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Asthma Pathophysiology - Asthma Functional Changes
Asthma Pathophysiology - Susceptibility to Asthma is set early in life, depending on Genetic Factors and Environmental Exposures. Asthma involves a complex interaction of Bronchial Inflammation, Bronchial Obstruction & Airflow Limitation, and Bronchial Hyperresponse, which may vary within and between Asthma patients...
This nhn Asthma Guide includes information about Asthma that is written primarily to help Asthma Patients better understand their condition and the range of Asthma treatment options that are currently available:
What is Asthma - Asthma Definition
Asthma Symptoms - Signs of Asthma
Asthma Stages - The 4 Stages of Asthma
Asthma Life Expectancy
Curing Asthma - Asthma Cures
4. Asthma Pathophysiology - Asthma Functional Changes
According to the US National Institutes of Health (NIH) Asthma Guidelines, our understanding of Asthma Pathophysiology and Pathogenesis has evolved dramatically over the past 25 years. A person's susceptibility to getting Asthma seems to be set early in life, and depends on the interaction between personal Genetic Factors and Environmental Exposures that occur at a crucial time in the development of the immune system.
We now understand that Asthma involves a complex interaction of 3 Major Components:
4.1. Bronchial Inflammation
4.2. Bronchial Obstruction & Airflow Limitation
4.3. Bronchial Hyperresponse
This interaction can vary considerably between patients, and even be variable within a specific patient at different points in time.
4.1. Bronchial Inflammation in Asthma
Bronchial Inflammation associated with Asthma can be either Acute or Chronic:
Acute Inflammation - is intermittent inflammation that usually occurs due to Bronchospasm and may be treated using Bronchodilators.
Chronic Inflammation - is persistent inflammation that is usually associated with Airway Remodeling
Airway Inflammation in Asthma invloves an interaction between a range of Inflammatory Mediators and multiple Cell Types within the airways, and is a consistent phenomenon within all the different Asthma Phenotypes:
Cells Types Involved In Airway Inflammation In AsthmaLymphocytes - these small white blood cells normally help defend the body against disease and have also been linked with allergic inflammation.
Mast Cells - activated Mucosal Mast Cells release bronchoconstrictor mediators, and Mast Cells can also release cytokines promoting inflammation.
Eosinophils - contain inflammatory enzymes, generate leukotrienes, are associated with pro-inflammatory cytokines, and increased Eosinophil numbers often correlate with greater asthma severity.
Neutrophils - are increased in the airways and in sputum during acute asthma exacerbations, in severe asthma patients, and in smokers.
Dendritic Cells - interact with allergens from the airways and then migrate to lymph nodes to interact with regulatory cells.
Macrophages - are activated by allergens to release inflammatory mediators and cytokines that amplify the inflammatory response.
Airway Smooth Muscle Cells - can undergo proliferation, activation, contraction, and hypertrophy, causing airway dysfunction.
Airway Epithelial Cells - inflammatory mediators, inflammatory cell activation, and infection by respiratory viruses can cause epithelial cells to produce more inflammatory mediators.
Inflammatory Mediators Involved In AsthmaChemokines - mainly in airway epithelial cells, are important in recruitment of inflammatory cells into the airways.
Cytokines - alter the inflammatory response and probably determine the severity of Asthma Symptoms.
Cysteinyl Leukotrienes - mainly from mast cells, are powerful bronchoconstrictors and can contribute to inflammation by recruiting neutrophils.
Nitric Oxide - is a potent vasodilator produced in airway epithelial cells and is associated with inflammation in Asthma.
Immunoglobulin E (IgE) - is the antibody responsible for activation of allergic reactions.
4.2. Bronchial Obstruction & Airflow Limitation in Asthma
Recurrent Airflow Limitation that is associated with Asthma may occur due to any one of 4 Types Of Airway Change:
Bronchoconstriction - is airway narrowing, due to bronchial muscle contraction, that restricts airflow. In Acute Asthma Exacerbations this may be rapidly triggered following Bronchial Inflammation in response to allergens or irritants.
Bronchial Edema - is airway swelling due to excess water accumulation, and this may occur as the disease progresses.
Airway Remodeling - is permanent change to the structural cells of the airways. According to the NIH, "These structural changes can include thickening of the sub-basement membrane, subepithelial fibrosis, airway smooth muscle hypertrophy and hyperplasia, blood vessel proliferation and dilation, and mucous gland hyperplasia and hypersecretion."
4.3. Bronchial Hyperresponse in Asthma
Bronchial Hyperresponse is exaggerated Bronchoconstriction which may occur in response to any of wide range of stimuli. Airway Inflammation appears to be the major factor in determining the degree of hyperesponsiveness, and treatments that reduce inflammation are therefore effective in controlling this issue in many cases. However, Dysfunctional Neuroregulation and Airway Remodeling may also be involved in Bronchial Hyperresponse.
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