How does asthma work
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Understanding How Asthma Works
Chronic Inflammation in Asthma
Asthma is a chronic inflammatory disease of the airways, characterized by the presence of activated mast cells, eosinophils, and T-helper 2 lymphocytes. This inflammation leads to increased airway responsiveness to various triggers such as exercise, allergens, and pollutants, resulting in symptoms like wheezing, coughing, shortness of breath, and chest tightness . The inflammation is driven by a complex interplay of multiple inflammatory mediators, including cytokines, chemokines, and growth factors, which are produced by both immune and structural cells in the airways .
Role of Eosinophils and Other Inflammatory Cells
Eosinophils play a significant role in the pathology of asthma by releasing toxic substances and pro-inflammatory mediators. The regulation of eosinophil production and function is controlled by cytokines such as IL-5, GM-CSF, and IL-3, which also inhibit eosinophil apoptosis, thereby prolonging their survival in the airways . Other key inflammatory cells involved include mast cells, dendritic cells, and various types of T-helper cells, which contribute to the chronic allergic inflammatory response .
Airway Hyper-Responsiveness (AHR)
A defining feature of asthma is airway hyper-responsiveness (AHR), which is the increased sensitivity and contraction of airway smooth muscle in response to stimuli. This leads to episodic and reversible airway narrowing, causing clinical symptoms such as cough, wheezing, and shortness of breath . G-protein-coupled receptors (GPCRs) play a central role in mediating these responses, and their regulation is crucial for controlling ASM tone and lung inflammation.
Structural Changes and Airway Remodeling
Chronic inflammation in asthma can lead to structural changes in the airways, known as airway remodeling. This includes epithelial cell apoptosis, airway smooth muscle cell proliferation, and fibroblast activation, which contribute to the clinical manifestations of the disease . These changes are driven by the interaction of various cell types within the airway wall and are exacerbated by environmental exposures such as allergens and pollutants.
Molecular Mechanisms and Corticosteroid Action
The molecular mechanisms underlying asthma involve the activation of pro-inflammatory transcription factors like NF-κB and AP-1, which increase the expression of inflammatory genes. Corticosteroids, the most effective treatment for asthma, work by reversing histone acetylation of these activated genes, thereby suppressing inflammation. This suppression helps control and prevent asthma symptoms in most patients .
Role of Epithelial-Derived Cytokines
Recent discoveries have highlighted the importance of epithelial-derived cytokines such as IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) in asthma. These cytokines, known as epithelial "alarmins," activate and potentiate the immune response, contributing to the chronic inflammation seen in asthma. Understanding their role may lead to the development of novel therapeutics targeting these pathways.
Conclusion
Asthma is a complex and multifaceted disease involving chronic inflammation, airway hyper-responsiveness, and structural remodeling. The interplay of various inflammatory cells and mediators drives the disease process, and treatments like corticosteroids are effective in controlling these mechanisms. Ongoing research into the molecular and cellular pathways involved in asthma holds promise for developing more targeted and effective therapies in the future.
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