Two Clinical management trial protocol proposals are included in The Duke/University of Arizona AsthmaNet Center. The adult asthma management trial will assess the role of TNF-alpha antagonists in improving asthma control in obese subjects who remain on control after optimization of pharmacotherapy and treatment of co-morbidities. The pediatric asthma management trial will test the hypothesis that azithromycin, a macrolyte, can be used at the first symptoms of acute asthma exacerbation to prevent such exacerbations, and if this preventive effect is specific for carriers of a genotype in a polymorphism in IL8 (IL8/-159 AA), which we have shown is associated with increased risk of neutrophilic exacerbations. We also propose two brief concept proposals: one in which we will test for the presence of steroid resistance in obese asthmatic subjects, and a second one in which we will determine the effect of myrisolated alanine-rich kinase substrate (MARCKS)-related peptide, which is a potential regulator of mucus secretion, in improving asthma control. Finally, we propose a clinical research skills development core plan that will use the many clinical, genetic and biological and training resources available in both our clinical research units to provide training opportunities for pulmonary and allergy fellows and other trainees in the design and implementation of clinical trials in a network setting. This proposal is leveraged on the complementary strengths on the Duke Asthma Center and the Arizona Respiratory Center in the areas of severe adult asthma and childhood asthma, respectively. The Duke Asthma Center has pioneered work in the cellular and molecular biology of asthma using invasive methods to obtain airway samples, whereas the Arizona Respiratory Center is a leader in the genetics and pharmacogenetics of asthma. Both teams have extensively participated in previous NHLBI-funded asthma networks, and they have access to large populations of both children and adults with asthma of a wide range of severities. These strategies, together with our demonstrated capacity to work effectively in collaborative environments, are unique contributions that the Duke/University of Arizona AsthmaNet Center can make to the AsthmaNet initiative.
In this proposal, we will apply novel genetic and clinical therapeutic approaches to three subgroups of patients that remain unable to control their disease: those who have persistent asthma exacerbations;those who are obese;and those who have excessive production of mucus. If successful, our clinical trials could yield new treatments for difficult to treat asthma in children and adults.
|Sorkness, Christine A; King, Tonya S; Dyer, Anne-Marie et al. (2018) Adapting clinical trial design to maintain meaningful outcomes during a multicenter asthma trial in the precision medicine era. Contemp Clin Trials 77:98-103|
|Cardet, Juan Carlos; Louisias, Margee; King, Tonya S et al. (2018) Income is an independent risk factor for worse asthma outcomes. J Allergy Clin Immunol 141:754-760.e3|
|Morris, Claudia R; Mauger, David T; Suh, Jung H et al. (2018) Glutathione and arginine levels: Predictors for acetaminophen-associated asthma exacerbation? J Allergy Clin Immunol 142:308-311.e9|
|Sheehan, William J; Mauger, David T; Paul, Ian M et al. (2016) Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma. N Engl J Med 375:619-30|
|Denlinger, Loren C; King, Tonya S; Cardet, Juan Carlos et al. (2016) Vitamin D Supplementation and the Risk of Colds in Patients with Asthma. Am J Respir Crit Care Med 193:634-41|
|von Mutius, Erika; Martinez, Fernando D (2016) Inconclusive Results of Randomized Trials of Prenatal Vitamin D for Asthma Prevention in Offspring: Curbing the Enthusiasm. JAMA 315:347-8|
|Jiao, Junfang; King, Tonya S; McKenzie, Matthew et al. (2016) Vitamin D3 therapy in patients with asthma complicated by sinonasal disease: Secondary analysis of the Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma trial. J Allergy Clin Immunol 138:589-592.e2|
|Voraphani, Nipasiri; Martinez, Fernando D (2015) Postnatal growth and the heterogeneity of preschool wheeze. J Pediatr 166:226-8|
|Bacharier, Leonard B; Guilbert, Theresa W; Mauger, David T et al. (2015) Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses: A Randomized Clinical Trial. JAMA 314:2034-2044|
|Castro, Mario; King, Tonya S; Kunselman, Susan J et al. (2014) Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial. JAMA 311:2083-91|
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