CH3txtInflammatory_diseases - MPET2008CH3-1 ASTHMA Asthma...

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MPET2008CH3 - 1 - ASTHMA Asthma is a disease of airways that is characterized by hyper-reactivity (increased responsiveness) of airways to a variety of stimuli. Essentially, it is a chronic relapsing allergic inflammatory disease with episodes of reversible airway obstruction . Clinically, it is characterized by episodes of dyspnoe (difficulty to breath) and wheezing. Exacerbations are interspersed with symptom free periods. Sometimes, however, this can result in a situation of persistent obstruction, known as status asthmaticus , which can be lethal. The prevalence (= number of cases in a population on a given moment) is 10-15% in children and 5 % in adults. Asthma is responsible for 1/3 of emergency admissions in children hospitals and in the USA the mortality is 0.3/100 000/yr. Both the mortality and the incidence (= the number of new cases in the population) are increasing. The reason for this is unknown, but various causes have been proposed. So, e.g. changes in housing (isolation, heated bedrooms), viral causes, air pollution and the spread of new chemicals, but also to a better hygiene and vaccination that would limit the contact with immunogens in young children, and result in a less matured immune system (“hygiene hypothesis”) . In any case, both genetic and environmental factors are involved in the pathogenesis. A variety of stimuli can trigger an exacerbation: v Exercise: rapid inhalation of cold, dry air v Infections v Environment, pollution: ozone, nitrogen dioxide and sulfur dioxide v Occupational hazards: dust, solvents, metals v Drugs: aspirin v Allergens v
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MPET2008CH3 - 2 - The central mechanism in asthma is a chronic inflammation resulting in hyper-reactive airways. During an attack, one distinguishes the early response (short, 15 minutes after the exposure) characterized by bronchospasm (= reduction of the diameter brought about by contraction of the smooth muscle) and a late response (4 to 6 hours after the exposure, lasting for several hours), which is essentially an inflammatory reaction. In this latter phase, one observes edema and secretions next to bronchospasm. The morphological disturbances in asthma were described starting from the necropsy material of patients who died from status asthmaticus. More recently, using bronchoscopical biopsy, one observed that similar phenomena are also present in non-fatal asthma. The most striking macroscopic observation is the obstruction of the airways by mucus plugs containing eosinophils, fibrin and detached epithelial cells. Microscopically one observes v thickening of the basal membrane v damage to the epithelium (detachment) v edema and infiltration of eosinophils, T-cells (and to a lesser degree neutrophils) in the submucosa v hypertrophy of smooth muscle cells in the bronchus wall v enlargement of submucosal glands The early response is caused predominantly by mast cell degranulation as a consequence of the triggering of their IgE receptors by the allergen. These granules contain cytokines and mediators (histamine, PGD2, LTC4)
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CH3txtInflammatory_diseases - MPET2008CH3-1 ASTHMA Asthma...

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