A 42-year-old woman is evaluated due to frequent episodes of shortness of breath, chest tightness, and cough. The patient has been hospitalized on several occasions because of these symptoms and recently required mechanical ventilation due to respiratory failure. She takes multiple inhaled and systemic medications. The patient does not use tobacco, alcohol, or illicit drugs. Physical examination reveals scattered expiratory wheezes in both lungs. Peak expiratory flow rate is decreased from baseline. The treatment regimen is expanded to include a monoclonal antibody that binds circulating IgE, with the resulting complexes being subsequently cleared by reticuloendothelial cells. This medication is most likely to help this patient through which of the following mechanisms?

Question

A 42-year-old woman is evaluated due to frequent episodes of shortness of breath, chest tightness, and cough.  The patient has been hospitalized on several occasions because of these symptoms and recently required mechanical ventilation due to respiratory failure.  She takes multiple inhaled and systemic medications.  The patient does not use tobacco, alcohol, or illicit drugs.  Physical examination reveals scattered expiratory wheezes in both lungs.  Peak expiratory flow rate is decreased from baseline.  The treatment regimen is expanded to include a monoclonal antibody that binds circulating IgE, with the resulting complexes being subsequently cleared by reticuloendothelial cells.  This medication is most likely to help this patient through which of the following mechanisms?

Quizplus · Accepted Answer

11ec160b_3c5d_bcdd_9249_118b116a90e1_MD0001_00 This patient's frequent episodes of shortness of breath, chest tightness, and cough complicated by respiratory failure requiring hospitalization is consistent with asthma. The mainstays of medication therapy for asthma include an as-needed short-acting beta agonist (eg, albuterol), an inhaled corticosteroid (eg, mometasone), and a long-acting beta agonist (eg, salmeterol). For patients whose symptoms remain uncontrolled after such therapy is optimized, the addition of an IgE-binding monoclonal antibody (eg, omalizumab) may be beneficial. Many patients with asthma have high levels of circulating IgE antibodies generated against environmental antigens (eg, dust mites, animal dander). Omalizumab binds to the IgE antibody heavy chain and blocks the binding of IgE to the IgE receptors on mast cells. By preventing this binding, omalizumab inhibits proinflammatory substance release (including histamine and leukotrienes) by mast cells, markedly reducing airway inflammation. (Choice A) Decreasing airway collagen deposition may help slow the progression of idiopathic pulmonary fibrosis (IPF). Certain tyrosine kinase inhibitors (eg, nintedanib) decrease fibroblast proliferation and have shown benefit in treating IPF. (Choice C) Decreasing alveolar destruction would be helpful in treating chronic obstructive pulmonary disease (COPD). Smoking cessation is the most effective way to prevent and/or slow the rate of progression of COPD. (Choice D) Beta-2 agonists (eg, albuterol, salmeterol) cause bronchodilation via cyclic AMP-mediated smooth muscle relaxation and are effective symptomatic treatments for asthma. These drugs do not significantly reduce airway inflammation. (Choice E) Increasing pulmonary vasodilation helps improve pulmonary arterial hypertension and can be achieved with several classes of drugs, including endothelin receptor antagonists (eg, bosentan), phosphodiesterase inhibitors (eg, sildenafil), and prostacyclin analogs. Educational objective: IgE-binding monoclonal antibodies (eg, omalizumab) are effective in treating asthma that remains uncontrolled despite optimal therapy with bronchodilators and inhaled corticosteroids. IgE-binding monoclonal antibodies reduce airway inflammation by blocking the binding of IgE to the IgE receptors on mast cells and preventing the release of proinflammatory substances, including histamine and leukotrienes. __________ References: Cost-effectiveness of omalizumab in patients with severe persistent allergic asthma. (http://www.ncbi.nlm.nih.gov/pubmed/17298423) Efficacy and safety of subcutaneous omalizumab vs placebo as add-on therapy to corticosteroids for children and adults with asthma: a systematic review. (http://www.ncbi.nlm.nih.gov/pubmed/20688929)

A 42-Year-Old Woman Is Evaluated Due to Frequent Episodes of Shortness