Treatment of Severe Asthma and Role of Biologics

Chronic lung disorders are serious health concerns. One of the most widely encountered chronic lung disorders is asthma. Around 235 million people all over the over are affected by asthma. Patients experience severe respiratory distress because of the shortage of oxygen in the tissues. Over the years, different medications have been used for the treatment of asthma, but the long-term efficiency of these drugs is questionable. Nowadays, different types of drugs known as biologics are being introduced, which are very effective in the treatment of severe asthma.

What Is Asthma?

Asthma is a chronic inflammatory lung disorder. This is characterized by obstruction or narrowing of the airway passage due to the secretion of excessive mucosa. Around 15 to 20 percent of people in developing countries and 2 to 4 percent of people in developed countries are affected by this condition. In almost 66 percent of cases, asthma is diagnosed before the age of 18 years.

The exact cause of asthma is not known, but it is associated with various risk factors. These are:

• Family history and genetic factors.

• Environmental substances which may cause allergy like dust and pollen.

• Respiratory tract infections are caused by viruses.

• Habits like smoking.

• Obesity.

• Stress, anxiety, and mental trauma.

• Use of drugs.

Due to the action of these factors, IgE antibody is released by the plasma cells (a type of immune cell). These IgE then binds to the basophils and mast cells. As a result, chemical mediators like histamine, prostaglandins, and cytokines are released. These substances cause the contraction of smooth muscles and constrictions of the airway. Gradually accumulation of inflammatory cells in the lungs takes place. This causes bronchoconstriction, inflammation, and the production of mucus. Asthma can be of various types based on nature, causative factors, and duration. These are:

• Allergic and non-allergic types of asthma according to the presence of allergens as the causative factor.

• Intermittent or persistent asthma according to the presence of symptoms.

• Occupational asthma, exercise-induced asthma, and asthma-COPD (chronic obstructive pulmonary disease) overlap syndrome (ACOS) are several types of asthma based on the etiology.

Severe asthma can be subdivided into two types. These are:

• Type 2-High Expression: This is caused by both allergic and non-allergic conditions. This process is mediated by the action of interleukin 4,5 and 13. Eosinophils recruited by this inflammatory process damage the bronchial epithelium and cause bronchial obstruction.

• Type 2-Low Asthma: This is the less severe type and is often called stable asthma or paucigranulocytic asthma. This is caused by the activation of T-helper cells with a high level of interleukin-17A. The neutrophil count in such cases is high.

What Are Biologics?

Biologics are biological molecules that are used for therapeutic properties. These substances are derived from various biological molecules like proteins, enzymes, hormones, and antibodies. There are severer types of biologics. These are:

• Tumor Necrosis Factor (TNF) Inhibitors: Tumor necrosis factor alpha is a type of cytokine that is produced during systemic inflammation. These are synthesized by macrophages and T lymphocytes. The primary function of these molecules is to regulate immune cells. This type of biologics inhibits the function and the formation of TNF. Such biologics are used in conditions like psoriasis, psoriatic arthritis, Crohn's disease, and rheumatic arthritis. Etanercept, Infliximab, and Adalimumab are examples of a few TNF inhibitors biologics.

• Interleukin (IL) Inhibitors: Interleukins are produced by macrophages, monocytes, and dendritic cells. Substances like IL-1, IL-6, and IL-12 play a vital role inflammatory process. Certain biologics bind to the receptor cities and disrupt the functioning of these molecules. Anakinra and Tocilizumab belong to this group of drugs.

• T-cell Inhibitors: T lymphocytes are one of the major components of the inflammatory process. These T-cells are activated via several signaling molecules. Biologics can inhibit such signaling pathways and block the T-cell receptor site. Thus the inflammatory pathways are blocked.

• B-cells Inhibitors: B- lymphocytes play an important role in the inflammatory process. The role of the B cell includes the destruction of the B cells in auto-immune conditions and in malignant disorders. Rituximab is a B- cell inhibitor agent used for this purpose.

What Are the Different Biologics Use in the Treatment Of Asthma?

Different biologics are used in the treatment of asthma. These are:

1. IgE Inhibitor: Omalizumab is used as an anti-immunoglobulin E molecule. It is a humanized monoclonal antibody that is first used in the treatment of asthma. As discussed, IgE is produced by the B-cells and binds with basophil and T-lymphocytes. Omalizumab binds to the IgE receptor site and reduces the inflammatory response. Also, the production of interferons (a natural substance for the immunity of the body) is reduced by the action of this drug due to viral infection. This drug is used mainly used for the treatment of allergic asthma. It can be given to patients older than 6 years subcutaneously (under the skin) every 2 to 4 weeks.

2. Anti- Interleukin 5: The function of such interleukins is to help in the growth of the B cells, activation of eosinophils, and immunoglobulin secretions. Several drugs inhibit the secretion of interleukins and prevent eosinophilic airway inflammation. These are:

• Benralizumab: This drug binds with the receptor site of eosinophils and basophils and prevents the binding of the interleukin 5. This is very useful for patients suffering from eosinophilic asthma. This can prevent acute exacerbation of asthma and can improve lung function. This drug can be given to patients older than 12 years.

• Mepolizumab: This drug binds to the IL5 ligand (a molecule that helps in the binding process) and prevents its binding to the receptor site. This drug is used for patients aged more than 12 years of age. It is administered subcutaneously every 4 weeks at 100 mg per dose. A zoster vaccine should be given 4 weeks before the start of this therapy in patients who are older than 50 years.

• Reslizumab: The mechanism of action of this drug is similar to Mepolizumab. This drug can reduce the eosinophil count and prevent acute exacerbation of asthma. This is advised as an add-on drug for patients older than 18 years.

3. Interleukin-4/Interleukin-13 Inhibitor: These cytokines are produced by the T-helper cells, mast cells, and basophils. These cytokines are mainly seen in allergic reactions and are responsible for the activation of macrophages. Also, the production of IgE maintained these cytokines. Dupilumab acts either on Interleukin-4 or interleukin-13. They mainly bind to the receptor side and reduce its action. This can reduce the eosinophil count and can reduce dependency on oral corticosteroids.

What Are the Side Effects?

The side effects include:

• Pain and discomfort at the injection site.

• Itching and burning sensations.

• Swelling of the face, mouth, and tongue.

• Difficulty in breathing.

• Fall of blood pressure.

Conclusion:

Biologics are derived from biological molecules. These substances are used to control inflammation. Regulation of inflammatory substances can reduce the symptoms of asthma. These can also increase the efficiency of lung function.