Understanding the Pathophysiologic causes, types and symptoms of Asthma - Research Paper Example

June 25, Understanding the Pathophysiologic causes, types and symptoms of Asthma Asthma is a disease we very often hear about, and it is termed as the most common chronic disorder worldwide. In the United States only, approximately 24 million people are currently asthmatic (Crockett 4). It is a disorder related to the very sensitive respiratory system. It becomes important now to understand why and how it causes serious troubles in our body and what are its types? This paper is an attempt to unfold all the physiologic causes and consequences of Asthma. Definition of Asthma: The International Consensus Report on Diagnosis and Management described Asthma as “A chronic inflammatory disorder of the airways in which many cells play a role, including mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells. In susceptible individuals this inflammation causes symptoms that are usually associated with widespread but variable airflow obstruction, that is often reversible and causes an increase in airway responsiveness to a variety of stimuli” (Crockett 4). According to this definition Asthma could be understood as a disease of the airways characterized by inflammation and reversible bronchospasm. This definition doesn't only emphasize on the importance of inflammation in the etiology of asthma, but also establishes the fact that this inflammation causes the airways to be hypersensitive to external stimuli. The clinical manifestations and severity of asthma is determined by the interaction of these features. Pathophysiological causes of Asthma: Pathologically, the airflow obstruction in asthma is due to combinations of bronchial smooth-muscle contraction, mucosal edema and inflammation, and viscid mucus secretion (Clark 35). The events that cause asthma are as detailed as follows: Bronchoconstriction: Bronchoconstriction is the most crucial physiological condition that eventually leads to airway narrowing and a subsequent interference with airflow. Bronchoconstriction occurs due to various stimuli like allergens or irritants. In acute asthma, inhalation of large volumes of dry, cold air during exercise leads to loss of heat and water from the bronchial mucosa, leading to airway cooling and drying (Navarra 332). The larger the amount of ventilation and the colder the air inspired, the greater becomes the probability of airway narrowing. There are two prominent theories on how airway narrowing leads to bronchoconstriction. One involves that the increase in osmolarity in the airway mucosa produced by airway drying and cooling stimulated the release of inflammatory mediators from mast cells, including histamine and leukotriene that cause bronchoconstriction (Navarra 332). While in the other mechanism, airway cooling does not directly cause bronchoconstriction, instead it is the rapid rewarming of the airway, after an activity like exercise, which causes smooth-muscle contraction. It is believed that with rapid rewarming, there is a “vascular phenomenon” of reactive hyperemia, with sudden blood flow and vascular permeability, leading to edema and airway obstruction (Navarra 332). Allergen-induced acute bronchoconstriction results from an IgE-dependent release of mediators from mast cells including histamine, tryptase, leukotrienes, and prostaglandins that directly contract airway smooth muscle (Navarra 332). In some patients acute airflow obstruction may be caused by Aspirin or any other nonsteroidal anti-inflammatory drugs (National Asthma Education and Prevention Program 11). This is a non IgE-dependent response, which involves the mediator release of airway cells (National Asthma Education and Prevention Program 11). Asthma exacerbation may also be caused by stress, and its mechanism involves enhanced generation of pro-inflammatory cytokines (Navarra 332). Airway Edema: Airway edema or “fluid in the airway” is caused by micro-vascular leakage in response to inflammatory mediators (Navarra 332). This may be reversible by anti-inflammatory medications (Clark 35). Mucus hyper-secretion is the term applied to the increased mucus secretion, and inflammatory exudates that occur in asthma. When the disease has established, the inflammation deepens its roots and leads to other factors, which cause the airflow blockage even more. These include the formation of inspissated mucus plugs, as well as structural changes including hypertrophy and hyperplasia of the airway smooth muscle (Clark 35). An increased number of goblet cells in the airway epithelium and increased size of sub-mucosal glands occur in asthma (Clark 35). Mucus plugging occurs when a portion of the airway becomes clogged and the air is not able to move in and out of the airways below (Clark 35). Airway Remodeling: It refers to the permanent structural changes of the airway. It is an established fact that before the onset of asthma symptoms, most asthma patients have some degree of airway modeling (National Asthma Education and Prevention Program 11). Subepithelial fibrosis occurs as a result of collagen fibers and proteoglycans forming under the basement membrane (Clark 36). These substances can also deposit in other layers of the airway wall, causing fibrosis in those areas (Currie 10). The airway’s smooth muscle increases in size due to two primary mechanisms, Hypertrophy and Hyperplasia (Currie 10). Hypertrophy refers to the increased size of individual cells, and hyperplasia refers to increased cell division (National Asthma Education and Prevention Program 11). This results in an increased thickness of airway wall. Inflammatory mediators play a prominent role in causing these changes. The increased thickness of airway wall is contributed by the increased proliferation of blood vessels in airway walls (Clark 36). Airway Hyper-responsiveness: This refers to the tendency of the airways to narrow, in response to exposure to a variety of stimuli (Currie 10). It is quantified by the degree of contractile responses to a methacholine challenge test (Currie 10). This helps in determining the clinical severity of an individual’s asthma. Multiple mechanisms can influence airway hyper-responsiveness, such as inflammation, dysfunctional neuroregulation and structural changes (Currie 10). PATHOPHYSIOLOGIC MECHANISMS IN THE DEVELOPMENT OF AIRWAY INFLAMMATION Airway inflammation is a defining characteristic of asthma. The factors contributing to airway inflammation in asthma are multiple, and involve a variety of different inflammatory cells (National Asthma Education and Prevention Program 11). It is to be noted that asthma is not caused by a single cell or single inflammatory mediator, but rather results from complex interactions among inflammatory cells, mediators, and other cells and tissues residing in the airways. This interaction later causes the characteristic features of asthma including bronchial inflammation and airflow limitation (Clark 37). Though usually called airway inflammation, it occurs throughout the respiratory system (Clark 37). It occurs regardless of the type of asthma i-e allergic or non-allergic. The inflammation associated with asthma follows the same pattern as inflammation occurring in an allergic response (Clark 37). The major components of airway inflammation are as follows: Immunoglobulin E or IgE: Allergic diseases are caused by adverse immune response to allergens (Clark 38). Allergens sensitized patients produce high levels of IgE which contributes in vasodiiation, increased vascular permeability, edema, smooth muscle contraction, and mucus secretion (Clark 38). These factors result in allergic reactions, and the individual is said to have had atopy or allergies. In such patients, IgE has been found circulating in the blood along with inflammatory cells called basophils, and bound to the surface of inflammatory cells throughout the body known as mast cells (Sullivan and Krieger 341). Mast cells and Basophils: Basophils are found in the blood stream, and mast cells reside in many tissues of the body, most significantly the airway tissue. These inflammatory cells have about 100,000 receptor sites each for IgE (Clark 38). When an individual is exposed to an allergen, and produces IgE that binds to these receptor sites, then the mast cells and basophils are termed as primed (Clark 38). When the individual is exposed to the same allergen again, these mast cells and basophils will release chemical mediators. These will then cause the allergic response associated with this disease. This is to be noted that if sensitized once, these mast cells and basophils may remain primed for months or years. Chemical mediators: Histamine is the most prominent chemical mediator that is released by the mast cells. Histamine, when attached to the histamine receptors (H1), stimulates allergic symptoms like swelling, sneezing, and itching (Busse and Holgate 846). Cysteinyl leukotrienes are the other family of chemical mediators, usually released between 5 and 30 minutes after activation of the mast cells and basophils (Busse and Holgate 847). They are more potent than histamine but have the same basic effect. Leukotriene D4 is ten times more prominent than histamine. These are the only chemical mediators whose inhibition have been associated with improvements in asthma symptoms and pulmonary function values (Clark 38). Chemokine is another chemical mediator associated with asthma. These are found in airway epithelial cells, and contribute dominantly to the recruitment of inflammatory cells into the airways (Busse and Holgate 847). Cytokines could be termed as signaling proteins. These mediators provide cellular communication during the inflammatory response in asthma. They are divided into four categories; Lymphokines, are those cytokines that are produced by T lymphocytes, Proinflammatory cytokines amplify and carry on the inflammatory response, anti-inflammatory cytokines inhibit inflammation and chemokine (Busse and Holgate 847). Nitric Oxide (NO): Nitric Oxide is produced predominantly from the action of inducible NO synthase in airway epithelial cells; it is a potent vasodilator (Busse and Holgate 846). NO plays a significant role in regulation of vascular tone, response to vascular injury, and hemostasis. It acts as a neurotransmitter for the non-adrenergic non-cholinergic nerves, and also possesses antimicrobial, immunologic, and pro-inflammatory activities (Clark 39). Classification of Asthma There are different ways of classifying asthma. It is separated into groups on the basis of certain characteristics. One way is according to the severity of attacks irrespective of its etiology, and the other is according to the trigger or source causing asthma attacks. Severity of attack: Severity refers to how often a person experiences asthma attacks. It is measured by the amount and type of medication needed to control the symptoms. The British Thoracic Society (BTS) - Scottish Intercollegiate Guidelines Network (SIGN) has provided five grades or categories for understanding the severity of asthma (Crockett 17). These include, asthma that can be controlled adequately by intermittent treatment, asthma that is adequately controlled by regular inhaled anti-inflammatory treatments, asthma that requires regular inhaled anti-inflammatory treatments plus long-acting ?2 –agonists, asthma that requires additional therapies along with these, and asthma that needs chronic oral steroid treatment (Crockett 17). GINA classifies asthma according to four grades of severity including mild, moderate intermittent, moderate persistent, and severe (Crockett 18). Source of attack: Asthma could be classified by the substance or situation that triggers an attack. These include exercise-induced asthma or EIA, in which vigorous exercise sessions are followed by asthma attacks. People whose asthma are triggered by allergies are said to have an allergy-related asthma. Infectious asthma is triggered by cold or respiratory infections. People who experience asthma attacks at night are believed to have nocturnal asthma. The most common triggers of asthma include infections, allergens (house dust mites, animal dander, fungi, and pollens), exercise, environmental pollutants, cold air, occupational agents, and hyperventilation. The difference between a Trigger, Allergen and an Allergic Reaction: It should be understood that all allergens are triggers but not triggers are allergens. The trigger is any such substance that induces or exacerbates asthma, such as cold air, exercise, and viral upper respiratory tract infections (Crockett 6). An allergen is an especial type or form of trigger that is capable of inducing asthma (Crockett 6). Allergens include cat dander, pollen, and house dust mites. An allergy or allergic reaction could be described as a type of immune response to external agents in which the response itself causes harm or damage to the body. Types of Asthma The majority of asthmas are initially triggered by allergies. Allergic asthma could be understood as, an allergic response involving airway inflammation, resulting from exposure of the susceptible individual to certain specific triggers such as pollen, animal dander or dust (Chung 4). There is a specific type of allergic asthma which involves an Immunoglobulin E (IgE) mediated reaction, this is known as Atopic asthma (Crockett 6). An exaggerated immune response occurs which activates IgE and mast cell degradation. It should be noted that all allergic asthmas are atopic (Crockett 6). Other manifestations of atopic asthma include allergic rhinitis, allergic conjunctivitis, and atopic dermatitis. There are other phenotypes of asthma, possessing different characteristics as compared to the common allergy-induced asthmas (Chung 4). These include intrinsic asthma, extrinsic asthma, aspirin-induced asthma, and exercise induced asthma. These types have unique characteristics that are not readily associated with allergens. The other sub-types of asthma include gastro-esophageal reflux associated asthma, obesity-related asthma, menstrual-cycle related asthma, and nocturnal asthma. Intrinsic Asthma: Intrinsic asthma is that type of asthma which occurs in a person who is not atopic (Harver and Kotses 25). Usually, patients with intrinsic asthma tend to be older, have later onset of asthma, and more severe disease. Patients with intrinsic asthma do not have allergies, family history of atopy, abnormal serum IgE levels, or hypersensitivity reactions to skin-prick tests (Harver and Kotses 25). Triggers of intrinsic asthma are usually non-specific, such as viral infections, changes in temperature and humidity, and smoke or dust. The pathogenesis of intrinsic asthma has not been elucidated and may reflect a heterogeneous process rather than a single disease entity (Harver and Kotses 25). Extrinsic Asthma: It is that particular type of asthma, which is triggered by an external allergen. The allergens include pollen, animals, and house dust (Harver and Kotses 26). Exposure to such triggers sets off an allergic reaction culminating in the symptoms and signs of asthma. The allergic reaction usually involves IgE, and therefore, it is termed as atopic (Harver and Kotses 26). Extrinsic asthma is specifically associated with childhood. People may have varying symptoms that may get provoked by a variety of triggers, but not all of them are allergens. For many years it was believed that both intrinsic and extrinsic asthmas possessed different pathological processes. More recently, however, the differences between them have become less clear (Harver and Kotses 26). It can be said that there is little difference between extrinsic and intrinsic asthma in terms of the histology of the airways or in response to the treatment with corticosteroids (Crockett 10). Although similarities between these two types of asthma exist, the concept that asthma does not necessarily represent a solely allergy-related disease is important, and speaks about the complexity of asthma. Exercise-Induced Asthma or EIA: It is a no-allergen mediated asthma. The asthmatic patient experiences increased airway resistance during exercise. This happens due to the dyspnea experienced during exercise. Many patients with EIA asthma often cannot pursue aerobic activities and are less fit. EIA is believed to be triggered by moving large amounts of air in and out of the lungs (Harver and Kotses 28). The mechanism of EIA involves two theories, the osmotic hypothesis, and the thermal hypothesis. In thermal hypothesis, it is suggested that bronchoconstriction during exercise occurs due to changes in temperature and water content of the airways (Harver and Kotses 28). Ventilation increases during exercise, due to which the conditioning of air moves from the upper airways to the lower airways, where more movement of heat and water from the airway cells is required to heat and humidify the air (Harver and Kotses 28). When exercise stops and ventilation decreases, the airways rewarm quickly, as they no longer are losing heat and water to the air. This cycle of cooling and rewarming is associated with airway narrowing and bronchoconstriction. The osmotic hypothesis suggests that airway dehydration during exercise causes a series of events leading to airway smooth muscle contraction, and increased airway resistance (Harver and Kotses 28). During exercise, large volumes of air move in and out of the lungs as respiratory rate and tidal volume increases. This movement of air is thought to cause evaporation of water in the airways. This loss of water causes osmolarity. Osmolarity then triggers cells to release inflammatory chemicals, and results in smooth muscle contraction. Aspirin-Induced Asthma: AIA is an example of how different mechanisms can result in asthma. Aspirin is one of the most widely used medications throughout the world (Harver and Kotses 27). AIA could be described as a kind of intrinsic asthma, because it occurs due to some specific triggers. The AIA syndrome usually includes symptoms of nasal polyps, nasal congestion, sinusitis, and chronic asthma symptoms (Harver and Kotses 27). Patients experience chronic severe asthma due to AIA, and acute symptoms occur soon after injection of aspirin or any other similar drug, such as Ibuprofen (Harver and Kotses 27). Symptoms may appear within three hours, and start with runny nose, swollen eyes, wheezing, and flushing of the face. It further leads to impaired breathing, and immediate hospitalization becomes necessary, because of the associated risk of respiratory failure. The mechanism of AIA involves enzymes blocking which results in increased production of cytokines called Leukotrienes (Harver and Kotses 27). These leukotrienes cause inflammation and promote asthma in the susceptible individual. Genetics and Asthma The mapping of the human genome is such that some of the genes become a potential candidate for asthma and atopy (Clark 40). As asthma is now classified by being a disease of airway hyper-responsiveness and inflammation, the genetic candidates of these pathways contribute in the origin of genetic asthma. Specifically, genes found on the cytokine gene cluster of chromosome 5, chromosome 11, chromosome 16, and chromosome 12, has all been implicated in asthma (Clark 41). It is possible that not even a single asthma gene could get identified. But it is possible to obtain an improved understanding of pathogenic factors and treatment options, if research is focused on these identified chromosomes. The different types of genes contributing to the triggering and severity of asthma may also get discovered by further research (Clark 42). As of now, no authentic information is available on the genetic combination of asthma in individuals. Symptoms of Asthma: As the mechanism of asthma is complex, so are its signs and symptoms. Asthma may prevail on a person and present overabundance of symptoms, or coexist with other illnesses (Harver and Kotses 33). Some of the most common symptoms are listed below: Wheezing: Many patients with asthma initially experience wheezing i-e a high pitched sound usually heard during exhalation. As the airways narrow and airway resistance increases, there is more turbulent flow causing vibrations known as wheeze (Harver and Kotses 33). Cough: Some patients may never develop the symptom of wheezing but instead experience coughing as an initial symptom. Dyspnea, shortness of breath, tightness in the chest, a lot of mucus in the throat, coughing attacks after laughing or crying, and coughing attacks at nights are some other common symptoms of asthma (Crockett 15). Works Cited Busse, Willian and Holgate, S. T. Asthma and Rhinitis. 2. 1. John Wiley & Sons, 2000. Print. Chung, Fan. Asthma: Mechanisms and Protocols. 44. Humana Press, 2000. Print. Clark, Margaret. Asthma: A Clinician's Guide. Jones & Bartlett Publishers, 2011. Print. Crockett, Antony. Asthma: Your Questions Answered. Elsevier Health Sciences, 2003. Print. Currie, Graeme. ABC of COPD. John Wiley & Sons, 2011. Print. Harver, Andrew, and Kotses, Harry. Asthma, Health and Society: A Public Health Perspective. Springer, 2011. Print. Sullivan, John and Krieger, Gary. Clinical Environmental Health and Toxic Exposures. 2. Lippincott Williams & Wilkins, 2001. Print. National Asthma Education and Prevention Program, Second Expert Panel on the Management of Asthma. Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. DIANE Publishing, 1997. Print. Navarra, Tova. The Encyclopedia of Asthma and Respiratory Disorders. Infobase Publishing, 2003. Print. Read More