Pathophysiology of Asthma

Pathophysiology

The pathophysiology of asthma is complex and involves the following components:

• Airway inflammation
• Intermittent airflow obstruction(Airway remodelling)
• Bronchial hyperresponsiveness

Asthma, allergic rhinitis, and atopic dermatitis are almost invariably accompanied by elevated levels of IgE.

Airway inflammation

Many asthmatics are atopic (an inherited a predisposition towards allergy) where your immune system develops an exaggerated response to certain foreign substances or allergens. Your body's immune system senses these allergens, perceives them as foreign, and begins to prepare to fight off them off as a foreign intruder. The process that takes place is often referred to as the allergic cascade, which generally occurs in 3 steps:

1. Sensitization
2. Early phase response
3. Late Phase response

1. Sensitization

Immunologically, your body senses the allergen as foreign and sets off a cascade of events stimulating several different types of immune cells (see diagram):

• T cells rapidly stimulate B cells
• B cells transform into plasma cells
• Plasma cells produce IgE antibodies specific to the allergen
• IgE antibodies bind to mast cells, lymphocytes, basophils

2. Early phase response

With re-exposure to the allergen your immune system senses the allergen as foreign leading to:

• The mast cell/ IgE complexes produced in the sensitization phase, binding to the allergen thinking that it is a foreign invader
• Mast cells then release inflammatory cells called mediators (e.g. histamine) that quickly travel throughout your body with the purpose of fighting off the foreign invaders such as bacteria and viruses.
• You begin to experience symptoms of your body’s overreaction to the allergen.

Cross-linking of IgE bound to mast cells triggers the release of preformed vasoactive mediators, synthesis of prostaglandins and leukotrienes, and the transcription of cytokines.

In the bronchial mucosa, these mediators of immediate-hypersensitivity reactions rapidly induce mucosal edema, mucous production, and smooth muscle constriction, and eventually elicit an inflammatory infiltrate.

You may begin wheezing, coughing or feeling short of breath as the immunologic response causes swelling and narrowing of the airways in your lung. You may only experience runny nose or watery, itchy eyes. The immunologic response begins nearly immediately with symptoms occurring very shortly after re-exposure lasting 3-4 hours.

3. Late Phase Response

Beginning at the same time as the early phase response, but not causing symptoms for several hours, is the late phase response. Mediators released by the re-exposure to an allergen also stimulate other kinds of immune cells called eosinophils. Eosinophils contain substances that when released normally fight off infections, but in asthma, the cells damage the lung causing more inflammation and worsening symptoms.

In the late phase, symptoms will not develop for at least 4 hours, but may last as long as 24 hours. Increased inflammation and obstruction of airflow may be more severe than what is seen during the early phase.

Airway remodelling

Airway remodeling in asthma is what happens in response to long-term, unresolved airway inflammation. When airway inflammation is not adequately treated, it can result in permanent structural changes in the airways.

In these cases, a certain degree of airway inflammation is always present. Over time, the body tries to fix this inflammation by triggering changes in the repair function of the lining of the airways.

• Increased airway wall thickness that involves both smooth muscle and collagen tissue
• Increased mucous glands and mucus production
• Increased vascularity, or blood supply, in the airways

Bronchial hyperresponsiveness(BHR)

Airway hyperresponsiveness is a characteristic feature of asthma and consists of an increased sensitivity of the airways to an inhaled constrictor agonist. Certain inhaled stimuli, such as environmental allergens, increase airway inflammation and enhance airway hyperresponsiveness. They are, however, similar to changes occurring in asthmatic patients that are associated with worsening asthma control.

The pathogenesis of exercise-induced bronchospasm is controversial. The disease may be mediated by water loss from the airway, heat loss from the airway, or a combination of both. The upper airway is designed to keep inspired air at 100% humidity and body temperature at 37°C (98.6°F). The nose is unable to condition the increased amount of air required for exercise, particularly in athletes who breathe through their mouths. The abnormal heat and water fluxes in the bronchial tree result in bronchoconstriction, occurring within minutes of completing exercise. Results from bronchoalveolar lavage studies have not demonstrated an increase in inflammatory mediators. These patients generally develop a refractory period, during which a second exercise challenge does not cause a significant degree of bronchoconstriction.

AV nicking (the Gunn sign): Impeded circulation results in a dilated or swollen vein peripheral to the crossing, causing hourglass constrictions on both sides of the crossing and aneurysmal-like swellings.