Aetiology
Asthma is a heterogeneous disease, and some patients with asthma have individual triggers that can potentially exacerbate their condition. Respiratory viruses are important triggers of asthma exacerbations. Rhinovirus has received the greatest attention, but other viruses can trigger asthma as well. Viruses may work in a synergistic manner with allergens or air pollution to trigger bronchospasm.[4] There is specific evidence for exposure to particulate matter with diameter <2.5 micrometres (PM2.5) as a risk factor for acute asthma exacerbation in adults.[5]
Exacerbations occur in susceptible people usually after exposure to an environmental allergen (which may be occupational), an irritant, or an infection: though some people may present more acutely without apparent exposure to triggers.[1] Poor adherence with inhaled corticosteroids is also commonly implicated.[1]
In the case of occupational exposure to allergens, sensitisation can occur after several years and onset of symptoms could be long after the initial exposure. After sensitisation, the level of allergen exposure needed to trigger symptoms may be very low and resulting exacerbations increasingly severe, with persistent exposure associated with worse asthma outcomes (e.g., irreversible airflow limitation).[1]
Occupational asthma is diverse, but professions commonly affected include bakers; farmers; veterinarians; carpenters; people involved in manufacturing plastics, foams, and glues; workers in metal factories or refineries; and workers in the textile and cotton industries.[6] It is likely that each allergen acts through a different mechanism. However, the final stage in the inflammatory cascade that leads to an asthma exacerbation is probably identical for all allergens, and it is this step that causes increased cellular inflammation and enhanced bronchial responsiveness, resulting in greater airflow obstruction relative to baseline.[7]
Pathophysiology
The patterns of airway inflammation are extremely complex and are allergen-specific. Detection of an allergen initiates a Th-2-mediated immunoglobulin E response that triggers an inflammatory reaction that leads to airway inflammation, occlusion of small airways with mucus, and bronchial hyperreactivity. Together, these processes contribute to the significant airway obstruction characteristic of asthma exacerbations. Airway inflammation leads to swollen bronchial membranes and airway hyperreactivity leads to bronchospasm. Both processes lead to narrowed airways. In addition, mucus secretion leads to occluded airways and further contributes to obstruction of airflow. It is thought that the final step is common to all inflammatory mechanisms, with vasoactive prostaglandins, leukotrienes, histamine, and other cellular mediators having a role in pathogenesis.
Airway epithelial damage may occur as the result of the inciting event (such as infection), as well as from the ensuing inflammation.[7] Epithelial damage from the inciting trigger may lead to activation of and subsequent release of chemokines from the epithelium, which amplifies the inflammatory cascade. Some allergens cause a predominately eosinophilic response (allergic and occupational triggers). Interleukin (IL)-5 and IL-13 are important cytokines in the recruitment of eosinophils.[7] Other allergens activate a more neutrophilic response (viruses).[7]
Diffuse mucus plugging of the airways is caused by increased mucus secretion and mucus cell hyperplasia.[8][9] Increased oxygen free radical production can overwhelm host antioxidant defences and result in oxidation of lipids and proteins. Lipid peroxidation increases markedly in acute asthma and decreases with resolution of exacerbation.[7][10]
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