Factors into the development of asthma

Asthma is a type of chronic inflammatory disorder. More specifically, it is a disorder of the airways, where there is increased responsiveness to stimuli (cellular components, allergens, and irritants). In those who have this chronic condition, inflammation can cause wheezing, chest tightness, loss of breath, and coughing. These specific episodes occur because of the airflow obstruction seen in the constriction of muscles. In most cases, narrowing of the airways is reversible. However, there can be irreversible airflow obstruction in those that have chronic asthma.

This chronic condition is one the most widespread diseases and roughly affects three hundred million people1. Studies have shown that children with asthma can become asymptomatic during their adolescence period, but present with the chronic condition later in adulthood. Adults tend to express persistent symptoms, with medications to keep the condition under control.

Disease cause/pathogenesis

Several factors play into the development of asthma during adulthood. It is found that women are more likely to develop the chronic condition after the age of 202. Also, obesity can also increase a person’s risk of developing asthma. There are also those individuals who developed asthma during their childhood, which can become recurrent later in life. Furthermore, asthma is a heterogeneous disease that possesses genetic and environmental factors. There are risk factors that can predispose someone to develop asthma and there are also specific triggers to establishing this disease.

A prevalent risk factor for asthma is atopy. This is the genetic tendency for allergic diseases to develop. Those who have asthma will usually suffer from an atopic disease, such as allergic rhinitis and or atopic dermatitis. Most commonly, environmental factors make those prone to atopy. These factors may include the following: dust mites, grass, pollen, fur from domestic pets, and cockroaches. Inhaled allergens, such as the factors just listed, are most often the common triggers for a person who suffers from asthma2. Places with poorly ventilated homes or carpets increase the occurrence of asthma, as dust mites and dander from domestic pets tend to cling to carpeted surfaces much easier. Furthermore, air pollutants have been found to trigger asthma, as well. Pollutants like ozone, particles of diesel, and sulfur dioxide create thick smog in the air, making it harder for people to breathe, thus triggering asthma.

In addition, environmental exposure to allergens will lead to chronic symptoms that are everlasting. Grass, pollen, ragweed, and fungal spores are considered seasonal allergens. These will more often cause allergic rhinitis rather than asthma. However, when it rains or, there is a thunderstorm, pollen grains are dispersed, and the particles that get released can prompt asthma. Coinciding with this, hot or humid weather can trigger asthma, as well.

Pathophysiology

The most important features of asthma include airflow obstruction (bronchospasm, edema, mucus hypersecretion), bronchial hyper-responsiveness, and airway inflammation. To further understand these mechanisms and how they activate the inflammatory response of the airways, we have to comprehend how these factors play into the overall airway defect.

Inhaled allergens significantly contribute to the occurrence of acute inflammation in asthma. It is a beneficial, nonspecific response of tissues to injury and leads to repair and restoration of the typical structure and function. Immunoglobulin E is responsible for establishing the early phase activation. In this phase, rapid activation of airway mast cells, along with macrophages, leads to the release of pro-inflammatory mediators3. These mediators include; histamine, eicosanoids, and reactive oxygen species. The direct cause of the release of these mediators is the contraction of the airways smooth muscle, mucus secretion, and vasodilation. Furthermore, inflammatory mediators are responsible for generating microvascular leakage with exudation of plasma in the airways. This further creates a viscous, water fluid that collects in the airway wall, that results in the narrowing of the airways lumen. Mucus clearance can be lessened by the presence of plasma in the lumen. The result is airflow obstruction. Furthermore, the late phase inflammatory reaction typically takes place about 6 to 9 hours after the early phase reaction. This phase recruits and activates eosinophils, T-cells, basophils, neutrophils, and macrophages. When the T-cells get activated, Th2 cytokines get released and end up regulating the overall late phase reaction.

In contrast, chronic inflammation is where remodeling occurs. Remodeling typically involves the renewal of tissue that has been injured by parenchymal cells. Connective tissue can also have scare tissue in it, so that may also be repaired. This occurs as an irreversible process that involves significant sequelae production, developing into COPD. In chronic inflammation, both central and peripheral airways tend to be irritated or inflamed4. Thus, when asthma occurs, all the cells that make up the airways become involved3. These cells include; eosinophils, T-cells, mast cells, epithelial cells, fibroblasts, macrophages, and bronchial smooth muscle cells. Airway inflammation can be regulated by these cells, as well as, the process of remodeling by cytokines and growth factors.

Eosinophils release pro-inflammatory mediators, cytokines, and cytotoxic mediators. They are actively circulating and they end up moving to the airways by a process called cell rolling. These cells do this by interactions with selectins. When this occurs, the eosinophils will actually attach to the endothelium by binding to integrin’s of adhesion proteins (VCAM-1 and ICAM-1). They further survive for a more extended period of time due to the presence of interleukin 5 and granulocyte-macrophage- colony-stimulating factor. Upon activation, eosinophils will release leukotrienes and granulate proteins, further injuring tissue of the airway.

In the overall inflammatory process in asthma, there are two types of T-helper CD4+ cells are involved. The purpose of Th1 cells is to produce interleukin 2 and interferon-gamma, as these are important in cellular defense. The production of cytokines is regulated by Th2 cells for the overall process of allergic inflammation. It is thought that inflammation that occurs in asthma from allergens occurs due to a Th2 mediated process. This means there is an imbalance between Th1 and Th2 cells. However, it has been found in adults that there are low Th2 cytokine phenotypes that exist in asthma.

There is a defense mechanism that aids against irritants is the mucociliary system. Mucus is produced by bronchial epithelial glands and goblet cells. The airways are lined by an aqueous layer that is regulated by active ion transport across the epithelium. Action of catecholamines and vagal stimulation increases transport. Transport of mucus is dependent on certain viscoelastic properties. If the consistency of mucus is too watery or viscous, then it will not be transported along the concentration gradient. Impairment of the transport of mucus is due to an exudative inflammatory process and the clearing of epithelial cells that are present in the airway lumen. Those with asthma, tend to have mucus that is high in viscosity, resulting in the clogging of airways. Epithelial and inflammatory cells also have the ability to plug airways, as well.

Signs and symptoms

The general symptoms of asthma are shortness of breath, wheezing, coughing, and chest tightness. In shortness of breath, someone can have the feeling of not being able to catch a breath or have a sense of being out of breath. Wheezing typically goes along with asthma most of the time. A person will notice a whistling sound that occurs when they breathe, more specifically exhale. Furthermore, coughing tends to be worse at night and in the morning5. Lastly, there can be an uncomfortable feeling of squeezing or a heavy feeling in the chest, this being a sign of chest tightness.

For those adults who have chronic asthma, common symptoms they can complain of is chest tightness most commonly at night, wheezing, and dyspnea. Signs of recurrent asthma would be wheezing when exhaling, allergic rhinitis, and a dry cough.

With acute asthma, the signs and symptoms are noticeably different than with chronic. Typically, an episode of this can occur for a few hours at a time. In most cases, a person will feel anxious when an acute event transpires. The common complaints are of shortness of breath, chest tightness, burning, and or dyspnea. Often, patients will have a tough time breathing, as well as, talking. The signs of this include wheezing when inhaling and exhaling, tachycardia, a dry cough, pale skin, and or hypoxic seizures.

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