Asthma

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Introduction0:00–0:27

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.

Anatomy0:27–0:48

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.

Pathophysiology0:48–2:58

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 crosslinks 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 one 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.

Diagnosis2:58–4:09

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.

Symptoms4:09–4:49

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 one hypersensitivity. Regardless of the type, repeated inflammation causes permanent structural changes in airways called airway remodeling.

Classification4:49–5:24

The smooth muscle cells around the airways grow thicker and multiply, which is known as hypertrophy and hyperplasia of smooth muscle cells.
Meanwhile, repeated inflammation and tissue damage activate fibroblasts, which deposit collagen, causing fibrosis of the airway walls.
Goblet cells also grow in size, ramping up mucus production. The excess mucus and sloughed mucosal epithelial cells can form thick plugs known as Kirshchman spirals.

Treatment5:24–6:30

Next, as eosinophils break down, they release a protein called galectin 10, which forms needle-like crystals in the mucus called Charcoleidin crystals.
In severe cases, thick mucus can completely block airflow, trapping air inside the alveoli and causing them to overinflate like tiny balloons.
Finally, immune cells release substances that promote blood vessel growth in the submucosa. Now, because the inflammation in the airways comes in waves, symptoms tend to show up in episodes or what we call asthma attacks.
During an attack, often the first sign is a dry cough. On top of that, as a person tries to breathe out, the air is forced through narrow airways, creating the classic high pitched whistling sound called wheezing.
Usually this is heard most clearly during expiration. Also, you might notice prolonged expiration because a person takes longer to blow the air out.
And because the airways are tight, fresh air can't reach the alveoli, which reduces oxygen delivery to the lungs, causing shortness of breath.

Review6:30–10:00

To compensate for this lack of air, a person will usually breathe much faster and use accessory muscles to help with breathing.
Many individuals also describe the feeling of chest tightness, like a heavy band squeezing around their chest. And because of these breathing difficulties, a person often has a hard time speaking in full sentences.
Finally, in severe cases, oxygen levels in the blood can drop, causing a bluish discoloration around the lips called cyanosis.
Once an asthma attack settles down, most people feel fine, but for some, subtle symptoms persist. These often follow a diurnal pattern, appearing early in the morning or late at night.
A common symptom is a dry cough, which may occur late at night and disturb sleep. Others might experience mild shortness of breath along with coughing during physical activity.
All these features are suggestive of asthma, but you need to determine the type and confirm the diagnosis. Atopic asthma often appears alongside other allergic conditions.
Many individuals early in life first experience atopic dermatitis, followed by allergic rhinitis, and eventually develop breathing difficulties suggestive of atopic asthma.
This pattern of progression is known as the atopic march. Next, allergen testing, such as a skin prick test, often shows a person is overreacting to everyday allergens.
And if you check IgE levels, they are typically high because B cells are pumping these antibodies to gear up the immune system for future exposures.
Finally, be sure to check how well the lungs are working using spirometry. This test will reveal that a person can't blow out as much air in 1 2nd as they should.
However, the key clue is that after they use a bronchodilator, which helps relax the airways, they can suddenly breathe out a lot more air.
This reversibility points to asthma. On the other hand, in non-atopic asthma, there's no history of allergies, and allergy testing is typically negative.
Instead, these individuals report that their symptoms show up during respiratory infections, physical activity, times of stress, or even when breathing cold air.
And just like with atopic asthma, spirometry shows the same breathing pattern, meaning a person has trouble blowing out air, which improves after using a bronchodilator.
In both types, the management of asthma attacks involves inhalation of short-acting beta agonists like albuterol. These medications relax smooth muscle cells in the airways, causing bronchodilation and making breathing much easier.
Additionally, systemic corticosteroids can help reduce airway inflammation. On the other hand, long-term management aims to keep the inflammation in check and prevent future asthma attacks.
That's where low doses of inhaled corticosteroids and long-acting beta agonists come in. All right, as a quick recap, 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.
Atopic asthma is triggered by allergens and involves an IGE mediated type one hypersensitivity response. In contrast, non-atopic asthma is associated with respiratory infections and air pollutants, and it's triggered by things like cold air, stress, or physical activity.