A 32-year-old woman is brought to the emergency department due to severe shortness of breath. She has no chest pain. The patient does not use tobacco. Temperature is 36.7 C (98 F), blood pressure is 132/81 mm Hg, pulse is 102/min, and respirations are 30/min. During physical examination, her condition deteriorates and she is emergently intubated due to acute respiratory failure. Shortly after intubation, she goes into cardiac arrest and dies despite resuscitation efforts. Review of the patient's medical records shows that she had been prescribed multiple medications but had a history of noncompliance. Autopsy shows hyperinflated lungs, airway mucus plugging, and cellular infiltration of the bronchial wall. Long-term use of which of the following drugs would have best prevented the cellular reaction in this patient's airways?

Question

A 32-year-old woman is brought to the emergency department due to severe shortness of breath.  She has no chest pain.  The patient does not use tobacco.  Temperature is 36.7 C (98 F), blood pressure is 132/81 mm Hg, pulse is 102/min, and respirations are 30/min.  During physical examination, her condition deteriorates and she is emergently intubated due to acute respiratory failure.  Shortly after intubation, she goes into cardiac arrest and dies despite resuscitation efforts.  Review of the patient's medical records shows that she had been prescribed multiple medications but had a history of noncompliance.  Autopsy shows hyperinflated lungs, airway mucus plugging, and cellular infiltration of the bronchial wall.  Long-term use of which of the following drugs would have best prevented the cellular reaction in this patient's airways?

Quizplus · Accepted Answer

This patient's autopsy findings of lung hyperinflation and bronchial inflammation are suggestive of uncontrolled asthma, a disease characterized by chronic airway inflammation, airway hyperresponsiveness, and intermittent bronchoconstriction. Chronic inflammation, composed mainly of eosinophils, helper T cells, and mast cells, causes airway remodeling (ie, bronchial wall thickening, increased smooth muscle), which further worsens airway obstruction and asthma symptoms. Corticosteroids inhibit the production of inflammatory mediators (eg, cytokines, prostaglandins, leukotrienes), reduce leukocyte extravasation into the respiratory epithelium, and induce apoptosis of inflammatory cells. In addition, corticosteroids decrease smooth muscle proliferation and mucus production by goblet cells. Systemic corticosteroids (eg, oral prednisone) are used in short courses to treat acute asthma exacerbations, whereas inhaled corticosteroids (eg, fluticasone) reduce the frequency and severity of exacerbations and are used for long-term asthma control in patients with persistent symptoms. Suppression of airway inflammation is evident within hours of administration but reaches maximal effect after several months of inhaled therapy. Nonadherence to long-term therapy can increase the risk of life-threatening asthma exacerbation. (Choices A and C) Albuterol is a selective beta-2 adrenergic agonist that induces bronchodilation. Acetylcholine released through vagal stimulation mediates bronchoconstriction via muscarinic receptors on bronchial smooth muscle cells; ipratropium is a muscarinic antagonist that promotes bronchodilation and reduced mucus production. Neither of these agents has anti-inflammatory properties, and although short-acting beta agonists are widely used to provide rapid relief of symptoms during an exacerbation, they do not prevent inflammation-induced airway remodeling or alter the chronic disease course. (Choice D) Magnesium sulfate inhibits calcium influx into airway smooth muscle and promotes bronchodilation when given intravenously during an acute asthma flare-up. Magnesium also reduces inflammation by stabilizing T cells and inhibiting mast cell degranulation; however, it is less effective than corticosteroids. (Choice E) Leukotrienes are potent inducers of airway bronchoconstriction and inflammation. Leukotriene inhibitors (eg, montelukast) are useful for long-term control in some patients with asthma. However, they possess less efficacy and have fewer anti-inflammatory properties than inhaled glucocorticoids. (Choice F) Theophylline, a phosphodiesterase inhibitor, results in increased intracellular cyclic AMP, which contributes to its role as a bronchodilator. Theophylline also has anti-inflammatory effects, although they are far less potent than glucocorticoids. Educational objective: Asthma is characterized by chronic airway inflammation, which leads to airway remodeling, airway hyperresponsiveness, and bronchoconstriction. Corticosteroids reduce airway inflammation and are used for both chronic asthma management (inhaled administration) and acute exacerbations (systemic administration).

A 32-Year-Old Woman Is Brought to the Emergency Department Due