Anti-Immunoglobulin E Omalizumab is a subcutaneously injectable recombinant humanized IgG1 monoclonal anti-IgE antibody administered every 2-4 weeks to patients with chronic allergic asthma who are sensitive to at least one airborne allergen and have elevated serum IgE levels (>30 units/mL). Omalizumab reduces circulating free IgE levels by binding to a constant region of the IgE molecule, preventing free IgE from interacting with IgE receptors on mast cells, basophils, and other immune cells at a dose and frequency of administration determined by total serum IgE levels and body weight prior to initiation of therapy. Studies in children with severe asthma have shown that omalizumab has a significant impact on reducing the rate of severe asthma exacerbations and hospitalizations, improving asthma control and quality of life in affected children. The study also showed a significant improvement in lung function and a reduction in steroid requirements after 1 year of omalizumab treatment. The review also showed that omalizumab was significantly effective in reducing the dose of inhaled steroids. Prophylactic omalizumab treatment was found to reduce fall asthma attacks when omalizumab was started 4-6 weeks before returning to school, especially in children with severe asthma who required step 5 treatment as defined by the guidelines. Anti-IL-5 drugs IL-5 is an eosinophilic cytokine that recruits eosinophils from the bone marrow and supports the activation and persistence of these cells, resulting in eosinophilic inflammation in the airways. Three anti-IL-5 biologic therapies have been tested in adolescents and adults with asthma; mepolizumab, ralizumab, and benalizumab. None of these biologic therapies has been tested in children under 12 years of age. mepolizumab and reslizumab are humanized monoclonal antibodies against IL-5. benralizumab is a humanized monoclonal antibody against the IL-5 receptor. Mepolizumab Mepolizumab is a humanized monoclonal antibody that binds directly to IL-5. By binding to circulating IL-5, mepolizumab prevents IL-5 from binding to IL-5R on eosinophils and blocks its action. mepolizumab reduces asthma exacerbations by approximately half in patients with severe eosinophilic asthma, improves quality of life, and provides better control of asthma in patients receiving high-dose inhaled oral glucocorticoid therapy.95 Studies have also shown that a significant increase in FEV1 before bronchodilators with mepolizumab treatment. There were no serious adverse events with mepolizumab; in fact, mepolizumab reduced serious adverse events, possibly due to a beneficial effect on asthma-related serious adverse events. mepolizumab was also shown to improve health-related quality of life in patients with severe eosinophilic asthma. mepolizumab is approved for use in patients 12 years of age and older with absolute eosinophilic at the time of presentation Granulocyte count ≥150 cells/μL or ≥300 cells/μL in the 12 months prior to initiation. asthma at a dose of 100 mg administered subcutaneously every 4 weeks Reslizumab Reslizumab is another humanized monoclonal antibody against IL-5 that, like mepolizumab, blocks the binding of IL-5 to IL-5R. It is currently approved for use in patients with severe asthma who are at least 18 years of age and have an eosinophil count ≥400 cells/μL.94 The recommended dosing regimen is 3 mg/kg administered by intravenous infusion every 4 weeks.100 Studies of Reslizumab have included eosinophilic asthmatics aged 12-75 years with less clinically significant asthma exacerbations compared with placebo, less improved FEV1, and improved health-related quality of life. There was no significant difference in the number of serious adverse events that occurred compared to placebo. Benralizumab Benralizumab is a humanized anti-eosinophil monoclonal antibody against IL-5 receptor alpha that is expressed on the surface of eosinophils and basophils. Two RDBPCTs (phase 3) showed that benralizumab significantly improved asthma exacerbation rates and asthma symptoms in adolescents and adults aged 12-75 years with severe uncontrolled asthma treated with high-dose ICS and LABA. Health-related quality of life also improved significantly in patients treated with benalizumab.97,103 Common adverse effects were worsening asthma, upper respiratory tract infections, and nasopharyngitis. The recommended dose is 30 mg every 4 weeks for the first 3 doses and then every 8 weeks by subcutaneous injection. Anti-IL-4/IL-13 therapy Dupilumab Dupilumab is a humanized monoclonal antibody against IL-4 receptor alpha that blocks the receptor shared by IL-4 and IL-13 and is essential for signal transduction. An RDBPCT study including patients aged 12 years or older with uncontrolled moderate to severe asthma showed that Dupilumab reduced the number of severe asthma exacerbations and increased FEV1, resulting in better control of asthma overall (p<0.001). Another study in adults with glucocorticoid-dependent severe asthma showed that Dupilumab treatment significantly reduced the use of oral glucocorticoids while reducing the incidence of severe exacerbations and increasing FEV1 (P<0.001). dupilumab was recently approved by the FDA as an add-on maintenance therapy for 12-year-old patients with eosinophilic phenotype or oral corticosteroid-dependent asthma. eosinophilic phenotype or oral corticosteroid-dependent asthma in patients 12 years of age and older with moderate-to-severe asthma. The recommended dose is an initial dose of 400-600 mg followed by 200-300 mg given every other week. Novel biologic agents under investigation CRTh2 is a prostaglandin D2 (PGD2) receptor expressed on adaptive and innate immune cells. binding of PGD2 to the CRTh2 receptor mediates chemotaxis of ILC2 and Th2 cells, leading to the type 2 cytokines IL-4 , IL-5, and IL-13 release.Fevipiprant is a CRTh2 antagonist.Phase 3 studies with Fevipiprant have shown improved FEV1, improved asthma control, and reduced sputum eosinophil counts, particularly in patients with high T2-hyper asthma.109,110 Thymic stromal lymphopoietin (TSLP) is an airway-derived TSLP acts on dendritic cells, mast cells, ILC-2 cells, and eosinophils.TSLP triggers the secretion of IL-4, IL-5, and IL-13 by Th2 cells.tezepimab is a novel anti-TLSP monoclonal antibody. In a phase 3 trial, tezepelumab reduced the frequency of exacerbations and significantly increased pre-bronchodilator FEV1 in the adult population.111 Current evidence on these biologic therapies is only for adults, and completed studies do not include children. Bronchial Thermoplasty Bronchial thermoplasty is a bronchoscopic therapy that delivers radiofrequency energy to the airways. Bronchial thermoplasty reduces airway smooth muscle mass and smooth muscle hypertrophy. The FDA approves bronchial thermoplasty for the treatment of adults with severe asthma whose symptoms are uncontrolled despite treatment with inhaled corticosteroids and long-acting bronchodilators. The prognosis of bronchial thermoplasty for patients with severe asthma is unknown. It improves quality of life and reduces missed school/work days, but leads to higher risk of hospitalization and adverse events and higher costs. The current literature is for adults only. It is not recommended as a treatment option for children.