Pathophysiology of Asthma: symptoms and treatment for asthma

When anyone has chronic diseases like asthma they should learn to cope.  Asthma is a chronic condition, but it’s unknown what exactly causes asthma to occur in some people. It often tends to run in families, so genetics may be a factor. Asthma is a fact that takes your breath away and makes you feel miserable. This content consists of the pathophysiology of asthma and its influence on risk factors that can help you to understand more easily.

What is Asthma?

Asthma is a long-term disease of the lungs that causes difficulty in breathing. It often starts in childhood and also affects all ages. Due to asthma your airway becomes narrow and also gets inflamed. Asthma is a serious condition of lungs although dangerous that affects around 2-2.5 million people. Asthma can be classified as a mild to moderate condition, severe type of asthma make it difficult to talk or be active.

How do you classify Asthma?

Asthma can be classified according to its severity. According to studies, doctors rank the asthma by its symptoms, these are:

1. Mild intermittent asthma 

Mild intermittent asthma is mild or least type of asthma. People with mild intermittent type of asthma have asthma symptoms come and go and people experienced the episode of asthma less than twice a week or at night time, while there are no symptoms to show and your lungs function properly. Even though it’s necessary to manage your asthma at this stage.

Good To Know: By properly managing the mild intermittent asthma you can reduce the severity of this disease. This type of asthma does not interfere in your daily activities, while the night time asthma occurs 2 days or less per month. People with mild intermittent usually do not need daily control medication for asthma but your doctors recommend you rapid relief bronchodilator (such as albuterol) because this rapid-relief inhaler helps to open the airway. Treatment of asthma is different for every person as it depends on their system and immunity.

2. Mild persistent asthma

People with mild persistent asthma experienced episodes of asthma more than twice a week or 3-6 times a week but not regularly. Symptoms appear three to six times a week. 

Good To Know: The symptoms or criteria for mild persistent asthma is: symptoms occur more than two weeks, while night symptoms appear 3-4 times a month. The use of a short-acting inhaler is less than once per week. This type of asthma gives a minor limitation and it can affect your normal activities. In mild persistence, your doctor recommends you first-line medication (such as inhalers and bronchodilators) to control the attack of asthma and also prescribe long-term medication which is taken regularly to prevent its severity. 

3. Moderate persistent asthma

People with moderate persistent asthma usually experience episodes of asthma lasting for several days with coughing and wheezing sound and it may disturb your activities.

Good to know: The symptoms may appear 3-6 times a week, while nighttime symptoms occur 3-4 times a month and it might affect your life. Your lungs function 60-80% of predicted values which are based on your age, height, and gender. People with moderate persistent asthma are generally under-treated and not well controlled on low doses of inhaled corticosteroids. A combination of Long-term acting inhaler (beta-2 agonist) and inhaled corticosteroids.

4. Severe persistent asthma

Patients with severe persistent asthma experience episodes of asthma daily, both day and night. Your normal activities and daily life disturbs badly with symptoms of dyspnea, wheezing, and chest tightness and it might become worse.

Good to Know: Due to a severe type of Asthma you are unable to do anything. Treatment may bring change in your condition and manage your symptoms. Your doctor prescribes medications to decrease the inflammation of your lungs and make you easier to breathe and these medicines are inhalers, injected medicines, or oral pills with anti-allergies. For a better lifestyle you should follow your doctor’s advice and use rescue inhalers less than 2-3 times a week.

Pathophysiology of Asthma

Asthma is a chronic disease and pathophysiology of asthma is somehow complex and difficult to understand. It may involve nasal passage, paranasal tissues, mouth, the larynx, the trachea, and bronchial trees. If each of these get inflamed and obstructed it might cause asthma but the main target or focus of asthma is bronchi (either large, medium, and small bronchus), it becomes swollen, inflamed, irritated, and hyporesponsive. The bronchial tree is the term which we used for various of branches and the function of bronchi is to provide air passageway to move the air in and out to lungs and also trap the damage and debris. Bronchial tree has 16 divisions before reaching to its terminal (bronchioles) and if an individual has asthma the terminals function abnormally, while remaining 5-7 divisions of bronchioles are normal. Supply of blood in your lungs come from two sources:

i) Pulmonary circulation: Passage of the blood which comes from your pulmonary arteries and provides venous (deoxygenated blood) to alveoli for exchange of gases.

ii) Bronchial circulation: It is part of your circulatory system and it arises from the aorta and provides oxygenated blood to your lungs. This comes from the aorta and provides blood supply to the bronchial walls, and it provides plexuses in the submucosa (around smooth cells).

If there are any changes or occur in walls of vessels or arteries, it may allow edema and inundation of inflammatory cells.

On the other hand, the immunopathologic factors of asthma also include inflammatory cell infiltration because inflammation plays a vital role in the pathophysiology of asthma and it involves an interconnection of many types of cells and mediators, but the process of interconnection events still under the investigation to find out more enhance the clinical concept of asthma, while the pattern of inflammation in diseases of asthma might vary according to its severity, duration, gender, and weight. The inflammatory cell infiltration factors include neutrophils, eosinophils, lymphocytes, mast cells activation, epithelial cells, and dendritic cells. 

1. Neutrophils

Neutrophils are also named as neurocytes and play an important role in the innate immune system. An increase in neutrophils in your airway and sputum, who has severe type of asthma, is due to acute exacerbation and aggravation. Neutrophilic airway inflammation appears as a pathologic condition of asthma but its role remains uncertain. The recruitment, activation, and alteration of neutrophils in lung function is still under the study.

2. Eosinophil

Eosinophil plays a vital role in asthma and it contains inflammatory enzymes that show a wide variety of pro-inflammatory cytokines, and is commonly seen in adulthood, children, and teens. An individual who has eosinophilic asthma usually does not have any history of allergic conditions. According to previous researches, increases of eosinophilic in your blood, lung tissues, and mucus increases the risks of asthma attack while the cause of eosinophilic asthma is still unknown but it is suggested that approximately 10% of all asthma is categorized as severe. Asthma treated with corticosteroids may reduce the airway eosinophilic inflammation.

3. Lymphocytes

Lymphocytes also play an important role in the origination, progression, determination, and persistence of allergic diseases, including asthma. Although, the immunoregulatory mechanisms that determine vulnerability to, extremity, or persistence of asthma. Sub-type of lymphocytes (T-helper 1 and T-helper 2 cells) are inflammatory mediator which affect the airway inflammation, while the concept of a disturbed (Th1 and Th2) balance having the present understanding of immunoregulation in asthma, which has recently been named a “procrustean paradigm”, because of its failure to sufficiently explain the pre-clinical observations. In current years, the researches regarding the regulation of infections, asthma, and allergen immunotherapy by T-regulatory cells, has rapidly increased. T-lymphocytes is an oversimplification of complicated processes to explain asthma as Th-2 disease and recognize the importance of cytokines and chemokines to understand the airway inflammation.

4. Mast cell activation

Mast cell activation (MCA) plays an important role in the pathophysiology of asthma because of the ability to release host pleiotropic autacoid mediator cytokines, due to the response of activation by both immunoglobulin and non-immunological stimuli. Various agents can activate mast cell activation. If in lungs, allergens induce the IgE mediators and due to this chemical mediators are released and cause immediate hypersensitivity, while connecting with inflammatory cells which infiltrate the airway passage. Increased in the number of mast cell activation, inflamed airway smooths cells which are linked with hyperresponsiveness.

5. Epithelial cells

Bronchial epithelium protects the internal environment of the lung and maintains homeostasis but epithelial cell injury is a key role in driving airway remodeling. Epithelium of airway is another airway of lining cells which is involved in asthma. The creation of an inflammatory arbitrator and its activation, recruitment by the respiratory virus becomes the cause of epithelial inflammatory mediators and it may harm the epithelium cells. The repair of epithelium cells in asthma is somehow abnormal because of obstructive lesions that occur in the airway.

6. Dendritic cells

DCS (dendritic cells) are important for persuading TH-2 immunity for several allergens. Dendritic cells of lungs are heterogeneous and epithelium cells play a vital role to activate dendritic cells in response to inhaling the allergens. Dendritic cells are situated at the basolateral side of your lungs and continually scan or examine the environment to pathogens presence. Dendritic cells function as anti-presenting cells to detect allergens and migrate to regional lymph nodes to regulate cells.

Pathophysiologic inflammatory mediators of Asthma

Mediators are substances that initiate the inflammatory reactions and it also play a key role in the pathophysiology of asthma, these are:

1. Cytokines

Cytokines play a fundamental role in the persistence of inflammatory processes in asthma and they can induce pro-inflammatory effects. In asthma, the wall of the airway is infiltrated by T-lymphocytes, neutrophils, eosinophil, and mast cells rather than cytokines modifying the response of inflammatory cells in asthma to determine its severity. Th2 derived cytokines which may include:

i) Interleukin-5: IL-5 is 155 of aminoacids in human beings along with Th2 cytokines which is a part of the hematopoietic family and it is associated with allergic diseases with an increased number of airway tissues with induced of eosinophil is observed because inhalation IL-5 increase percentage of eosinophils. IL-5 is required for eosinophil differentiation and its survival.

ii)Interleukin-4: The interleukin-4 has compact folds just similar to cytokines. IL-4 is cytokines that innervate differentiation of T-cells helper. IL-4 is also involved in the pathogenesis of allergic responses and it may occur in asthma for stimulation of mucus-producing cells. IL-4 has a function to evaluate the numbers and Th2 cells are responsible to produce additional IL-4 in positive feedback. IL-4 cells are produced by inducing additional Th2 but it is not identified. Researchers suggest that basophil might be the effector cell which is related to a similar function of IL-4. 

iii) Interleukin-13: Interleukin-13 is a protein that is found in humans and encoded by the IL-13 gene. IL-13 is manufactured as a monomer which is activated by T-cells, stoma cells, and monocytes. IL-13 increases the amounts of allergy in asthmatic airways. IL-133 affects your immune cell which is almost similar to IL-4. IL-3 is involved in airway diseases and have anti-inflammatory properties.

2. Chemokines 

Chemokines are a family of cytokines which are secreted by cells and they are similar to cytokines in behavior and structure. Mass of chemokines is about 8-10 kilodaltons (KD) with four cysteine residues. It plays the role of inflammatory cells and found epithelial cells. Name of chemokines is derived from chemotaxis due to its induced ability. Chemokines are categorized into four subfamilies which are named as CXC, XX, CX3C, and XC and they interact with G-protein that is linked by transmembrane receptors called chemokine receptors.

5. Nitric oxide: 

Nitric Oxide (NO) is produced by the action of inducible or persuaded nitric oxide synthase in the airway epithelial cells. Nitric Oxide is usually a potent vasodilator, even though measurements of fractional exhaled nitric oxide can be useful for monitoring response to asthma.

6. Cysteinyl-leukotrienes:

Cysteinyl leukotrienes are energetic and potent bronchoconstrictor which is derived by mast cells. Cysteinyl leukotriene are mediators whose inhibition is associated with an enhancement in lung function and with symptoms of asthma. 

7. Immunoglobulin E

Immunoglobulin E (IgE) is antibody type which is found in mammals and is synthesized by plasma cells. It plays an essential role in the pathophysiology of asthma and manifests by various allergic diseases. IgE is responsible for the allergic reactions. The Mast Cells (MSc) have a lot of IgE receptors which are activated by interaction with antigens and also release the numbers of mediators to start the acute bronchospasm. IgE also releases the pro-inflammatory cytokines. The development of monoclonal antibodies to reduce the IgE is an effective treatment of asthma.

Pathophysiology of airway inflammation

In asthma, the airway inflammation is caused by various changes occur in your airway, and these changes are:

1. Airway Edema

Upper airway mucosal edema is caused by obstruction of airway after the extubation and due to any medical trauma leads to play a role in asthma. As the disease become more severe so the other factors are also involved to limit the airflow and it may include inflammation, mucus hypersecretion, structural changes (such as hypertrophy and hyperplasia).

 2. Bronchoconstriction 

Bronchoconstriction is the narrowing of your airways due to the attack of asthma. The dominant pathophysiological event in asthma is the narrowing of airways. In asthma, smooth muscles of bronchi constrict (bronchoconstriction) happen and narrow the airway due to exposure of allergens and irritants. In asthmatic attacks bronchoconstriction is an immediate symptom of triggering. An induce of allergen bronchoconstriction is due to IgE and also releasing of mediators from mast cells. While the exercise, irritants, cold air also lead to acute bronchoconstriction. The regulation mechanism of the airway response to these factors is less defined, but the intensity of the response present is related to underlying airway inflammation. 

3. Airway remodeling

Limitation of airflow might be partially reversible in a few cases of asthma and the structural changes happen in the airway permanently and it is present with progressive function loss which is not prevented by fully reversible. Modeling of the airway may involves an activation of many of the structural cells, with permanent changes in the airway that increase obstruction of the airway and these changes include with thickening of sub-basement membranes, hypertrophy, and hyperplasia of smooth muscles, blood vessels proliferation, and mucus glands.

4. Airway hyperresponsiveness

Airway hyperresponsiveness overemphasizes bronchoconstrictor response with a variety of stimuli, but features of asthma are not necessarily unique. The airway hyperresponsiveness is defined by contractile responses to challenges with methacholine correlates with the clinical severity of asthma. The influencing mechanism of airway hyperresponsiveness are multiple factors and it may include inflammation, dysfunctional neural regulation, and structural changes, while the inflammation is a major factor in determining the degree of airway hyperresponsiveness. 

What risk factors affect pathophysiology and pathogenesis of asthma?

There are several reasons or risk factors that affect asthma and a variety of respiratory problems. Asthma can occur with anyone, but it is less likely if there are no risk factors present. Let’s read how some risk factors increase the chance of asthma.

Genetics and Asthma

We all know that asthma has an inheritable component to its expression, but the involvement of genetics in the development of asthma remains an incomplete picture. While many genes have been found that they are correlated with asthma.

The involvement in clinical asthma is observed by linkages to certain characters of phenotypic, but it’s not necessarily the pathophysiologic disease process of asthma done by itself. The inflammatory mediators played a vital role in the pathophysiology of asthma, while the variation in genes determines the responses to therapy.

Gender and Asthma

Atopy and Asthma

Atopy asthma refers to a genetic disposition to develop eczema, allergic rhinitis, and asthma. Atopy leads to an increase in sensitivity to common allergens, especially those that are in the food and in the air. Mostly the children with atopic dermatitis may have chances to develop asthma.

Environmental Factors and Asthma

The air pollution such as cigarette smoke, mold, and noxious fumes from household cleaners, and paints can cause allergic reactions and also have chances to develop asthma.

The environmental factors (such as pollution, sulfur dioxide SO2, nitrogen oxide, cold temperatures, and changes in humidity) are all known to trigger asthma. Ozone is also the major destructive ingredient in smog and it may cause coughing, shortness of breath (SOB). Sulfur dioxide is another component of smog that can also irritate the airways and constricts the airway passages. Changes in weather also lead to pathophysiology of asthma in some people, cold air causes the congestion and production of mucus, while changes or increases in humidity also lead to difficulty in breathing.

Sign and symptoms of Asthma

The signs and symptoms of asthma are:

• Dyspnea-difficulty and shortness of breath
• Cough-mostly worsen at night time
• Wheezing-occurs with high-pitched whistling sound that is produced by turbulent airflow because of narrowing airways.
• Chest tightness-with squeezing and sharp exacerbation pain.
• Triggers with asthma also include exposure of allergens, exercises, and due to viral infections.
• Other triggering symptoms include or refer to strong emotions, extreme temperatures, lightheadedness, uses of accessory muscles, diminished breathing sounds, and use of tobacco.
• On the other hand, symptoms of asthma are nonspecific and it also includes new symptoms such as onset in older age.
• Many of the symptoms and signs of asthma are nonspecific and can be seen in other conditions such as onset in older age. It’s important to note the symptoms either they are episodic with long or short periods to find out a proper diagnosis.

You should know that the most effective treatment for asthma is short-term relief, long-term control, and nebulizers, even though you should always know about when you have an asthma attack and when to call your doctor to give emergency treatment. Your doctor makes a strategy and action plan to prevent asthma.

1. Rescue Inhalers (or Quick-Relief Inhalers)

The rescue inhalers are a type of medication that you breathe in. You may use them to ease the asthma symptoms. The short-term rescue inhalers help to relax the muscles that tighten around the airways and help to open them, so you can breathe easier.

These medications are:

i. Short-acting beta-agonists: These are the first choice for quick relief of asthma symptoms.

ii. Anticholinergics: Anticholinergic reduces mucus production and helps to open your airways. They take longer to work than short-acting beta-agonists.

iii. Oral corticosteroids: Oral medication of corticosteroids helps to lower the swelling in your airways.

iv. Combination quick-relief medicines: Combination of quick-relief medicines include both an anticholinergic and a short-acting beta-agonist. If patients can’t use an inhaler, you also might get them from a nebulizer (it is a machine that helps you breathe in medicine).

2. Long-term medications

These types of medications work over the long-term to treat the symptoms and prevent asthma attacks. Long-term medications decrease swelling and mucus production in the airway. They include:

i. Inhaled corticosteroids: Inhaled corticosteroids help to prevent swelling. They also help to reduce the mucus production in your lungs. Corticosteroids are the most effective long-term control medicines. Inhaled long-acting beta-agonists to open your airways by relaxing the smooth muscles around them. You’ll take this medication along with an inhaled corticosteroid.

ii. Combination inhaled medicines: Combination of long term medication corticosteroids and long-acting beta-agonists are effective to prevent asthma.

iii. Biologics: These target cells or proteins in your body to prevent inflammation of the airway and they can be shots or infusions you may get every few weeks. They are expensive and prescribed when no medications work.

iv. Leukotriene modifiers: Leukotriene modifiers are relaxing the smooth muscles around your airways and reducing swelling. You may take them as pills or liquids.

v. Cromolyn: This may prevent airways from swelling and inflammation. It’s a non-steroid medicine that comes in an inhaler.

vi. Theophylline: Theophylline relax your smooth muscles that constrict or narrow your airways. It comes as a tablet, capsule, solution, and syrup to take by mouth.

vii. Long-acting bronchodilators: You may use it with corticosteroids if you have ongoing symptoms of asthma. But remember, don’t use long-acting bronchodilators lonely as long-term treatment of asthma. 

viii. Oral corticosteroids: If not a single medication gives you benefits on your asthma attack and your attack is not under control, your doctor recommends you oral corticosteroids for a couple of weeks. This may come in pills or liquid form. 

3. Asthma Nebulizer

If patients get difficulty and have trouble using small inhalers, then doctors prescribe asthma nebulizers. This machine changes the medication of asthma from a liquid to a mist and it’s easier to get this and easily reach your lungs. Mouthpiece and mask are good options for infants, children, and older adults. 

Before you leave!

Not all asthma have annoying symptoms. Asthma is a chronic lung condition in which your airway gets inflamed and becomes narrow and makes it harder to breathe easily in a proper manner especially when you exhale and cause wheezing, cough, and chest pain. But the good news is that the majority of patients can treat asthma more easily. If asthma is taking over your life, you may just use inhalers for rescue and you should visit your doctor for a routine checkup to find out the solution to your problem and do not use any medication without prescriptions from your doctor.