Airway pathology in asthma

What is asthma?

Asthma, as I'm sure you know, is a problem when the airways narrow too much. Airway narrowing is usually in response to a normally innocuous trigger such as an allergen, respiratory virus, exercise, irritant etc. Airway narrowing is usually a combination of contraction of airway smooth muscle, inflammation of the airway wall and/or hypersecretion of mucus. All of this leads to the characteristic symptoms of asthma, including wheezing, breathlessness, chest tightness and coughing.

Asthma is a chronic disease, which basically means that you have it for life. This doesn't mean, however, that asthmatics have issues breathing all the time: it's normally kind of on and off, with acute episodes and all the bits in between when the airways are working fine. As the disease progresses, however, airway function might not return to normal between episodes. Treatment normally aims to reduce the intensity, duration and frequency of acute episodes.

Asthma is very common, but not every asthma sufferer suffers in the same way. There are many different phenotypes of asthma, such as allergic asthma and exercise-induced asthma. Many of these patients can be treated effectively (though not cured), but 5-10% of patients have severe disease that doesn't respond well.

What are the pathologic features of asthma?

As I just mentioned earlier, airway narrowing may be due to hypersecretion of mucus. This excessive mucus can form mucus plugs that block the airway lumen. This kind of pathologic feature is considered to be part of the "gross pathology" of asthma, probably because it can be seen by the naked eye on a lung slice taken during an autopsy.

On a more microscopic level, asthmatic airways tend to have goblet cell hyperplasia (i.e. excessive amounts of goblet cells), which, along with the hypertrophy of mucus glands, are responsible for the excessive mucus secretion. There is also hyperplasia of the smooth muscle lining the airway, leading to excess contractility. Subepithelial fibrosis (i.e. formation of fibrous tissue below the epithelium) is also present. All of this leads to narrowing of the airway lumen.

Allergic asthma

In this lecture, we mainly focused on allergic asthma: asthma precipitated by exposure to an allergen. These allergens often do not cause problems for people without asthma. Interestingly enough, the immune system of asthmatic patients responds to these allergens much the same way as it responds to parasites such as worms and ticks (by recruiting eosinophils and so on).

Many of these allergens are actually proteases (like Der p 1 in the faeces of house dust mites), so they can cleave the tight junctions between epithelial cells and burrow their way in. The allergens can then activate dendritic cells, which activate T_H2 cells (see here for a reminder of the function of immune cells). These T_H2 cells then release a shit-ton of cytokines, such as IL-4, IL-5, IL-9 and IL-13 (but we will only be focusing on IL-4 and IL5 for now).

IL-4 can activate B-cells, which can create IgE specific to the allergen, which can bind to mast cells. When the allergen binds to IgE which is bound to a mast cell, the mast cell can degranulate and release histamine, proteases and so on. These contribute towards the narrowing of the airways.

IL-5 can activate eosinophils, which are usually active more in parasitic infections (as mentioned above). In fact, eosinophils usually aren't even present in the lung in healthy patients. When eosinophils are activated, they release cytotoxic proteins that can damage the airways. If the airways are damaged and repaired over and over again, over a long period of time they can be remodelled (i.e. have longer-term changes).

In my next post for this unit, I'll talk about drugs used to treat asthma. Stay tuned!