Asthma is a chronic inflammatory disorder of the airways, characterized by intermittent chest symptoms (wheezing, tightness, cough, and dyspnea), reversible airways obstruction, and bronchial hyperresponsiveness. Airway obstruction can be triggered by for instance exposure to airborne allergens, cold air, or exercise. Progressive asthma often leads to irreversible airway obstruction. Asthma has many phenotypes, such as early-onset mild allergic asthma, later-onset asthma associated with obesity, and severe non-atopic asthma with frequent exacerbations. Asthma occurs usually in the first five years of life. Obesity is a risk factor for asthma (Dixon et al., 2010). Different, but often overlapping, pathophysiological mechanism are present in these subgroups. Accordingly, patients with asthma need individual diagnosis and treatment.
The inflammation is highly heterogeneous, but it is predominantly mediated by T helper 2 (Th2) response, including cytokines IL-4, IL-5, and IL-13. Other leukocytes (eosinophils, mast cells), platelets, and epithelial cells are involved in the disorder. Excessive generation of NO and reactive oxygen species ultimately results in bronchial epithelial injury and airway remodelling (Pitchford & Page, 2006; Comhair & Erzurum, 2009).
Asthma is commonly treated using β agonists, targeting β2 adrenoceptors on bronchial smooth muscle cells, epithelial cells, submucosal glands, vascular endothelial and smooth muscle cells, and leukocytes. Ephedrine activates β2ARs indirectly via noradrenaline.
Parasympathetic activity is increased in patients with asthma. Parasympathetic nervous system is almost exclusively cholinergic, using acetylcholine (ACh) as neurotransmitter, which activates muscarinic receptors (mAChRs). Muscarinic receptor antagonists are used for treatment in asthma and COPD.
Glucocorticosteroids and glucocorticoids, endogenously synthesized in the cortex of adrenal glands, are the most effective anti-inflammatory medication for many inflammatory diseases, including asthma. Glucocorticoid receptors are located in the cytoplasm, and after activation they are imported into the nucleus, affecting gene transcription.
Anti-IgE and antibodies against other targets such as interleukins are used for treatment of specific subgroups of asthma patients.
Leukotriene receptor antagonists (such as montelukast) are useful for long-term treatment of exercise-induced asthma and allergic rhinitis. Cysteinyl leukotrienes (cys-LTs) are potent smooth muscle constrictors, and they are produced from arachidonic acid in eosinophils, basophils, mast cells, macrophages, and myeloid dendritic cells.
Histamine H1 receptor antagonists are not effective for treatment of asthma, but in combination with other medications can be beneficial for allergic rhinitis and atopic dermatitis.
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Updated at: 2019-02-03
Created at: 2019-02-02
Written by: Vesa Oikonen