Pathophysiology of Asthma

Pathophysiology of Asthma

• Asthma is a chronic inflammatory disease characterized by activation of mast cells, infiltration of eosinophils, and T helper 2 (TH2) lymphocytes.
• Mast cell activation by allergens and physical stimuli releases bronchoconstrictor mediators, such as histamine, leukotriene D4, and prostaglandin D2, causing bronchoconstriction, microvascular leakage, and plasma exudation.
• Airflow obstruction in asthma is due to bronchoconstriction resulting from contraction of bronchial smooth muscle, inflammation of the bronchial wall, and increased secretion of mucous.
• Underlying inflammation of the airways contributes to airway hyperresponsiveness, airflow limitation, respiratory symptoms, and disease chronicity.
• Asthma attacks may be triggered by exposure to allergens, exercise, stress, and respiratory infections.

Treatment of Asthma

• The goals of asthma therapy are to decrease the intensity and frequency of asthma symptoms and the degree of airflow limitation.
• All patients need to have a “quick-relief” medication to treat acute asthma symptoms.
• Drug therapy for long-term control of asthma is designed to reverse and prevent airway inflammation.

Bronchodilators

• Sympathomimetic agents (epinephrine, ephedrine, isoproterenol, and β2-agonists) are used to dilate the bronchi, inhibit the release of bronchoconstricting mediators from mast cells, and stimulate adenylyl cyclase to increase the formation of intracellular cAMP.
• Non-selective sympathomimetics (epinephrine, ephedrine, and isoproterenol) are not selective for bronchial smooth muscle and can cause adverse effects such as tachycardia, arrhythmias, and skeletal muscle tremor.
• β2-selective agonists (albuterol and terbutaline) are used to treat acute and chronic asthma.

Muscarinic Antagonists

• Ipratropium bromide and tiotropium are used to control only a portion of bronchospasm produced by parasympathetic stimulation.

Anti-Inflammatory Agents

• Corticosteroids (beclomethasone, budesonide, fluticasone, mometasone, triamcinolone, prednisone, and methylprednisolone) are used to lower the production and release of inflammatory substances, reduce mucus and edema, and may be inhaled or taken orally, as well as IV.
• Corticosteroids have anti-inflammatory activity, lowering and inhibiting peripheral lymphocytes and macrophages, and blocking the release of arachidonic acid.

Status Asthmaticus

• Characterized by very severe and sustained attack of asthma that fails to respond to usual treatment.
• Management includes administration of oxygen, frequent administration of β-agonists, systemic corticosteroids, IV fluid to avoid dehydration, antibiotics if there is an infection, and combination medications.