A 28-year-old man comes to the clinic due to cough and shortness of breath. The patient has a history of intermittent asthma controlled with an as-needed albuterol inhaler. Over the last month, he has noticed increased severity and frequency of his symptoms. The patient occasionally wakes up at night with coughing spells and has had to use his albuterol inhaler several times per week due to shortness of breath. An inhaled corticosteroid is prescribed to achieve better symptom control. In addition to an anti-inflammatory effect, which of the following effects also directly occurs as a result of this therapy?

Question

A 28-year-old man comes to the clinic due to cough and shortness of breath.  The patient has a history of intermittent asthma controlled with an as-needed albuterol inhaler.  Over the last month, he has noticed increased severity and frequency of his symptoms.  The patient occasionally wakes up at night with coughing spells and has had to use his albuterol inhaler several times per week due to shortness of breath.  An inhaled corticosteroid is prescribed to achieve better symptom control.  In addition to an anti-inflammatory effect, which of the following effects also directly occurs as a result of this therapy?

Quizplus · Accepted Answer

Asthma is a complex disease involving both chronic inflammation and airway hyperreactivity. Inhaled corticosteroids (eg, fluticasone, budesonide) are a mainstay of asthma therapy. Corticosteroids reduce inflammation by inhibiting nuclear transcription of inflammatory genes (in part leading to downregulation of the enzyme phospholipase A2) to decrease the production of leukotrienes and other inflammatory mediators. Although corticosteroids have no direct effect on bronchodilation, these drugs provide an additional benefit in asthma by potentiating the bronchodilatory effect of beta-2 agonists (eg, albuterol). This is accomplished by stimulating the upregulation of beta-2 receptors in bronchial smooth muscle, increasing cellular responsiveness to adrenergic stimulus. This medication effect is similar to the permissive effect of endogenous cortisol on blood pressure, which involves upregulation of alpha-1 receptors and increased responsiveness of vascular smooth muscle cells to epinephrine. (Choice A) Corticosteroids increase, rather than decrease, the production of lung surfactants and may be used to help prevent infant respiratory distress syndrome in premature infants. (Choice B) Guaifenesin reduces the viscosity (ie, thickness) of respiratory tract mucus and is often used in the symptomatic management of viral upper respiratory tract infections. Decreased mucus viscosity is not a direct effect of corticosteroids. (Choice C) Theophylline provides benefit in asthma by stimulating bronchodilation via inhibition of phosphodiesterase-3 and may also create an anti-inflammatory effect via inhibition of phosphodiesterase-4. Corticosteroids may somewhat decrease phosphodiesterase activity but likely do not have a significant effect. (Choice D) Omalizumab is a monoclonal antibody that treats asthma by binding to free IgE to decrease IgE binding to surface receptors on mast cells and basophils. This inhibits the degranulation of inflammatory mediators. The anti-inflammatory effects of corticosteroids may also contribute to a decrease, rather than an increase, in surface-bound IgE. Educational objective: Corticosteroids (eg, fluticasone, budesonide) have multiple beneficial effects in the treatment of asthma. In addition to their anti-inflammatory effect, corticosteroids upregulate beta-2 receptors on bronchial smooth muscle to increase cellular responsiveness to adrenergic stimuli and potentiate the bronchodilatory response to inhaled beta-2 agonists (eg, albuterol). __________ References: Glucocorticosteroids increase beta 2-adrenergic receptor transcription in human lung. (http://www.ncbi.nlm.nih.gov/pubmed/7840227)

A 28-Year-Old Man Comes to the Clinic Due to Cough