Asthma

Asthma is a chronic respiratory condition characterized by recurrent episodes of airway inflammation and obstruction, known as asthma attacks, which result in breathing difficulties, such as dry cough, wheezing, and shortness of breath.

When you take a breath, the air travels through your nose or mouth down the trachea. From here, it moves into the primary bronchi, which branch into smaller secondary bronchi, then tertiary bronchi, and finally into the bronchioles. Bronchioles lead directly to tiny alveoli, where the gas exchange occurs.

Now, the airway walls contain smooth muscle cells and elastic tissue that help them open and return to their shape as we breathe.

The lining of the airways includes epithelial cells with tiny brush-like projections called cilia and goblet cells that produce sticky mucus. The mucus traps dust and other unwanted particles; while the cilia move together in coordinated waves, pushing the mucus and trapped particles toward the throat. This system, known as the mucociliary escalator, allows us to either swallow or cough out foreign particles. And if the mucus traps a pathogen, immune cells in our airways step in to eliminate the threat.

Now, asthma develops when the immune system in the airways becomes hypersensitive and overreacts to triggers that should be harmless. Based on the underlying cause, asthma can be classified as atopic- and non-atopic asthma.

Atopic asthma, also known as allergic asthma, is the most common type of asthma. It usually begins when someone breathes in allergens like pollen or dust mites. Instead of ignoring these harmless substances, the immune system identifies them as threats. As a result, antigen-presenting cells in the respiratory mucosa capture the allergen through a process called phagocytosis and break it down. Next, they present some of its fragments, known as antigens, on their surface. It’s their way of signaling to the immune system: “We have an intruder!” Using these antigens, they alert Th2 cells to release pro-inflammatory cytokines called interleukins, which signal other immune cells to jump into action.

Interleukin 5 activates eosinophils to join the response, while interleukins 4 and 13 stimulate B cells to differentiate into plasma cells. Next, these plasma cells begin producing allergen-specific IgE antibodies, which latch onto mast cells. This process is known as sensitization, and initially, it does not cause any symptoms. Instead, it prepares mast cells for future encounters.

So, when the body meets the same allergen again, the allergen cross-links the IgE on the surface of mast cells, triggering the release of histamine and other inflammatory mediators, such as leukotrienes and prostaglandins. This IgE-mediated immune response is known as type I hypersensitivity.

The activation of mast cells and eosinophils occurs minutes after exposure to a specific allergen and represents the beginning of the early phase of atopic asthma. First, inflammatory mediators cause smooth muscle cells to contract, causing bronchospasm and narrowing of the airways. Second, the surrounding small blood vessels dilate and become leaky, causing local edema and further narrowing the airways. Third, the inflammatory response stimulates goblet cells to increase the production of thick mucus that can plug the already narrowed airways.

Then, hours after the exposure, the late phase of atopic asthma sets in. During this phase, epithelial cells release chemokines to recruit more immune cells to the site. These include more Th2 cells and eosinophils, as well as neutrophils, basophils, lymphocytes, and monocytes. Meanwhile, eosinophils release substances that also damage the epithelium. This late phase can last for hours after the exposure, keeping the walls of airways swollen long after the initial trigger is gone.

Now, let’s switch our focus to non-atopic or non-allergic asthma, which is typically associated with respiratory infections and exposure to air pollutants. When a pathogen, like a virus, reaches the airways, it activates the immune system, causing local inflammation. As the immune system fights the pathogen, it also damages the surrounding epithelial lining and the Vagus nerve endings beneath it.

This damage makes the nerve endings overly sensitive to irritants that would not typically cause a reaction. So, besides viruses and pollutants, things like cold air, cigarette smoke, or physical activity can trigger these hypersensitive nerves and cause bronchospasm. And, since non-atopic asthma does not involve IgE antibodies, it does not represent type I hypersensitivity.