Amanda K Rudman Spergel1, Michelle L Sever2, Jacqueline Johnson2, Michelle A Gill3, Veronique Schulten4, April Frazier4, Carolyn M Kercsmar5, Stephanie Lovinsky-Desir6, Dan A Searing7, Alessandro Sette4,8, Baomei Shao9, Stephen J Teach10, James E Gern11, William W Busse11, Alkis Togias1, Robert A Wood12, Andrew H Liu7. 1. Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 2. Rho, Inc., Durham, NC, USA. 3. Departments of Pediatrics, Internal Medicine, and Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA. 4. La Jolla Institute for Immunology, La Jolla, CA, USA. 5. Department of Pediatrics, Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA. 6. Department of Pediatrics, Division of Pulmonary Medicine, Columbia University Irving Medical Center, New York, NY, USA. 7. Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA. 8. Department of Medicine, University of California San Diego, La Jolla, CA, USA. 9. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA. 10. Children's National Hospital, Washington, DC, USA. 11. School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 12. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Abstract
BACKGROUND: Nasal allergen challenge (NAC) could be a means to assess indication and/or an outcome of allergen-specific therapies, particularly for perennial allergens. NACs are not commonly conducted in children with asthma, and cockroach NACs are not well established. This study's objective was to identify a range of German cockroach extract doses that induce nasal symptoms and to assess the safety of cockroach NAC in children with asthma. METHODS: Ten adults (18-37 years) followed by 25 children (8-14 years) with well-controlled, persistent asthma and cockroach sensitization underwent NAC with diluent followed by up to 8 escalating doses of cockroach extract (0.00381-11.9 µg/mL Bla g 1). NAC outcome was determined by Total Nasal Symptom Score (TNSS) and/or sneeze score. Cockroach allergen-induced T-cell activation and IL-5 production were measured in peripheral blood mononuclear cells. RESULTS: 67% (6/9) of adults and 68% (17/25) of children had a positive NAC at a median response dose of 0.120 µg/mL [IQR 0.0380-0.379 µg/mL] of Bla g 1. Additionally, three children responded to diluent alone and did not receive any cockroach extract. Overall, 32% (11/34) were positive with sneezes alone, 15% (5/34) with TNSS alone, and 21% (7/34) with both criteria. At baseline, NAC responders had higher cockroach-specific IgE (P = .03), lower cockroach-specific IgG/IgE ratios (children, P = .002), and increased cockroach-specific IL-5-producing T lymphocytes (P = .045). The NAC was well tolerated. CONCLUSION: We report the methodology of NAC development for children with persistent asthma and cockroach sensitization. This NAC could be considered a tool to confirm clinically relevant sensitization and to assess responses in therapeutic studies.
BACKGROUND: Nasal allergen challenge (NAC) could be a means to assess indication and/or an outcome of allergen-specific therapies, particularly for perennial allergens. NACs are not commonly conducted in children with asthma, and cockroach NACs are not well established. This study's objective was to identify a range of German cockroach extract doses that induce nasal symptoms and to assess the safety of cockroach NAC in children with asthma. METHODS: Ten adults (18-37 years) followed by 25 children (8-14 years) with well-controlled, persistent asthma and cockroach sensitization underwent NAC with diluent followed by up to 8 escalating doses of cockroach extract (0.00381-11.9 µg/mL Bla g 1). NAC outcome was determined by Total Nasal Symptom Score (TNSS) and/or sneeze score. Cockroach allergen-induced T-cell activation and IL-5 production were measured in peripheral blood mononuclear cells. RESULTS: 67% (6/9) of adults and 68% (17/25) of children had a positive NAC at a median response dose of 0.120 µg/mL [IQR 0.0380-0.379 µg/mL] of Bla g 1. Additionally, three children responded to diluent alone and did not receive any cockroach extract. Overall, 32% (11/34) were positive with sneezes alone, 15% (5/34) with TNSS alone, and 21% (7/34) with both criteria. At baseline, NAC responders had higher cockroach-specific IgE (P = .03), lower cockroach-specific IgG/IgE ratios (children, P = .002), and increased cockroach-specific IL-5-producing T lymphocytes (P = .045). The NAC was well tolerated. CONCLUSION: We report the methodology of NAC development for children with persistent asthma and cockroach sensitization. This NAC could be considered a tool to confirm clinically relevant sensitization and to assess responses in therapeutic studies.
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