A 10-year-old boy with a history of mild, persistent asthma is brought to the office for follow-up. His asthma symptoms are controlled with an inhaled beta-agonist and inhaled glucocorticoid therapy. There is no family history of asthma, but both his parents and older brother have short stature. The patient's mother is concerned about the use of glucocorticoids because she read on the Internet that they cause growth retardation. The patient's glucocorticoid medication is stopped, and he is started on a trial of inhaled cromolyn. Which of the following is the most likely site of action of this new medication?

Question

A 10-year-old boy with a history of mild, persistent asthma is brought to the office for follow-up.  His asthma symptoms are controlled with an inhaled beta-agonist and inhaled glucocorticoid therapy.  There is no family history of asthma, but both his parents and older brother have short stature.  The patient's mother is concerned about the use of glucocorticoids because she read on the Internet that they cause growth retardation.  The patient's glucocorticoid medication is stopped, and he is started on a trial of inhaled cromolyn.  Which of the following is the most likely site of action of this new medication?

Quizplus · Accepted Answer

11ec160b_3c5c_ab6b_9249_3f12acee8333_MD0001_00 Acute bronchial constriction during an asthma exacerbation begins with mast cell activation secondary to allergen interaction with IgE antibodies or nonimmune triggers (eg, exercise, cold exposure, chemical irritants). This results in the release of chemical mediators that cause immediate bronchial constriction, bronchial wall edema, and increased mucus production (early phase reaction). These mediators recruit additional inflammatory cells (eg, eosinophils, basophils, neutrophils, T lymphocytes) that lead to bronchial obstruction, which occurs several hours after the triggering event (late phase reaction). Cromolyn and nedocromil inhibit mast cell degranulation and prevent release of preformed chemical mediators. These medications do not influence bronchial constriction directly; therefore, they are typically used to prevent acute attacks, rather than to treat acute exacerbations. Even though these drugs are less efficacious than inhaled glucocorticoids, they are very effective prophylactic agents for patients with seasonal symptoms, aspirin hypersensitivity, and exercise-induced asthma. (Choice A) The anti-IgE antibody, omalizumab, inhibits IgE binding to mast cells, preventing mast cell degranulation. Omalizumab is used in some patients with severe, persistent asthma to lower IgE levels and reduce allergen-induced bronchial constriction. (Choice B) Cleavage of membrane phospholipids by the enzyme phospholipase A2 leads to the formation of arachidonic acid, which is in turn converted into prostaglandins and leukotrienes. By inhibiting phospholipase A2 synthesis, glucocorticoids inhibit the release of these downstream mediators, decreasing airway hyperresponsiveness and inflammation. (Choices C and D) Zileuton is a selective inhibitor of the lipoxygenase pathway that leads to decreased formation of leukotrienes. Zafirlukast and montelukast are leukotriene receptor antagonists. These agents are typically used for chronic asthma prophylaxis. (Choice F) Antihistamines are used to prevent and blunt an acute allergic response (as seen in allergic rhinitis) but have not been shown to improve bronchoconstriction in asthma. Educational objective: Cromolyn and nedocromil are mast cell-stabilizing agents that inhibit mast cell degranulation independent of the triggering stimulus. They are less effective than inhaled glucocorticoids and are considered second-line treatments for allergic rhinitis and bronchial asthma. __________ References: The effects of anti-asthma drugs on mediator release from cultured human mast cells. (http://www.ncbi.nlm.nih.gov/pubmed/9824389) Mast-cell stabilising agents to prevent exercise-induced bronchoconstriction. (http://www.ncbi.nlm.nih.gov/pubmed/14583951)

A 10-Year-Old Boy with a History of Mild, Persistent Asthma