___________________________________________________________ Asthma: Diagnosis and Management
PATHOGENESIS OF ASTHMA The pathogenesis of an asthma attack can be described as an inflammatory cascade composed of triggered, acute inflam- mation and chronic inflammatory changes. In the body of a person without asthma, the immune responses in the bronchi (e.g., swelling, excretion of mucus, recruitment of inflammatory cells) are present in a lesser degree to protect the body against any infectious agents or foreign objects. However, a person with asthma produces an extreme reaction to otherwise rela- tively harmless irritants, referred to as asthmagens or triggers. Exposure to a trigger causes inflammatory mast cells to release specific inflammatory mediators, including histamine and interleukins, resulting in an acute response. Histamine causes local tissue edema; interleukins generally act as chemotactic factors and activate other inflammatory cells. Studies reveal that leukotrienes, another chemical released by mast cells, prolong bronchial muscle and airway constriction [8; 12]. After the inflammatory cells are activated, bronchospasm occurs. Bronchospasm and local tissue edema cause narrowing of the airways. Release of interleukins and other chemotactic substances causes migration of other inflammatory cells, including eosinophils, airway macrophages, and neutrophils. The physical presence of these cells can also cause airway nar- rowing. The migration of the inflammatory cells starts within 30 minutes of exposure and may take hours to reach peak levels. Several different types of antibodies contribute to the inflam- mation process. One group of antibodies has evolved to be par- ticularly harmful: IgE. Researchers believe that IgE once helped individuals ward off common ancient parasites; although IgE is not needed today, the body continues to manufacture it. Most individuals are unaffected by the presence of IgE, as it only accounts for about 1% of all antibodies. However, mil- lions of individuals have inherited the genetic predisposition to overproduce IgE; in some cases, B cells release up to 20 times the normal amount of IgE. If an excess of the antibody is produced, the immune system may overreact to routine substances. Each substance to which an individual is sensitive triggers a different IgE antibody; any one of these substances could result in allergies that can trigger asthma [8; 12]. CAUSES OF HYPER-RESPONSIVENESS IN PERSONS WITH ASTHMA The actual cause of the hyper-reaction by the immune system in persons with asthma is unclear. While many cases may be attributed to a reaction in response to exposure to an asthma- gen, the possibility of nervous system involvement is also an accepted theory. Generally, the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS) work in harmony to balance the body’s functions; the PNS stimulates the bronchial tubes to constrict while, at the same time, the SNS stimulates the bronchial tubes to dilate. Ideally, these two systems coordinate to maintain open airways, allowing an
Asthma is considered a disorder of exhalation, not inhalation. Patients with asthma are uncomfortable not because they cannot inhale enough air, but because obstructed airways are preventing them from exhaling the air that is already in their lungs. In fact, autopsies of patients who died of asthma com- plications have revealed lungs full of air. When bronchioles narrow during an asthma attack, upstream obstruction causes premature closure of airways with expiration, as pleural pres- sure becomes greater than the pressure inside the airway (the equal pressure point, or EPP). Downstream airways become compressed with expiration, trapping air in the alveolar sacs. Reduced respiratory muscle efficiency and function can be caused by lung hyperinflation and thoracic hyperexpansion, resulting in air trapping. Respiratory muscle advantage is compromised, and the flattened diaphragm is forced to con- tract with shortened muscle fibers, resulting in a feeling of chest tightness. This can lead to airway rupture, manifested as pneumothorax, pneumomediastinum, or subcutaneous emphysema [13]. INFLAMMATION AND THE IMMUNE SYSTEM The most common features of asthma are inflammation and edema (swelling) of the airways, and treatments have focused on the connection between inflammation and asthma since the mid-1980s. At that time, researchers developed fiber-optic bronchoscopes with which they were able to view the lungs (and take samples of airway tissues) of those with chronic asthma. With this advancement, researchers concluded that airway inflammation in individuals with asthma never clears, even with mild asthma; therefore, treatment focusing on inflammation reduction was determined to be the most effective for long-term management. When the inflammatory cascade, the physiologic process of an asthma attack, is not treated, rebound of acute symptoms can occur, resulting in extreme damage and potentially permanent scarring [8; 13]. Inflammation is a process involving the immune system’s reaction to what it identifies as foreign or harmful items. The immune system consists of three primary components: the thymus gland, lymph nodes, and bone marrow. These parts produce two major types of blood cells: red blood cells, which transport oxygen from the lungs to the tissues of the body, and white blood cells, which defend the body against invasion and infection. Lymphocytes, a type of white blood cell, are divided into two categories: B cells, which manufacture antibodies or immu- noglobulins that identify foreign contacts as harmful agents, and T cells (from the thymus gland), which release chemicals known as cytokines that kill the invading antigen. Antibodies aid the immune system in recognizing organisms that have infected the body in the past, allowing the immune system to fortify and strengthen the body against future invasions by the recognized antigen [8; 13].
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