(anonymous)

[Virtual Presenter] In severe asthma, patients often require high doses of inhaled corticosteroids combined with other medications like long-acting beta agonists or systemic corticosteroids to control their symptoms. Patients who experience uncontrolled symptoms despite optimal treatment may also be classified as having severe asthma. To make an accurate diagnosis, several factors must be excluded from consideration, including non-adherence to treatment, improper use of inhalers, continued exposure to allergens, occupational hazards, smoking, and untreated health conditions. Once these factors have been ruled out, the focus shifts to identifying characteristic symptoms of uncontrolled asthma, such as frequent daytime symptoms, nighttime awakenings, repeated episodes of worsening symptoms, persistent airflow limitations, or hospitalizations. A thorough evaluation is necessary to distinguish between difficult-to-treat asthma and truly severe asthma..

[Audio] Severe asthma has a significant impact on individuals worldwide. Approximately 3-8% of people with asthma experience severe forms of the condition. This may seem like a relatively small percentage, but severe asthma accounts for a disproportionately large share of healthcare costs, hospitalizations, and asthma-related deaths. In fact, patients with severe asthma often experience accelerated lung function decline, leading to more frequent exacerbations, persistent symptoms, and significantly impaired quality of life. Furthermore, the use of chronic oral corticosteroids can have serious side effects, including diabetes, hypertension, osteoporosis, cataracts, adrenal suppression, and increased infection risk. Additionally, the socioeconomic burden of severe asthma extends beyond healthcare costs, encompassing absenteeism, disability, and psychological distress. Overall, severe asthma poses a substantial challenge for individuals, families, as well as healthcare systems around the world..

[Audio] The role of risk factors and comorbidities in severe asthma cannot be overstated. Several environmental exposures and host susceptibility factors contribute to its development. Tobacco smoke exposure, air pollution, occupational irritants, and viral respiratory infections are among those that increase the risk of developing severe asthma. Obesity is a significant contributor to systemic inflammation and reduced corticosteroid responsiveness, making it an essential consideration. Smoking also affects airway neutrophilia and steroid resistance. Comorbidities such as chronic rhinosinusitis, nasal polyposis, GERD, obstructive sleep apnea, anxiety, depression, and fungal sensitization are commonly associated with severe asthma. Effective management of these conditions is necessary for effective treatment of severe asthma..

[Audio] The clinical phenotypes of severe asthma encompass various subtypes, each with distinct characteristics. Early-onset allergic asthma typically presents with elevated levels of immunoglobulin E and an atopic background, which can lead to more predictable responses to treatment. In contrast, late-onset eosinophilic asthma is often linked to nasal polyposis, a condition characterized by the growth of polyps within the nasal passages. This subtype may exhibit different inflammatory patterns and biomarker profiles compared to other forms of asthma. Furthermore, obese female-predominant asthma tends to manifest with frequent exacerbations, particularly in women who are overweight or obese. Additionally, steroid-dependent asthma is marked by fixed airflow limitation resulting from airway remodeling, leading to a more challenging therapeutic landscape. Notably, these phenotypes vary significantly in terms of their inflammatory patterns, biomarker profiles, response to therapy, and long-term outcomes..

[Audio] Molecular Endotypes and Immunopathology describes how severe asthma is classified based on its underlying molecular mechanisms. Severe asthma is divided into two distinct types at the molecular level: Type 2 high and non-Type 2 low inflammation. Type 2 high asthma is characterized by specific markers such as eosinophilic inflammation, elevated blood eosinophils, increased fractional exhaled nitric oxide, and cytokine activity involving IL-4, IL-5, and IL-13. This type of asthma tends to respond well to corticosteroid treatments and targeted biologic therapies. Non-Type 2 low inflammation involves different molecular pathways, including neutrophilic inflammation, Th1/Th17 pathways, innate immune activation, and microbial dysbiosis. Non-Type 2 asthma is typically resistant to corticosteroid treatment and remains an area of ongoing research. Understanding these molecular differences can help guide treatment decisions and improve patient outcomes..

[Audio] The airway epithelial cells are responsible for initiating the immune response when they come into contact with allergens, viruses, and pollutants. They release specific cytokines that trigger an inflammatory response. This leads to the activation of various immune cells, including dendritic cells and type 2 helper T cells. The result is eosinophilic inflammation, which involves the production of IgE antibodies. Chronic inflammation causes irreversible changes to the airways, resulting in subepithelial fibrosis, smooth muscle hypertrophy, goblet cell hyperplasia, and excessive mucus production. Furthermore, angiogenesis occurs, contributing to persistent airflow limitation, airway hyperresponsiveness, and reduced effectiveness of bronchodilators. These structural changes have a profound impact on the patient's quality of life..

[Audio] The use of biomarkers in guiding precision medicine has been shown to be highly effective in treating severe asthma. Blood eosinophil counts are key indicators of this condition. The levels of FeNO and total serum IgE also serve as critical markers. Sputum eosinophils provide further evidence of the presence of severe asthma. These biomarkers help predict the likelihood of responding well to corticosteroid and biologic therapies. In managing severe asthma, these biomarkers follow established guidelines such as those outlined by the Global Initiative for Respiratory Disease (GINA). The pharmacological treatments used to manage severe asthma include high-dose inhaled corticosteroids (ICS) combined with long-acting beta agonists (LABAs), adding long-acting muscarinic antagonists (LAMAs) to triple therapy, and using systemic corticosteroids for acute exacerbations. Biologic therapies have significantly reduced the frequency of exacerbations, decreased the need for oral corticosteroids, and improved lung function and overall quality of life. Further research is needed to target specific inflammatory pathways that contribute to airway remodeling..