Asthma types
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Understanding Asthma Types: Phenotypes and Endotypes
Asthma is a complex and heterogeneous disease characterized by chronic airway inflammation and variable respiratory symptoms. Recent research has shifted the understanding of asthma from a single disease entity to a collection of distinct diseases with unique mechanistic pathways (endotypes) and clinical presentations (phenotypes) .
Asthma Phenotypes: Clinical Presentations
Type 2-High Asthma
Type 2-high asthma is characterized by the presence of type 2 cytokines such as IL-4, IL-5, and IL-13, which promote eosinophilia, mucus overproduction, bronchial hyperresponsiveness (BHR), and IgE production . This phenotype is often associated with allergic reactions and is responsive to corticosteroids and biologic therapies targeting type 2 cytokines . Common clinical features include eosinophilic inflammation and a higher likelihood of comorbid conditions like allergic rhinitis and atopic dermatitis.
Type 2-Low Asthma
Type 2-low asthma, on the other hand, is less understood and is characterized by the absence of type 2 cytokine signatures. This phenotype is often associated with neutrophilic inflammation, obesity, and a poor response to corticosteroids . It includes subtypes such as neutrophilic asthma, which can be triggered by infections, cigarette smoke, and pollution, and is often driven by IL-17 produced by Th17 cells .
Asthma Endotypes: Molecular Mechanisms
Type 2 Inflammation
Type 2 inflammation involves both innate and adaptive immune responses, including the activation of T-helper type 2 (Th2) cells and type 2 innate lymphoid cells (ILC2s) . These cells produce cytokines like IL-4, IL-5, and IL-13, which lead to the recruitment of eosinophils and the production of IgE, contributing to airway inflammation and hyperresponsiveness . This endotype is the target of several biologic therapies, such as anti-IL-5 and anti-IL-4/IL-13 treatments, which have shown efficacy in managing severe asthma .
Non-Type 2 Inflammation
Non-type 2 inflammation encompasses a variety of mechanisms that do not involve the classic type 2 cytokines. This includes neutrophilic inflammation driven by Th17 cells and type 3 ILCs, which produce IL-17 and other pro-inflammatory cytokines . This endotype is often associated with environmental triggers like pollutants and infections and is less responsive to conventional asthma therapies .
Implications for Treatment
Understanding the distinct phenotypes and endotypes of asthma is crucial for personalized treatment approaches. For instance, patients with type 2-high asthma may benefit from biologic therapies targeting specific cytokines, while those with type 2-low asthma may require alternative strategies focusing on reducing neutrophilic inflammation or addressing comorbid conditions like obesity . The identification of biomarkers such as fractional exhaled nitric oxide (FeNO), serum IgE, and blood eosinophils can aid in diagnosing and monitoring the response to these targeted treatments.
Conclusion
Asthma is a multifaceted disease with diverse phenotypes and endotypes, each requiring tailored therapeutic approaches. Advances in understanding the molecular mechanisms underlying these different types of asthma have paved the way for more effective and personalized treatments, improving outcomes for patients with this chronic condition.
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