Asthma is a very common obstructive inflammatory disease of the lungs. When I say "obstructive", I mean obstruction of the air to get out of the lungs. There is another type, "restrictive" which means difficulty in filling the air into the lungs. More precisely, asthma is defined as bronchial hyperresponsiveness which includes constrictions of the airway and secretion of the mucus. All of these symptoms are easily triggered. Also, the person may experience chest tightness and shortness of breath. The frequency of the attacks can be a few times per week to a few times per day. But, of course, this depends on the severity of the disease. It is observed that the symptoms get worse at night and with exercise. Let's talk about a brief history of asthma

^{Asthma by}^Brucebalus^,^Wikimedia^{licensed under}^{CC BY SA 4.0}

A Brief History

This disease has a very long history. It's documented that, asthma was first observed and treated in ancient Egypt. It was treated by a mixture called "kyphi". In 450 BC Hippocrates named this disease "Panting". Panting means short and quick breaths. Also, he said, this disease was triggered by the emotions.

In 1873, the first journal published which explained the pathophysiology of asthma. In 1880, The journal included the use of a first intravenous drug to treat asthma known as "Pilocarpine". With some more research and progress, within a few years, the connection between asthma and hay fever was seen.

In 1905, Epihephrine was the first drug to be officially prescribed for the treatment. It was not found to be that effective. In the 1950s, oral cortico-steroids were being used and the 1960s, inhaled corticosteroids began to be used. During this period, all of these drugs were experimental, and asthma was considered a psychological illness. The characteristic wheezing sound produced was taken as crying children. They thought the children are just depressed and crying loudly. Therefore, most of the asthma patients were treated for depression too.

Short Intro

As I said Asthma is defined as bronchial hyperresponsiveness. This means something triggers the bronchial system to act this way. This might be to allergy or something else. Well, this helps us to categorize asthma into two types:

	Extrinsic Asthma	Intrinsic Asthma
Cause	Allergic, Type-1 Hypersensitivity	Non-allergic
Trigger	Environmental antigens like pollen, dust	Drugs like aspirin Cold Exercise Stress
IgE mediated	Yes	No

This table, explains the differences quite well, one thing I want to add is, Extrinsic asthma mostly starts in childhood.

There is no definitive cure for asthma. We can only prevent the symptoms by avoiding the triggers. And if the symptoms appear, we need to use the specific drugs like corticosteroids or Long-acting beta-agonist to control the symptoms.

Sign and Symptoms

The signs and symptoms might differ from according to person. Some patients rarely show any symptoms in response to the allergic reaction, whereas, some patients might show severe and life-threatening symptoms in response to the reaction.

most common signs and symptoms seen are:

Shortness of breath.
Characteristics wheezing or whistling sound produced while exhaling.
Sound is mostly produced in children
Chest tightness
Sleeping difficulties
Symptoms become worse at night or early morning
Symptoms become worse in the presence of other conditions like flu.

Sputum may or may not be produced. If there is heavy coughing, sputum might be produced by the lungs but it feels like being stuck in the lungs. It's very difficult to bring up which makes the patients even more uncomfortable.

For some people, only certain conditions trigger the attack of asthma.

Occupational asthma: This type is only triggered by the workplace where dust and other irritants are at high levels like a chemical factory.
Allergy Induced: This type is triggered in the presence of certain allergens. Most of the patients are allergic to one or two allergens only. Most of them are allergic to dust or pollens. But it can be anything.
Exercise-induced: As, the name suggests, too much exercise leads to shortness of breath which acts as a trigger for asthma.

Different Causes

Till now, no single cause of asthma has been identified. There can be multiple causes at once. Scientist believes that this condition is triggered by several factors.

Environmental Causes
Genetic causes
associated with other medical condition
History of respiratory infection
History of allergy
Hygiene hypothesis.

Environmental Causes: Environment plays a major role. Many environmental factors such as dust, grains, minute particles, pollens, etc have been associated with asthma. Air pollution is often associated with the development of asthma. Most of the cases are found where air quality is below the EPA standards.

^{Image: Trigger for asthma by}^7mike000^,^Wikimedia^{licensed under}^{CC BY-SA 3.0}

Not only outdoors, but Asthma is also often developed by indoor environmental causes too. Organic compounds like formaldehyde, PVC, etc are some of the examples. Indoor allergens such as mites, dust, animal fur, fungus, molds, etc have been found to develop the case of asthma.

Genetic causes: If a person gets asthma in childhood, then its more likely due to genetic cause. Family's Positive history is one of the risk factors. The association between genetic and environmental factors leads to a trigger of asthma. If a person gets asthma in childhood, then its more likely due to genetic cause. The association between genetic and environmental factors leads to a trigger of asthma.

Not only a single gene but, many genes are associated with this condition. In 2005, 25 genes were found to be associated, and in 2006, above 100 genes were found to be associated in a single study.

Association with other medical conditions: Many other allergic conditions can lead to asthma. If the person has a positive history for atopic disease, it's considered one of the risk factors. Rhinitis and atopic eczema are atopic diseases. Atopic eczema is long-term allergic inflammation of the skin.

Asthma has been also associated with
Churg–Strauss syndrome which is a type of autoimmune disease. Blood vessels are inflamed by a person's own immune system also known as vasculitis. In recent years, a link between obesity and asthma is also noticed.

accumulation of fats decreases the respiratory function which later leads to inflammation of the respiratory tract.

Hygiene Hypothesis
This is an interesting one. it basically says, if a person is not introduced to pathognomonic bacteria or viruses in childhood, then the person might not have developed the immunity to fight against those which make him/her even more susceptible to asthma. It's been proposed that exposure to bacterial endotoxins in the past, helps prevent the development of asthma but the same exposure in adulthood might lead to a severe allergic reaction.

Pathophysiology

Now, asthma can be of two types, one that is allergic and the other non-allergic. So, there are two ways to trigger asthma. The main player in allergic or extrinsic asthma is the IgE antibody. These antibodies are important because they can bind to the receptor on the Mast cells. This is known as the mast-cell IgE complex. The function of this complex is to identify the allergen present in the system and trigger an immune reaction which releases histamine.

Other cells that play important roles are Eosinophils, Dendritic cells, and T-helper cells. T-helper cells are furthermore classified into T-helper -1 and T-helper-2 cells. In a normal person, T-helper 1 is more number than 2 in the lungs. However, in asthma, upregulation of T-helper 2 is seen leading to more number of T-helper 2 in the lungs. The main function of T-helper 2 cells is to produce humoral immunity meaning antibody-mediated immunity.

What happens after inhaling an allergen?

Let's see this step by step to have a clear picture. When the asthmatic patient inhales an allergen series of events can happen.

^{Pathophysiology of Asthma by}^Mk4716^,^Wikimedia^{licensed under}^{CC BY-SA 4.0}

Dendritic cells might engulf the allergen which in turn activates the cell.
Another thing that can happen is, the columnar epithelium can sense the allergen and can secrete something called thymine stromal lymphocyte. This helps to attract T-helper 2 cells.
The activated dendritic cells, itself help mature T-helper cells to differentiate into T-helper-2 cells and also release chemicals to attract the T-helper 2 cells to the needed area which can be bronchial or the lungs.
The activated T-helper 2 cells promote the humoral immunity which leads to the production of IgE antibodies.
Now, IgE will bind to mast cells to make the IgE-mast cell complex.
This complex will now trigger the release of histamines, prostaglandin, and leukotrienes.
These 3 mediators will now act on the smooth muscles of the bronchioles leading to its constriction.
The person suffers from bronchoconstriction, leading to chest tightness, shortness of breath, and wheezing sound while exhaling.

Diagnosis of Asthma

Now, let's talk about some gold standard tests, that can be done to confirm the diagnosis. Here are some of them:

Methacholine test: This test is considered to be a little bit cruel. In a normal person, the airways are big. When methacholine is inhaled, this contracts the airways. In a normal person, contraction is only a little bit, but if the person is asthmatic, this can trigger the attack of asthma which confirms the diagnosis.

Pulmonary Function Test: (Spirometry)

This test a bit more technical and actually involves some math. A person is given a mouthpiece and is asked to blow air in it. Everything is recorded by a computer. All the patients have to do is take a gigantic breath in as much as they can and blow out the air into the mouthpiece as hard as they can and as long as they can. Believe it or not but most of the air comes out in the 1st second which is termed as "FEV1". Also, the term of all the air you ever breathe out into the mouthpiece is "FVC" or full vital capacity.

^{Spirometry by}^NIH^,^Wikimedia^{licensed under the Public domain.}

In this test, the ratio of FEV1 and FVC is calculated. The ratio must be more than 80%. This tells that, the person has no obstruction in the lungs. In asthma, the ratio is less than 80% which suggests that there is something wrong during exhalation. there might be obstruction or bronchoconstriction. This test can be done with a methacholine test or can be done alone.

Peak flow test:

This test is done with the help of a handheld device "peak flow meter". This device measures the volume of air moving out of your lungs. During a bronchoconstriction period, it can help to keep a track record and help in the diagnosis. Not only diagnosis, but it is also used to monitor asthma patients.

X-ray

X-ray is not particularly helpful in diagnosis Asthma but it can be needed to rule out other similar conditions that can have similar symptoms. Such as phenomena, pneumothorax, foreign bodies obstruction in the airway.

Management of Asthma

There is no definitive cure for asthma but certainly, we can treat the symptoms and reduce them. Each patient is different in the case of asthma and a specific and customized plan is made for each patient according to their symptoms and their severity. This plan includes the reduction of the exposure of the specific allergens, monitor the symptoms very closely, and adjusting the medications accordingly.

The first step is to identify the allergen or the trigger. It can be anything like dust, pollution, smoke, fur, etc. The second step is to reduce exposure. This alone reduces the attacks of asthma. If the symptoms are progressing and increasing in severity, mediations are used.

Stress is also one of the triggers in asthma patients. Even after medication, stress can lead to poor control. Therefore, behavior therapy is recommended in those cases.

Lifestyle modification is also key management for asthma. Improving the quality of living such as painting hygiene, standing aways from pollution and dust, quitting smoking, and staying away from passive smoking can be a big help in management. Also, yoga is found to beneficial in improving lung functions.

Medications:

The medications are broadly classified into two types: Short-acting medication and Long-acting medication. The short-term medications are bronchodilators. Relieves the symptoms very fast. If there are only occasional attacks with less severity then this medication alone is enough. If the attacks are more than 2 times a week then low-dose inhaled corticosteroids are used. For those with high severity and daily attacks, high dose corticosteroids with other combinations are used.

Short-acting Medication:

Short-acting beta 2 receptor agonist (SABA): Such as salbutamol, albuterol. These are the first-line medications for an acute attack. This medication basically acts on the Beta 2 receptors of the bronchioles, which stimulates it and leads to its relaxation.

^{Inhalers use by}^Bruceblaus^,^Wikimedia^{licensed under}^{CC BY-SA 4.0}

Anticholinergic medication: this medication acts on the smooth muscles too and acts as a bronchodilator. It quickly relaxes the airway. Some drugs are Ipratromium and tiotropium. These drugs can be used in combination with SABA. These can be also be used in the patient who is unable to tolerate SABA.

Oral corticosteroids: These are only used for the short term and help to reduce the inflammation caused in the airway by a severe attack of asthma. Some examples are prednisolone and methylprednisolone.

Long-term Medication:

Long-acting beta-agonist (LABA): Some drugs in this category are Salmeterol and Formoterol. They act up to 12 hours after a single-use. They are not used alone, rather they are used in combination with inhaled corticosteroids.

Inhaled Corticosteroids: This medication is very effective in long term treatment. Basically, it reduces inflammation by blocking the reaction to the allergen and inhibiting inflammatory cell activation. Beclomethasone is one of the examples.

Leukotriene Modifiers: These included leukotriene receptor antagonists. Two forms are available "Montelukast" and "Zafirlukast". These are not used alone rather used in combination with inhaled corticosteroids for better results.

Immunomodulators: These medications interfere with the immune system. Omalizumab is one of the drugs in this category. It's an anti-IgE. It means, it prevents IgE from binding to the suitable receptors, most likely on mast cells or on basophils. Hence, decreasing the symptoms.

Methods of Drug Delivery

Drugs are delivered in various ways. Here are some of them:

Metered Dose Inhaler: These are also called MDI's and are provided in combination with asthma spacer and dry powder drug. The spacer is basically a small cylinder, that mixes up the air with the dry powdered drug and makes it easier to inhale.

Nebulizer: It's a device that changes the drug to mist which is easier to inhale. They are larger and need an electrical outlet or a battery. Nebulizers are mostly used for the children because all they have to do is breathe normally. But most of the people prefer Inhalers because they are cheaper, smaller and easier to use.

^{Image: MDI by}^{James Heilman}^,^Wikimedia^{licensed uneder}^{CC BY SA 3.0}

^{Image: Nebulizer by}^Imgz^,^Wikimedia^{licensed under}^{CC BY-SA 3.0}

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That's it for this article guys, see you in the next one. I hope you liked it.

*All images used are copyright free and are cited with appropriate credits*

References:

http://www.allergyandasthma.com/home/articles/history-of-asthma
https://zana.com/a/asthma-introduction.367
https://acaai.org/asthma/asthma-symptoms
https://toolkit.severeasthma.org.au/management/asthma-pathophysiology/
https://www.uptodate.com/contents/pathogenesis-of-asthma
https://www.cdc.gov/asthma/management.html