Asthma is a chronic inflammatory disorder that causes shortness of breath, a feeling of tightness in the chest, and persistent cough. There are two primary types of asthma: intrinsic and extrinsic. Intrinsic asthma comes about through non-allergic means: cigarette smoke, stress, cold air, cleaning agents – basically anything that does not involve an allergen. Extrinsic asthma, on the other hand, comes about through an allergen such as dander, pollen or others. It leads to a constriction of the airway during an attack, leaving the victim out of breath, unable to take in more air, and with a tight feeling in their chest. In this essay, we will discuss the way in which asthma affects the homeostasis of the respiratory system, the various processes that the body goes through during an asthma attack, and the various treatments that are used (or are considered) for the management of extrinsic asthma.
A disease is defined as a condition that leads a part of the body to malfunction in some way; an organ or an entire bodily system is therefore diminished in efficiency and function as a result of the presence of this disease. While extrinsic, or allergic, asthma fits this description, it is not a chronic disease; merely a chronic condition. It is more typically defined as a restrictive pulmonary disorder. Since the airway obstruction in asthma is typically reversible, the airway can be remodeled in such a way during an asthma attack that it can quickly become irreversible if not treated quickly, or at least provide long-term detriments to the airway.
Extrinsic asthma negatively affects the respiratory system, and so it is necessary to understand how the system functions normally, making it easier to identify the symptoms of the disease. There are two processes that maintain homeostasis in the respiratory system: blood pH regulation and gas exchange. The pH of the blood must be regulated in order to prevent acidosis and alkalosis; there must be a good balance of hydrogen ions in the blood, and not too much or too little. This is done through the process of respiration, which is the primary form of gas exchange. The frequency of breathing helps regulate the pH of the blood as well; when a patient is approaching alkalosis (having too much O2 in the blood), they breathe less in order to release the HCO3 created during chemical reactions in your body. If the body is oxygen-starved, hyperventilation will often lower the levels of CO2 in the blood and bring the pH back to normal. (Patel and Kerr, 1975)
Gas exchange is performed through respiration, which happens both externally and internally. Internally, cells themselves are exchanging gases, but external respiration is the phenomenon we most associate with the act of breathing. The alveoli, which are the main site for respiratory diffusion, diffuse gases in both directions: oxygen going to the blood, carbon dioxide bring exhaled out of the body. The gas that is being exchanged comes from the blood in the pulmonary capillaries, which is expelling the carbon dioxide produced during the extraction of oxygen from air. With this simple process, homeostasis and the normal functioning of the lungs are maintained, as well as offering the needed oxygen required for the function of the rest of the body. (Voelkel and Spiegel, 2009)
The reason that asthma can occur is due to cellular defects in the immune system, which can take the form of a SCID, or severe combined immunodeficiency. The most common cases of SCID are known as X-linked, wherein the gene that encodes the common gamma chain is mutated in such a way that the T cells (or T lymp-hocytes) are not able to connect or link to the interleukin receptors. It is the role of the T cell in the creation of asthmatic problems that has led many researchers to consider the roles of Con A and PHA stimulation in changing lymphocytes to better resist asthmatic reactions. However, nothing conclusive has come out of these studies to date. (Thomson et al., 1978)
The cellular defect (SCID) has the effect of diminishing the efficiency of the human immune system, making it much less able to fight off disease – this makes the perfect environment for conditions such as extrinsic asthma to set in. Fluid forms in the intracellular tissue space, known as edema, and the cells in the airways become inflamed. The muscles in the airway contract and swell, filling up with mucus. Spasms occur in the smooth muscle of the bronchioles, known as bronchospasms, and this has the effect of restricting airflow. (Voelker and Spiegel, 2009)
Often, airway remodeling also takes place during asthma, as the small bronchi undergo structural changes including smooth muscle hypertrophy, fibrosis, and epithelial cell hyperplasia. This is a longer-term result of frequent asthma attacks, and happens when the airway is inflamed for far too long. Airway remodeling as a result of extrinsic asthma can result in a thicker airway wall, more production of mucus, and greater vascularity in airways as well. This same airway remodeling is often attributed to the lack of effectiveness of regimens that involve bronchodilator drugs, as well as the persistence of the disease – these changes provide an ideal environment for asthma to continue. (Voelkel and Spiegel, 2009)
Patients who normally suffer from extrinsic asthma are evidenced by persistent cough that leads to the expulsion of mucus, wheezing, shortness of breath and a tightened feeling in the chest area. The wheezing and shortness of breath are caused by the restriction of the airways, brought about by the inflammation of the airway walls. The patient then finds it much harder to breathe normally, and will often find themselves suffocating. These symptoms are recurring and variable within extrinsic asthma, as it very largely depends on the presence of an allergen in order to trigger it. (Voelkel and Spiegel, 2009)
The immune system in an asthma patient is lowered to the point where there is not much the body itself can do to fight off the symptoms of an asthma attack – the very nature of its existence necessitates a dramatic failure on the part of the lymphatic system. Immunoglobulin E, a very specific type of antibody which is closely related to allergies and immune defense, is a mediator for asthma, an asthma sufferer often carrying higher levels of IgE in their blood. However, some studies have shown that there may not be as much of a relationship between diminished function of beta receptors and the presence of higher IgE production. (Patel and Kerr, 1974) The body’s own efforts to maintain homeostasis in the face of the disease are severely diminished by the mere virtue of the diminished immune system that brings about the condition itself - this is why, if left untreated, many instances of asthma result in death. (Voelkel and Spiegel, 2009)
During an asthma attack, the airway swells and the body receives less oxygen. Given sufficient time, hypoxia can occur, which is potentially fatal, as the brain runs out of oxygen. Hypoxia occurs by binding the hypoxia-inducible transcription factor-1 alpha to hypoxia-response element in environments where insufficient oxygen is found, such as victims of asthma attacks. Homeostasis through internal, bodily means is often not possible in cases of severe extrinsic asthma; medication and outside treatment is required in order to open up the airway and prevent bronchospasms. (Voelkel and Spiegel, 2009)
Treatments for asthma are usually palliative; the immunodeficiency experienced by the patient is genetic and therefore much more difficult to treat. The aforementioned airway remodeling also brings about an environment that will continue the persistent asthma attacks. In a patient. There are both short-term and long-term treatments for extrinsic asthma, but none of them will act as a permanent cure. For the most part, the most effective type of treatment for asthma is avoiding the irritants and conditions that bring about an attack in the first place: in the case of extrinsic asthma, that would be to avoid allergens that aggravate the respiratory system. (Voelkel and Spiegel, 2009)
In order to test for the presence of extrinsic asthma, an allergen challenge is typically administered, wherein allergens are inhaled and the resulting respiratory function is assessed. If there is an asthmatic reaction, a diagnosis of extrinsic asthma is then made. Allergen challenge is also used to determine the effectiveness of certain drugs and potential treatments in various studies; for example, Patel and Kerr used it to evaluate the effectiveness of isoproterenol in their study. (1974)
Bronchodilator drugs are a very common treatment for asthma; it is a B2-agonist that helps prevent bronchoconstriction by dilating bronchioles. This has the effect of lowering resistance in the airway, bringing more air into the lungs and allowing the patient to breathe. Inhalers are used to administer short-form bronchodilators such as Salbutamol, which work within a half hour and are the default medication to address a sudden, unexpected asthma attack. However, many patients who have extrinsic asthma use longer-term bronchodilators to provide persistent, preventative treatment. Long-acting beta-adrenoceptor agonists such as Salmeteral or Bambuterol work by adding a lipophilic side-chain which binds to adrenergic receptors via a specific exosite, which perpetually binds and unbinds beta-adrenoreceptors within the lung’s smooth muscle. (Voelkel and Spiegel, 2009)
Corticosteroids are another method of controlling asthma; they act as an inflammatory, lowering the swelling of the airway and offering a clearer level of oxygen intake in much the same way as bronchodilators do. They inhibit cytokine and leukotriene production, which then lowers the levels of mediator cells, as well as vascular permeability; all of these factors have the effect of diminishing the symptoms of an asthma attack, and as such corticosteroids are used on a regular basis as a recurring treatment for extrinsic asthma. (Voelkel and Spiegel, 2009)
Other methods of treatment have gone under considerable study and consideration: Patel and Kerr (1975) successfully used thymoxamine, an alpha receptor blocking drug, to inhibit allergen induced bronchoconstriction. The thymoxamine acts by boosting the levels of cyclic AMP within cells, inhibiting the release of mediators; alternatively, it also changes the bronchomotor tone, making the airway react differently to the mediators present. (311) Patel and Kerr, in a different study, also examined the effects of cell stimulation with isoproterenol, which is a sympathomimetic beta adrenergic agonist medication. (1974) In this study, they saw that limited beta receptor function had the potential to counter-regulate the presence or onset of asthma, as opposed to causing the actual bronchial hyperactivity in the first place. (311)
Some attempts at other methods of treatment have not been so successful. Studies that have used ketotifen and disodium cromoglycate, both types of antihistamine, to provide long-term treatment of exstrinsic asthma have led to no serious results (Mattson et al., 1981), while Thomson et al. attempted to see if lymphocytes would be reactive to phytohaemagglutinin and concanavalin A stimulation to no avail. (1978)
There are not many surgical options for treatment, but the most prevalent option available to asthma sufferers is called bronchial thermoplasty; in this procedure, specialists seek to diminish the amount of smooth muscle in the airway wall with the help of heat energy. procedure calls for specialized equipment (namely, the Alair Bronchial Thermoplasty System), which is inserted into the throat. Once there, it emits heat energy to burn and wear away the smooth muscle in the bronchi. When the smooth muscle is worn away sufficiently by the heat, it cannot contract as dramatically during an asthma attack – this leaves the patient better able to breathe in most circumstances. Due to the surgical nature of this procedure, it is often used only on patients who are experiencing severe extrinsic asthma, with little to no relief found from corticosteroids and beta-agonists. It is also a fairly new procedure, and as such does not have the benefit of extensive clinical testing to fully examine its side effects and persistent effectiveness. (Castro et al., 2010)
Voelkel and Spiegel believe that the disease may be more integrated into the entirety of the respiratory system than previously thought. According to their research and hypothesis, bone marrow also plays a part in the presence of extrinsic asthma. Hematopoetic progenitor cells are often mobilized from the bone marrow to facilitate the inflammation of the bronchioles in an asthma attack. This leads to greater chronicity of asthma attacks, and adds to the theory that asthma’s function is more pervasive in the human body than previously thought. (Voelkel and Spiegel, 2009) In fact, asthma may involve the whole lung, as opposed to just the bronchial areas and the airway.
Extrinsic asthma is a pervasive, but controllable, condition of the body. It affects homeostasis by severely diminishing the effectiveness of the immune system in fighting off irritants to the respiratory system and bronchioles, bringing about substantial bronchioconstriction. This leads to shortness of breath, coughing, and wheezing. If left untreated, a severe asthma attack can lead to hypoxia and death, as the body has no effective way of providing its own methods of homeostasis. Fortunately, there are a number of treatments that exist to offer short term and long term management of the symptoms; however, they are only palliative, and cannot offer permanent relief from the disease. They function by dilating the bronchial cells, which has the effect of reducing swelling and opening up the airway, giving the patient a chance to take in oxygen and allow respiration to continue as normal.
The prognosis for an asthma victim is typically very positive; treatments are readily available to the point where it is easy to administer the medication that an asthma victim needs, and in the case of extrinsic asthma, one only needs to stay away from allergens and take steps to prepare themselves for the possibility of exposure to them. (Voelkel and Spiegel, 2009) However, while the condition is extremely manageable, it is by no means temporary or curable – those who have extrinsic asthma have to take these management and treatment measures for the rest of their lives. With that in mind, a great deal of education and preventative measures must be taken in order to limit the circumstances in which an asthma attack may occur.
References
M., C., A.S., R., & M., L. (2010). Effectiveness and Safety of Bronchial Thermoplasty in the
Treatment of Severe Asthma. Journal of Asthma, 47(4), 490. doi:10.3109/02770901003669486
Mattson, K. K., Poppius, H. H., Ahonen, A. A., Haahtela, T. T., Hurmes, R. R., Maasilta, P. P.,
& ... Vanho, K. K. (1981). Comparison of ketotifen, disodium cromoglycate and placebo in the treatment of adult patients with mild extrinsic asthma. Clinical Allergy: Journal of the British Allergy Society, 11(3), 237-242. Retrieved from EBSCOhost.
Patel, K. R., & Kerr, J. W. (1975). Effect of alpha receptor blocking drug, thymoxamine, on
allergen induced bronchoconstriction in extrinsic asthma. Clinical Allergy: Journal of the British Allergy Society, 5(3), 311-316. Retrieved from EBSCOhost.
Patel, K. R., Alston, W. C., & Kerr, J. W. (1974). The relationship of leucocyte adenyl cyclase
activity and airways response to beta blockade and allergen challenge in extrinsic asthma. Clinical Allergy: Journal of the British Allergy Society, 4(3), 311-322. Retrieved from EBSCOhost.
Thomson, N. C., MacDonald, C., & Kirkwood, E. (1978). Lymphocyte transformation in
extrinsic bronchial asthma. Clinical Allergy: Journal of the British Allergy Society, 8(5), 487-491. Retrieved from EBSCOhost.
Voelkel, N. F., & Spiegel, S. (2009). Why is effective treatment of asthma so difficult? An
integrated systems biology hypothesis of asthma. Immunology & Cell Biology, 87(8), 601-605. doi:10.1038/icb.2009.45
