adrenal axis, growth suppression, hypoglycemia, weight gain, psychosis, osteoporosis, cataracts/glaucoma, and opportunistic infection.
The adverse effects of theophylline include nausea, headache, insomnia, diarrhea, irritability, tremors, diuresis, vomiting, cardiac arrhymias, and seizures. 11 Also many medications interfere with this drug and can possibly increase theophylline levels. Other medications can interfere and lower theophylline levels.
Besides the cost and inconvenience of immunotherapy, safety is a concern. Between 1985 and 1989, there were seventeen deaths reported in the United States. This is about one fatality in every 2.8 million injections. Most of the fatalities occurred during the build-up phase of the therapy. This is because of a reaction to the allergenic extract with IgE. Thanks to recombinant technology, the possibility exists of modifying the major allergens so that they have reduced reactivity with IgE 12. Recombinant technology is when you splice up DNA from one organism and recombine it with another organism.
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