Severe asthma - challenges, and management

By Dr.Pavan Yadav, MBBS, MD, FCCP

Asthma is a chronic respiratory condition that affects the airways in the lungs, causing inflammation and constriction, leading to symptoms such as coughing, wheezing, shortness of breath, and chest tightness. While asthma can usually be well managed with appropriate medications and lifestyle modifications, some individuals may have more severe forms of asthma that are challenging to treat.

Severe asthma, also known as difficult-to-treat asthma or refractory asthma, is a subset of asthma that is characterized by persistent and severe symptoms despite optimized treatment. It is estimated that up to 10% of individuals with asthma have severe asthma, and these individuals often experience significant limitations in their daily activities and quality of life due to their asthma symptoms.

There are several factors that can contribute to the development of severe asthma. These may include:

1. Airway inflammation: In individuals with severe asthma, the airway inflammation may be more pronounced and difficult to control with standard anti-inflammatory medications, such as inhaled corticosteroids. This can lead to persistent symptoms and exacerbations despite regular use of these medications.
2. Airway hyperresponsiveness: Severe asthma may also be associated with increased airway hyperresponsiveness, which means that the airways are more sensitive to triggers, such as allergens, irritants, or exercise, leading to exaggerated bronchoconstriction and symptoms.
3. Comorbidities: Individuals with severe asthma may have other medical conditions, such as allergic rhinitis, chronic sinusitis, gastroesophageal reflux disease (GERD), or obesity, which can worsen asthma symptoms and make it more difficult to control.
4. Genetic factors: Genetic factors may also play a role in the development of severe asthma. Some individuals may have genetic predispositions that make them more susceptible to severe asthma or poor response to standard asthma medications.

• Diagnosis-

The diagnosis of severe asthma typically involves a comprehensive evaluation that includes a thorough medical history, physical examination, and objective testing to assess lung function and airway inflammation. Here are some common steps in the diagnostic process for severe asthma:

1. Medical history: The healthcare provider will take a detailed medical history, including information about the patient's symptoms, frequency and severity of asthma attacks, triggers, response to previous treatments, and family history of asthma or other respiratory conditions. This helps in identifying potential risk factors and understanding the patient's asthma history.
2. Physical examination: A physical examination is performed to assess respiratory symptoms, lung sounds, and other physical findings related to asthma. The healthcare provider may listen to the patient's lungs with a stethoscope, check for signs of respiratory distress, and assess for other potential underlying causes of respiratory symptoms.
3. Objective testing: Objective testing is essential for confirming the diagnosis of severe asthma. Several tests may be used, including:

• Spirometry: Spirometry is a common lung function test that measures the amount and speed of air exhaled from the lungs. It can help determine the severity of airflow limitation and assess the response to bronchodilators.
• Peak expiratory flow (PEF) monitoring: PEF monitoring involves using a handheld device called a peak flow meter to measure the maximum speed at which a person can blow air out of their lungs. It can help assess the severity of asthma and monitor changes in lung function over time.
• FeNO (Fractional exhaled Nitric Oxide) testing: FeNO testing measures the level of nitric oxide in the breath, which is a marker of airway inflammation. Elevated FeNO levels may indicate eosinophilic inflammation, which is often seen in asthma.
• Allergy testing: Allergy testing may be performed to identify specific allergens that trigger asthma symptoms, especially in cases of allergic asthma.
• Blood tests: Blood tests may be done to assess eosinophil levels, total IgE levels, and other markers of inflammation and immune response, which can help in identifying specific asthma phenotypes.

4. Other evaluations: In some cases, additional evaluations may be needed to rule out other conditions that could mimic or exacerbate asthma symptoms, such as vocal cord dysfunction, gastroesophageal reflux disease (GERD), or other respiratory conditions.

• Management-

Managing severe asthma requires a comprehensive approach that goes beyond standard asthma treatments. It involves careful evaluation and management of various contributing factors, addressing comorbidities, and tailoring treatment plans to the individual's specific needs. Treatment options for severe asthma may include:

1. High-dose inhaled corticosteroids: In individuals with severe asthma, higher doses of inhaled corticosteroids may be necessary to adequately control airway inflammation and reduce symptoms.
2. Long-acting beta-agonists (LABAs): LABAs are bronchodilators that are often used in combination with inhaled corticosteroids to provide additional bronchodilation and improve asthma control in individuals with severe asthma.
3. Systemic corticosteroids: In some cases, short courses of systemic corticosteroids, such as oral prednisone, may be needed to quickly control severe asthma exacerbations or persistent symptoms. However, long-term use of systemic corticosteroids is generally avoided due to their potential side effects.
4. Biologic therapies: Biologic therapies are a newer class of medications that target specific pathways involved in the immune response, and they have been shown to be effective in certain subtypes of severe asthma. These medications are typically administered by injection or infusion and may include options such as monoclonal antibodies targeting immunoglobulin E (IgE), interleukin-5 (IL-5), or interleukin-4/interleukin-13 (IL-4/IL-13).
5. Bronchial thermoplasty: Bronchial thermoplasty is a minimally invasive procedure that uses radiofrequency energy to reduce the smooth muscle thickness in the airways, which can help to reduce the frequency and severity of asthma symptoms in some individuals with severe asthma.
6. Comprehensive asthma education and self-management.

Asthma self-management typically includes the following components:

1. Asthma action plan: An asthma action plan is a personalized written plan that provides guidance on how to manage asthma symptoms and exacerbations. It typically includes instructions on medication use, symptom recognition, and steps to take when symptoms worsen, such as adjusting medication doses or seeking medical attention. A well-defined asthma action plan helps individuals with severe asthma to proactively manage their condition and take appropriate actions when needed.
2. Trigger avoidance: Identifying and avoiding triggers that can worsen asthma symptoms is crucial in managing severe asthma. Triggers can vary among individuals and may include allergens such as dust mites, pollen, pet dander, or mold, as well as irritants like smoke, strong odors, or air pollution. Educating individuals on how to reduce exposure to triggers in their environment can help minimize asthma exacerbations.
3. Proper inhaler technique: Correct inhaler technique is critical for ensuring that medications are delivered effectively to the airways. Many individuals with severe asthma may use multiple inhalers with different medications, and it is essential to educate them on the correct technique for each inhaler to ensure optimal medication delivery and asthma control.
4. Monitoring symptoms and peak flow: Regular monitoring of asthma symptoms and peak flow readings can help individuals with severe asthma track their asthma control and detect early signs of worsening. This can enable timely intervention, such as adjusting medications, to prevent severe exacerbations.
5. Regular follow-up visits: Regular follow-up visits with the healthcare provider are important for individuals with severe asthma to assess their asthma control, review their medications, monitor for side effects, and make necessary adjustments to the treatment plan based on the individual's response.
6. Psychological support: Managing severe asthma can be emotionally challenging, as it can significantly impact an individual's quality of life. Providing psychological support, such as counseling or therapy, can help individuals cope with the emotional burden of living with severe asthma and improve their overall well-being.

• Monoclonal antibodies-

Monoclonal antibodies have emerged as a promising treatment option for the management of severe asthma, which is often difficult to treat using conventional medications. Monoclonal antibodies are laboratory-engineered molecules that target specific proteins or cells involved in the immune response, and they have been developed to specifically target pathways that are known to play a role in asthma inflammation. Here is a detailed discussion about monoclonal antibodies in the management of severe asthma:

Mechanism of action: Monoclonal antibodies used in the management of severe asthma target specific proteins or cells that are involved in the immune response, thereby reducing inflammation and improving asthma control. For example, monoclonal antibodies such as omalizumab, mepolizumab, reslizumab, and benralizumab target proteins such as immunoglobulin E (IgE), interleukin-5 (IL-5), and interleukin-4 receptor alpha (IL-4Rα), respectively. These proteins play a key role in the inflammatory processes associated with asthma.

Clinical efficacy: Clinical trials have shown that monoclonal antibodies can be effective in reducing asthma exacerbations, improving lung function, and reducing the need for oral corticosteroids in patients with severe asthma. Omalizumab, for example, has been shown to reduce asthma exacerbations and improve asthma control in patients with allergic asthma by targeting IgE, which plays a role in triggering asthma symptoms in response to allergens. Mepolizumab, reslizumab, and benralizumab, which target IL-5 and IL-4Rα, respectively, have shown effectiveness in reducing eosinophilic inflammation and asthma exacerbations in patients with eosinophilic asthma, a subtype of severe asthma characterized by high levels of eosinophils, a type of white blood cell.

Administration and dosing: Monoclonal antibodies used in the management of severe asthma are typically administered via subcutaneous injections or intravenous infusions. The frequency and dosing of these medications may vary depending on the specific monoclonal antibody and the severity of asthma. Some monoclonal antibodies, such as omalizumab, are administered every 2-4 weeks, while others, such as mepolizumab and reslizumab, may be administered monthly. Benralizumab, on the other hand, maybe administered every 4-8 weeks, depending on the dosing regimen. The dosing schedule and route of administration are determined by the prescribing healthcare provider based on the individual patient's condition and response to treatment.

Safety profile: Overall, monoclonal antibodies used in the management of severe asthma have been shown to have a favorable safety profile. However, as with any medication, there are potential risks and side effects. Common side effects may include injection site reactions, headaches, and fatigue. Serious side effects are rare but may include hypersensitivity reactions, such as anaphylaxis, which can be life-threatening. It is important for healthcare providers to carefully assess each patient's individual risk factors and medical history before prescribing monoclonal antibodies, and to monitor patients closely during treatment for any signs of adverse reactions.

Footer Note

Dr. Pavan Yadav is a leading pulmonologist in Bangalore (Bengaluru), currently practicing at KIMS Hospital, Electronic City. He specializes in interventional pulmonology, lung transplantation, sleep disorders, and advanced respiratory care. With a patient-focused and preventive approach, Dr. Yadav is dedicated to improving lung health and respiratory wellness, especially for individuals living in urban environments. n.