Factors into the Development of Asthma

Asthma is a type of chronic inflammatory disorder; more specifically, it's a disorder of the airways where there's increased responsiveness to stimuli, such as cellular components, allergens, and irritants. In those with this chronic condition, inflammation can cause wheezing, chest tightness, shortness of breath, and coughing. These specific episodes occur due to the airflow obstruction seen in the constriction of muscles. In most cases, narrowing of the airways is reversible. However, irreversible airflow obstruction can occur in those with chronic asthma.

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

Disease cause/pathogenesis

Several factors contribute to the development of asthma during adulthood. It is found that women are more likely to develop this chronic condition after the age of 20. Additionally, obesity can increase a person's risk of developing asthma. There are some individuals who developed asthma during their childhood; this condition can recur later in life. Furthermore, asthma is a heterogeneous disease influenced by genetic and environmental factors. There are risk factors that can predispose someone to develop asthma, and there are also specific triggers for this disease.

A prevalent risk factor for asthma is atopy, a genetic tendency for allergic diseases to develop. Individuals who have asthma often suffer from an atopic disease, such as allergic rhinitis or atopic dermatitis. Most commonly, environmental factors increase the likelihood of atopy. These factors may include: dust mites, grass, pollen, fur from domestic pets, and cockroaches. Inhaled allergens, like those just listed, are often the common triggers for a person with asthma. Locations with poorly ventilated homes or carpets facilitate the occurrence of asthma, as dust mites and dander from domestic pets tend to adhere more easily to carpeted surfaces. Furthermore, air pollutants like ozone, diesel particles, and sulfur dioxide – which contribute to thick smog – have been found to trigger asthma by making it difficult for people to breathe.

Moreover, exposure to allergens can lead to chronic, everlasting symptoms. Grass, pollen, ragweed, and fungal spores are considered seasonal allergens. These are more likely to cause allergic rhinitis than asthma. However, when it rains or there's a thunderstorm, the dispersion of pollen grains and the subsequent release of particles can prompt asthma. Alongside this, hot or humid weather can also trigger asthma.

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 must comprehend how these factors play into the overall airway defect.

Inhaled allergens significantly contribute to the occurrence of acute inflammation in asthma. This inflammation 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 mediators. 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, which 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. 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 ultimately regulate the overall late-phase reaction.

In contrast, chronic inflammation is when remodeling occurs. Remodeling typically involves the renewal of tissue that has been injured by parenchymal cells. Connective tissue can also have scar tissue in it, which may likewise be repaired. This occurs as an irreversible process that involves significant sequelae production, eventually developing into COPD. In chronic inflammation, both central and peripheral airways tend to be irritated or inflamed. Thus, when asthma occurs, all the cells that make up the airways become involved. 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 remodeling process by cytokines and growth factors.

Eosinophils release pro-inflammatory mediators, cytokines, and cytotoxic mediators. They are actively circulating and move to the airways by a process called cell rolling. These cells do this by interactions with selectins. When this occurs, the eosinophils attach to the endothelium by binding to integrins of adhesion proteins (VCAM-1 and ICAM-1). They survive for a more extended period of time due to the presence of interleukin 5 and granulocyte-macrophage-colony-stimulating factor. Upon activation, eosinophils release leukotrienes and granulate proteins, further injuring the tissue of the airway.
In the overall inflammatory process in asthma, 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. Th2 cells regulate the production of cytokines for the overall process of allergic inflammation. It is thought that the inflammation that occurs in asthma from allergens is due to a Th2 mediated process. This indicates an imbalance between Th1 and Th2 cells. However, in adults, it has been found that there are low Th2 cytokine phenotypes that exist in asthma.

The mucociliary system is a defense mechanism that protects against irritants. Mucus is produced by bronchial epithelial glands and goblet cells. The airways are lined with an aqueous layer and this is regulated by active ion transport across the epithelium. The action of catecholamines and vagal stimulation increases transport. The transport of mucus is dependent on certain viscoelastic properties. If the consistency of mucus is too watery or viscous, it will not be transported along the concentration gradient. The impairment in mucus transport is due to an exudative inflammatory process and the clearing of epithelial cells that are present in the airway lumen. People with asthma tend to have mucus that is high in viscosity, leading to clogged airways. Epithelial and inflammatory cells also have the potential to block airways.

Signs and symptoms

The general symptoms of asthma are shortness of breath, wheezing, coughing, and chest tightness. With shortness of breath, an individual may feel unable to catch their breath or sense being out of breath. Wheezing is typically associated with asthma most of the time. A person will notice a whistling sound that occurs when they breathe, specifically when they exhale. Furthermore, coughing tends to be worse at night and in the morning. Lastly, there can be an uncomfortable feeling of squeezing or a heavy sensation in the chest, which is a sign of chest tightness.

For adults who have chronic asthma, common symptoms can include chest tightness (most commonly at night), wheezing, and dyspnea. Signs of recurrent asthma may include wheezing when exhaling, allergic rhinitis, and a dry cough.

With acute asthma, the signs and symptoms differ from those accompanying chronic asthma. Typically, an episode can occur for a few hours at a time. In most cases, a person will feel anxious when an acute event occurs. Common complaints include shortness of breath, chest tightness, a burning sensation, and dyspnea. Often, patients will have difficulty breathing and talking. Signs can include wheezing when inhaling and exhaling, tachycardia, a dry cough, pale skin, or hypoxic seizures.

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