BACKGROUND: For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), evidence to guide step-up therapy is lacking. METHODS: We randomly assigned 182 children (6 to 17 years of age), who had uncontrolled asthma while receiving 100 microg offluticasone twice daily, to receive each of three blinded step-up therapies in random order for 16 weeks: 250 microg of fluticasone twice daily (ICS step-up), 100 microg of fluticasone plus 50 microg of a long-acting beta-agonist twice daily (LABA step-up), or 100 microg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up). We used a triple-crossover design and a composite of three outcomes (exacerbations, asthma-control days, and the forced expiratory volume in 1 second) to determine whether the frequency of a differential response to the step-up regimens was more than 25%. RESULTS: A differential response occurred in 161 of 165 patients who were evaluated (P<0.001). The response to LABA step-up therapy was most likely to be the best response, as compared with responses to LTRA step-up (relative probability, 1.6; 95% confidence interval [CI], 1.1 to 2.3; P=0.004) and ICS step-up (relative probability, 1.7; 95% CI, 1.2 to 2.4; P=0.002). Higher scores on the Asthma Control Test before randomization (indicating better control at baseline) predicted a better response to LABA step-up (P=0.009). White race predicted a better response to LABA step-up, whereas black patients were least likely to have a best response to LTRA step-up (P=0.005). CONCLUSIONS: Nearly all the children had a differential response to each step-up therapy. LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up. However, many children had a best response to ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy. (ClinicalTrials.gov number, NCT00395304.) 2010 Massachusetts Medical Society
RCT Entities:
BACKGROUND: For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), evidence to guide step-up therapy is lacking. METHODS: We randomly assigned 182 children (6 to 17 years of age), who had uncontrolled asthma while receiving 100 microg of fluticasone twice daily, to receive each of three blinded step-up therapies in random order for 16 weeks: 250 microg of fluticasone twice daily (ICS step-up), 100 microg of fluticasone plus 50 microg of a long-acting beta-agonist twice daily (LABA step-up), or 100 microg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up). We used a triple-crossover design and a composite of three outcomes (exacerbations, asthma-control days, and the forced expiratory volume in 1 second) to determine whether the frequency of a differential response to the step-up regimens was more than 25%. RESULTS: A differential response occurred in 161 of 165 patients who were evaluated (P<0.001). The response to LABA step-up therapy was most likely to be the best response, as compared with responses to LTRA step-up (relative probability, 1.6; 95% confidence interval [CI], 1.1 to 2.3; P=0.004) and ICS step-up (relative probability, 1.7; 95% CI, 1.2 to 2.4; P=0.002). Higher scores on the Asthma Control Test before randomization (indicating better control at baseline) predicted a better response to LABA step-up (P=0.009). White race predicted a better response to LABA step-up, whereas black patients were least likely to have a best response to LTRA step-up (P=0.005). CONCLUSIONS: Nearly all the children had a differential response to each step-up therapy. LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up. However, many children had a best response to ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy. (ClinicalTrials.gov number, NCT00395304.) 2010 Massachusetts Medical Society
Authors: Mariam Naqvi; Shannon Thyne; Shweta Choudhry; Hui-ju Tsai; Daniel Navarro; Richard A Castro; Sylvette Nazario; Jose R Rodriguez-Santana; Jesus Casal; Alfonso Torres; Rocio Chapela; H Geoffrey Watson; Kelley Meade; Michael LeNoir; Pedro C Avila; William Rodriguez-Cintron; Esteban González Burchard Journal: J Asthma Date: 2007-10 Impact factor: 2.515
Authors: Mariam Naqvi; Haig Tcheurekdjian; Julie A DeBoard; L Keoki Williams; Daniel Navarro; Richard A Castro; Jose R Rodriguez-Santana; Rocio Chapela; H Geoffrey Watson; Kelley Meade; William Rodriguez-Cintron; Michael LeNoir; Shannon M Thyne; Pedro C Avila; Shweta Choudhry; Esteban González Burchard Journal: Ann Allergy Asthma Immunol Date: 2008-06 Impact factor: 6.347
Authors: Christine A Sorkness; Robert F Lemanske; David T Mauger; Susan J Boehmer; Vernon M Chinchilli; Fernando D Martinez; Robert C Strunk; Stanley J Szefler; Robert S Zeiger; Leonard B Bacharier; Gordon R Bloomberg; Ronina A Covar; Theresa W Guilbert; Gregory Heldt; Gary Larsen; Michael H Mellon; Wayne J Morgan; Mark H Moss; Joseph D Spahn; Lynn M Taussig Journal: J Allergy Clin Immunol Date: 2006-11-30 Impact factor: 10.793
Authors: F E Simons; J R Villa; B W Lee; A M Teper; B Lyttle; G Aristizabal; W Laessig; A Schuster; J Perez-Frias; B E Sekerel; J Menten; J A Leff Journal: J Pediatr Date: 2001-05 Impact factor: 4.406
Authors: Harriet Corvol; Anthony De Giacomo; Celeste Eng; Max Seibold; Elad Ziv; Rocio Chapela; Jose R Rodriguez-Santana; William Rodriguez-Cintron; Shannon Thyne; H Geoffrey Watson; Kelley Meade; Michael LeNoir; Pedro C Avila; Shweta Choudhry; Esteban González Burchard Journal: Pharmacogenet Genomics Date: 2009-07 Impact factor: 2.089
Authors: Rajesh Kumar; Max A Seibold; Melinda C Aldrich; L Keoki Williams; Alex P Reiner; Laura Colangelo; Joshua Galanter; Christopher Gignoux; Donglei Hu; Saunak Sen; Shweta Choudhry; Edward L Peterson; Jose Rodriguez-Santana; William Rodriguez-Cintron; Michael A Nalls; Tennille S Leak; Ellen O'Meara; Bernd Meibohm; Stephen B Kritchevsky; Rongling Li; Tamara B Harris; Deborah A Nickerson; Myriam Fornage; Paul Enright; Elad Ziv; Lewis J Smith; Kiang Liu; Esteban González Burchard Journal: N Engl J Med Date: 2010-07-07 Impact factor: 91.245
Authors: Gaëtane C Michaud; Colleen L Channick; Chad R Marion; Robert M Tighe; James A Town; Andrew M Luks; Jeremy B Richards; Sucharita Kher; Prerna Mota; Gina Hong; Natalie E West; Craig Rackley; Luke Neilans; Josanna Rodriguez-Lopez; Hilary DuBrock; Cassie C Kennedy; Diana J Kelm; Carey C Thomson Journal: Ann Am Thorac Soc Date: 2015-09
Authors: Avraham Beigelman; Tonya S King; David Mauger; Robert S Zeiger; Robert C Strunk; H William Kelly; Fernando D Martinez; Robert F Lemanske; Katherine Rivera-Spoljaric; Daniel J Jackson; Theresa Guilbert; Ronina Covar; Leonard B Bacharier Journal: J Allergy Clin Immunol Date: 2013-03-14 Impact factor: 10.793